Phase 1 Study of Safety, Tolerability, and Bioavailability of Oral Edaravone Administered Orally and via a Nasogastric Feeding Tube in Healthy Adults

Topic:

Clinical Trials

Poster Number: 37

Author(s):

Antoinette Harrison, PharmD, BCGP, BCPP, FASCP, Mitsubishi Tanabe Pharma America, Inc., Bryan Alan Hill, PharmD, Mitsubishi Tanabe Pharma America, Inc., Hidetoshi Shimizu, Mitsubishi Tanabe Pharma Corporation, Yukiko Nishimura, Mitsubishi Tanabe Pharma Corporation, Kaori Yoshida, Mitsubishi Tanabe Pharma Corporation, Shoko Yokota, Mitsubishi Tanabe Pharma Corporation, Manabu Hirai, MS, Mitsubishi Tanabe Pharma Corporation, Kazuoki Kondo, MD, Mitsubishi Tanabe Pharma Corporation

Background: Radicava® (edaravone injection) is a US FDA-approved treatment for amyotrophic lateral sclerosis (ALS) shown to slow the rate of physical functional decline. As intravenous administration can burden patients, orally administered treatments are needed. Some patients with ALS may undergo a percutaneous endoscopic gastrostomy (PEG) due to dysphagia; therefore, the possibility of administering drugs via a PEG tube should be considered.
Objectives: To assess the comparative bioavailability and pharmacokinetics (PK) of an investigational oral suspension formulation of edaravone (MT-1186) when administered via a nasogastric feeding tube (NGT) as a model of administration via a PEG tube (MT-1186-Z-101).
Methods: Study Z-101 was a randomized, open-label, crossover-design, single-dose, phase 1 study with 36 healthy Japanese adults (aged 20–45 years) randomly allocated into two even groups. Subjects received a single dose of MT-1186 either orally or via NGT, and PK was assessed over 48 hours, followed by crossover to the other form of administration.
Results: Mean plasma concentration-time profiles of unchanged edaravone were similar between groups. The geometric least squares mean ratio between groups and 90% confidence interval (CI) of unchanged edaravone was 1.052 (90% CI, 0.903–1.227) and 0.981 (90% CI, 0.931–1.033) for maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time 0 extrapolated to infinity(AUC 0–infinity), respectively. Other PK parameters were also similar between groups. One adverse event (AE) was reported (n=1) after oral administration, and five AEs were reported (n=3) after NGT administration. All AEs were mild and reported as elevated laboratory test results. Two adverse drug reactions were reported (n=1) after NGT administration, none were reported after oral administration. No serious AEs occurred.
Conclusions: These results suggest that oral edaravone suspension can be administered directly to the stomach with a feeding tube (eg, PEG) without the need for dose adjustment.