Method-of-use study of naltrexone sustained release (SR)/bupropion SR on body weight in individuals with obesity

Abstract

Objective: This study assessed the effects of 32 mg naltrexone sustained release (SR)/360 mg bupropion SR (NB) on body weight in adults with obesity, with comprehensive lifestyle intervention (CLI), for 78 weeks.

Methods: In this phase 3b, randomized, open-label, controlled study, subjects received NB + CLI or usual care (standard diet/exercise advice) for 26 weeks. NB subjects not achieving 5% weight loss at week 16 were discontinued, as indicated by product labeling. After week 26, usual care subjects began NB + CLI. Assessments continued through week 78. The primary end point was percent change in weight from baseline to week 26 in the per protocol population. Other end points included percentage of subjects achieving ≥5%, ≥10%, and ≥15% weight loss, percent change in weight at week 78, and adverse events (AEs) necessitating study medication discontinuation.

Results: NB + CLI subjects lost significantly more weight than usual care subjects at week 26 (8.52% difference; P < 0.0001). Weight loss persisted through 78 weeks. In total, 20.7% of subjects discontinued medication for AEs, including 7.0% for nausea.

Conclusions: Treatment with NB, used as indicated by prescribing information and with CLI, significantly improved weight loss over usual care alone. NB-facilitated weight loss was sustained for 78 weeks and was deemed safe and well tolerated.

Trial registration: ClinicalTrials.gov NCT01764386.

© 2016 The Authors. Obesity published by Wiley Periodicals, Inc. onbehalf of The Obesity Society (TOS).

Figures

Figure 1

Study participants and group assignments. A total of 242 subjects were randomly assigned 1.75:1 to NB + CLI and usual care groups, all of whom were also treated and included in the intent‐to‐treat (ITT) analysis. AE, adverse event; LTFU, lost to follow‐up; other, protocol deviation or withdrawal of consent; N/A, not applicable; NB + CLI, naltrexone/bupropion and comprehensive lifestyle intervention; week 16, evaluation to continue treatment at week 16 visit; week 42, evaluation to continue treatment at week 42 visit.

Figure 2

Change in body weight over time. (A) In the week 26 PP population, subjects in the NB + CLI treatment group (squares) lost a significantly higher percentage of baseline body weight compared with those in the usual care group (circles) beginning at the week 2 assessment and continuing through week 26. *P < 0.0001 for LS mean difference between treatment groups. (B) Observed changes in body weight between weeks 0 and 16 in all subjects in the NB + CLI treatment group who either responded (squares) or did not respond (triangles) to NB by losing at least 5% of their initial body weight at week 16. In both panels panels A and B, LS mean and SE are displayed.

Figure 3

Percentage of body weight lost through week 78. (A) Weight lost by subjects in the NB + CLI group and the usual care/NB + CLI group at week 78. Subjects in the NB + CLI group (squares) lost 90% of their maximum weight lost by 6 months. Subjects in the usual care/NB + CLI group (circles) had lost comparable body weight percentages to those of the NB + CLI group by week 78, despite beginning NB + CLI treatment at week 26. (B) Overall weight lost by individual subjects at week 78.