Phase 3, Open-Label, Multicenter Safety Study of Oral Edaravone in Patients With Amyotrophic Lateral Sclerosis (MT-1186-A01): 48-Week Results
Angela Genge1, Gary Pattee2, Gen Sobue3, Philippe Couratier4, Daniel Selness5, Sachin Bidani5, Manabu Hirai6, Takeshi Sakata6, Alejandro Salah7, Stephen Apple7
1Montreal Neurological Institute and Hospital, 2University of Nebraska Medical Center, 3Nagoya University Graduate School Of Medicine, 4CRMR SLA Service de Neurologie, CHU de Limoges, 5Mitsubishi Tanabe Pharma Development America, Inc., 6Mitsubishi Tanabe Pharma Corporation, 7Mitsubishi Tanabe Pharma America, Inc.
Objective:
Study MT-1186-A01 assessed the safety and tolerability of oral edaravone (MT-1186) in patients with ALS. NCT04165824.
Background:
An intravenous (IV) formulation of edaravone (Radicava®/Radicut) has been shown to slow the rate of physical functional decline in amyotrophic lateral sclerosis (ALS). Radicava ORS® (edaravone) oral suspension was recently approved by the US Food and Drug Administration for use in patients with ALS.
Design/Methods:
Study MT-1186-A01 was a global, multicenter, open-label, phase 3 study that evaluated the long-term safety and tolerability of oral edaravone in patients with ALS. The primary safety analysis was assessed at weeks 24 and 48. Patients received a 105-mg dose of oral edaravone administered in treatment cycles that replicated IV edaravone dosing.
Results:
In the safety analysis population (n=185), the most common treatment-emergent adverse events (TEAEs) reported by ≥5% of patients were fall (22.2%), muscular weakness (21.1%), constipation (17.8%), dyspnea (10.8%), dysphagia (10.3%), and back pain (10.3%). TEAEs considered to be study drug-related were reported by 46/185 (24.9%) patients, with the most common being fatigue (3.2%), dizziness (2.7%), headache (2.2%), and constipation (2.2%). Serious TEAEs were reported by 48/185 (25.9%) patients, with the most common being worsening of ALS symptoms (6.5%), dysphagia (3.2%), dyspnea (2.7%), and respiratory failure (2.7%). TEAEs leading to death were reported in 12/185 (6.5%) patients, including respiratory failure (2.2%), worsening of ALS (1.1%), pneumonia (1.1%), acute respiratory failure (0.5%), lung disorder (0.5%), diabetic ketoacidosis (0.5%), feeding disorder (0.5%), and suicide (0.5%). TEAEs leading to discontinuation were reported by 2/185 patients (tremor, n=1; gait disturbance, n=1); both TEAEs considered by the investigator to be study drug-related. No serious TEAEs, or TEAEs leading to death, were study drug-related.
Conclusions:
This study demonstrates that oral edaravone was generally safe and well tolerated during 48 weeks of treatment, with no new safety concerns identified.
Acknowledgements: p-value communications provided editorial support.