Abstract
BACKGROUND: Two randomized, double-blind, placebo-controlled, Phase III studies of incobotulinumtoxinA for treating upper facial lines (UFLs; ie, a combination of glabellar frown lines [GFLs], horizontal forehead lines [HFLs], and lateral canthal lines [LCLs]) were conducted in the United States (ULTRA I: NCT04594213) and Germany (ULTRA II: NCT04622254). OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of simultaneous intramuscular injections for UFLs. Longer-term safety and efficacy were assessed in open-label extension periods. METHODS: Healthy participants (≥18 years) with moderate-to-severe GFLs, HFLs, and symmetric LCLs at maximum contraction on the 5-point Merz Aesthetics Scales were randomized 2:1:1 to receive up to 64 units of incobotulinumtoxinA in the main period for each trial. Treatment groups were: UFLs, GFLs, and HFLs (ULTRA I), LCLs (ULTRA II), and placebo. Primary efficacy endpoints were the proportions of GFL, HFL, and LCL responders, defined as a Merz Aesthetics Scale score for the respective area of 0 (no) or 1 (mild) and a ≥2-grade improvement from baseline to Day 30, as assessed by both investigator and participant. RESULTS: Overall, 362 and 368 participants received treatment in ULTRA I and ULTRA II, respectively. In both studies, incobotulinumtoxinA treatment was significantly more effective than placebo with respect to the primary endpoints (P < .0001) and key secondary endpoints (P < .0001). The open-label extension period results were consistent with those seen in the main period. No new safety findings were identified. CONCLUSIONS: In ULTRA I and ULTRA II, the safety and efficacy of incobotulinumtoxinA for the simultaneous treatment of moderate-to-severe UFLs were demonstrated, with significant improvements across all primary and secondary endpoints vs placebo.