Study Evaluating Intepirdine (RVT-101) in Subjects With Mild to Moderate Alzheimer's Disease on Donepezil: MINDSET Study

Study Overview
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Brief Summary
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This study seeks to confirm a demonstrated treatment effect of intepirdine (RVT-101) as an adjunctive therapy to donepezil for the treatment of subjects with Alzheimer's disease.

Detailed Description
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This Phase 3 study seeks to confirm a demonstrated treatment effect of intepirdine (RVT-101) on both cognition and activities of daily living when added to stable donepezil treatment in subjects with mild-to-moderate Alzheimer's disease after 24 weeks of double-blind treatment. This study will also provide further information on the safety and tolerability of the 35-mg dose of intepirdine (RVT-101) when used in combination with donepezil compared to donepezil alone. This study is being conducted under the agreement of a Special Protocol Assessment by FDA. Subjects completing this study will be eligible to enroll in a 12 month open-label study of RVT-101 (RVT-101-3002) in which concomitant medications for the treatment of Alzheimer's disease including memantine will be allowed.

Official Title
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A Phase 3, Double-blind, Randomized Study of RVT-101 Versus Placebo When Added to Existing Stable Donepezil Treatment in Subjects With Mild to Moderate Alzheimer's Disease

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: RVT-101
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject with AD Ongoing donepezil therapy for AD An MMSE score 12 to 24 inclusive at Screening; MMSE score 10-26 inclusive at Baseline Hachinski Ischaemia score less than or equal to 4 at Screening. If female, subject must be: a. of non-childbearing potential or surgically sterile; or, b. willing to use an adequate methods of birth control. Male subjects who are sexually active will also be required to use an adequate form of birth control. Subject has the ability to comply with procedures for cognitive and other testing in the opinion of the investigator. Subject has a reliable caregiver who is willing to report on subject's status throughout the study. Exclusion Criteria: Other Causes for Dementia Diagnosis of vascular dementia Atypical clinical features or clinical course of dementia that would lead the investigator to conclude symptoms are more likely due to an alternate dementia diagnosis including, but not limited to, frontotemporal dementia, Lewy body dementia, or others. Confounding Medical Conditions History of significant psychiatric illness such as schizophrenia or bipolar affective disorder or any other significant psychiatric illness that in the opinion of the investigator would interfere with participation in the study; Any clinically relevant concomitant disease, which, in the opinion of the investigator, makes the subject unsuitable for inclusion in the study.

Ages Eligible for Study
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Minimum Age: 50 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: RVT-101<br>RVT-101 adjunct to 5 mg or 10 mg donepezil | Drug: RVT-101<br>* once daily, oral, 35 mg tablets<br>|
| Placebo Comparator: Placebo<br>Placebo adjunct to 5 mg or 10 mg donepezil | Drug: Placebo<br>* once daily, oral, pill manufactured to match RVT-101 35 mg tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alzheimer's Disease Assessment Scale - Cognitive Subscale 11 Items (ADAS-Cog-11) Score Change From Baseline to Week 24 | The 11-item ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place, and spontaneous speech. The ADAS-Cog-11 total score range is from 0 to 70, with a higher score indicating more severe cognitive impairment. | Baseline, 24 weeks | 
| Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Score Change From Baseline to Week 24 | The ADCS-ADL scale measures functional impairment in terms of activities of daily living. The score ranges from 0 to 78. The lower the score, the greater the impairment; higher scores indicate better (more desirable) function | Baseline, 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression of Change - Plus Caregiver Interview (CIBIC+) Score at Week 24 | The CIBIC+ assessment measures the global functioning of the subject. The CIBIC+ is scored as a seven-point categorical rating, ranging from a score of 1 (indicating very much improved), to a score of 4 (indicating no change), or to a score of 7 (indicating very much worse.) Lower CIBIC+ scores indicate better (more desirable) function | 24 weeks | 
| The Dependence Scale (DS) Score Change From Baseline to Week 24 | The DS measures the amount of assistance patients with dementia require in performing daily activities. The scale consists of 13 items, representing a range of severity from mild to severe levels of dependency. The score range is from 0 to 15 with higher scores indicating greater dependency. | Baseline, 24 weeks | 
| Neuropsychiatric Inventory (NPI) Score Change From Baseline to Week 24 | The NPI is a behavior rating scale composed of a 12-item structured interview of the caregiver that is scored from 0 to 144 (the higher the score, the greater the psychiatric disturbance). It assesses 12 behavioral disturbances occurring in dementia patients: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor activity, night-time behavior disturbances, and eating disturbances. Both the frequency and the severity of each behavior are determined. | Baseline and Week 24 | 
| ADAS-Cog-13 Score Change From Baseline to Week 24 | 13-item ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place, and spontaneous speech. Most items are evaluated by tests, but some are dependent on clinician ratings on a 5-point scale. The ADAS-Cog-13 is the ADAS-Cog-11 with 2 additional items: delayed word recall and total digit cancellation. Scores for the ADAS-Cog-13 range from 0 to 85 with higher scores indicating greater dysfunction. | Baseline, 24 weeks | 
| Measurement of Concentrations of RVT-101 (Intepirdine) in Plasma | Measurement collected at timepoints Week 6, Week 12, Week 18, and Week 24 | Week 6, Week 12, Week 18, Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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donepezil, Alzheimer's disease, RVT-101, intepirdine, dementia