Empatic Clinical Data
Efficacy
In October 2007, Orexigen® presented 24 week results from a randomized, double-blind, placebo-controlled trial, the Company's first large, multi-center trial of its novel SR formulation of zonisamide paired with bupropion SR. The primary trial objective was to determine the optimal dose ratios of bupropion and zonisamide. The trial randomized 623 obese patients. Each of the six Empatic groups experienced weight loss that was statistically significantly greater than seen with placebo.
Safety
Results of this trial also indicated that Empatic was safe and generally well tolerated. Nearly 80% of patients completed the trial. The rates of discontinuation due to adverse events for all Empatic patients in the trial (14.0%) and the highest dose group (16.9%) were not significantly different than the 9.1% reported with placebo. Moreover, this overall rate was meaningfully lower than the rate see in Empatic patients in the Company's previous proof-of-concept trial employing an immediate-release form of zonisamide (37.3%). Adverse events were consistent with the existing package labels for one or both of the Empatic constituents and most commonly included headache, nausea, insomnia, anxiety or dry mouth.
The trial protocol permitted all patients who completed 24 weeks of treatment to continue on their existing double-blind therapy for an additional 24 weeks. Alternatively, patients who failed to achieve at least a 5% response 24 weeks after the start of treatment were permitted to switch to the highest Empatic dose in a 24-week open label extension. Most patients receiving Empatic therapy elected to continue on their existing double-blind therapy for an additional 24 weeks and continued to lose weight in the time period from weeks 24 to 48. Analysis of their weight loss, as specified by the study protocol, is referred to as the intent-to-treat—double blind extension. Patients from this group who completed treatment through week 48 are referred to as completers—double blind extension. The double-blind extension results for the 48 weeks are summarized as follows:
(a) Represents placebo weight loss at 24 weeks. The study design for the trial permitted patients who did not achieve a 5% weight loss from baseline to switch to the highest Empatic dose after 24 weeks. Because most (approximately 88%) of the placebo patients did not achieve a 5% clinical response at 24 weeks, most (approximately 79%) of the placebo patients who completed 24 weeks switched into the highest Empatic dose. This aspect of the trial, which permitted patients not achieving a 5% response to switch to the highest Empatic dose after 24 weeks, introduces selection bias for patients most likely to lose weight and enhances the results for all groups in the trial. However, the impact is greatest in the placebo arm because of the significantly higher proportion of placebo patients who switched to the highest Empatic dose after 24 weeks. As such, data for the actual 48-week double-blind placebo treatment arm are not presented.
Discontinuations due to adverse events in the extension period of the trial are detailed as follows:
