When Pfizer Medivation released the disappointing results of its Dimebon Connection study it was a real set back for the Alzheimer's community....By Bob DeMarco
Alzheimer's Reading Room
So far the news from Medivation on the Dimebon Connection study is limited. This is understandable. Both Pfizer (PFE) and Medivation (MDVN) will need time to analyze the results and determine where to go from here with Dimebon.
Those currently enrolled in the three additional Dimebon clinical trials are feeling sad and confused.
"The results from the CONNECTION study are unexpected, and we are disappointed for the Alzheimer's community," said Dr. David Hung, president and chief executive officer of Medivation. "We are working with our colleagues at Pfizer to better understand the CONNECTION data and we plan to present these data at an upcoming medical meeting."
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"We are evaluating the CONNECTION data with Medivation. After that review, Pfizer will be in a position to determine appropriate next steps regarding the dimebon program," said Dr. Briggs W. Morrison, senior vice president, clinical development, Primary Care Business Unit at Pfizer. "We recognize the significant medical need, and we are committed to advancing treatment options for Alzheimer's disease."
CONNECTION Study Results
CONNECTION is a Phase 3, multi-national, double-blind, placebo-controlled safety and efficacy trial involving 598 patients with mild-to-moderate AD at 63 sites in North America, Europe, and South America.
Patients had a mean age of 74.4 years and a mean score of 17.7 on the Mini-Mental State Examination (MMSE) upon entry into the study. More than 40 percent of the patients enrolled were in the United States. In the study, patients were randomized to one of three treatment groups, receiving dimebon 20 mg three times a day (TID), dimebon 5 mg TID, or placebo TID for six months. The 5 mg arm was included in the study to help define the effective dose range for dimebon treatment.
No statistically significant improvements for the 20 mg TID group relative to placebo were achieved on the co-primary endpoints.
- One primary endpoint evaluated the effect of dimebon on cognition, as measured by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), and showed that dimebon-treated patients achieved a 0.1 point difference from patients receiving placebo (p=0.86). Neither group was significantly changed from baseline.
- The other primary endpoint evaluated the effect of dimebon on independently-rated global function over the course of the six-month trial, as measured by the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-plus; p=0.81).
- According to the CIBIC-plus scale, 64.9 percent of the patients treated with dimebon 20 mg TID showed improvement or no change at Week 26 compared to 65.4 percent of placebo-treated patients.
- Results for the dimebon 5 mg dose were similar to the dimebon 20 mg and placebo, although they were numerically lower.
The 20 mg TID dimebon-treated patients also showed no statistically significant differences compared to placebo on the secondary efficacy endpoints.
- After six months of treatment, patients treated with dimebon showed a 0.4 point difference from patients taking placebo on activities of daily living (p=0.61), as measured by the Alzheimer's Disease Cooperative Study Activities of Daily Living Scale (ADCS-ADL). Neither group was significantly changed from baseline.
- The dimebon-treated group showed a 1.6 point improvement on behavior compared to placebo (p=0.17), as measured by the Neuropsychiatric Inventory (NPI). Compared to baseline, each group was improved, but this change was only significant for the dimebon group.
- On the Mini Mental State Examination (MMSE), another measure of cognition, both groups improved significantly over baseline (dimebon 0.7; placebo 1.2). The difference favoring placebo was not significant (p=0.10).
- Results for the dimebon 5 mg dose were similar to dimebon 20 mg and placebo, although they were numerically lower.
- Dimebon, 20 mg orally three-times daily, was well tolerated in the study. The number of patients with at least one adverse event was similar in the dimebon 20 mg and placebo groups (72.0% vs. 74.2%, respectively).
- The most frequently reported adverse events (.5%) in patients in the 20 mg dimebon group occurring more commonly than in the placebo group included somnolence (11.0% vs. 10.1%), dry mouth (8.5% vs. 6.6%), headache (9.5% vs. 5.6%), dizziness (7.5% vs. 5.1%), constipation (5.5% vs. 3.5%), cough (7.5% vs. 3.5%) and depression (6.0% vs. 3.5%).
- Similar rates of adverse events were observed for the 5 mg TID group. No clinically significant findings were noted in assessment of vital signs, clinical laboratories or on electrocardiography (ECG).
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Original content Bob DeMarco, the Alzheimer's Reading Room