A Phase 3 Study To Evaluate The Safety And Tolerability Of Dimebon Patients With Mild To Moderate Alzheimer's Disease

Study Overview
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Brief Summary
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This is a multi-center, randomized, double-blind placebo-controlled safety study conducted in 2 study cohorts. In Cohort 1, subjects with Alzheimer's disease (n=250) will receive Dimebon 20 mg or placebo TID for 26 weeks. In Cohort 2 AD subjects (n=500) will be treated with Dimebon 20 mg or placebo TID for 12 weeks After completion of the randomized portion of the study, subjects in both Cohorts will have the opportunity to enroll in a Dimebon open label extension study.

Official Title
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A Phase 3, Multi-Center, Randomized, Double-Blind Placebo-Controlled Study To Evaluate The Safety And Tolerability Of Dimebon (PF-01913539) For Up To 26-Weeks In Patients With Mild To Moderate Alzheimer's Disease

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: Dimebon
* Drug: Placebo
* Drug: Dimebon
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Alzheimer's Disease. MMSE 12-26 inclusive. If on existing anti-dementia therapy, have been on a stable dose of anti-dementia therapy (cholinesterase inhibitors and/or memantine) for at least 60 days prior to dosing in study. If not taking existing anti-dementia therapy, have not received therapy with cholinesterase inhibitors and/or memantine within 60 days prior to dosing in this study. Exclusion Criteria: Have major structural brain disease (e.g., ischemic infarcts, subdural hematoma, hemorrhage, hydrocephalus, brain tumors, multiple subcortical ischemic lesions, or a single lesion in a critical region [e.g., thalamus, hippocampus]). Have any major medical illness or unstable medical condition within six months of screening that may interfere with the patient's ability to comply with study procedures and abide by study restrictions. Have not been on a stable dose of anti-dementia therapy for at least 60 days prior to dosing or intend to start anti-dementia therapy during the double blind portion of the study. Reside in a nursing home or assisted care facility with need for 24-hour care and supervision.

Ages Eligible for Study
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Minimum Age: 50 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dimebon 20 mg TID (Cohort 1)<br> | Drug: Dimebon<br>* 10 mg TID for week 1 followed by 20 mg TID through Week 26<br>|
| Placebo Comparator: Placebo TID (Cohort 1)<br> | Drug: Placebo<br>* 10 mg TID for week 1 followed by 20 mg TID through Week 26<br>|
| Experimental: Dimebon 20 mg TID (Cohort 2)<br> | Drug: Dimebon<br>* 10 mg TID for week 1 followed by 20 mg TID through Week 12<br>|
| Placebo Comparator: Placebo TID (Cohort 2)<br> | Drug: Placebo<br>* 20 mg matched Placebo (Cohort 2) 10 mg TID for week 1 followed by 20 mg TID through Week 12<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 1 | Abnormal clinically significant vital signs included absolute systolic blood pressure (BP) values: less than (<) 90 millimeter of mercury (mmHg), maximum increase or decrease of greater than or equal to (>=) 30 mmHg from baseline; absolute diastolic BP value: <50 mmHg, maximum increase or decrease of >=20 mmHg from baseline; absolute heart rate values: >120 beats per minute (bpm). | Baseline up to Week 30 (follow-up) | 
| Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 2 | Abnormal clinically significant vital signs included absolute systolic BP values: <90 mmHg, maximum increase or decrease of >=30 mmHg from baseline; absolute diastolic BP values: <50 mmHg, maximum increase or decrease of >=20 mmHg from baseline; absolute heart rate values: >120 bpm. | Baseline up to Week 16 (follow-up) | 
| Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1 | Abnormal ECG findings included maximum value of >=300 millisecond (msec), maximum increase of >=25% for baseline value of >200 msec and maximum increase of >=50% for baseline value of <=200 msec for PR interval (int); maximum value of >=200 msec, maximum increase of >=25% for baseline value of >100 msec and maximum increase of >=50% for baseline value of <=100 msec for QRS interval; maximum value of >=500 msec for QT interval; maximum value of 450 to <480, 480 to <500 and >=500 msec, increase of >=30 to <60 and >=60 msec for QT interval corrected using Fridericia's formula (QTcF interval). | Baseline up to Week 30 (follow-up) | 
| Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2 | Abnormal ECG findings included maximum value of >=300 msec, maximum increase of >=25% for baseline value of >200 msec and maximum increase of >=50% for baseline value of <=200 msec for PR interval; maximum value of >=200 msec, maximum increase of >=25% for baseline value of >100 msec and maximum increase of >=50% for baseline value of <=100 msec for QRS interval; maximum value of >=500 msec for QT interval; maximum value of 450 to <480, 480 to <500 and >=500 msec, increase of >=30 to <60 and >=60 msec for QT interval corrected using Fridericia's formula (QTcF interval). | Baseline up to Week 16 (follow-up) | 
| Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1 | For hematology, liver function, renal function, electrolytes, clinical chemistry, abnormality was reported if the observed value was more than or less than X times the upper limit of normal (ULN) or lower limit of normal (LLN) respectively; X=specified in categories of each parameter in the measured values section. For urinalysis of glucose, ketones, protein, blood, abnormality was reported if result was >=1 in qualitative test of respective parameters, indicating levels in urine were abnormal. Urine pH and specific gravity abnormality reported if pH >8 and specific gravity <1.003 or >1.030. | Baseline up to Week 30 (follow-up) | 
| Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2 | For hematology, liver function, renal function, electrolytes, clinical chemistry, abnormality was reported if the observed value was more than or less than X times the ULN or LLN respectively; X=specified in categories of each parameter in the measured values section. For urinalysis of glucose, ketones, protein, blood, abnormality was reported if result was >=1 in qualitative test of respective parameters, indicating levels in urine were abnormal. Urine pH and specific gravity abnormality reported if pH >8 and specific gravity <1.003 or >1.030. | Baseline up to Week 16 (follow-up) | 
| Percentage of Participants With Adverse Events (AEs) in Cohort 1 | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. | Baseline up to Week 30 (follow-up) | 
| Percentage of Participants With Adverse Events (AEs) in Cohort 2 | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. | Baseline up to Week 16 (follow-up) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's Disease, Dimebon, Safety, Tolerability