Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial

Abstract

This 56-week, randomized, placebo-controlled trial examined the efficacy and safety of naltrexone plus bupropion as an adjunct to intensive behavior modification (BMOD). A total of 793 participants (BMI = 36.5 ± 4.2 kg/m²) was randomly assigned in a 1:3 ratio to: (i) placebo + BMOD (N = 202); or (ii) naltrexone sustained-release (SR, 32 mg/day), combined with bupropion SR (360 mg/day) plus BMOD (i.e., NB32 + BMOD; N = 591). Both groups were prescribed an energy-reduced diet and 28 group BMOD sessions. Co-primary end points were percentage change in weight and the proportion of participants who lost ≥5% weight at week 56. Efficacy analyses were performed on a modified intent-to-treat population (ITT; i.e., participants with ≥1 postbaseline weight while taking study drug (placebo + BMOD, N = 193; NB32 + BMOD, N = 482)). Missing data were replaced with the last observation obtained on study drug. At week 56, weight loss was 5.1 ± 0.6% with placebo + BMOD vs. 9.3 ± 0.4% with NB32 + BMOD (P < 0.001). A completers analysis revealed weight losses of 7.3 ± 0.9% (N = 106) vs. 11.5 ± 0.6% (N = 301), respectively (P < 0.001). A third analysis, which included all randomized participants, yielded losses of 4.9 ± 0.6 vs. 7.8 ± 0.4%, respectively (P < 0.001). Significantly more NB32 + BMOD- vs. placebo + BMOD-treated participants lost ≥5 and ≥10% of initial weight, and the former had significantly greater improvements in markers of cardiometabolic disease risk. NB32 + BMOD was generally well tolerated, although associated with more reports of nausea than placebo + BMOD. The present findings support the efficacy of combined naltrexone/bupropion therapy as an adjunct to intensive BMOD for obesity.

Figure 1

Flow of participants through the study. Participants were included in the modified-ITT analysis population if they had ≥1 postbaseline measurement of weight while on study drug. Participants were included in the completers analysis if they had a week 56 weight measurement on study drug. The discrepancy between the number of participants who completed the trial (N = 460) and those included in the completers analysis (N = 407) reflects participants who had not taken a dose of study drug within 24 h of their weight being measured at week 56. BMOD, behavior modification; ITT, intent-to-treat.

Figure 2

Percentage weight loss from baseline for the modified-ITT-LOCF population (placebo + BMOD, N = 193; NB32 + BMOD, N = 482) and the completer population (placebo + BMOD, N = 106; NB32 + BMOD, N = 301). *P < 0.001 for NB32 + BMOD vs. placebo + BMOD. BMOD, behavior modification; ITT, intent-to-treat; LOCF, last observation carried forward.

Figure 3

Percentage of study participants losing ≥5, ≥10, or ≥15% of their baseline body weight at week 56. (a) Modified-ITT-LOCF population (placebo + BMOD, N = 193; NB32 + BMOD, N = 482). (b) Completer population (placebo + BMOD, N = 106; NB32 + BMOD, N = 301). (c) Randomized-LOCF population (placebo + BMOD, N = 202; NB32 + BMOD, N = 591). BMOD, behavior modification; ITT, intent-to-treat; LOCF, last observation carried forward.

Figure 4

Change from baseline to week 56 in IWQOL-Lite total and subscale scores for the modified-ITT-LOCF population. ITT, intent-to-treat; IWQOL, Impact of Weight on Quality of Life; LOCF, last observation carried forward. Ns for the placebo + BMOD group ranged from 174–179 across the different variables and from 438–448 for the NB32 + BMOD group.