Lorcaserin (APD356) is a potent, selective 5-HT(2C) agonist with ~15-fold and 100-fold selectivity vs. 5-HT(2A) and 5-HT(2B) receptors, respectively. This study evaluated the safety and efficacy of lorcaserin for weight reduction in obese patients during a 12-week period. The randomized, double-blind, placebo-controlled, parallel-arm study enrolled 469 men and women between ages 18 and 65 and with BMI 30-45 kg/m(2). Patients received placebo, lorcaserin 10 mg q.d., lorcaserin 15 mg q.d., or lorcaserin 10 mg b.i.d. for 12 weeks, and were counseled to maintain their usual diet and activity. The primary end point was change in weight from baseline to day 85 by completer analysis. Safety analyses included echocardiograms at Screening and day 85/study exit. Lorcaserin was associated with progressive weight loss of 1.8 kg, 2.6 kg, and 3.6 kg at 10 mg q.d., 15 mg q.d., and 10 mg b.i.d., respectively, compared to placebo weight loss of 0.3 kg (P < 0.001 for each group). Similar results were seen by intent-to-treat last observation-carried forward (ITT-LOCF) analysis. The proportions of completers achieving > or =5% of initial body weight were 12.8, 19.5, 31.2, and 2.3% in the 10 mg q.d., 15 mg q.d., 10 mg b.i.d., and placebo groups, respectively. The most frequent adverse events (AEs) were transient headache, nausea, and dizziness. Echocardiograms showed no apparent drug-related effects on heart valves or pulmonary artery pressure (PAP). Lorcaserin was well tolerated and efficacious for weight reduction in this 12-week study. Longer-term trials employing behavior modification will be needed to more fully assess its safety and efficacy.
Trial registration: ClinicalTrials.gov NCT00116740.