MAyflOwer RoAD

CompletedPhase 2

A Study of RO4602522 in Participants With Moderate Severity Alzheimer Disease on Background Alzheimer Disease Therapy

A Phase II, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Investigate the Efficacy and Safety of RO4602522 Added to Background Alzheimer's Disease Therapy in Patients With Moderate Severity Alzheimer's Disease

Lead sponsor

Hoffmann-La Roche

Assets

Donepezil / Galantamine / Memantine / Rivastigmine / RO4602522

Listed sites

142

Recruiting sites

Enrollment

542

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 13-20•Study partner/caregiver required

Primary endpoint

•ADAS-Cog

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

Eudract number2012-000943-29

Org study IDBP28248

NCT IDNCT01677754

Timeline

Milestones

Study first posted2012-09-03estimated

Study start2012-10-24actual

Primary completion2015-06-12actual

Study completion2015-06-12actual

Last update posted2017-05-30actual

Assets

Drug assets

Donepezil Galantamine Memantine Rivastigmine RO4602522

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

•Probable Alzheimer disease, based on the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS)/Alzheimer's Disease and Related Disorders Association (ADRDA) and Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV-TR) criteria

•Mini-Mental State Exam (MMSE) score at screening between 13 and 20, inclusive

•Body mass index (BMI) between 18 and 36 kilograms per square meter (kg/m^2) (inclusive) at screening

•Modified Hachinski Ischemia Score of less than or equal to (</=) 4

•Participants with Cornell Scale for Depression in Dementia (CSDD) scores </= 13 at screening

•Receiving treatment with donepezil, rivastigmine, galantamine or any AChEIs in combination with memantine for at least 4 months before screening, with their dose and formulation stabilized at least 3 months before screening. All formulation and dosages are allowed except donezepil 23 mg (alone or in combination)

•Females of childbearing potential must have a negative pregnancy test and must agree to use effective contraception

•Generally healthy and ambulatory or ambulatory-aided (i.e., walker or cane)

•Have a reliable caregiver or some other identified responsible person who has frequent contact with the participant

Exclusion criteria

•Any neurological or psychiatric condition that may occur currently or during the course of the study that can impair cognition or functioning that is not associated with Alzheimer's disease

•Background of mental retardation

•Uncontrolled behavioral symptoms incompatible with compliance or evaluability

•Alcohol and/or substance abuse or dependence (DSM-IV-TR) in the past 2 years, except nicotine use which is allowed. However, smokers treated with nicotine replacement therapy or bupropion are excluded

•Unstable or poorly controlled hypertension as assessed by the investigator regardless of whether or not the participant is taking antihypertensive medications

•Unstable or clinically significant cardiovascular disease that could be expected to progress, recur, or change during study period to such an extent that it could bias the assessment of the clinical or mental status of the participant

•Inadequate hepatic, renal or thyroid function

•Positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection

•Poorly controlled diabetes (glycosylated hemoglobin [HbA1c] greater than or equal to [>/=] 9 percent at screening)

•Requiring nursing home care. Participants living in assisted living facilities are allowed if a reliable caregiver is available (see inclusion criteria)

•Current treatment for Alzheimer's disease other than those listed in inclusion criteria

•Participation at any time in an active Alzheimer's disease vaccine study

•Participation in a passive Alzheimer's disease immunization study less than 1 year before screening except for

a)participants where documented medical history indicate that they were randomized to the placebo group in these studies,

b)participants treated with bapineuzumab where a 6-month exclusion period applies

•Recent (</= 12 weeks) or concomitant use of other Monoamine oxidase inhibitors (selective or not) including selegiline or rasagiline

•Antidepressant treatments are not allowed except for citalopram up to 20 mg daily, escitalopram up to 10 mg daily, paroxetine up to 30 mg daily, sertraline up to 100 mg daily and trazodone up to 100 mg daily. If treated with one of these antidepressants, the treatment should be present for at least 6 weeks at screening. All other antidepressants including other SSRIs, tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), St. John's wort and bupropion are excluded

•Anti-psychotic use within 4 weeks before screening is not permitted except risperidone up to 1.5 mg/day, quetiapine up to 100 milligrams per day (mg/day), olanzapine up to 5 mg/day, and aripiprazole up to 10 mg daily

•Anxiolytics/ hypnotics use is not permitted except for benzodiazepines of short or intermediate half-life for anxiety/sleeping disorders. Zolpidem (up to 5 mg/day), zopiclone (up to 7.5 mg/day), eszopiclone (up to 2 mg/day), trazodone (up to 50 mg/day, at bedtime) or zaleplon (up to 5 mg/day) is permitted for insomnia

•Anti-Parkinson's agents within 2 weeks before screening are not permitted

•Recent (less than 4 weeks prior to screening) or concomitant use of anticonvulsants

•Anticholinergics/ antihistaminics within 2 weeks before screening are not permitted, except i) if used episodically more than 3 days before the screening cognitive measurement, ii) non-sedating antihistaminic medications (without anticholinergic effects such as cetirizine) or peripheral anticholinergics without central anticholinergic effects (such as, trospium for the treatment of hyperactive bladder), which are permitted

•Recent (less than 1 week prior to screening) or concomitant use of opioid drugs (tramadol, methadone, propoxyphene, or meperidine), cyclobenzaprine and dextromethorphan

•Concomitant use of sympathomimetic drugs, including sympathomimetics in local anesthetics and ephedra supplements

Endpoints (19)

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

Other (unclassified)

Safety / tolerability / PK

Global cognition

Function / daily living

Behavior / neuropsychiatric

Disease progression

Global cognition

2 endpoints

Primary/protocol endpoint

Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Behavior Subscale (ADAS-Cog-11) Score at Month 12

Time frame:Baseline, Month 12

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Percentage of Participants Achieving Response, Defined as an Increase From Baseline of Less Than or Equal to (<=) 4 Points in ADAS-Cog-11

Time frame:Baseline, Month 12

ADAS-Cog

threshold achievement, improvement

Function / daily living

1 endpoint

Secondary/protocol endpoint

Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Scale Score at Month 12

Time frame:Baseline, Month 12

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Behavior / neuropsychiatric

1 endpoint

Secondary/protocol endpoint

Change From Baseline in Apathy Evaluation Scale (AES) Score at 12 months

Time frame:Baseline, Month 12

change from baseline, improvement

Disease progression

1 endpoint

Secondary/protocol endpoint

Change From Baseline in Global Deterioration Scale (GDS) Score at 12 months

Time frame:Baseline, Month 12

change from baseline, improvement

Safety / tolerability / PK

3 endpoints

Secondary/protocol endpoint

Percentage of Participants with Adverse Events

Time frame:Baseline up to 13 months

threshold achievement, event

Secondary/protocol endpoint

Area Under the Plasma Concentration-Time Curve of RO4602522

Time frame:Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364

concentration, descriptive

Secondary/protocol endpoint

Maximum Plasma Concentration of RO4602522

Time frame:Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364

concentration, descriptive