CompletedPhase 2Results posted

Safety and Efficacy of Piromelatine in Mild Alzheimer's Disease Patients (ReCOGNITION)

Randomized, Double-blind, Parallel-group, Placebo-controlled, Dose Ranging Study of Piromelatine in Patients With Mild Dementia Due to Alzheimer's Disease

Lead sponsor

Neurim Pharmaceuticals Ltd.

Asset

Piromelatine

Listed sites

Recruiting sites

Enrollment

371

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 21-26•AD symptomatic therapy: stable ≥3 months

Primary endpoint

•Computerized Neuropsychological Test Battery (cNTB) Z-Scores - Change

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

NCT IDNCT02615002

Org study IDNeuP11-AD2

Timeline

Milestones

Study start2015-11 (month precision)

Study first posted2015-11-25estimated

Primary completion2019-06actual (month precision)

Study completion2019-11-19actual

Last update posted2024-07-05actual

Results first posted2024-07-05actual

Assets

Drug assets

Piromelatine

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age60 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Patient and caregiver are willing to take part in the entire study

•Signed informed consent from the patient and the caregiver

•Patient has a documented history either in medical records or from an informant of cognitive decline over at least 6 months

•Patient has mild probable AD as consistent with criteria established by the National Institute on Aging and Alzheimer's Association (NIA-AA).

•CT/MRI scan with finding consisting of probable AD obtained during the last 12 months before Screening

•Patient has an MMSE score of 21-26 (inclusive) at Screening

•Patient has a Clinical Dementia Rating Global Score (CDR-GS) of 0.5-1 (mild dementia) at Screening

•Patients receiving prescribed drugs for treatment of AD including acetyl cholinesterase inhibitors [eg, donepezil, galantamine, rivastigmine] should be on a stable dose for at least 3 months before Screening

•Patient has a negative drug screen (benzodiazepines or opiates) at Screening

•Female patients must have had last natural menstruation ≥ 24 months before Screening, OR being surgically sterile

•Male patients must agree to the use of effective contraception if the female partner is of childbearing potential, OR be surgically sterile

Exclusion criteria

•Patient has an alternative cause for dementia other than AD as determined by CT or MRI scan

•Patient has evidence of any clinically significant neurodegenerative disease

•Patient has been diagnosed with the following Axis I disorders (DSM V criteria)

•Patient has a history of uncontrolled or untreated cardiovascular, endocrine, gastrointestinal, respiratory, or rheumatologic disorders within the past 5 years

•Patient has severe pain that is likely to interfere with sleep

•Continuous use of benzodiazepines or other sedative-hypnotics during the 2 weeks before Screening

•Use of any kind of melatonin/melatonin agonist during the 2 weeks before Screening

•Patient has known or suspected hypersensitivity to exogenous melatonin or melatonin receptor agonists

•Patients with an irregular lifestyle or life pattern (eg, shift workers, patients likely to be jet lagged).

Endpoints (22)

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

Safety / tolerability / PK

Global cognition

Behavior / neuropsychiatric

Function / daily living

Other (unclassified)

Global cognition

4 endpoints

Primary/protocol endpoint

Computerized Neuropsychological Test Battery (cNTB) Z-Scores - Change From Baseline

Time frame:26 weeks

change from baseline, improvement

Primary/registry result

Computerized Neuropsychological Test Battery (cNTB) Z-Scores - Change From Baseline

Time frame:26 weeks

change from baseline, improvement

Posted result

Group	Value (mean), z-score	Reported bounds
Piromelatine 5 mgn=83 Participants	0.0434	--0.0728 - 0.1391
Piromelatine 20 mgn=87 Participants	0.1175	-0.0121 - 0.2153
Piromelatine 50 mgn=80 Participants	0.0297	--0.0900 - 0.1247
Placebo Comparatorn=102 Participants	0.0591	--0.0435 - 0.1483

Secondary/protocol endpoint

Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog14)

Time frame:Baseline, 13 weeks, and 26 weeks

ADAS-Cog

descriptive

Secondary/registry result

Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog14)

Time frame:Baseline, 13 weeks, and 26 weeks

ADAS-Cog

descriptive

Posted result

Group	Value (mean), score on a scale	Standard deviation
Piromelatine 5 mgBaselinen=83 Participants	26.1	7.72
13 weeksn=83 Participants	25.1	8.39
26 weeksn=83 Participants	25.3	8.93
Piromelatine 20 mgBaselinen=87 Participants	26.3	9.16
13 weeksn=87 Participants	26.7	9.37
26 weeksn=87 Participants	26.0	10.12
Piromelatine 50 mgBaselinen=80 Participants	26.4	7.91
13 weeksn=80 Participants	25.5	10.01
26 weeksn=80 Participants	24.9	9.35
Placebo ComparatorBaselinen=102 Participants	26.6	8.62
13 weeksn=102 Participants	26.6	9.87
26 weeksn=102 Participants	25.2	9.97

Function / daily living

2 endpoints

Secondary/protocol endpoint

Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for MCI (Mild Cognitive Impairment) Patients (ADCS-MCI-ADL)

Time frame:Baseline, 13 weeks, and 26 weeks

ADCS-Activities of Daily Living (ADCS-ADL)

descriptive

Secondary/registry result

Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for MCI (Mild Cognitive Impairment) Patients (ADCS-MCI-ADL)

Time frame:Baseline, 13 weeks, and 26 weeks

ADCS-Activities of Daily Living (ADCS-ADL)

descriptive

Posted result

Group	Value (mean), score on a scale	Standard deviation
Piromelatine 5 mgBaselinen=83 Participants	40.7	6.73
13 weeksn=83 Participants	40.4	6.72
26 weeksn=83 Participants	40.6	6.59
Piromelatine 20 mgBaselinen=87 Participants	38.4	8.98
13 weeksn=87 Participants	39.6	8.89
26 weeksn=87 Participants	39.3	9.11
Piromelatine 50 mgBaselinen=80 Participants	39.2	7.60
13 weeksn=80 Participants	39.1	8.81
26 weeksn=80 Participants	39.8	7.94
Placebo ComparatorBaselinen=102 Participants	39.4	8.60
13 weeksn=102 Participants	39.5	8.06
26 weeksn=102 Participants	40.4	8.07

Behavior / neuropsychiatric

4 endpoints

Other/protocol endpoint

NeuroPsychiatric Inventory (NPI) Total Score

Time frame:Baseline, and 26 weeks

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Other/protocol endpoint

Pittsburgh Sleep Quality Index (PSQI) - Global Component Score

Time frame:Baseline, 4 weeks, 13 weeks, 26 weeks

ratio, descriptive

Other_pre_specified/registry result

NeuroPsychiatric Inventory (NPI) Total Score

Time frame:Baseline, and 26 weeks

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), NPI total score	Standard deviation
Piromelatine 5 mgBaselinen=83 Participants	11.2	10.30
26 weeksn=83 Participants	11.4	11.60
Piromelatine 20 mgBaselinen=87 Participants	10.3	8.39
26 weeksn=87 Participants	9.0	7.85
Piromelatine 50 mgBaselinen=80 Participants	12.0	8.75
26 weeksn=80 Participants	11.9	10.66
Placebo ComparatorBaselinen=102 Participants	10.8	10.13
26 weeksn=102 Participants	9.8	10.34

Other_pre_specified/registry result

Pittsburgh Sleep Quality Index (PSQI) - Global Component Score

Time frame:Baseline, 4 weeks, 13 weeks, 26 weeks

ratio, descriptive

Posted result

Group	Value (mean), PSQI global score	Standard deviation
Piromelatine 5 mgBaselinen=83 Participants	6.8	4.39
4 weeksn=83 Participants	5.8	3.97
13 weeksn=83 Participants	6.2	3.85
26 weeksn=83 Participants	5.7	3.62
Piromelatine 20 mgBaselinen=87 Participants	5.9	3.99
4 weeksn=87 Participants	5.4	3.36
13 weeksn=87 Participants	5.2	3.04
26 weeksn=87 Participants	4.7	3.26
Piromelatine 50 mgBaselinen=80 Participants	6.0	4.14
4 weeksn=80 Participants	5.4	3.56
13 weeksn=80 Participants	5.5	3.20
26 weeksn=80 Participants	5.2	3.21
Placebo ComparatorBaselinen=102 Participants	5.6	3.66
4 weeksn=102 Participants	5.6	3.39
13 weeksn=102 Participants	5.1	3.11
26 weeksn=102 Participants	5.1	3.68

Safety / tolerability / PK

10 endpoints

Secondary/protocol endpoint

Safety and Tolerability - Blood Pressure (mmHg)

Time frame:Baseline, and 26 weeks

descriptive

Secondary/protocol endpoint

Safety and Tolerability - Heart Rate (Bpm)

Time frame:Baseline, and 26 weeks

descriptive

Secondary/protocol endpoint

Safety and Tolerability - ECG Interval Results - QTcF (Msec)

Time frame:Baseline, and 26 weeks

descriptive

Secondary/protocol endpoint

Safety and Tolerability - Hematology

Time frame:Baseline, and 26 weeks

descriptive

Secondary/protocol endpoint

Safety and Tolerability - Blood Chemistry (mmol/L)

Time frame:Baseline, and 26 weeks

descriptive

Secondary/registry result

Safety and Tolerability - Blood Pressure (mmHg)

Time frame:Baseline, and 26 weeks

descriptive

Posted result

Group	Value (mean), mmHg	Standard deviation
Piromelatine 5 mgSystolic BP - Baselinen=83 Participants	128.7	14.51
Systolic BP - 26 weeksn=83 Participants	131.9	13.61
Diastolic BP - Baselinen=83 Participants	75.3	9.15
Diastolic BP - 26 weeeksn=83 Participants	76.3	8.48
Piromelatine 20 mgSystolic BP - Baselinen=87 Participants	130.8	13.19
Systolic BP - 26 weeksn=87 Participants	132.4	12.31
Diastolic BP - Baselinen=87 Participants	76.5	8.37
Diastolic BP - 26 weeeksn=87 Participants	76.2	8.47
Piromelatine 50 mgSystolic BP - Baselinen=80 Participants	128.5	11.35
Systolic BP - 26 weeksn=80 Participants	129.9	10.01
Diastolic BP - Baselinen=80 Participants	76.3	7.57
Diastolic BP - 26 weeeksn=80 Participants	77.3	8.78
Placebo ComparatorSystolic BP - Baselinen=102 Participants	132.3	15.13
Systolic BP - 26 weeksn=102 Participants	131.5	12.93
Diastolic BP - Baselinen=102 Participants	76.3	8.26
Diastolic BP - 26 weeeksn=102 Participants	76.3	8.52

Secondary/registry result

Safety and Tolerability - Heart Rate (Bpm)

Time frame:Baseline, and 26 weeks

descriptive

Posted result

Group	Value (mean), bpm	Standard deviation
Experimental: Piromelatine 5 mgHeart rate - baselinen=83 Participants	68.1	10.67
Heart rate - 26 weeksn=83 Participants	65.9	9.89
Experimental: Piromelatine 20 mgHeart rate - baselinen=87 Participants	68.7	9.44
Heart rate - 26 weeksn=87 Participants	67.0	9.95
Experimental: Piromelatine 50 mgHeart rate - baselinen=80 Participants	69.6	9.55
Heart rate - 26 weeksn=80 Participants	66.9	9.28
Placebo Comparator: PlaceboHeart rate - baselinen=102 Participants	67.2	9.68
Heart rate - 26 weeksn=102 Participants	67.9	10.13

Secondary/registry result

Safety and Tolerability - ECG Interval Results - QTcF (Msec)

Time frame:Baseline, and 26 weeks

descriptive

Posted result

Group	Value (mean), msec	Standard deviation
Experimental: Piromelatine 5 mgBaselinen=83 Participants	417.1	24.16
26 weeksn=83 Participants	414.3	27.29
Experimental: Piromelatine 20 mgBaselinen=87 Participants	416.4	34.97
26 weeksn=87 Participants	421.2	24.86
Experimental: Piromelatine 50 mgBaselinen=80 Participants	413.9	50.48
26 weeksn=80 Participants	416.6	24.87
Placebo Comparator: PlaceboBaselinen=102 Participants	416.5	20.57
26 weeksn=102 Participants	408.9	54.47

Secondary/registry result

Safety and Tolerability - Hematology

Time frame:Baseline, and 26 weeks

descriptive

Posted result

Group	Value (mean), GI/L	Standard deviation
Piromelatine 5 mgBasophils - baselinen=83 Participants	0.050	0.0141
Basophils - 26 weeksn=83 Participants	0.080	0
Eosinophils - baselinen=83 Participants	0.290	0.0990
Eosinophils - 26 weeksn=83 Participants	0.170	0
Leukocytes - baselinen=83 Participants	6.455	1.5768
Leukocytes - 26 weeksn=83 Participants	5.210	0
Lymphocytes - baseline (GI/L)n=83 Participants	1.605	0.7425
Lymphocytes - 26 weeksn=83 Participants	0.920	0
Monocytes - baselinen=83 Participants	0.510	0.2828
Monocytes - 26 weeksn=83 Participants	0.450	0
Neutrophils - baselinen=83 Participants	3.990	0.4525
Neutrophils - 26 weeksn=83 Participants	3.600	0
Platelets - baselinen=83 Participants	238.5	84.15
Platelets - 26 weeksn=83 Participants	144.0	0
Piromelatine 20 mgBasophils - baselinen=87 Participants	0.070	0.0141
Basophils - 26 weeksn=87 Participants	0.050	0
Eosinophils - baselinen=87 Participants	0.215	0.0354
Eosinophils - 26 weeksn=87 Participants	0.180	0
Leukocytes - baselinen=87 Participants	8.715	2.7224
Leukocytes - 26 weeksn=87 Participants	10.050	0
Lymphocytes - baseline (GI/L)n=87 Participants	2.535	0.0071
Lymphocytes - 26 weeksn=87 Participants	2.370	0
Monocytes - baselinen=87 Participants	0.405	0.0919
Monocytes - 26 weeksn=87 Participants	0.700	0
Neutrophils - baselinen=87 Participants	5.495	2.6658
Neutrophils - 26 weeksn=87 Participants	6.750	0
Platelets - baselinen=87 Participants	299.0	2.83
Platelets - 26 weeksn=87 Participants	301.0	0
Piromelatine 50 mgBasophils - baselinen=80 Participants	0.067	0.0153
Basophils - 26 weeksn=80 Participants	0.050	0.0141
Eosinophils - baselinen=80 Participants	0.110	0.0693
Eosinophils - 26 weeksn=80 Participants	0.130	0.0283
Leukocytes - baselinen=80 Participants	6.140	0.6940
Leukocytes - 26 weeksn=80 Participants	5.885	0.3465
Lymphocytes - baseline (GI/L)n=80 Participants	1.943	0.2397
Lymphocytes - 26 weeksn=80 Participants	1.805	0.3182
Monocytes - baselinen=80 Participants	0.357	0.1102
Monocytes - 26 weeksn=80 Participants	0.370	0.0141
Neutrophils - baselinen=80 Participants	3.660	0.2905
Neutrophils - 26 weeksn=80 Participants	3.525	0.0071
Platelets - baselinen=80 Participants	241.0	46.13
Platelets - 26 weeksn=80 Participants	223.0	48.08
Placebo ComparatorBasophils - baselinen=102 Participants	0.063	0.0153
Basophils - 26 weeksn=102 Participants	0.080	0.0283
Eosinophils - baselinen=102 Participants	0.153	0.0208
Eosinophils - 26 weeksn=102 Participants	0.250	0.0283
Leukocytes - baselinen=102 Participants	5.407	0.8755
Leukocytes - 26 weeksn=102 Participants	6.970	0.9617
Lymphocytes - baseline (GI/L)n=102 Participants	1.363	0.3320
Lymphocytes - 26 weeksn=102 Participants	2.085	1.3223
Monocytes - baselinen=102 Participants	0.347	0.0611
Monocytes - 26 weeksn=102 Participants	0.345	0.0495
Neutrophils - baselinen=102 Participants	3.483	1.1801
Neutrophils - 26 weeksn=102 Participants	4.205	0.3041
Platelets - baselinen=102 Participants	167.3	26.95
Platelets - 26 weeksn=102 Participants	283.0	111.72

Secondary/registry result

Safety and Tolerability - Blood Chemistry (mmol/L)

Time frame:Baseline, and 26 weeks

descriptive

Posted result

Group	Value (mean), mmol/L	Standard deviation
Experimental: Piromelatine 5 mgGlucose - baselinen=83 Participants	5.89	1.883
Glucose - 26 weeksn=83 Participants	5.86	1.770
Calcium - baselinen=83 Participants	2.385	0.1626
Calcium - 26 weeksn=83 Participants	2.270	0
Sodium - baselinen=83 Participants	140.5	2.12
Sodium -26 weeksn=83 Participants	135.0	0
Urea Nitrogen - baselinen=83 Participants	7.35	0.778
Urea Nitrogen - 26 weeksn=83 Participants	8.20	0
Experimental: Piromelatine 20 mgGlucose - baselinen=87 Participants	5.97	2.045
Glucose - 26 weeksn=87 Participants	6.25	2.121
Calcium - baselinen=87 Participants	2.470	0.0707
Calcium - 26 weeksn=87 Participants	2.370	0
Sodium - baselinen=87 Participants	141.5	0.71
Sodium -26 weeksn=87 Participants	141.0	0
Urea Nitrogen - baselinen=87 Participants	7.70	3.818
Urea Nitrogen - 26 weeksn=87 Participants	5.70	0
Experimental: Piromelatine 50 mgGlucose - baselinen=80 Participants	5.51	1.322
Glucose - 26 weeksn=80 Participants	5.99	2.351
Calcium - baselinen=80 Participants	2.307	0.1007
Calcium - 26 weeksn=80 Participants	2.300	0
Sodium - baselinen=80 Participants	139.3	2.31
Sodium -26 weeksn=80 Participants	143.0	2.83
Urea Nitrogen - baselinen=80 Participants	5.00	0.400
Urea Nitrogen - 26 weeksn=80 Participants	5.35	0.495
Placebo Comparator: PlaceboGlucose - baselinen=102 Participants	5.78	1.598
Glucose - 26 weeksn=102 Participants	5.80	1.461
Calcium - baselinen=102 Participants	2.363	0.1290
Calcium - 26 weeksn=102 Participants	2.335	0.0495
Sodium - baselinen=102 Participants	139.0	1.73
Sodium -26 weeksn=102 Participants	140.0	1.41
Urea Nitrogen - baselinen=102 Participants	5.00	1.212
Urea Nitrogen - 26 weeksn=102 Participants	4.50	1.273

Other (unclassified)

2 endpoints

Secondary/protocol endpoint/low confidence

Change From Baseline in Global Impression of Change (CGIC)

Time frame:13 weeks, and 26 weeks

change from baseline, improvement

Secondary/registry result/low confidence

Change From Baseline in Global Impression of Change (CGIC)

Time frame:13 weeks, and 26 weeks

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
Experimental: Piromelatine 5 mg13 weeksn=83 Participants	3.93	0.88
26 weeksn=83 Participants	4.13	1.07
Experimental: Piromelatine 20 mg13 weeksn=87 Participants	3.95	0.78
26 weeksn=87 Participants	3.94	1.02
Experimental: Piromelatine 50 mg13 weeksn=80 Participants	3.87	0.92
26 weeksn=80 Participants	3.87	0.98
Placebo Comparator: Placebo13 weeksn=102 Participants	3.89	0.80
26 weeksn=102 Participants	3.99	1.01

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

Schneider LS, Laudon M, Nir T, Caceres J, Ianniciello G, Capulli M, Zisapel N. A Polymorphism Cluster at the 2q12 locus May Predict Response to Piromelatine in Patients with Mild Alzheimer's Disease. J Prev Alzheimers Dis. 2022;9(2):247-254. doi: 10.14283/jpad.2021.61.
PMID35542997via DERIVED

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.