Efficacy and safety of abobotulinumtoxinA liquid formulation in cervical dystonia: A randomized-controlled trial

Mov Disord. 2016 Nov;31(11):1649-1657. doi: 10.1002/mds.26760. Epub 2016 Sep 21.

Abstract

Background: Approved botulinum toxin A products require reconstitution. AbobotulinumtoxinA solution for injection is a ready-to-use liquid formulation of abobotulinumtoxinA.

Objectives: The objective of this study was to demonstrate the superior efficacy of abobotulinumtoxinA solution for injection to placebo and to test the noninferior efficacy of abobotulinumtoxinA solution for injection versus abobotulinumtoxinA (dry formulation) in cervical dystonia.

Methods: This was a phase-3, multicenter, prospective, double-blind, randomized, active, and placebo-controlled study (N = 369). Patients with cervical dystonia were randomized (3:3:1) to abobotulinumtoxinA solution for injection 500 U, abobotulinumtoxinA 500 U, or placebo. Following the double-blind phase, patients received abobotulinumtoxinA solution for injection, open-label, for up to 4 cycles. The primary outcome was change from baseline at week 4 of the Toronto Western Spasmodic Torticollis Rating Scale total score. Secondary measures included change from baseline or cycle baseline in Toronto Western Spasmodic Torticollis Rating Scale scores.

Results: At week 4, both products were superior to placebo (Toronto Western Spasmodic Torticollis Rating Scale total score least square mean decrease from baseline, abobotulinumtoxinA solution for injection 500 U -12.5, abobotulinumtoxinA 500 U -14.0, placebo -3.9; P < .0001 vs placebo). The noninferiority limit of 3 points in the Toronto Western Spasmodic Torticollis Rating Scale total score at week 4 was not met for abobotulinumtoxinA solution for injection versus abobotulinumtoxinA. Toronto Western Spasmodic Torticollis Rating Scale total score reductions were maintained for up to 4 cycles of abobotulinumtoxinA solution for injection open-label follow-up treatment. Safety profiles of abobotulinumtoxinA solution for injection and abobotulinumtoxinA were similar, with dysphagia and injection-site pain the most frequent drug-related adverse events.

Conclusions: Although the predefined noninferiority criterion was not met, abobotulinumtoxinA solution for injection was similarly effective to freeze-dried abobotulinumtoxinA in reducing Toronto Western Spasmodic Torticollis Rating Scale total scores with a similar safety profile. AbobotulinumtoxinA solution for injection efficacy was maintained with chronic open-label treatment, and this novel formulation may add convenience as well as dosing accuracy to treatment with abobotulinumtoxinA. © 2016 International Parkinson and Movement Disorder Society.

Trial registration: ClinicalTrials.gov NCT01261611.

Keywords: Toronto Western Spasmodic Torticollis Rating Scale; abobotulinumtoxinA solution for injection; cervical dystonia.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acetylcholine Release Inhibitors / administration & dosage
  • Acetylcholine Release Inhibitors / adverse effects
  • Acetylcholine Release Inhibitors / pharmacology*
  • Adult
  • Botulinum Toxins, Type A / administration & dosage
  • Botulinum Toxins, Type A / adverse effects
  • Botulinum Toxins, Type A / pharmacology*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care / methods*
  • Prospective Studies
  • Severity of Illness Index
  • Torticollis / drug therapy*

Substances

  • Acetylcholine Release Inhibitors
  • Botulinum Toxins, Type A
  • abobotulinumtoxinA

Associated data

  • ClinicalTrials.gov/NCT01261611