Multicenter, Randomized, Phase III Study of a Single Dose of IncobotulinumtoxinA, Free from Complexing Proteins, in the Treatment of Glabellar Frown Lines

Carruthers Clinical Research, Vancouver, British Columbia, Canada.
Dermatologic Surgery (Impact Factor: 2.11). 02/2013; 39(4). DOI: 10.1111/dsu.12100
Source: PubMed


BACKGROUND: Botulinum toxin type A is a proven, effective aesthetic treatment for glabellar frown lines. IncobotulinumtoxinA (NT 201, Xeomin/Xeomeen/Bocouture, Merz Pharmaceuticals GmbH, Frankfurt, Germany) is a 150-kDa botulinum toxin type A free of complexing proteins. OBJECTIVE: To assess the efficacy and safety of incobotulinumtoxinA in a randomized, double-blind, placebo-controlled, Phase III study in patients with moderate to severe glabellar frown lines. MATERIALS AND METHODS: Two hundred seventy-six patients were randomized 2:1 to receive a single injection of 20 U of incobotulinumtoxinA or placebo, respectively. Efficacy was assessed at day 30 using a Food and Drug Administration-mandated composite endpoint; a responder was defined as a patient with a 2-point or greater improvement in glabellar frown lines on a 4-point scale as assessed by investigator and patient. Safety was assessed periodically through Day 120. RESULTS: Treatment with a single dose of incobotulinumtoxinA was significantly superior to placebo in the treatment of glabellar frown lines at Day 30 using the composite endpoint (p < .001), with investigators and patients assessing glabellar frown lines as significantly more improved after incobotulinumtoxinA injection than with placebo (p < .001). IncobotulinumtoxinA was well tolerated. CONCLUSION: A single dose of 20 U of incobotulinumtoxinA demonstrated efficacy and safety in the treatment of glabellar frown lines using new Food and Drug Administration efficacy variables.

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    • "Overall, 84% of the maximal effect also occurred during this timeframe.20 Similarly, a median time to onset of effect of 3 days was reported in a prospective, randomized, double-blind Phase III trial investigating a single dose of incobotulinumtoxinA.25 An onset of effect described by the authors as occurring in the “first few days after treatment” has also been observed in a second, similarly designed, randomized Phase III trial,26 and in a long-term study assessing a maximum of eight treatment cycles of incobotulinumtoxinA over a 2-year period.27 "
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    ABSTRACT: Three botulinum neurotoxin type A preparations (incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA) are widely approved in Europe and in the US for the treatment of glabellar frown lines. The purpose of this study was to determine and compare the time to onset and duration of treatment effect of incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA for the treatment of glabellar frown lines. Subjects aged 20-60 years with moderate to severe glabellar frown lines received one treatment of either 21 units (U) incobotulinumtoxinA, 21 U onabotulinumtoxinA, or 63 U abobotulinumtoxinA. Assessments were made over a period of 180 days. Onset of treatment effect was defined as the day that the observer noted a decrease in glabellar muscle activity compared with baseline photographs and videos. Duration of treatment effect was defined as the time until glabellar muscle action returned to the baseline level. Analyses were performed using a Weibull log(T) regression model. The study enrolled 180 subjects; 60 per group. For all three products, onset of treatment effect occurred earlier in female subjects compared to male subjects. For both sexes, a significantly earlier time to onset of treatment effect was seen for incobotulinumtoxinA compared to onabotulinumtoxinA and abobotulinumtoxinA; in female subjects these times were 3.02 days, 5.29 days, and 5.32 days, respectively. The duration of treatment effect was longer for incobotulinumtoxinA compared to onabotulinumtoxinA and abobotulinumtoxinA; for all products, treatment effect duration was longer in females than in males. Time to onset was not a predictor of treatment duration. IncobotulinumtoxinA demonstrated a more rapid onset and a longer duration of treatment effect than onabotulinumtoxinA (1:1 dose ratio) and abobotulinumtoxinA (1:3 dose ratio). Onset of effect was faster and duration of effect was longer in female subjects compared to male subjects.
    Clinical, Cosmetic and Investigational Dermatology 09/2013; 6:211-219. DOI:10.2147/CCID.S41537
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    ABSTRACT: This review examines the pharmacologic and clinical characteristics of incobotulinumtoxinA (Xeomin(®)/Xeomeen(®)/Bocouture(®)/XEOMIN Cosmetic™; botulinum toxin type A [150 kDa]), which is free from complexing proteins, and discusses its efficacy and safety in the treatment of glabellar frown lines. Differences between incobotulinumtoxinA and other commercially available botulinum neurotoxin type A (BoNT/A) products that have been approved by the European Medicines Agency, US Food and Drug Administration, and other regulatory agencies for this indication are also discussed. IncobotulinumtoxinA differs from other commercially available BoNT/A preparations, in that it is free from complexing proteins and contains only active neurotoxin, minimizing foreign protein load. IncobotulinumtoxinA is commonly used at a 1:1 dose ratio with onabotulinumtoxinA and displays comparable efficacy and safety; furthermore, it is associated with early onset and long duration of effect, and high levels of subject satisfaction. In terms of practical considerations, incobotulinumtoxinA does not require cold storage and demonstrates low spread, enabling precise treatment and good tolerability. IncobotulinumtoxinA is an efficacious and well-tolerated treatment for glabellar frown lines. It differs from other BoNT/A preparations, in that it is free from complexing proteins and contains only active neurotoxin, which is relevant clinically, as this reduces the foreign protein load and minimizes the risk of neutralizing antibody production. In practical terms, incobotulinumtoxinA has a long shelf-life, remaining stable without the need for refrigeration, and due to its limited spread is a precise localized treatment.
    Clinical Pharmacology: Advances and Applications 03/2013; 5:39-52. DOI:10.2147/CPAA.S37582
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    ABSTRACT: IncobotulinumtoxinA (Bocouture(®)) is free from complexing proteins and effective for treating glabellar frown lines. To determine the efficacy, onset, and duration of action of incobotulinumtoxinA for the treatment of glabellar frown lines. In this single-arm, prospective, proof-of-concept study, 23 patients were treated with 25 U incobotulinumtoxinA, equally split between five injection sites in the glabella. Severity of glabellar frown lines was rated by an independent rater from standardized photographs using the validated Merz 5-point scale at several visits over 5 months following treatment. To assess patient satisfaction, patients completed a questionnaire before and 2 weeks after treatment. The percentage of responders at maximum frown 2-4 days after treatment was 95.2% and 85.0% when responders were defined as patients with ≥1-point and ≥2-point improvement on the 5-point scale compared with baseline, respectively. At this time point, 84% of the maximum effect had occurred. The responder rate at maximum frown, according to both definitions, was 100% for at least the next two visits (days 8 ± 1 and 14 ± 2). At all visits, the change from baseline in the mean glabellar frown-line score at maximum frown was statistically significant, with on average an almost 1-point improvement from baseline 5 months after treatment. IncobotulinumtoxinA is an effective and well-tolerated treatment for glabellar frown lines, with a rapid onset of action and a long duration of effect lasting for more than 5 months.
    Clinical Interventions in Aging 04/2013; 8:449-56. DOI:10.2147/CIA.S34854 · 2.08 Impact Factor
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