Abstract

Background: Zonisamide with bupropion has been shown to cause weight loss but the optimal dose ratio is unknown. A novel sustained-release (SR) zonisamide was tested in combination with bupropion SR in six different dose ratios vs. placebo. Methods: A double-blind, placebo-controlled trial randomized 623 healthy obese subjects equally to one of the seven treatment groups: Z120mg/B280mg, Z120/B360, Z240/B280, Z240/B360, Z360/B280, Z360/B360, or placebo. A minimalist ancillary therapy comprised of diet instruction as well as advice on behavior modification and exercise was included. Dosage titration occurred during Weeks 1 through 8, and maintenance dosage was administered from Weeks 9 through 24. Data collected during this 24-week period were included in the primary analysis. An additional 24 weeks of open label treatment continued per protocol. Results: The results of the primary analysis on the percent change from baseline total body weight at the Week 24 visit are summarized in Figure 1. All active treatment groups showed statistically significant weight loss in comparison with placebo (P <0.001), while percentage weight loss at the two highest dosages (Z360/B280 and Z360/B360) were statistically significantly superior to that observed with the Z120/B280, the lowest active dosage tested. Conclusions: The extent of weight loss with the combination treatment increased with higher ZB dosage. Five of the six active ZB groups (including the highest Z360/B360) exhibited a rate of discontinuation rate due to an adverse event comparable to that seen with placebo.