First Pivotal Trial

Doody RS, Gavrilova SI, et al. Effect of Dimebon on cognition, activities of daily living, behavior, and global function in patients with mild-to-moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled study. The Lancet. 2008;372:207-15

Study Design: The trial enrolled 183 patients with mild-to-moderate Alzheimer’s disease (mini-mental state examination [MMSE] scores 10–24) at 11 sites in Russia. Patients were randomly assigned to receive oral dimebon, 20 mg three times a day (60 mg/day [n=89]), or matched placebo (n=94). Other antidementia drugs were not allowed. The primary outcome measure assessed cognition, the difference in mean change from baseline to week 26, or last completed observation on the cognitive subscale of the Alzheimer’s disease assessment scale (ADAS-cog). All patients and study personnel were blinded throughout the study. 134 patients (68 in dimebon group, 66 in placebo group) enrolled in the 6-month blinded extension phase of the study.

Findings: 155 (85%) patients completed the trial - 78 [88%] in dimebon group and 77 [82%] in placebo group. Treatment with dimebon resulted in significant benefits in ADAS-cog compared with placebo at week 26 (mean drug-placebo difference –4∙0; p<0∙0001). Patients given dimebon were significantly improved over baseline for ADAS-cog (mean difference –1·9; p=0·0005). Dimebon was well tolerated: dry mouth and depressed mood or depression were the most common adverse events associated with dimebon (12 [14%] patients for each symptom by week 26). The percentage of patients who had adverse events in the two groups did not differ.

Interpretation: Dimebon was well tolerated, and significantly improved the clinical course of patients with mild-to-moderate Alzheimer’s disease.

Additional analyses of the dimebon pivotal study data presented at medical conferences showed that:

• Dimebon’s impact extended to caregivers, reducing caregiver distress and time spent caring for patients each day. Click here for abstract.
• Dimebon’s clinical benefit continued through 18 months. These results were based on data from a six-month, open-label extension of the 12-month placebo-controlled study of dimebon in patients with mild-to-moderate Alzheimer's disease. Click here for press release and click here for poster.

Clinical Trial Status

In order to support a broad and differentiated label, we and Pfizer have expanded our Alzheimer’s Phase 3 clinical development program to include the following trials:

• The Phase 3 CONNECTION trial in patients with mild-to-moderate disease, for which enrollment is completed;
• The Phase 3 CONCERT study, which is currently enrolling patients with mild-to-moderate Alzheimer’s disease who are already being treated with donepezil, the leading Alzheimer’s disease medication worldwide;
• A placebo-controlled Phase 3 safety trial in patients on a variety of background anti-dementia medications being conducted to meet international safety database requirements, for which enrollment is completed;
• The Phase 3 CONSTELLATION trial, which is currently enrolling patients with moderate-to-severe Alzheimer’s disease and is evaluating as primary endpoints the effects of adding dimebon to memantine, a standard of care Alzheimer’s disease medicine, on cognition, memory and activities of daily living;
• The Phase 3 CONTACT study, which is currently enrolling patients with moderate-to-severe Alzheimer’s disease and is assessing as primary endpoints the potential benefits of adding dimebon to ongoing treatment with donepezil on neuropsychiatric symptoms and activities of daily living.