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

Study Overview
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Brief Summary
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This study is a Phase 2, randomized, placebo controlled, dose ranging study of piromelatine (5, 20, and 50 mg daily for 6 months) versus placebo to determine an effective dose based on efficacy (cognitive performance), safety and tolerability in patients with mild dementia due to AD.

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

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: Piromelatine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 clearly 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 NIA-AA CT/MRI scan with finding consisted with 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 be surgically sterile Male patients must agree to use of effective contraception if 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).

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: piromelatine 5 mg<br>5 mg tablets once daily | Drug: Piromelatine<br> <br> * Other names: Neu-P11;|
| Experimental: piromelatine 20 mg<br>20 mg tablets once daily | Drug: Piromelatine<br> <br> * Other names: Neu-P11;|
| Experimental: piromelatine 50 mg<br>50 mg tablets once daily | Drug: Piromelatine<br> <br> * Other names: Neu-P11;|
| Placebo Comparator: Placebo<br>Placebo tablet once daily | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Computerized neuropsychological test battery (cNTB) |  | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Global Impression of Change (CGIC) |  | 26 weeks | 
| Change from baseline in Alzheimer's Disease Cooperative Study/Activities of Daily Living scale adapted for MCI patients (ADCS-MCI-ADL) |  | 4, 13, 26 weeks | 
| Change from baseline in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog14) |  | 13, 26 weeks | 
| Safety and tolerability of piromelatine | Vital signs measurements (heart rate and blood pressure), reported AEs or SAEs, physical examinations results, clinical laboratory evaluations (hematology, biochemistry, and urinalysis), 12-lead ECGs results and Sheehan Suicidality Tracking Scale scores will be collected throughout the study. | 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cognition, mild Alzheimer's disease, Sleep