Oral Edaravone – Introducing a Flexible Treatment Option for Amyotrophic Lateral Sclerosis

Figures & data

Table 1. Effect of the type and timing of meals on the pharmacokinetics of oral edaravone relative to fasted conditions in healthy subjects.

Type and timing of meal consumed	Effect on Cmax and AUC relative to fasted conditions
ORS administered with a high-fat meal	Cmax decreased by 82%, AUC decreased by 61%
ORS administered 4 hours after a high-fat meal	Cmax decreased by 44%, AUC decreased by 24%
ORS administered 2 hours after a low-fat meal	Cmax decreased by 45%, AUC decreased by 21%

AUC, area under the curve; C_max, maximum drug concentration; ORS, oral edaravone.

Table 2. Oral edaravone (MT-1186) clinical trials.

	Oral edaravone clinical trial (ClinicalTrials.gov identifier)	Description
Phase 1	MT-1186-J01 (NCT04481750)	Placebo-controlled, randomized, dose-ranging evaluation of the PK, safety, and tolerability of oral edaravone in healthy adult males studying single and multiple ascending doses of oral edaravone Evaluated the Cmax and AUC values of the 105 mg of oral edaravone dose vs the 60-mg/60-minute IV edaravone dose
	MT-1186-J02 (NCT04481789)	Co-administration of oral edaravone with other drugs to determine drug-drug interactions in healthy adult males Preliminary regimen-finding study investigating food and the effect of Japanese vs Caucasian race on the PK of oral edaravone in healthy adult males
	MT-1186-J03 (NCT04493281)	Single-dose, randomized, 2-period, 2-sequence crossover, open-label study that evaluated the bioequivalence between the 60-mg IV edaravone dose and the 105-mg oral edaravone dose in healthy adult subjects
	MT-1186-J04 (NCT04176224)	Single-dose, open-label clinical pharmacology study that investigated the PK and safety of oral edaravone in adult Japanese patients with ALS vs healthy volunteers
	MT-1186-J05 (NCT04254913)	Single-dose, open-label study that investigated the difference in PK and safety of the administration of oral edaravone in patients with ALS via a PEG tube vs historic oral administration
	MT-1186-J06 (NCT05342597)	Single-dose, randomized, open-label, crossover study evaluating food effect on the PK of 105 mg of oral edaravone in healthy adult Japanese participants
	MT-1186-Z-101 (NCT04776135)	Randomized, open-label, crossover, single-dose clinical pharmacology study investigating the safety, tolerability, and comparative bioavailability of oral edaravone administered orally and via a nasogastric tube (as a surrogate for PEG/RIG administration) in healthy adult volunteers
Phase 3	MT-1186-A01 (NCT04165824)	Open-label, multicenter safety study evaluating the safety and tolerability of oral edaravone in patients with ALS using the FDA-approved dosing schedule over a 48-week treatment period
	MT-1186-A03 (NCT04577404)	Long-term safety and tolerability extension study for patients with ALS who complete Study A01 and will continue to receive oral edaravone without interruption for an additional treatment period of 96 weeks
	Extension of MT-1186-A03 (NCT05568615)	Ongoing, multicenter, single-group, open-label extension study following Study A03 to evaluate the safety of the FDA-approved on/off dosing regimen of oral edaravone in Japanese adults with ALS

Note: ALS, amyotrophic lateral sclerosis; AUC, area under the curve; C_max, maximum drug concentration; FDA, Food and Drug Administration; IV, intravenous; PEG, percutaneous endoscopic gastrostomy; PK, pharmacokinetics; RIG, radiologically inserted gastrostomy; TEAE, treatment-emergent adverse event.