Weight loss was more common than weight gain in adults treated with viloxazine extended-release for Attention-Deficit/Hyperactivity Disorder in short and long-term phase 3 clinical trials
Objective: Evaluate body weight (BW) changes with viloxazine extended release (VLX-ER) in a phase 3, double-blind, 6-week trial [NCT04016779] for adult ADHD, and its ensuing long-term, open-label extension (OLE) trial [NCT04143217].
Methods: Post-hoc analysis measuring mean and categorical (≥5%) BW changes from baseline (CFB) throughout double-blind end of study (EOS) to OLE-Week-52.
Results: At baseline, BW was 80.3±16.42kg (full analysis set, Nf354; VLX-ER, n=175; placebo, n=179); 65.8% of participants had BMI ≥25 kg/m2 (overweight/obese). VLX-ER-treated participants showed significant weight loss relative to placebo by double-blind EOS (treatment difference:
-1.1±0.40 kg; P < 0.0055). Additionally, more VLX-ER-treated participants lost vs. gained ≥5% BW (7.2% vs 0.0%) whereas placebo-treated participants showed opposite effects (1.1% vs. 2.2%). Similar to VLX-ER-treated participants in DB, placebo-treated participants lost weight upon switching to VLX-ER in the OLE (CFB -0.433±3.4709 kg at OLE-Week-12). Overall, weight loss appeared maintained throughout OLE treatment (CFB at OLE-Week 52 of -2.022±5.6019 kg, n=54). Participants with BMI ≥25 vs. < 25 kg/m2 showed larger BW changes at both DB EOS (placebo-subtracted CFB: 1.4±0.60 kg, P < .0220 vs -0.8±0.30 kg, P=.0062) and OLE-Week-52: -2.965±6.3920 kg (n=34) vs. -0.42±3.505 (n=20).
Conclusions: Decreases in BW with VLX-ER persisted throughout treatment and were larger in adults with ADHD who were overweight/obese at baseline. Reductions in BW appear consistent with unique VXL-ER pharmacologic effects to inhibit norepinephrine transport (NET), and modulate serotonin activity, with agonistic effects at 5-HT2C, and antagonistic effects at 5-HT2B and 5-HT7, potentially facilitating weight loss by decreasing impulsive overeating.
