Mark F Lew1, Allison Brashear2, Khashayar Dashtipour3, Stuart Isaacson4, Robert A Hauser5, Pascal Maisonobe6, Daniel Snyder7, William Ondo8. 1. a Department of Neurology , Keck/University of Southern California School of Medicine , Los Angeles , CA , USA. 2. b Department of Neurology , Wake Forest School of Medicine , Medical Center Blvd. Winston Salem , NC , USA. 3. c Department of Neurology/Movement Disorders , School of Medicine, Faculty Medical Offices , Loma Linda University , Loma Linda , CA , USA. 4. d Parkinson's Disease and Movement Disorders Center of Boca Raton , Boca Raton , FL , USA. 5. e University of South Florida Health Byrd Parkinson's Disease and Movement Disorders Center of Excellence , Tampa , FL , USA. 6. f Ipsen Pharma , Boulogne-Billancourt , France. 7. g Ipsen Biopharmaceuticals , Basking Ridge , NJ , USA. 8. h Methodist Neurological Institute , Houston , TX , USA.
Abstract
Purpose/aim: AbobotulinumtoxinA (Dysport®, Ipsen Biopharmaceuticals, Inc., Basking Ridge, NJ, USA) is an acetylcholine release inhibitor and a neuromuscular blocking agent. The United States prescribing information for abobotulinumtoxinA previously indicated only one dilution for cervical dystonia: 500 U/1 mL. Clinical trial data supporting a larger volume with a 500 U/2 mL dilution would offer clinicians flexibility with injection volume to better meet patient needs. MATERIALS AND METHODS: We conducted a 12-week, phase 3b, multicenter, randomized, double-blind, placebo-controlled trial (NCT01753310). Adult subjects with a primary diagnosis of cervical dystonia were randomized (2:1) to receive a single injection of either abobotulinumtoxinA, 500 U/2 mL dilution, or placebo. The primary efficacy endpoint was changed from baseline in Toronto Western Spasmodic Torticollis Rating Scale total score at Week 4. RESULTS: A total of 134 subjects (abobotulinumtoxinA, n = 89; placebo, n = 45) were randomized (intent-to-treat population) and 129 (abobotulinumtoxinA, n = 84; placebo, n = 45) completed the Week 4 primary endpoint evaluation (modified intent-to-treat population). In the modified intent-to-treat population, subjects receiving abobotulinumtoxinA experienced significantly greater changes from baseline versus placebo on the primary endpoint (weighted overall treatment difference -8.3, P < 0.001). The most common treatment-emergent adverse events (TEAEs) were dysphagia, muscle weakness, neck pain and headache. Overall, TEAEs were consistent with those reported in the abobotulinumtoxinA prescribing information (1 mL dilution) for cervical dystonia patients. CONCLUSIONS: This trial provides evidence that a 500 U/2 mL dilution is an effective treatment for cervical dystonia and exhibits a safety profile consistent with the known safety profile of abobotulinumtoxinA.
RCT Entities:
Purpose/aim: AbobotulinumtoxinA (Dysport®, Ipsen Biopharmaceuticals, Inc., Basking Ridge, NJ, USA) is an acetylcholine release inhibitor and a neuromuscular blocking agent. The United States prescribing information for abobotulinumtoxinA previously indicated only one dilution for cervical dystonia: 500 U/1 mL. Clinical trial data supporting a larger volume with a 500 U/2 mL dilution would offer clinicians flexibility with injection volume to better meet patient needs. MATERIALS AND METHODS: We conducted a 12-week, phase 3b, multicenter, randomized, double-blind, placebo-controlled trial (NCT01753310). Adult subjects with a primary diagnosis of cervical dystonia were randomized (2:1) to receive a single injection of either abobotulinumtoxinA, 500 U/2 mL dilution, or placebo. The primary efficacy endpoint was changed from baseline in Toronto Western Spasmodic Torticollis Rating Scale total score at Week 4. RESULTS: A total of 134 subjects (abobotulinumtoxinA, n = 89; placebo, n = 45) were randomized (intent-to-treat population) and 129 (abobotulinumtoxinA, n = 84; placebo, n = 45) completed the Week 4 primary endpoint evaluation (modified intent-to-treat population). In the modified intent-to-treat population, subjects receiving abobotulinumtoxinA experienced significantly greater changes from baseline versus placebo on the primary endpoint (weighted overall treatment difference -8.3, P < 0.001). The most common treatment-emergent adverse events (TEAEs) were dysphagia, muscle weakness, neck pain and headache. Overall, TEAEs were consistent with those reported in the abobotulinumtoxinA prescribing information (1 mL dilution) for cervical dystoniapatients. CONCLUSIONS: This trial provides evidence that a 500 U/2 mL dilution is an effective treatment for cervical dystonia and exhibits a safety profile consistent with the known safety profile of abobotulinumtoxinA.
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: Atul T Patel; Mark F Lew; Khashayar Dashtipour; Stuart Isaacson; Robert A Hauser; William Ondo; Pascal Maisonobe; Stefan Wietek; Bruce Rubin; Allison Brashear Journal: PLoS One Date: 2021-02-01 Impact factor: 3.240
Authors: Mark F Lew; Robert A Hauser; Stuart H Isaacson; Daniel Truong; Atul T Patel; Allison Brashear; William Ondo; Pascal Maisonobe; Khashayar Dashtipour; Laxman Bahroo; Stefan Wietek Journal: Clin Park Relat Disord Date: 2021-11-20