Phentermine/Topiramate for the Treatment of Adolescent Obesity

Abstract

Background: Antiobesity medication may be useful for the treatment of pediatric obesity, yet few safe and effective options exist. We evaluated phentermine/topiramate (PHEN/TPM) for weight management in adolescents with obesity.

Methods: This 56-week, randomized, double-blind trial enrolled adolescents 12 to less than 17 years of age with obesity. Participants were randomly assigned 1:1:2 to receive either placebo (n=56), mid-dose PHEN/TPM (7.5 mg/46 mg; n=54), or top-dose PHEN/TPM (15 mg/92 mg; n=113), respectively. All participants received lifestyle therapy. The primary end point was mean percent change in body-mass index (BMI) from randomization to week 56.

Results: Participants had a mean (±SD) age of 14.0±1.4 years and a mean (±SD) BMI of 37.8±7.1 kg/m²; 54.3% were female. The primary end point of percent change in BMI at week 56 showed differences from placebo of -10.44 percentage points (95% CI, -13.89 to -6.99; P<0.001) and -8.11 percentage points (95% CI, -11.92 to -4.31; P<0.001) for the top and mid doses of PHEN/TPM, respectively. Differences from placebo in percent change in triglycerides nominally favored PHEN/TPM (mid dose, -21%; 95% CI, -40 to -2; and top dose, -21%; 95% CI, -38 to -4), as did differences in percent change in high-density lipoprotein cholesterol (HDL-C) (mid dose, 10%; 95% CI, 3 to 18; and top dose, 9%; 95% CI, 2 to 15). The incidence of participants reporting at least one adverse event was 51.8%, 37.0%, and 52.2% in the placebo, mid-dose, and top-dose groups, respectively. Serious adverse events were reported for two participants in the top-dose group.

Conclusions: PHEN/TPM at both the mid and top doses offered a statistically significant reduction in BMI and favorably impacted triglyceride and HDL-C levels in adolescents with obesity. (Funded by VIVUS LLC, with project support provided by Covance LLC; ClinicalTrials.gov number, NCT03922945.).

Figure 1. CONSORT Diagram.

The mid and top doses are 7.5 mg/46 mg and 15 mg/92 mg of phentermine/topiramate, respectively. For randomly assigned and not treated, the denominator for the percentage in each treatment group is the number of total participants randomly assigned to treatment. For discontinued, the percentage is calculated from participants in the safety population in each treatment group. For primary reason discontinued from study treatment, the percentage is calculated from participants in the intent-to-treat population in each treatment group.

Figure 2. Percent Body-Mass Index Change Over Time.

Plot of least square means (±SE) of percentage change in body-mass index (BMI) using observed data from baseline to week 56 by treatment group (with the primary analysis, modified intent-to-treat [ITT], and other imputation models). The mid and top doses are 7.5 mg/46 mg and 15 mg/92 mg of phentermine/topiramate (PHEN/TPM), respectively. LOCF denotes last observation carried forward, MAR missing at random, MI multiple imputation, and MNAR, missing not at random. *P<0.001 versus placebo.

Figure 3. Percentage of Participants Achieving Various Body-Mass Index Reduction Benchmarks.

Percentage of participants achieving a reduction of 5%, 10%, and 15% or greater in body-mass index (BMI) from baseline to week 56 by treatment group, intent-to-treat (ITT) population. The mid and top doses are 7.5 mg/46 mg and 15 mg/92 mg of phentermine/ topiramate (PHEN/TPM), respectively.