Based on its end-of-phase II meeting with the US Food and Drug Administration (FDA), Medivation, Inc, unveiled its plans to begin a pivotal confirmatory phase III trial of Dimebon for mild-to-moderate Alzheimer's Disease in the second quarter of 2008.
The FDA informed Medivation that the company's previously completed trial conducted in Russia can be used as one of the two pivotal studies required to support the approval of Dimebon to treat mild-to-moderate Alzheimer's disease, as long as a significant proportion of the sites in the confirmatory phase III trial are located in the United States.
"We are now a phase III company with clear regulatory guidance on the pivotal trials required to seek marketing approval for Dimebon in the United States," said David T. Hung, M.D., president and chief executive officer, Medivation. "This is a significant step forward for Medivation, and validates our strategy to advance Dimebon directly into a pivotal phase III trial."
The phase III clinical trial will enrol approximately 525 patients with mild-to-moderate Alzheimer's disease at sites in the United States, Europe and South America. Patients will be randomised to one of three treatment groups: Dimebon 20 mg three times per day (TID); Dimebon 5 mg TID; and placebo. Patients will be treated for six months and may not be taking any other Alzheimer's disease drugs. The primary endpoints are the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) and the Clinician's Interview-Based Impression of Change plus caregiver interview (CIBIC-plus).
In the previously completed trial Dimebon-treated patients were significantly improved over placebo patients on both the ADAS-cog and CIBIC-plus, with p values of less than 0.0001. This level of statistical significance is several times better than what is required to obtain marketing approval.
"We changed as little as possible in the design of the phase III trial given the highly statistically significant results of our previous trial," said Lynn Seely, M.D., chief medical officer, Medivation. "The primary endpoints, duration of treatment and patient inclusion and exclusion criteria are all substantially identical to the previous trial. The primary differences are that the phase III trial will be global and will test two doses of Dimebon -- the dose studied in the previous trial plus a lower dose to address the regulatory recommendation that minimum effective dose be explored in the development of investigational drugs."
Medivation expects to complete the pivotal confirmatory phase III trial and apply for marketing approval in 2010.
Medivation, Inc. is a biopharmaceutical company with small molecule drugs in clinical development to treat three large, unmet medical needs -- Alzheimer's disease, Huntington's disease and hormone-refractory prostate cancer.