Cipher Pharmaceuticals Inc. has announced preliminary results from the 02.05 phase III study of Cip-Tramadol ER, an extended-release capsule formulation of the pain medication tramadol. While all three active treatment groups in the study demonstrated a reduction in pain from baseline, the 02.05 efficacy results did not achieve a statistically significant effect relative to placebo with respect to the primary endpoint. A higher than anticipated placebo effect was observed in the control arm.
The US Food has accepted cipher's New Drug Application (NDA) for Cip-Tramadol ER for review and Drug Administration (FDA) as disclosed by the company on September 5, 2006. In January 2006, Cipher announced that it had been advised by the FDA that its existing clinical data package met the requirements to file a NDA. The NDA contains data from six completed pharmacokinetic studies and five phase III studies (three of these providing pivotal efficacy data and two providing long-term safety data). Data analysis on the 02.05 trials is continuing and Cipher will provide the final report on the 02.05 trial to the FDA once it is available.
"The clinical package we submitted to the FDA in June met the requirements for a complete NDA submission as evidenced by the fact it has now been accepted for review. We believe there is sufficient data in the package to support regulatory approval," said Larry Andrews, president and CEO of Cipher Pharmaceuticals. "The 02.05 trial is the latest in a series of six phase III trials completed by Cipher for CIP-TRAMADOL ER. The high placebo effect observed is disappointing; however, this is not an uncommon occurrence in placebo controlled pain trials. We intend to complete our analysis of the 02.05 study and assess the potential contribution that the higher than anticipated placebo effect may have had on the outcome. This analysis will form part of the final report on the study".
The 02.05 study enrolled 860 patients in a double-blind randomised fixed-dose trial designed to compare efficacy and safety of CIP-TRAMADOL ER with placebo. The primary efficacy endpoint of the study was WOMAC pain intensity. The trial was conducted over a 12-week treatment period in patients with moderate to moderately severe chronic pain from osteoarthritis of the knee or hip. Patients were randomly assigned to one of four arms, a placebo arm and three active arms consisting of a 100 mg, 200 mg, or 300 mg dose of CIP-TRAMADOL ER. Patients in the 100 mg arm were on 100 mg for the entire 12-week period, while patients in the 200 mg and 300 mg arms were titrated up from 100 mg to the respective dosage.