REFLECT-3

CompletedPhase 3Results posted

Rosiglitazone (Extended Release Tablets) As Adjunctive Therapy In Subjects With Mild To Moderate Alzheimer's Disease

A 54 Week, Double-blind, Randomised, Placebo-controlled, Parallel Group Study to Investigate the Effects of Rosiglitazone (Extended Release Tablets) as Adjunctive Therapy to Acetylcholinesterase Inhibitors on Cognition and Overall Clinical Response in APOE4-stratified Subjects With Mild to Moderate Alzheimer's Disease

Lead sponsor

GlaxoSmithKline

Asset

Rosiglitazone

Listed sites

194

Recruiting sites

Enrollment

1,468

actual

Study population

Alzheimer’s disease

Key I/E criteria

•mild-to-moderate AD•MMSE 10-26•Study partner/caregiver required

Primary endpoints

•ADAS-Cog•Clinical Dementia Rating-Sum of Boxes (CDR-SB)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study IDAVA102670

NCT IDNCT00348140

Timeline

Milestones

Study first posted2006-07-04estimated

Study start2006-07-12actual

Primary completion2009-03-20actual

Study completion2009-03-20actual

Last update posted2017-09-05actual

Results first posted2017-09-05actual

Assets

Drug assets

Rosiglitazone

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age90 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

A subject will be eligible for inclusion in this study only if all of the following criteria apply:

•Male or female subject with a clinical diagnosis of probable Alzheimer's disease in accordance with NINCDS-ADRDA criteria (Appendix 2).

(Note: National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and Alzheimer's Disease and Related Disorders Association (ADRDA).)

•Subject has mild to moderate Alzheimer's disease as defined by a MMSE score 10 to 26 inclusive at Screening.

•Hachinski Ischemia Score ≤ 4 at Screening (See Appendix 3).

•Age ≥50 and ≤90 years.

•At least 6 months of ongoing acetylcholinesterase inhibitor therapy for Alzheimer's disease, with stable dosing for at least the last 2 months (and with no intent to change for the duration of the study).

•Current use of medication is in accordance with the criteria listed in Table 2 (Permitted Medications, Section 8.1).

•Female subjects must be post-menopausal (i.e. >1 year without menstrual period), surgically sterile, or agree to use adequate method of contraception (Appendix 4) for the duration of the study. Female subjects who are pre-menopausal or who have been post-menopausal for <1 year must undertake pregnancy testing (urine test) at Visit 1, which must be negative.

•Brain CT or MRI scan performed within the past 12 months or at Screening, showing no evidence of any other potential cause of dementia other than Alzheimer's disease.

(Note: Questionable CT or MRI scans should be discussed with the medical monitor, using central imaging guidelines.)

•Neurological exam without focal changes (excluding changes attributable to AD or peripheral trauma).

•Subject has the ability to comply with procedures for cognitive and other testing.

•Subject lives with (or has substantial periods of contact with) a regular caregiver who is willing to attend all visits, oversee the subject's compliance with protocol-specified procedures and study medication, and report on subject's status.

(Note: A non-cohabiting caregiver must spend sufficient time with the subject so that, in the opinion of the Investigator, the caregiver can reliably assess cognitive function, activities and behavior, and report on the subject's compliance and health. As caregiver time spent with a potential subject is anticipated to be highly variable across countries and cultures, GSK will consider a variety of different measures by which this stipulation may be met, and GSK should be consulted if adequacy of a caregiver situation is in doubt. However, as guidance, the ability for a caregiver to meet his/her expected responsibilities for this study would normally be possible when the caregiver spends no less than 10 hours per week with the subject, divided over multiple days.)

•Subject has provided full written informed consent prior to the performance of any protocol-specified procedure; or if unable to provide informed consent due to cognitive status, full written informed consent on behalf of the subject has been provided by a legally acceptable representative.

(Note: Consent by legally acceptable representative is allowed where this is in accordance with local laws, regulations and ethics committee policy.)

•Caregiver has provided full written informed consent on his/her own behalf prior to the performance of any protocol-specified procedure.

•Subjects considered for enrolment must have a QTc (either QTc B (Bazett's correction) or QTc F (Fridericia's correction)) <450msec at Visit 1, with the exception of subjects with bundle branch block (for whom either QTc B or QTc F must be <480msec).

(Note: For the purposes of these criteria, QTc B is defined as (QT interval [msec]) / (square root of RR interval [seconds]); and QTc F is defined as (QT interval [msec]) / (cube root of RR interval [seconds]).)

Exclusion criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

•Diagnosis of possible, probable, or definite vascular dementia in accordance with NINDS-AIREN criteria (Appendix 5).

(Note: National Institute of Neurological Disorders and Stroke (NINDS) and Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN).)

•History or evidence of any other CNS disorder that could be interpreted as a cause of dementia: e.g. cerebrovascular disease (stroke, hemorrhage), structural abnormality, epilepsy, infectious or inflammatory/demyelinating CNS conditions, Parkinson's disease.

•Evidence of the following disorders: current vitamin B12 deficiency, positive syphilis serology, or active thyroid dysfunction (particularly that suggestive of hypothyroidism), including abnormally high or low serum levels of thyroid stimulating hormone (TSH), that are clinically significant in the opinion of the investigator.

(Note: Testing is required for each parameter only when no result is available from previous 12 months.)

•History of Type 1 diabetes mellitus or secondary diabetes mellitus.

•Type 2 diabetes mellitus where the subject is being treated with insulin, a PPARγ agonist, or an insulin secretagogue (e.g. a sulfonylurea or glitinide).

•Any patient with an HbA1c ≥8.5%. (See Section 6.3.8.4 for Safety Measures for Enrolled Subjects with Type 2 Diabetes Mellitus.)

•History or clinical/investigational evidence of congestive heart failure defined by the New York Heart Association criteria (Class I to IV cardiac status; Appendix 6).

•History of cardiovascular event within the last 6 months (i.e. intervention, percutaneous coronary intervention, vascular surgery, acute coronary syndrome [non Q-wave myocardial infarction, Q-wave myocardial infarction, unstable angina] or significant arrhythmia; or major intervention (e.g. cardiac surgery or angiography plus stenting) scheduled).

•History of significant psychiatric illness such as schizophrenia or bipolar affective disorder that in the opinion of the Investigator would interfere with participation in the study, major depressive disorder (according to DSM-IV) in the past year, or current active depression requiring initiation of treatment.

(Note: If not currently treated, but active depression is suspected, the Cornell Scale for Depression in Dementia (CSDD, Appendix 7) can be used by the Investigator as a guide for deciding whether a prospective subject requires treatment. If the subject has a CSDD score >7, the Investigator should decide if the subject has depression in need of prescribed medication, and a CSDD >12 is considered a strong indicator that treatment is needed. Subjects will be allowed to re-screen after their depression has been adequately managed for >3 months.)

•History or presence of gastro-intestinal, hepatic, or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs, or any other clinically relevant abnormality, medical or psychiatric condition, which, in the opinion of the Investigator, makes the subject unsuitable for inclusion in the study.

•Clinically significant peripheral edema at the time of screening.

•Current or recent drug or alcohol abuse or dependence (defined by DSM-IV criteria for substance-related disorders), or recent or remote history of the same if that could be a contributing factor to the dementia.

•Systolic blood pressure >165 or <90 mmHg or diastolic blood pressure >95 or <60 mmHg at the time of screening.

•Clinically significant anemia (i.e. hemoglobin <11 g/dL for males or <10 g/dL for females) or presence of hemoglobinopathies which would prevent accurate assessment of HbA1c.

•Abnormal kidney function tests (>1.5 times the upper limit of normal (ULN)).

•ALT, AST, or alkaline phosphatase values >2.5 times the ULN, total bilirubin values >1.5 times the ULN, or history of severe hepatobiliary disease (e.g. hepatitis B or C, or cirrhosis, Child-Pugh Class B/C).

(Note: For subjects with a diagnosis of Gilberts Syndrome and an isolated increase in total bilirubin >1.5 ULN, fractionation should be performed. If all of the following conditions are met, the patient may enter or remain in the study, even if total bilirubin >1.5 ULN:

•an elevated unconjugated (indirect) bilirubin;

•the percentage of direct bilirubin <35%;

•ALT, AST, and alkaline phosphatase <2.5 ULN if subject is in screening (<2.0 ULN for Canadian subjects only), or ≤3 ULN if subject is already randomized into the study)

•History of a bone marrow transplant.

•Subject is unable (with assistance, if appropriate) to take study medication as prescribed throughout the study or is at risk of non-compliance with study medication or procedures.

•Subject is an immediate family member or employee of the participating Investigator, of any of the participating site staff, or of GSK.

•In France, a subject is neither affiliated with nor a beneficiary of a social security category.

•The French subject has participated in any study using an investigational drug during the previous 30 days or 5 half-lives (whichever is longer).

•Cognitive tasks prescribed for cognitive rehabilitation and performed under medical supervision are prohibited for 6 months prior to Screening, as well as for the duration of the study.

Endpoints (62)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Global cognition

Other (unclassified)

Safety / tolerability / PK

Behavior / neuropsychiatric

Caregiver / quality of life

Function / daily living

Global cognition

24 endpoints

Primary/protocol endpoint

Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 48, as a Function of APOE ε4 Status in APOE4 Negatives Cohort

Time frame:Baseline (Week 0) and Week 48

ADAS-Cog

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in ADAS-Cog Total Score at Week 48, as a Function of APOE ε4 Status in All Except E4/E4s Cohort

Time frame:Baseline (Week 0) and Week 48

ADAS-Cog

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in ADAS-Cog Total Score at Week 48, as a Function of APOE ε4 Status in Full Population Cohort

Time frame:Baseline (Week 0) and Week 48

ADAS-Cog

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score at Week 48, as a Function of APOE ε4 Status in APOE4 Negatives Cohort

Time frame:Baseline (Week 0) and Week 48

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in CDR-SB Score at Week 48, as a Function of APOE ε4 Status in All Except E4/E4s Cohort

Time frame:Baseline (Week 0) and Week 48

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in CDR-SB Score at Week 48, as a Function of APOE ε4 Status in Full Population Cohort

Time frame:Baseline (Week 0) and Week 48

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Primary/registry result

Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 48, as a Function of APOE ε4 Status in APOE4 Negatives Cohort

Time frame:Baseline (Week 0) and Week 48

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Scores on a scale	Standard error
Placebon=145 Participants	3.2	0.54
RSG XR 2mgn=142 Participants	3.5	0.53
RSG XR 8mgn=137 Participants	4.0	0.63

Mean Difference (Net)0.395% CI-1.2 - 1.8p0.739Mixed model for repeated measures

Mean Difference (Net)0.895% CI-0.8 - 2.4p0.343Mixed model for repeated measures

Primary/registry result

Change From Baseline in ADAS-Cog Total Score at Week 48, as a Function of APOE ε4 Status in All Except E4/E4s Cohort

Time frame:Baseline (Week 0) and Week 48

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Scores on a scale	Standard error
Placebon=303 Participants	3.8	0.38
RSG XR 2mgn=302 Participants	3.6	0.35
RSG XR 8mgn=274 Participants	3.8	0.41

Mean Difference (Net)-0.195% CI-1.1 - 0.9p0.783Mixed model for repeated measures

Mean Difference (Net)0.095% CI-1.1 - 1.1p0.940Mixed model for repeated measures

Primary/registry result

Change From Baseline in ADAS-Cog Total Score at Week 48, as a Function of APOE ε4 Status in Full Population Cohort

Time frame:Baseline (Week 0) and Week 48

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Scores on a scale	Standard error
Placebon=361 Participants	3.9	0.35
RSG XR 2mgn=343 Participants	3.8	0.33
RSG XR 8mgn=331 Participants	3.8	0.36

Mean Difference (Net)-0.195% CI-1.1 - 0.8p=0.763Mixed model for repeated measures

Mean Difference (Net)-0.195% CI-1.1 - 0.9p=0.800Mixed model for repeated measures

Primary/registry result

Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score at Week 48, as a Function of APOE ε4 Status in APOE4 Negatives Cohort

Time frame:Baseline (Week 0) and Week 48

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Scores on a scale	Standard error
Placebon=146 Participants	1.8	0.20
RSG XR 2mgn=144 Participants	1.7	0.20
RSG XR 8mgn=138 Participants	1.7	0.17

Mean Difference (Net)-0.195% CI-0.7 - 0.4p0.611Mixed model for repeated measures

Mean Difference (Net)-0.195% CI-0.6 - 0.4p0.741Mixed model for repeated measures

Primary/registry result

Change From Baseline in CDR-SB Score at Week 48, as a Function of APOE ε4 Status in All Except E4/E4s Cohort

Time frame:Baseline (Week 0) and Week 48

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Scores on a scale	Standard error
Placebon=302 Participants	1.8	0.13
RSG XR 2mgn=311 Participants	1.8	0.13
RSG XR 8mgn=272 Participants	1.7	0.13

Mean Difference (Net)0.095% CI-0.4 - 0.3p0.913Mixed model for repeated measures

Mean Difference (Net)-0.195% CI-0.5 - 0.2p0.481Mixed model for repeated measures

Primary/registry result

Change From Baseline in CDR-SB Score at Week 48, as a Function of APOE ε4 Status in Full Population Cohort

Time frame:Baseline (Week 0) and Week 48

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Scores on a scale	Standard error
Placebon=360 Participants	1.9	0.12
RSG XR 2mgn=349 Participants	1.8	0.13
RSG XR 8mgn=331 Participants	1.8	0.12

Mean Difference (Net)-0.195% CI-0.4 - 0.2p0.557Mixed model for repeated measures

Mean Difference (Net)-0.195% CI-0.5 - 0.2p0.404Mixed model for repeated measures

Secondary/protocol endpoint

Change From Baseline in ADAS-Cog Total Score at Weeks 8, 16, 24 and 36

Time frame:Baseline (Week 0) and Week 8, 16, 24, 36

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in CDR-SB Score at Weeks 12, 24 and 36

Time frame:Baseline (Week 0) and Week 12, 24, 36

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/protocol endpoint

Change From Screening in Mini Mental State Examination (MMSE) Total Score

Time frame:Screening (Week -4) and Week 48

Mini-Mental State Examination (MMSE)

concentration, descriptive

Secondary/protocol endpoint

Change in ADAS-Cog Total Score for Observed Cases at Week 54 Compared to Week 48

Time frame:Week 48 and Week 54

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Change in CDR-SB Total Score for Observed Cases at Week 54 Compared to Week 48

Time frame:Week 48 and Week 54

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Short Term Memory Assessment

Time frame:Baseline (Week 0) and upto Week 48

ADAS-Cog

change from baseline, improvement

Secondary/registry result

Change From Baseline in ADAS-Cog Total Score at Weeks 8, 16, 24 and 36

Time frame:Baseline (Week 0) and Week 8, 16, 24, 36

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Scores on a scale	Standard error
PlaceboWeek 8n=460 Participants	0.1	0.23
Week 16n=440 Participants	0.2	0.24
Week 24n=422 Participants	1.1	0.26
Week 36n=383 Participants	2.6	0.31
RSG XR 2mgWeek 8n=451 Participants	0.2	0.23
Week 16n=430 Participants	0.3	0.23
Week 24n=408 Participants	1.5	0.28
Week 36n=381 Participants	2.8	0.29
RSG XR 8mgWeek 8n=440 Participants	0.3	0.23
Week 16n=411 Participants	0.2	0.24
Week 24n=379 Participants	1.1	0.27
Week 36n=352 Participants	2.6	0.31

Mean Difference (Net)0.195% CI-0.5 - 0.8p0.633Mixed model for repeated measures

For Week 8

Mean Difference (Net)0.295% CI-0.4 - 0.8p0.575Mixed model for repeated measures

For Week 8

Mean Difference (Net)0.195% CI-0.6 - 0.7p0.820Mixed model for repeated measures

For Week 16

Mean Difference (Net)0.095% CI-0.7 - 0.6p0.908Mixed model for repeated measures

For Week 16

Mean Difference (Net)0.495% CI-0.3 - 1.1p0.292Mixed model for repeated measures

For Week 24

Mean Difference (Net)0.095% CI-0.7 - 0.7p0.978Mixed model for repeated measures

For Week 24

Mean Difference (Net)0.295% CI-0.6 - 1.0p0.691Mixed model for repeated measures

For Week 36

Mean Difference (Net)-0.195% CI-0.9 - 0.8p0.849Mixed model for repeated measures

For Week 36

Secondary/registry result

Change From Baseline in CDR-SB Score at Weeks 12, 24 and 36

Time frame:Baseline (Week 0) and Week 12, 24, 36

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Scores on a scale	Standard error
PlaceboWeek 12n=437 Participants	0.3	0.07
Week 24n=413 Participants	0.9	0.10
Week 36n=382 Participants	1.4	0.11
RSG XR 2mgWeek 12n=432 Participants	0.4	0.08
Week 24n=400 Participants	0.8	0.10
Week 36n=374 Participants	1.3	0.11
RSG XR 8mgWeek 12n=422 Participants	0.3	0.07
Week 24n=376 Participants	0.9	0.09
Week 36n=350 Participants	1.3	0.10

Mean Difference (Net)0.095% CI-0.2 - 0.2p0.938Mixed model for repeated measures

For Week 12

Mean Difference (Net)0.095% CI-0.2 - 0.2p0.887Mixed model for repeated measures

For Week 12

Mean Difference (Net)-0.195% CI-0.4 - 0.2p0.465Mixed model for repeated measures

For Week 24

Mean Difference (Net)0.195% CI-0.2 - 0.3p0.596Mixed model for repeated measures

For Week 24

Mean Difference (Net)-0.195% CI-0.4 - 0.2p0.452Mixed model for repeated measures

For Week 36

Mean Difference (Net)-0.195% CI-0.4 - 0.2p0.429Mixed model for repeated measures

For Week 36

Secondary/registry result

Change From Screening in Mini Mental State Examination (MMSE) Total Score

Time frame:Screening (Week -4) and Week 48

Mini-Mental State Examination (MMSE)

concentration, descriptive

Posted result

Group	Value (least_squares_mean), Scores on a scale	Standard error
Placebon=366 Participants	-2.0	0.21
RSG XR 2mgn=356 Participants	-2.3	0.22
RSG XR 8mgn=336 Participants	-2.0	0.22

Mean Difference (Net)-0.395% CI-0.8 - 0.3p0.386ANCOVA

Mean Difference (Net)0.095% CI-0.6 - 0.6p0.999ANCOVA

Secondary/registry result

Change in ADAS-Cog Total Score for Observed Cases at Week 54 Compared to Week 48

Time frame:Week 48 and Week 54

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Scores on a scale	Standard error
Placebon=338 Participants	1.0	0.27
RSG XR 2mgn=319 Participants	0.4	0.28
RSG XR 8mgn=307 Participants	0.5	0.28

Mean Difference (Net)-0.695% CI-1.3 - 0.1p0.106ANCOVA

Mean Difference (Net)-0.495% CI-1.2 - 0.3p0.229ANCOVA

Secondary/registry result

Change in CDR-SB Total Score for Observed Cases at Week 54 Compared to Week 48

Time frame:Week 48 and Week 54

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Scores on a scale	Standard error
Placebon=335 Participants	0.3	0.07
RSG XR 2mgn=316 Participants	0.2	0.08
RSG XR 8mgn=303 Participants	0.3	0.08

Mean Difference (Net)-0.195% CI-0.3 - 0.1p0.324ANCOVA

Mean Difference (Net)0.095% CI-0.2 - 0.2p0.987ANCOVA

Secondary/registry result

Change From Baseline in Short Term Memory Assessment

Time frame:Baseline (Week 0) and upto Week 48

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Scores on an scale	Standard error
PlaceboWeek 8n=453 Participants	-0.2	0.14
Week 16n=433 Participants	-0.3	0.14
Week 24n=414 Participants	-0.0	0.15
Week 36n=376 Participants	0.6	0.15
Week 48n=354 Participants	0.6	0.16
RSG XR 2mgWeek 8n=449 Participants	-0.2	0.14
Week 16n=423 Participants	-0.4	0.14
Week 24n=401 Participants	-0.0	0.15
Week 36n=374 Participants	0.7	0.15
Week 48n=335 Participants	0.6	0.17
RSG XR 8mgWeek 8n=437 Participants	-0.1	0.13
Week 16n=406 Participants	-0.5	0.13
Week 24n=373 Participants	0.2	0.14
Week 36n=349 Participants	0.7	0.15
Week 48n=329 Participants	0.9	0.16

Mean Difference (Net)-0.195% CI-0.4 - 0.3p0.748Mixed model for repeated measures

For Week 8

Mean Difference (Net)0.195% CI-0.3 - 0.5p0.617Mixed model for repeated measures

For Week 8

Mean Difference (Net)-0.195% CI-0.5 - 0.3p0.708Mixed model for repeated measures

Week 16

Mean Difference (Net)-0.295% CI-0.5 - 0.2p0.400Mixed model for repeated measures

Week 16

Mean Difference (Net)0.095% CI-0.4 - 0.4p0.928Mixed model for repeated measures

For Week 24

Mean Difference (Net)0.395% CI-0.1 - 0.7p0.178Mixed model for repeated measures

For Week 24

Mean Difference (Net)0.195% CI-0.3 - 0.5p0.626Mixed model for repeated measures

For Week 36

Mean Difference (Net)0.195% CI-0.3 - 0.5p0.608Mixed model for repeated measures

For Week 36

Mean Difference (Net)0.095% CI-0.5 - 0.4p0.865Mixed model for repeated measures

For Week 48

Mean Difference (Net)0.395% CI-0.1 - 0.8p0.149Mixed model for repeated measures

For Week 48

Function / daily living

2 endpoints

Secondary/protocol endpoint

Change From Baseline in Disability Assessment for Dementia (DAD) Total Score

Time frame:Baseline (Week 0) and Week 8, 16, 24, 48

change from baseline, improvement

Secondary/registry result

Change From Baseline in Disability Assessment for Dementia (DAD) Total Score

Time frame:Baseline (Week 0) and Week 8, 16, 24, 48

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Scores on a scale	Standard error
PlaceboWeek 8n=464 Participants	-2.3	0.50
Week 16n=443 Participants	-3.0	0.57
Week 24n=427 Participants	-4.6	0.60
Week 48n=373 Participants	-9.5	0.81
RSG XR 2mgWeek 8n=455 Participants	-1.2	0.50
Week 16n=433 Participants	-2.3	0.55
Week 24n=412 Participants	-2.8	0.62
Week 48n=359 Participants	-9.4	0.81
RSG XR 8mgWeek 8n=442 Participants	-2.3	0.46
Week 16n=417 Participants	-3.9	0.59
Week 24n=387 Participants	-4.7	0.63
Week 48n=342 Participants	-10.4	0.82

Mean Difference (Net)1.195% CI-0.2 - 2.5p0.090Mixed model for repeated measures

For Week 8

Mean Difference (Net)0.095% CI-1.3 - 1.3p0.957Mixed model for repeated measures

For Week 8

Mean Difference (Net)0.795% CI-0.9 - 2.2p0.395Mixed model for repeated measures

For Week 16

Mean Difference (Net)-0.995% CI-2.5 - 0.7p0.275Mixed model for repeated measures

For Week 16

Mean Difference (Net)1.795% CI0.1 - 3.4p0.039Mixed model for repeated measures

For Week 24

Mean Difference (Net)-0.195% CI-1.8 - 1.6p0.895Mixed model for repeated measures

For Week 24

Mean Difference (Net)0.195% CI-2.1 - 2.3p0.914Mixed model for repeated measures

For Week 48

Mean Difference (Net)-0.995% CI-3.2 - 1.3p0.430Mixed model for repeated measures

For Week 48

Behavior / neuropsychiatric

6 endpoints

Secondary/protocol endpoint

Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score

Time frame:Baseline (Week 0) and Week 8, 16, 24, 48

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Scale Total Score- Thermometer Score

Time frame:Baseline (Week 0) and Week 12, 36, 48

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in EQ-5D Scale Total Score- Utility Score

Time frame:Baseline (Week 0) and Week 12, 36, 48

change from baseline, improvement

Secondary/registry result

Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score

Time frame:Baseline (Week 0) and Week 8, 16, 24, 48

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Scores on a scale	Standard error
PlaceboWeek 8n=464 Participants	-0.0	0.32
Week 16n=443 Participants	0.1	0.34
Week 24n=428 Participants	1.3	0.43
Week 48n=374 Participants	2.6	0.52
RSG XR 2mgWeek 8n=457 Participants	-0.3	0.33
Week 16n=433 Participants	0.2	0.37
Week 24n=413 Participants	0.3	0.41
Week 48n=360 Participants	1.5	0.49
RSG XR 8mgWeek 8n=443 Participants	-0.2	0.31
Week 16n=417 Participants	0.1	0.37
Week 24n=384 Participants	0.2	0.39
Week 48n=342 Participants	1.9	0.50

Mean Difference (Net)-0.295% CI-1.1 - 0.6p0.583Mixed model for repeated measures

For Week 8

Mean Difference (Net)-0.295% CI-1.1 - 0.6p0.631Mixed model for repeated measures

For Week 8

Mean Difference (Net)0.195% CI-0.8 - 1.1p0.812Mixed model for repeated measures

For Week 16

Mean Difference (Net)0.095% CI-0.9 - 1.0p0.952Mixed model for repeated measures

For Week 16

Mean Difference (Net)-0.995% CI-2.1 - 0.2p0.117Mixed model for repeated measures

For Week 24

Mean Difference (Net)-1.095% CI-2.1 - 0.1p0.074Mixed model for repeated measures

For Week 24

Mean Difference (Net)-1.095% CI-2.4 - 0.3p0.141Mixed model for repeated measures

For Week 48

Mean Difference (Net)-0.795% CI-2.1 - 0.7p0.331Mixed model for repeated measures

For Week 48

Secondary/registry result

Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Scale Total Score- Thermometer Score

Time frame:Baseline (Week 0) and Week 12, 36, 48

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Scores on a scale	Standard error
PlaceboThermometer score Week 12n=442 Participants	2.4	0.82
Thermometer score Week 36n=396 Participants	1.7	0.87
Thermometer score Week 48n=366 Participants	2.1	0.91
RSG XR 2mgThermometer score Week 12n=439 Participants	-0.0	0.89
Thermometer score Week 36n=383 Participants	1.3	0.94
Thermometer score Week 48n=354 Participants	-0.5	1.00
RSG XR 8mgThermometer score Week 12n=424 Participants	0.1	0.87
Thermometer score Week 36n=361 Participants	-0.4	0.95
Thermometer score Week 48n=342 Participants	-1.4	0.96

Mean Difference (Net)-2.495% CI-4.7 - -0.1p0.043Mixed model for repeated measures

Thermometer score Week 12

Mean Difference (Net)-2.295% CI-4.5 - 0.1p0.056Mixed model for repeated measures

Thermometer score Week 12

Mean Difference (Net)-0.495% CI-2.8 - 2.1p0.758Mixed model for repeated measures

Thermometer score Week 36

Mean Difference (Net)-2.095% CI-4.5 - 0.5p0.109Mixed model for repeated measures

Thermometer score Week 36

Mean Difference (Net)-2.695% CI-5.2 - -0.0p0.050Mixed model for repeated measures

Thermometer score Week 48

Mean Difference (Net)-3.495% CI-6.0 - -0.9p0.009Mixed model for repeated measures

Thermometer score Week 48

Secondary/registry result

Change From Baseline in EQ-5D Scale Total Score- Utility Score

Time frame:Baseline (Week 0) and Week 12, 36, 48

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Scores on a scale	Standard error
PlaceboUltility score Week 12n=442 Participants	-0.02	0.009
Utility score Week 36n=397 Participants	-0.03	0.011
Utility score Week 48n=368 Participants	-0.03	0.011
RSG XR 2mgUltility score Week 12n=441 Participants	-0.01	0.009
Utility score Week 36n=385 Participants	-0.03	0.011
Utility score Week 48n=355 Participants	-0.05	0.012
RSG XR 8mgUltility score Week 12n=423 Participants	-0.03	0.009
Utility score Week 36n=362 Participants	-0.06	0.010
Utility score Week 48n=342 Participants	-0.04	0.010

Mean Difference (Net)0.0195% CI-0.02 - 0.03p0.662Mixed model for repeated measures

Ultility score Week 12

Mean Difference (Net)-0.0195% CI-0.03 - 0.02p0.503Mixed model for repeated measures

Ultility score Week 12

Mean Difference (Net)0.0095% CI-0.03 - 0.03p0.892Mixed model for repeated measures

Utility score Week 36

Mean Difference (Net)-0.0395% CI-0.05 - 0.00p0.083Mixed model for repeated measures

Utility score Week 36

Mean Difference (Net)-0.0195% CI-0.05 - 0.02p0.366Mixed model for repeated measures

Utility score Week 48

Mean Difference (Net)-0.0095% CI-0.03 - 0.02p0.769Mixed model for repeated measures

Utility score Week 48

Caregiver / quality of life

4 endpoints

Secondary/protocol endpoint

Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours

Time frame:Baseline (Week 0) and Week 12, 24, 36, 48

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Alzheimer's Carer's Quality of Life Instrument (ACQLI) Score

Time frame:Baseline (Week 0) and Week 12, 36, 48

change from baseline, improvement

Secondary/registry result

Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours

Time frame:Baseline (Week 0) and Week 12, 24, 36, 48

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Caregiver hours	Standard error
PlaceboQ1 Week 12n=449 Participants	-2.4	2.72
Q1 Week 24n=427 Participants	7.4	3.43
Q1 Week 36n=393 Participants	11.2	4.36
Q1 Week 48n=371 Participants	15.7	4.14
Q2 Week 12n=448 Participants	-1.1	4.06
Q2 Week 24n=427 Participants	5.6	4.41
Q2 Week 36n=393 Participants	16.4	5.52
Q2 Week 48n=371 Participants	21.8	5.62
RSG XR 2mgQ1 Week 12n=441 Participants	1.8	2.56
Q1 Week 24n=411 Participants	9.0	2.92
Q1 Week 36n=383 Participants	12.7	3.70
Q1 Week 48n=357 Participants	19.7	4.06
Q2 Week 12n=440 Participants	5.8	3.70
Q2 Week 24n=410 Participants	15.6	4.90
Q2 Week 36n=382 Participants	23.4	6.10
Q2 Week 48n=356 Participants	26.0	5.69
RSG XR 8mgQ1 Week 12n=425 Participants	3.5	2.68
Q1 Week 24n=385 Participants	10.9	3.69
Q1 Week 36n=359 Participants	13.4	4.09
Q1 Week 48n=341 Participants	19.2	4.54
Q2 Week 12n=425 Participants	6.4	4.04
Q2 Week 24n=385 Participants	12.3	4.79
Q2 Week 36n=359 Participants	15.2	4.53
Q2 Week 48n=341 Participants	21.6	4.92

Mean Difference (Net)4.195% CI-2.9 - 11.2p0.251Mixed model for repeated measures

Q1 Week 12

Mean Difference (Net)5.995% CI-1.4 - 13.2p0.113Mixed model for repeated measures

Q1 Week 12

Mean Difference (Net)1.695% CI-7.1 - 10.2p0.723Mixed model for repeated measures

Q1 Week 24

Mean Difference (Net)3.595% CI-6.3 - 13.2p0.482Mixed model for repeated measures

Q1 Week 24

Mean Difference (Net)1.595% CI-9.5 - 12.6p0.785Mixed model for repeated measures

Q1 Week 36

Mean Difference (Net)2.295% CI-9.4 - 13.8p0.711Mixed model for repeated measures

Q1 Week 36

Mean Difference (Net)4.095% CI-7.2 - 15.2p0.484Mixed model for repeated measures

Q1 Week 48

Mean Difference (Net)3.495% CI-8.5 - 15.4p0.572Mixed model for repeated measures

Q1 Week 48

Mean Difference (Net)6.895% CI-3.6 - 17.3p0.197Mixed model for repeated measures

Q2 Week 12

Mean Difference (Net)7.495% CI-3.5 - 18.4p0.183Mixed model for repeated measures

Q2 Week 12

Mean Difference (Net)10.095% CI-2.6 - 22.6p0.121Mixed model for repeated measures

Q2 Week 24

Mean Difference (Net)6.895% CI-5.8 - 19.3p0.291Mixed model for repeated measures

Q2 Week 24

Mean Difference (Net)7.095% CI-8.9 - 22.9p0.389Mixed model for repeated measures

Q2 Week 36

Mean Difference (Net)-1.295% CI-15.0 - 12.6p0.865Mixed model for repeated measures

Q2 Week 36

Mean Difference (Net)4.295% CI-11.3 - 19.6p0.596Mixed model for repeated measures

Q2 Week 48

Mean Difference (Net)-0.295% CI-14.7 - 14.2p0.975Mixed model for repeated measures

Q2 Week 48

Secondary/registry result

Change From Baseline in Alzheimer's Carer's Quality of Life Instrument (ACQLI) Score

Time frame:Baseline (Week 0) and Week 12, 36, 48

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Scores on a scale	Standard error
PlaceboWeek 12n=447 Participants	0.3	0.19
Week 36n=400 Participants	1.2	0.24
Week 48n=373 Participants	1.1	0.27
RSG XR 2mgWeek 12n=443 Participants	0.1	0.19
Week 36n=384 Participants	0.8	0.25
Week 48n=356 Participants	1.3	0.29
RSG XR 8mgWeek 12n=419 Participants	0.2	0.21
Week 36n=361 Participants	1.4	0.25
Week 48n=341 Participants	1.2	0.27

Mean Difference (Net)-0.295% CI-0.7 - 0.3p0.529Mixed model for repeated measures

Week 12

Mean Difference (Net)-0.195% CI-0.7 - 0.4p0.620Mixed model for repeated measures

Week 12

Mean Difference (Net)-0.495% CI-1.0 - 0.3p0.284Mixed model for repeated measures

Week 36

Mean Difference (Net)0.295% CI-0.4 - 0.9p0.488Mixed model for repeated measures

Week 36

Mean Difference (Net)0.295% CI-0.5 - 1.0p0.549Mixed model for repeated measures

Week 48

Mean Difference (Net)0.195% CI-0.6 - 0.9p0.780Mixed model for repeated measures

For Week 48

Safety / tolerability / PK

10 endpoints

Secondary/protocol endpoint

Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs

Time frame:Upto Week 48

event count, event

Secondary/protocol endpoint

Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Weight

Time frame:Upto Week 54

change from baseline, event

Secondary/protocol endpoint

Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Time frame:Upto Week 54

change from baseline, event

Secondary/protocol endpoint

Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Heart Rate (HR)

Time frame:Upto Week 54

change from baseline, event

Secondary/protocol endpoint

Changes From Baseline in Electrocardiogram (ECG) Parameters- HR

Time frame:Baseline (Week 0) and Weeks 4, 8, 16, 24, 36, 48, 54

change from baseline, event

Secondary/registry result

Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs

Time frame:Upto Week 48

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboOn treatment AEsn=487 Participants	275	-
On treatment SAEsn=487 Participants	60	-
Mild AEsn=487 Participants	109	-
Moderate AEsn=487 Participants	111	-
Severe AEsn=487 Participants	55	-
RSG XR 2mgOn treatment AEsn=490 Participants	298	-
On treatment SAEsn=490 Participants	58	-
Mild AEsn=490 Participants	119	-
Moderate AEsn=490 Participants	128	-
Severe AEsn=490 Participants	50	-
RSG XR 8mgOn treatment AEsn=491 Participants	319	-
On treatment SAEsn=491 Participants	66	-
Mild AEsn=491 Participants	112	-
Moderate AEsn=491 Participants	158	-
Severe AEsn=491 Participants	48	-

Secondary/registry result

Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Weight

Time frame:Upto Week 54

change from baseline, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboIncrease from Baseline >=7%n=355 Participants	33	-
Decrease from Baseline >=7%n=355 Participants	28	-
RSG XR 2mgIncrease from Baseline >=7%n=342 Participants	31	-
Decrease from Baseline >=7%n=342 Participants	32	-
RSG XR 8mgIncrease from Baseline >=7%n=318 Participants	47	-
Decrease from Baseline >=7%n=318 Participants	23	-

Secondary/registry result

Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Time frame:Upto Week 54

change from baseline, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboSBP >140 or <90n=356 Participants	67	-
SBP Increase from Baseline>=40n=356 Participants	1	-
SBP Decrease from Baseline>=30n=356 Participants	19	-
DBP >90 or <50n=356 Participants	8	-
DBP Increase from Baseline>=30n=356 Participants	0	-
DBP Decrease from Baseline >=20n=356 Participants	12	-
RSG XR 2mgSBP >140 or <90n=343 Participants	72	-
SBP Increase from Baseline>=40n=343 Participants	3	-
SBP Decrease from Baseline>=30n=343 Participants	19	-
DBP >90 or <50n=343 Participants	15	-
DBP Increase from Baseline>=30n=343 Participants	0	-
DBP Decrease from Baseline >=20n=343 Participants	18	-
RSG XR 8mgSBP >140 or <90n=322 Participants	86	-
SBP Increase from Baseline>=40n=322 Participants	3	-
SBP Decrease from Baseline>=30n=322 Participants	14	-
DBP >90 or <50n=322 Participants	12	-
DBP Increase from Baseline>=30n=322 Participants	1	-
DBP Decrease from Baseline >=20n=322 Participants	13	-

Secondary/registry result

Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Heart Rate (HR)

Time frame:Upto Week 54

change from baseline, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Placebo>100 or <50n=355 Participants	12	-
Increase from Baseline >=30n=355 Participants	0	-
Decrease from Baseline >=30n=355 Participants	2	-
RSG XR 2mg>100 or <50n=344 Participants	5	-
Increase from Baseline >=30n=344 Participants	0	-
Decrease from Baseline >=30n=344 Participants	0	-
RSG XR 8mg>100 or <50n=322 Participants	5	-
Increase from Baseline >=30n=322 Participants	4	-
Decrease from Baseline >=30n=322 Participants	1	-

Secondary/registry result

Changes From Baseline in Electrocardiogram (ECG) Parameters- HR

Time frame:Baseline (Week 0) and Weeks 4, 8, 16, 24, 36, 48, 54

change from baseline, event

Posted result

Group	Value (mean), Beats per minute (BPM)	Standard deviation
PlaceboWeek 0, +1hrn=455 Participants	-1.6	6.20
Week 0, +2hrn=362 Participants	-1.4	7.05
Week 0, +3hrn=229 Participants	0.0	6.84
Week 0, +4hrn=163 Participants	0.6	6.64
Week 4, Pre-dosen=443 Participants	0.2	7.01
Week 4, +1hrn=429 Participants	-1.4	7.98
Week 4, +2hrn=402 Participants	-1.4	8.57
Week 4, +3hrn=223 Participants	-0.4	8.02
Week 4, +4hrn=150 Participants	0.2	8.79
Week 8n=349 Participants	0.2	8.15
Week 16n=199 Participants	-0.1	8.06
Week 24n=183 Participants	0.2	7.91
Week 36n=150 Participants	0.7	8.27
Week 48n=156 Participants	0.9	9.01
Week 54n=326 Participants	-0.5	9.33
RSG XR 2mgWeek 0, +1hrn=469 Participants	-1.1	5.80
Week 0, +2hrn=378 Participants	-0.5	6.88
Week 0, +3hrn=234 Participants	-0.1	7.02
Week 0, +4hrn=145 Participants	1.0	6.29
Week 4, Pre-dosen=442 Participants	0.7	7.73
Week 4, +1hrn=435 Participants	-0.4	8.14
Week 4, +2hrn=405 Participants	-0.3	8.57
Week 4, +3hrn=220 Participants	-0.2	8.25
Week 4, +4hrn=137 Participants	0.7	6.92
Week 8n=337 Participants	0.2	8.27
Week 16n=204 Participants	0.3	9.17
Week 24n=175 Participants	-0.3	9.85
Week 36n=136 Participants	0.5	8.74
Week 48n=143 Participants	1.2	9.11
Week 54n=323 Participants	-0.2	8.89
RSG XR 8mgWeek 0, +1hrn=469 Participants	-1.8	6.05
Week 0, +2hrn=383 Participants	-1.0	7.33
Week 0, +3hrn=246 Participants	0.1	7.49
Week 0, +4hrn=155 Participants	0.4	7.84
Week 4, Pre-dosen=443 Participants	1.0	7.56
Week 4, +1hrn=437 Participants	-0.1	7.92
Week 4, +2hrn=403 Participants	-0.2	8.01
Week 4, +3hrn=238 Participants	0.2	8.32
Week 4, +4hrn=142 Participants	1.4	8.31
Week 8n=321 Participants	2.4	8.50
Week 16n=175 Participants	1.5	9.05
Week 24n=157 Participants	2.3	8.86
Week 36n=117 Participants	2.9	8.09
Week 48n=133 Participants	2.4	8.94
Week 54n=304 Participants	1.7	8.87

Other (unclassified)

16 endpoints

Secondary/protocol endpoint/low confidence

Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 48

Time frame:Baseline (Week 0) and Week 48

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in Weight

Time frame:Baseline (Week 0) and Weeks 4, 8, 12, 16, 24, 36, 48, 54

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in Hemoglobin

Time frame:Baseline (Week 0) and Weeks 4, 16, 36, 48

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in Hematocrit

Time frame:Baseline (Week 0) and Weeks 4, 16, 36, 48

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range

Time frame:Up to Week 48

concentration, descriptive

Secondary/protocol endpoint/low confidence

Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range

Time frame:Upto Week 48

ratio, descriptive

Secondary/protocol endpoint/low confidence

Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration

Time frame:Baseline (Week 0) and Weeks 4, 8, 16, 24, 36, 48, 54

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in HbA1c up to Week 54

Time frame:Baseline (Week 0) and Weeks 12, 24, 36, 48, 54

change from baseline, improvement

Secondary/registry result/low confidence

Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 48

Time frame:Baseline (Week 0) and Week 48

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Percentage	Standard error
Placebon=337 Participants	0.13	0.018
RSG XR 2mgn=326 Participants	0.18	0.019
RSG XR 8mgn=309 Participants	0.26	0.019

Mean Difference (Net)0.0595% CI0.00 - 0.10p0.038ANCOVA

Mean Difference (Net)0.1395% CI0.08 - 0.18p<0.001ANCOVA

Secondary/registry result/low confidence

Change From Baseline in Weight

Time frame:Baseline (Week 0) and Weeks 4, 8, 12, 16, 24, 36, 48, 54

change from baseline, improvement

Posted result

Group	Value (mean), Kilograms (Kg)	Standard deviation
PlaceboWeek 4n=470 Participants	-0.1	1.95
Week 8n=459 Participants	0.1	2.10
Week 12n=447 Participants	0.0	2.35
Week 16n=440 Participants	0.0	2.88
Week 24n=428 Participants	0.1	2.85
Week 36n=397 Participants	-0.0	4.53
Week 48n=375 Participants	0.1	3.51
Week 54n=355 Participants	0.1	3.70
RSG XR 2mgWeek 4n=471 Participants	0.1	1.61
Week 8n=447 Participants	0.2	2.15
Week 12n=436 Participants	0.1	2.66
Week 16n=428 Participants	0.2	2.85
Week 24n=412 Participants	0.1	3.28
Week 36n=389 Participants	0.2	3.69
Week 48n=358 Participants	0.2	4.33
Week 54n=342 Participants	0.1	5.88
RSG XR 8mgWeek 4n=469 Participants	0.5	1.70
Week 8n=443 Participants	0.9	2.34
Week 12n=420 Participants	1.2	2.50
Week 16n=416 Participants	1.3	2.78
Week 24n=387 Participants	1.2	3.59
Week 36n=359 Participants	1.5	3.28
Week 48n=341 Participants	1.9	3.69
Week 54n=318 Participants	1.2	3.57

Secondary/registry result/low confidence

Change From Baseline in Hemoglobin

Time frame:Baseline (Week 0) and Weeks 4, 16, 36, 48

change from baseline, improvement

Posted result

Group	Value (mean), Gram\Liter (G\L)	Standard deviation
PlaceboWeek 4n=460 Participants	-0.5	6.50
Week 16n=428 Participants	-0.6	7.37
Week 36n=381 Participants	-0.7	7.78
Week 48n=362 Participants	-0.7	9.10
RSG XR 2mgWeek 4n=453 Participants	-2.9	6.76
Week 16n=422 Participants	-6.1	7.79
Week 36n=376 Participants	-6.2	8.73
Week 48n=336 Participants	-5.8	8.66
RSG XR 8mgWeek 4n=461 Participants	-3.9	6.80
Week 16n=403 Participants	-11.2	9.37
Week 36n=343 Participants	-10.6	9.67
Week 48n=332 Participants	-10.7	10.15

Secondary/registry result/low confidence

Change From Baseline in Hematocrit

Time frame:Baseline (Week 0) and Weeks 4, 16, 36, 48

change from baseline, improvement

Posted result

Group	Value (mean), Ratio	Standard deviation
PlaceboWeek 4n=459 Participants	-0.0020	0.02050
Week 16n=428 Participants	-0.0018	0.02340
Week 36n=381 Participants	-0.0017	0.02428
Week 48n=362 Participants	-0.0026	0.02776
RSG XR 2mgWeek 4n=453 Participants	-0.0088	0.02150
Week 16n=422 Participants	-0.0166	0.02442
Week 36n=376 Participants	-0.0174	0.02705
Week 48n=336 Participants	-0.0167	0.02683
RSG XR 8mgWeek 4n=461 Participants	-0.0121	0.02128
Week 16n=403 Participants	-0.0320	0.02922
Week 36n=343 Participants	-0.0300	0.02880
Week 48n=332 Participants	-0.0303	0.03015

Secondary/registry result/low confidence

Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range

Time frame:Up to Week 48

concentration, descriptive

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboEosinophils- Highn=474 Participants	3	-
Hematocrit- Lown=474 Participants	3	-
Hemoglobin- Highn=474 Participants	1	-
Hemoglobin- Lown=474 Participants	9	-
Lymphocytes- Highn=474 Participants	3	-
Lymphocytes- Lown=474 Participants	11	-
MCH- Highn=474 Participants	0	-
MCH- Lown=474 Participants	1	-
MCV- Highn=474 Participants	0	-
MCV- Lown=474 Participants	0	-
Monocytes- Lown=474 Participants	44	-
Platelet count- Highn=475 Participants	3	-
Platelet count- Lown=475 Participants	3	-
RDW- Highn=474 Participants	11	-
RDW- Lown=474 Participants	1	-
Red Blood Cell count- Highn=474 Participants	0	-
Red Blood Cell count- Lown=474 Participants	3	-
Total Neutrophils (ANC)- Highn=474 Participants	4	-
Total Neutrophils (ANC)- Lown=474 Participants	4	-
White Blood Cell count- Highn=474 Participants	5	-
White Blood Cell count- Lown=474 Participants	4	-
RSG XR 2mgEosinophils- Highn=473 Participants	1	-
Hematocrit- Lown=473 Participants	3	-
Hemoglobin- Highn=473 Participants	3	-
Hemoglobin- Lown=473 Participants	14	-
Lymphocytes- Highn=473 Participants	1	-
Lymphocytes- Lown=473 Participants	3	-
MCH- Highn=473 Participants	0	-
MCH- Lown=473 Participants	3	-
MCV- Highn=473 Participants	0	-
MCV- Lown=473 Participants	1	-
Monocytes- Lown=473 Participants	21	-
Platelet count- Highn=473 Participants	2	-
Platelet count- Lown=473 Participants	0	-
RDW- Highn=474 Participants	18	-
RDW- Lown=474 Participants	0	-
Red Blood Cell count- Highn=473 Participants	0	-
Red Blood Cell count- Lown=473 Participants	3	-
Total Neutrophils (ANC)- Highn=473 Participants	0	-
Total Neutrophils (ANC)- Lown=473 Participants	2	-
White Blood Cell count- Highn=473 Participants	2	-
White Blood Cell count- Lown=473 Participants	3	-
RSG XR 8mgEosinophils- Highn=472 Participants	1	-
Hematocrit- Lown=472 Participants	6	-
Hemoglobin- Highn=474 Participants	1	-
Hemoglobin- Lown=472 Participants	36	-
Lymphocytes- Highn=472 Participants	1	-
Lymphocytes- Lown=472 Participants	7	-
MCH- Highn=472 Participants	1	-
MCH- Lown=472 Participants	3	-
MCV- Highn=472 Participants	1	-
MCV- Lown=472 Participants	1	-
Monocytes- Lown=472 Participants	44	-
Platelet count- Highn=472 Participants	4	-
Platelet count- Lown=472 Participants	2	-
RDW- Highn=472 Participants	50	-
RDW- Lown=472 Participants	0	-
Red Blood Cell count- Highn=472 Participants	1	-
Red Blood Cell count- Lown=472 Participants	11	-
Total Neutrophils (ANC)- Highn=472 Participants	0	-
Total Neutrophils (ANC)- Lown=472 Participants	10	-
White Blood Cell count- Highn=472 Participants	0	-
White Blood Cell count- Lown=472 Participants	12	-

Secondary/registry result/low confidence

Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range

Time frame:Upto Week 48

ratio, descriptive

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboALT- Highn=475 Participants	2	-
Aldolase- Highn=24 Participants	2	-
Aldolase- Lown=24 Participants	2	-
Alkaline Phosphatase- Highn=475 Participants	2	-
AST- Highn=474 Participants	1	-
BUN/Creatinine ratio- Highn=475 Participants	17	-
Calcium- Lown=474 Participants	1	-
Carbondioxide content/BicarbonateLown=474 Participants	0	-
Cholesterol- Highn=436 Participants	21	-
Creatine Kinase- Highn=475 Participants	33	-
Creatinine- Highn=475 Participants	10	-
Direct Bilirubin- Highn=475 Participants	1	-
GGT- Highn=475 Participants	6	-
Glucose- Highn=475 Participants	81	-
Glucose- Lown=475 Participants	14	-
Glycosylated Hemoglobin A1Cn=395 Participants	1	-
HDL Cholesterol, direct- Lown=436 Participants	0	-
LDL Cholesterol calculation- Highn=434 Participants	65	-
Lactate Dehydrogenase- Highn=474 Participants	0	-
Magnesium- Lown=475 Participants	1	-
Phosphorus, inorganic- Highn=475 Participants	2	-
Potassium- Highn=474 Participants	11	-
Potassium- Lown=474 Participants	3	-
Sodium- Highn=475 Participants	2	-
Sodium- Lown=475 Participants	4	-
Total Bilirubin- Highn=475 Participants	5	-
Troponin I- Highn=21 Participants	1	-
Urea/BUN- Highn=475 Participants	27	-
RSG XR 2mgALT- Highn=474 Participants	1	-
Aldolase- Highn=23 Participants	2	-
Aldolase- Lown=23 Participants	1	-
Alkaline Phosphatase- Highn=474 Participants	0	-
AST- Highn=474 Participants	1	-
BUN/Creatinine ratio- Highn=474 Participants	25	-
Calcium- Lown=474 Participants	0	-
Carbondioxide content/BicarbonateLown=474 Participants	0	-
Cholesterol- Highn=425 Participants	32	-
Creatine Kinase- Highn=474 Participants	63	-
Creatinine- Highn=474 Participants	12	-
Direct Bilirubin- Highn=474 Participants	0	-
GGT- Highn=474 Participants	2	-
Glucose- Highn=474 Participants	60	-
Glucose- Lown=474 Participants	22	-
Glycosylated Hemoglobin A1Cn=374 Participants	1	-
HDL Cholesterol, direct- Lown=425 Participants	0	-
LDL Cholesterol calculation- Highn=418 Participants	106	-
Lactate Dehydrogenase- Highn=474 Participants	0	-
Magnesium- Lown=474 Participants	0	-
Phosphorus, inorganic- Highn=474 Participants	0	-
Potassium- Highn=474 Participants	12	-
Potassium- Lown=474 Participants	1	-
Sodium- Highn=474 Participants	0	-
Sodium- Lown=474 Participants	6	-
Total Bilirubin- Highn=474 Participants	1	-
Troponin I- Highn=22 Participants	1	-
Urea/BUN- Highn=474 Participants	40	-
RSG XR 8mgALT- Highn=472 Participants	1	-
Aldolase- Highn=20 Participants	0	-
Aldolase- Lown=20 Participants	0	-
Alkaline Phosphatase- Highn=472 Participants	0	-
AST- Highn=472 Participants	2	-
BUN/Creatinine ratio- Highn=472 Participants	40	-
Calcium- Lown=472 Participants	0	-
Carbondioxide content/BicarbonateLown=472 Participants	3	-
Cholesterol- Highn=403 Participants	61	-
Creatine Kinase- Highn=472 Participants	69	-
Creatinine- Highn=472 Participants	15	-
Direct Bilirubin- Highn=472 Participants	1	-
GGT- Highn=472 Participants	5	-
Glucose- Highn=472 Participants	55	-
Glucose- Lown=472 Participants	22	-
Glycosylated Hemoglobin A1Cn=364 Participants	0	-
HDL Cholesterol, direct- Lown=403 Participants	3	-
LDL Cholesterol calculation- Highn=399 Participants	162	-
Lactate Dehydrogenase- Highn=472 Participants	1	-
Magnesium- Lown=472 Participants	1	-
Phosphorus, inorganic- Highn=472 Participants	0	-
Potassium- Highn=472 Participants	12	-
Potassium- Lown=472 Participants	0	-
Sodium- Highn=472 Participants	2	-
Sodium- Lown=472 Participants	2	-
Total Bilirubin- Highn=472 Participants	1	-
Troponin I- Highn=21 Participants	1	-
Urea/BUN- Highn=472 Participants	48	-

Secondary/registry result/low confidence

Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration

Time frame:Baseline (Week 0) and Weeks 4, 8, 16, 24, 36, 48, 54

change from baseline, improvement

Posted result

Group	Value (mean), MSEC	Standard deviation
PlaceboRR Interval, Week 0, +1hrn=455 Participants	26.7	92.91
RR Interval, Week 0, +2hrn=362 Participants	23.8	105.24
RR Interval, Week 0, +3hrn=229 Participants	3.5	103.09
RR Interval, Week 0, +4hrn=163 Participants	-8.8	91.08
RR Interval, Week 4, Pre-Dosen=443 Participants	-0.2	99.28
RR Interval, Week 4, +1hrn=429 Participants	23.2	115.71
RR Interval, Week 4, +2hrn=402 Participants	24.0	123.53
RR Interval, Week 4, +3hrn=223 Participants	7.4	117.68
RR Interval, Week 4, +4hrn=150 Participants	-2.1	117.25
RR Interval, Week 8n=349 Participants	0.6	110.81
RR Interval, Week 16n=199 Participants	9.0	110.76
RR Interval, Week 24n=183 Participants	-1.3	119.93
RR Interval, Week 36n=150 Participants	-8.0	114.49
RR Interval, Week 48n=156 Participants	-8.2	125.15
RR Interval, Week 54n=326 Participants	10.9	128.93
QT interval, Week 0, +1hrn=455 Participants	5.2	18.01
QT Interval, Week 0, +2hrn=362 Participants	6.4	19.64
QT Interval, Week 0, +3hrn=229 Participants	2.2	19.38
QT Interval, Week 0, +4hrn=163 Participants	-0.3	18.65
QT Interval, Week 4, Pre-Dosen=443 Participants	-0.8	19.18
QT Interval, Week 4, +1hrn=429 Participants	3.6	21.53
QT Interval, Week 4, +2hrn=402 Participants	5.2	22.96
QT Interval, Week 4, +3hrn=223 Participants	3.8	22.82
QT Interval, Week 4, +4hrn=150 Participants	1.9	25.13
QT Interval, Week 8n=349 Participants	-1.4	21.30
QT Interval, Week 16n=199 Participants	2.4	23.39
QT Interval, Week 24n=183 Participants	1.6	24.35
QT Interval, Week 36n=150 Participants	0.5	21.85
QT Interval, Week 48n=156 Participants	2.0	24.53
QT Interval, Week 54n=326 Participants	2.1	24.97
QTcB interval, Week 0, +1hrn=155 Participants	-0.4	13.49
QTcB Interval, Week 0, +2hrn=362 Participants	1.6	14.35
QTcB Interval, Week 0, +3hrn=229 Participants	1.9	15.19
QTcB Interval, Week 0, +4hrn=163 Participants	1.7	13.48
QTcB Interval, Week 4, Pre-Dosen=443 Participants	-0.5	15.98
QTcB Interval, Week 4, +1hrn=429 Participants	-0.9	16.84
QTcB Interval, Week 4, +2hrn=402 Participants	0.4	17.13
QTcB Interval, Week 4, +3hrn=223 Participants	2.4	18.56
QTcB Interval, Week 4, +4hrn=150 Participants	2.8	17.83
QTcB Interval, Week 8n=349 Participants	-1.3	15.27
QTcB Interval, Week 16n=199 Participants	1.1	18.12
QTcB Interval, Week 24n=183 Participants	2.2	19.04
QTcB Interval, Week 36n=150 Participants	2.5	17.87
QTcB Interval, Week 48n=156 Participants	4.5	18.91
QTcB Interval, Week 54n=326 Participants	0.2	18.42
QTcF interval, Week 0, +1hrn=455 Participants	1.5	11.92
QTcF Interval, Week 0, +2hrn=362 Participants	3.2	12.50
QTcF Interval, Week 0, +3hrn=229 Participants	1.9	13.34
QTcF Interval, Week 0, +4hrn=163 Participants	1.0	12.31
QTcF Interval, Week 4, Pre-Dosen=443 Participants	-0.6	13.82
QTcF Interval, Week 4, +1hrn=429 Participants	0.6	14.45
QTcF Interval, Week 4, +2hrn=402 Participants	2.0	14.65
QTcF Interval, Week 4, +3hrn=223 Participants	2.9	16.15
QTcF Interval, Week 4, +4hrn=150 Participants	2.5	16.51
QTcF Interval, Week 8n=349 Participants	-1.4	13.29
QTcF Interval, Week 16n=199 Participants	1.4	16.62
QTcF Interval, Week 24n=183 Participants	2.0	17.21
QTcF Interval, Week 36n=150 Participants	1.8	15.23
QTcF Interval, Week 48n=156 Participants	3.5	16.61
QTcF Interval, Week 54n=326 Participants	0.8	16.08
PR Interval, Week 0, +1hrn=437 Participants	0.6	10.45
PR Interval, Week 0, +2hrn=349 Participants	0.0	10.82
PR Interval, Week 0, +3hrn=220 Participants	0.2	10.74
PR Interval, Week 0, +4hrn=155 Participants	1.8	12.62
PR Interval, Week 1, Pre-dosen=427 Participants	-0.2	12.81
PR Interval, Week 1, +1hrn=415 Participants	0.3	13.50
PR Interval, Week 1, +2hrn=389 Participants	0.7	13.27
PR Interval, Week 1, +3hrn=216 Participants	0.7	14.43
PR Interval, Week 1, +4hrn=145 Participants	0.9	15.31
PR Interval, Week 8n=338 Participants	-1.3	13.20
PR Interval, Week 16n=193 Participants	-0.7	15.22
PR Interval, Week 24n=178 Participants	-1.9	12.43
PR Interval, Week 36n=142 Participants	-1.2	13.87
PR Interval, Week 48n=148 Participants	-0.6	16.83
PR Interval, Week 54n=313 Participants	-0.5	13.66
QRS Interval, Week 0, +1hrn=455 Participants	0.2	5.49
QRS Interval, Week 0, +2hrn=362 Participants	0.2	5.44
QRS Interval, Week 0, +3hrn=229 Participants	-0.1	5.30
QRS Interval, Week 0, +4hrn=163 Participants	0.1	5.72
QRS Interval, Week 4, Pre-Dosen=443 Participants	0.6	7.45
QRS Interval, Week 4, +1hrn=429 Participants	1.1	7.17
QRS Interval, Week 4, +2hrn=402 Participants	1.0	7.60
QRS Interval, Week 4, +3hrn=223 Participants	1.3	8.86
QRS Interval, Week 4, +4hrn=150 Participants	0.1	9.19
QRS Interval, Week 8n=349 Participants	0.2	7.17
QRS Interval, Week 16n=199 Participants	0.8	8.91
QRS Interval, Week 24n=183 Participants	0.9	8.72
QRS Interval, Week 36n=150 Participants	1.7	9.14
QRS Interval, Week 48n=156 Participants	1.5	9.52
QRS Interval, Week 54n=326 Participants	0.8	9.29
RSG XR 2mgRR Interval, Week 0, +1hrn=469 Participants	17.9	83.58
RR Interval, Week 0, +2hrn=378 Participants	11.0	100.67
RR Interval, Week 0, +3hrn=234 Participants	4.6	105.04
RR Interval, Week 0, +4hrn=145 Participants	-12.1	92.98
RR Interval, Week 4, Pre-Dosen=442 Participants	-9.6	104.15
RR Interval, Week 4, +1hrn=435 Participants	8.7	115.70
RR Interval, Week 4, +2hrn=405 Participants	6.8	119.63
RR Interval, Week 4, +3hrn=220 Participants	8.5	124.69
RR Interval, Week 4, +4hrn=137 Participants	-4.7	108.17
RR Interval, Week 8n=337 Participants	0.5	110.70
RR Interval, Week 16n=204 Participants	-1.5	127.38
RR Interval, Week 24n=175 Participants	2.8	141.97
RR Interval, Week 36n=136 Participants	-3.7	127.72
RR Interval, Week 48n=143 Participants	-17.0	132.82
RR Interval, Week 54n=323 Participants	5.4	119.76
QT interval, Week 0, +1hrn=469 Participants	4.5	17.29
QT Interval, Week 0, +2hrn=378 Participants	3.8	20.70
QT Interval, Week 0, +3hrn=234 Participants	3.2	20.61
QT Interval, Week 0, +4hrn=145 Participants	-1.6	20.13
QT Interval, Week 4, Pre-Dosen=442 Participants	-0.7	20.35
QT Interval, Week 4, +1hrn=435 Participants	2.7	22.14
QT Interval, Week 4, +2hrn=405 Participants	4.2	24.09
QT Interval, Week 4, +3hrn=220 Participants	3.6	25.24
QT Interval, Week 4, +4hrn=137 Participants	0.8	22.66
QT Interval, Week 8n=337 Participants	0.5	21.60
QT Interval, Week 16n=204 Participants	-0.3	24.52
QT Interval, Week 24n=175 Participants	2.4	25.99
QT Interval, Week 36n=136 Participants	0.0	23.58
QT Interval, Week 48n=143 Participants	-0.7	26.19
QT Interval, Week 54n=323 Participants	2.4	23.41
QTcB interval, Week 0, +1hrn=469 Participants	0.7	14.41
QTcB Interval, Week 0, +2hrn=378 Participants	1.6	15.70
QTcB Interval, Week 0, +3hrn=234 Participants	2.4	15.73
QTcB Interval, Week 0, +4hrn=145 Participants	1.2	19.50
QTcB Interval, Week 4, Pre-Dosen=442 Participants	1.3	17.14
QTcB Interval, Week 4, +1hrn=435 Participants	0.9	17.51
QTcB Interval, Week 4, +2hrn=405 Participants	2.8	16.73
QTcB Interval, Week 4, +3hrn=220 Participants	2.1	17.72
QTcB Interval, Week 4, +4hrn=137 Participants	2.3	20.30
QTcB Interval, Week 8n=337 Participants	0.7	18.78
QTcB Interval, Week 16n=204 Participants	0.3	18.73
QTcB Interval, Week 24n=175 Participants	1.5	18.81
QTcB Interval, Week 36n=136 Participants	0.9	19.37
QTcB Interval, Week 48n=143 Participants	3.1	18.34
QTcB Interval, Week 54n=323 Participants	1.4	18.74
QTcF interval, Week 0, +1hrn=469 Participants	2.0	12.78
QTcF Interval, Week 0, +2hrn=378 Participants	2.3	14.24
QTcF Interval, Week 0, +3hrn=234 Participants	2.6	13.89
QTcF Interval, Week 0, +4hrn=145 Participants	0.2	17.24
QTcF Interval, Week 4, Pre-Dosen=442 Participants	0.6	14.80
QTcF Interval, Week 4, +1hrn=435 Participants	1.5	15.13
QTcF Interval, Week 4, +2hrn=405 Participants	3.3	15.10
QTcF Interval, Week 4, +3hrn=220 Participants	2.6	16.19
QTcF Interval, Week 4, +4hrn=137 Participants	1.7	17.88
QTcF Interval, Week 8n=337 Participants	0.6	15.94
QTcF Interval, Week 16n=204 Participants	0.1	16.20
QTcF Interval, Week 24n=175 Participants	1.9	16.00
QTcF Interval, Week 36n=136 Participants	0.6	16.22
QTcF Interval, Week 48n=143 Participants	1.8	16.49
QTcF Interval, Week 54n=323 Participants	1.7	15.93
PR Interval, Week 0, +1hrn=449 Participants	0.0	10.39
PR Interval, Week 0, +2hrn=364 Participants	0.2	11.79
PR Interval, Week 0, +3hrn=226 Participants	-0.1	11.02
PR Interval, Week 0, +4hrn=136 Participants	1.5	10.47
PR Interval, Week 1, Pre-dosen=420 Participants	0.4	13.78
PR Interval, Week 1, +1hrn=412 Participants	1.6	13.43
PR Interval, Week 1, +2hrn=386 Participants	0.9	12.17
PR Interval, Week 1, +3hrn=211 Participants	1.4	13.81
PR Interval, Week 1, +4hrn=130 Participants	1.1	15.56
PR Interval, Week 8n=319 Participants	0.7	11.94
PR Interval, Week 16n=191 Participants	0.6	12.00
PR Interval, Week 24n=166 Participants	0.1	12.28
PR Interval, Week 36n=128 Participants	-2.3	12.25
PR Interval, Week 48n=136 Participants	-2.5	13.48
PR Interval, Week 54n=307 Participants	-0.6	13.47
QRS Interval, Week 0, +1hrn=469 Participants	0.6	6.26
QRS Interval, Week 0, +2hrn=378 Participants	0.8	6.82
QRS Interval, Week 0, +3hrn=234 Participants	0.8	6.34
QRS Interval, Week 0, +4hrn=145 Participants	0.5	7.95
QRS Interval, Week 4, Pre-Dosen=442 Participants	0.2	7.91
QRS Interval, Week 4, +1hrn=435 Participants	0.4	8.44
QRS Interval, Week 4, +2hrn=405 Participants	0.7	7.87
QRS Interval, Week 4, +3hrn=220 Participants	0.7	7.48
QRS Interval, Week 4, +4hrn=137 Participants	0.8	9.10
QRS Interval, Week 8n=337 Participants	0.8	7.15
QRS Interval, Week 16n=204 Participants	-0.5	8.42
QRS Interval, Week 24n=175 Participants	1.3	8.02
QRS Interval, Week 36n=136 Participants	1.7	12.81
QRS Interval, Week 48n=143 Participants	1.3	11.52
QRS Interval, Week 54n=323 Participants	0.9	9.40
RSG XR 8mgRR Interval, Week 0, +1hrn=469 Participants	30.4	92.97
RR Interval, Week 0, +2hrn=383 Participants	17.7	109.40
RR Interval, Week 0, +3hrn=246 Participants	0.6	108.88
RR Interval, Week 0, +4hrn=155 Participants	-5.7	108.33
RR Interval, Week 4, Pre-Dosen=443 Participants	-14.0	107.71
RR Interval, Week 4, +1hrn=437 Participants	4.3	118.85
RR Interval, Week 4, +2hrn=403 Participants	2.5	122.39
RR Interval, Week 4, +3hrn=238 Participants	-3.0	125.89
RR Interval, Week 4, +4hrn=142 Participants	-20.6	124.14
RR Interval, Week 8n=321 Participants	-32.6	118.98
RR Interval, Week 16n=175 Participants	-20.8	123.59
RR Interval, Week 24n=157 Participants	-31.3	126.48
RR Interval, Week 36n=117 Participants	-43.4	107.83
RR Interval, Week 48n=133 Participants	-32.7	121.98
RR Interval, Week 54n=304 Participants	-26.0	125.53
QT interval, Week 0, +1hrn=469 Participants	5.4	17.07
QT Interval, Week 0, +2hrn=383 Participants	5.0	19.62
QT Interval, Week 0, +3hrn=246 Participants	1.9	21.79
QT Interval, Week 0, +4hrn=155 Participants	1.8	20.67
QT Interval, Week 4, Pre-Dosen=443 Participants	-1.7	23.63
QT Interval, Week 4, +1hrn=437 Participants	1.4	23.26
QT Interval, Week 4, +2hrn=403 Participants	3.2	24.54
QT Interval, Week 4, +3hrn=238 Participants	0.6	26.70
QT Interval, Week 4, +4hrn=142 Participants	-1.4	25.73
QT Interval, Week 8n=321 Participants	-4.1	24.46
QT Interval, Week 16n=175 Participants	-1.3	25.71
QT Interval, Week 24n=157 Participants	-2.2	25.06
QT Interval, Week 36n=117 Participants	-4.7	27.25
QT Interval, Week 48n=133 Participants	-2.7	29.56
QT Interval, Week 54n=304 Participants	-1.2	25.41
QTcB interval, Week 0, +1hrn=469 Participants	-0.7	14.02
QTcB Interval, Week 0, +2hrn=383 Participants	1.5	15.68
QTcB Interval, Week 0, +3hrn=246 Participants	2.0	14.60
QTcB Interval, Week 0, +4hrn=155 Participants	3.2	14.99
QTcB Interval, Week 4, Pre-Dosen=443 Participants	1.5	18.50
QTcB Interval, Week 4, +1hrn=437 Participants	1.0	16.88
QTcB Interval, Week 4, +2hrn=403 Participants	2.9	17.74
QTcB Interval, Week 4, +3hrn=238 Participants	1.6	17.87
QTcB Interval, Week 4, +4hrn=142 Participants	3.6	15.95
QTcB Interval, Week 8n=321 Participants	3.2	18.09
QTcB Interval, Week 16n=175 Participants	3.6	16.81
QTcB Interval, Week 24n=157 Participants	5.2	17.97
QTcB Interval, Week 36n=117 Participants	4.3	19.16
QTcB Interval, Week 48n=133 Participants	5.0	18.39
QTcB Interval, Week 54n=304 Participants	4.5	18.67
QTcF interval, Week 0, +1hrn=469 Participants	1.3	11.99
QTcF Interval, Week 0, +2hrn=383 Participants	2.6	13.08
QTcF Interval, Week 0, +3hrn=246 Participants	1.9	13.44
QTcF Interval, Week 0, +4hrn=155 Participants	2.8	12.93
QTcF Interval, Week 4, Pre-Dosen=443 Participants	0.4	17.02
QTcF Interval, Week 4, +1hrn=437 Participants	1.1	15.15
QTcF Interval, Week 4, +2hrn=403 Participants	2.9	16.01
QTcF Interval, Week 4, +3hrn=238 Participants	1.3	16.97
QTcF Interval, Week 4, +4hrn=142 Participants	1.9	15.19
QTcF Interval, Week 8n=321 Participants	0.7	16.39
QTcF Interval, Week 16n=175 Participants	1.9	15.77
QTcF Interval, Week 24n=157 Participants	2.6	15.84
QTcF Interval, Week 36n=117 Participants	1.3	19.30
QTcF Interval, Week 48n=133 Participants	2.4	18.86
QTcF Interval, Week 54n=304 Participants	2.6	16.74
PR Interval, Week 0, +1hrn=450 Participants	0.4	10.00
PR Interval, Week 0, +2hrn=366 Participants	-0.8	10.97
PR Interval, Week 0, +3hrn=234 Participants	-0.8	11.78
PR Interval, Week 0, +4hrn=149 Participants	0.0	11.04
PR Interval, Week 1, Pre-dosen=424 Participants	0.7	11.51
PR Interval, Week 1, +1hrn=418 Participants	1.3	11.73
PR Interval, Week 1, +2hrn=385 Participants	1.5	11.98
PR Interval, Week 1, +3hrn=228 Participants	2.6	12.96
PR Interval, Week 1, +4hrn=138 Participants	0.8	11.62
PR Interval, Week 8n=310 Participants	0.8	12.52
PR Interval, Week 16n=167 Participants	0.1	15.06
PR Interval, Week 24n=152 Participants	-0.5	13.38
PR Interval, Week 36n=114 Participants	-0.9	13.70
PR Interval, Week 48n=130 Participants	-0.8	12.99
PR Interval, Week 54n=294 Participants	0.0	11.99
QRS Interval, Week 0, +1hrn=469 Participants	0.4	5.64
QRS Interval, Week 0, +2hrn=383 Participants	0.4	5.61
QRS Interval, Week 0, +3hrn=246 Participants	0.5	6.20
QRS Interval, Week 0, +4hrn=155 Participants	-0.2	6.15
QRS Interval, Week 4, Pre-Dosen=443 Participants	0.8	7.38
QRS Interval, Week 4, +1hrn=437 Participants	1.0	7.51
QRS Interval, Week 4, +2hrn=403 Participants	1.5	7.71
QRS Interval, Week 4, +3hrn=238 Participants	1.5	8.08
QRS Interval, Week 4, +4hrn=142 Participants	1.4	9.12
QRS Interval, Week 8n=321 Participants	0.5	8.26
QRS Interval, Week 16n=175 Participants	0.1	6.96
QRS Interval, Week 24n=157 Participants	1.1	6.71
QRS Interval, Week 36n=117 Participants	0.4	6.66
QRS Interval, Week 48n=133 Participants	1.0	7.19
QRS Interval, Week 54n=304 Participants	1.1	8.28

Secondary/registry result/low confidence

Change From Baseline in HbA1c up to Week 54

Time frame:Baseline (Week 0) and Weeks 12, 24, 36, 48, 54

change from baseline, improvement

Posted result

Group	Value (mean), Percentage of HbA1c	Standard deviation
PlaceboWeek 12n=107 Participants	0.02	0.300
Week 24n=152 Participants	0.09	0.370
Week 36n=125 Participants	0.15	0.398
Week 48n=339 Participants	0.16	0.394
Week 54n=19 Participants	0.09	0.346
RSG XR 2mgWeek 12n=86 Participants	0.13	0.278
Week 24n=147 Participants	0.17	0.415
Week 36n=127 Participants	0.19	0.273
Week 48n=326 Participants	0.19	0.323
Week 54n=20 Participants	0.03	0.483
RSG XR 8mgWeek 12n=79 Participants	0.15	0.398
Week 24n=133 Participants	0.17	0.422
Week 36n=107 Participants	0.25	0.418
Week 48n=309 Participants	0.27	0.400
Week 54n=22 Participants	0.03	0.338

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Harrington C, Sawchak S, Chiang C, Davies J, Donovan C, Saunders AM, Irizarry M, Jeter B, Zvartau-Hind M, van Dyck CH, Gold M. Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer's disease: two phase 3 studies. Curr Alzheimer Res. 2011 Aug;8(5):592-606. doi: 10.2174/156720511796391935.
PMID21592048via BACKGROUND

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.