Slow release? No, thank you!

One of the most important argument for development of new drug delivery systems is possibility to provide controlled or just simply slow release of an API. It is almost accepted that controlled release is “always” preferable. But something went wrong with a controlled-release formulation of pregabalin, a GABA receptor agonist.

Pfizer Inc. (NYSE:PFE) said once-daily 165 and 330 mg Lyrica CR pregabalin controlled-release as adjunctive treatment of partial onset seizures in adults with epilepsy each missed the primary endpoint in a Phase III trial. Specifically, both doses missed the primary endpoint of reducing the log-transformed 28-day seizure rate for all partial onset seizures collected during the 14-week double-blind treatment period from baseline vs. placebo (p=0.907 for high-dose; low-dose p-value not disclosed). Pfizer did not disclose detailed data for the primary endpoint, but said the non-significant reduction in seizure frequency may be due to a higher than expected placebo response. Responder rates, defined as the proportion of patients with a 50% or greater reduction in seizure frequency from baseline, were 37.8% for low-dose pregabalin CR, 45.9% for high-dose pregabalin CR and 35.8% for placebo.

Next time we have just to be more careful regarding slow release: slow or controlled release is not better per automatic!