Werner Poewe1, Pierre Burbaud2,3, Giovanni Castelnovo4, Wolfgang H Jost5, Andres O Ceballos-Baumann6, Marta Banach7, Anna Potulska-Chromik8, Joaquim J Ferreira9, Katalin Bihari10, Edvard Ehler11, Martin Bares12,13,14, Lyudmyla A Dzyak15,16, Anna N Belova17, Emmanuel Pham18, Wenzhong Jerry Liu19, Philippe Picaut17. 1. Department of Neurology, Innsbruck Medical University/University Hospital, Innsbruck, Austria. 2. Department of Clinical Neurophysiology, CHU de Bordeaux, Bordeaux, France. 3. Institut des Maladies Neurodégénératives, Université de Bordeaux, Bordeaux, France. 4. Department of Neurology, University Hospital Caremeau, Nimes, France. 5. Department of Neurology, University of Freiburg, Freiburg, Germany. 6. Schön Klinik München Schwabing, Department of Neurology, Technische Universität München, München, Germany. 7. Department of Neurology, Jagiellonian University Medical College, Kraków, Poland. 8. Department of Neurology, Medical University of Warsaw, Warsaw, Poland. 9. Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal. 10. National Institute of Clinical Neurosciences, Budapest, Hungary. 11. Department of Neurology, County Hospital Pardubice, Pardubice, Czech Republic. 12. 1st Department of Neurology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. 13. St Anne's University Hospital, Brno, Czech Republic. 14. Department of Neurology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA. 15. Dnipropetrovsk State Medical Academy, Dnipropetrovsk Regional Clinical Hospital Mechnykov, Mechnykov, Ukraine. 16. Department of Neurology, Zhovtneva, Ploshcha, Ukraine. 17. Research Institute of Traumatology and Orthopaedics, Nizhnyi Novgorod, Russia. 18. Ipsen Innovation, Les Ulis, France. 19. Ipsen Biopharmaceuticals Inc, Basking Ridge, New Jersey, USA.
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.
RCT Entities:
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.
Authors: Mafalda Castelão; Raquel E Marques; Gonçalo S Duarte; Filipe B Rodrigues; Joaquim Ferreira; Cristina Sampaio; Austen P Moore; João Costa Journal: Cochrane Database Syst Rev Date: 2017-12-12
Authors: Christian Blahak; Marc E Wolf; Assel Saryyeva; Hansjoerg Baezner; Joachim K Krauss Journal: J Neural Transm (Vienna) Date: 2021-07-06 Impact factor: 3.575
Authors: Filipe B Rodrigues; Gonçalo S Duarte; Raquel E Marques; Mafalda Castelão; Joaquim Ferreira; Cristina Sampaio; Austen P Moore; João Costa Journal: Cochrane Database Syst Rev Date: 2020-11-12
Authors: Joseph Jankovic; Daniel Truong; Atul T Patel; Allison Brashear; Marian Evatt; Roman G Rubio; Chad K Oh; Daniel Snyder; Gill Shears; Cynthia Comella Journal: Mov Disord Clin Pract Date: 2018-04-26