Liquid Formulation of AbobotulinumtoxinA: A 6-Month, Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of a Single Treatment, Ready-to-Use Toxin for Moderate-to-Severe Glabellar Lines

Abstract

BackgroundSafety and efficacy of botulinum toxin A for glabellar line (GL) treatment are well established. Currently approved formulations require reconstitution before injection.ObjectivesThe authors sought to assess 6-month efficacy, safety, and patient satisfaction of new ready-to-use abobotulinumtoxinA solution for injection (ASI) in patients with moderate-to-severe GL at maximum frown.MethodsThe authors conducted a phase 3, double-blind, randomized, placebo-controlled trial (NCT02353871). Patients (N = 185) were randomized (2:1) to receive ASI 50 U or placebo. GL severity was evaluated at days 8, 15, 29, 57, 85, 113, 148, and 183 employing a 4-point scale for investigator’s live assessment (ILA) and subject's self-assessment (SSA). Primary endpoint was ILA of GL at maximum frown at day 29, and secondary endpoints were ILA and SSA of GL at maximum frown (all time points), patient satisfaction with GL appearance, time to onset, and duration of action.ResultsResponder rates were significantly higher for ASI vs placebo (88.3% vs 1.4%; P < 0.0001) at day 29 by ILA and all time points by ILA (P < 0.0001-0.0441) and SSA (P < 0.0001-0.0036). Sixty percent of patients reported onset of treatment response on or before day 3 (P < 0.0001 vs placebo), and in 5% of patients, efficacy by ILA lasted 6 months (day 183; P = 0.0441 vs placebo). Patient satisfaction rates were significantly higher for ASI vs placebo at all visits (P < 0.0001). Safety was comparable with the known abobotulinumtoxinA profile.ConclusionsASI was significantly efficacious for improving moderate or severe GL vs placebo by investigator and patient assessment. ASI was associated with high patient satisfaction, a long duration of action, and comparable safety profile to abobotulinumtoxinA.Level of Evidence: 1

Significantly Increased Patient Satisfaction Following Liquid Formulation AbobotulinumtoxinA Treatment in Glabellar Lines: FACE-Q Outcomes From a Phase 3 Clinical Trial

“…The recent phase 3 trial in GL reported high rates of treatment response with ASI compared with placebo, by both investigator and patient assessment (88.3% and 76.0% at day 29, respectively; P < 0.0001 compared with placebo for both), as well as a long duration of response and a safety profile comparable with that of reconstituted abobotulinumtoxinA (Ipsen Ltd; Azzalure). 17 During the previous phase 2 comparator and placebo-controlled study, similar efficacy results were observed for both ASI and reconstituted abobotulinumtoxinA. 16 This was the first phase 3 clinical trial to include scales from the FACE-Q, a validated PRO instrument, to assess patient satisfaction with BoNT-A treatment for GL.…”

“…The study protocol and achievement of primary and secondary endpoints were previously published. 17 In brief, this was a phase 3, randomized, double-blind, placebo-controlled trial with a follow-up period of 6 months that was conducted at 9 study centers across France and Germany between January 2015 and August 2015 (NCT02353871). Eligible patients were aged between 18 and 65 years (men and nonpregnant women), were botulinum toxin-naïve, and presented with moderate or severe (grade 2 or 3) vertical GL at maximum frown by investigator’s live assessment (ILA; 4-point photographic scale) and patient’s self-assessment (SSA; 4-point categorical scale) at baseline.…”

“…The primary endpoint was assessed using ILA of GL at maximum frown at day 29, the results of which were previously reported. 17 Secondary endpoints were assessed using ILA at maximum frown and at rest, and SSA of GL at maximum frown and at rest across all time points. Time to onset, duration of treatment response, and safety have also been reported.…”

“…Sample size power calculations are detailed in the primary manuscript. 17 The FACE-Q efficacy endpoints were analyzed with a general linear model with stratification and center as a fixed effect. Results are presented as the parameter estimates, standard error (SE), and P value.…”

“…A liquid formulation of ready-to-use abobotulinumtoxinA (Dysport; abobotulinumtoxinA solution for injection [ASI]; Ipsen Ltd, Slough, UK; Azzalure, Galderma Ltd, Lausanne, Switzerland) has been proven to be efficacious and well tolerated for improving the appearance of moderate-to-severe glabellar lines (GL) in phase 2b and phase 3 trials. 16 , 17 ASI is of great interest as a means to avoid reconstitution errors, reduce preparation time, and improve consistency of dosing. The recent phase 3 trial in GL reported high rates of treatment response with ASI compared with placebo, by both investigator and patient assessment (88.3% and 76.0% at day 29, respectively; P < 0.0001 compared with placebo for both), as well as a long duration of response and a safety profile comparable with that of reconstituted abobotulinumtoxinA (Ipsen Ltd; Azzalure).…”