A PLACEBO-CONTROLLED, DOSE-RESPONSE STUDY OF DEXFENFLURAMINE IN THE TREATMENT OF OBESE PATIENTS

A randomized, placebo-controlled, multicenter, parallel-group study wa s performed to determine which of three dose levels of dexfenfluramine (Dfen)-10, 30, or 60 mg/d-in combination with a sex- and body weight- specific reduction in caloric intake best reduced body weight and prod uced the fewest adverse events over a 12-week period. Three hundred th irty-nine patients whose body weight was 120% to 180% of ideal body we ight were randomized to one of four treatment groups: placebo, Dfen 10 mg/d, Dfen 30 mg/d, or Dfen 60 mg/d. Patients were treated in a doubl e-masked fashion for 12 weeks and were monitored during a 4-week postt reatment period. Data from 322 patients (placebo, 82 patients; Dfen 10 mg, 84 patients; Dfen 30 mg, 79 patients; Dfen 60 mg, 77 patients) we re available for efficacy analysis. After 12 weeks, a statistically si gnificant weight loss was observed in the 30-mg and 60-mg Dfen treatme nt groups but not in the 10-mg Dfen group, when compared with placebo. Mean absolute weight losses were 2.83 kg (placebo), 2.79 kg (Dfen 10 mg), 5.63 kg (Dfen 30 mg), and 7.23 kg (Dfen 60 mg). All treatment gro ups showed a tendency to regain weight during the posttreatment period , but the Dfen 30-mg and 60-mg groups still ranked highest for overall weight loss at the end of this period. The frequency of diarrhea, ast henia, dizziness, dry mouth, and somnolence increased with increasing doses of Dfen. Blood pressure slightly decreased with higher doses of Dfen but returned toward normal after treatment ceased. Plasma concent rations of Dfen increased with increasing doses; no tendency for accum ulation of Dfen or D-nor-fenfluramine was observed. The results of thi s study show that 12 weeks of treatment with Dfen was effective in red ucing weight in a dose-dependent manner; based on the efficacy analysi s and side-effect profile, the dose of 30 mg/d was found to be optimal .