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- Title
Results from a first-in-human study of dersimelagon, an investigational oral selective MC1R agonist.
- Authors
Ogasawara, Akihito; Ogawa, Kei; Ide, Ryosuke; Ikenaga, Yuka; Fukunaga, Chie; Nakayama, Satoshi; Tsuda, Minoru
- Abstract
Purpose: To describe outcomes from the first-in-human study of dersimelagon, an investigational oral selective MC1R agonist, under development for the treatment of erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP). Methods: In this double-blind, placebo-controlled phase 1 study, the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending oral doses of dersimelagon in healthy participants were evaluated. Results: Dersimelagon was generally well tolerated in healthy participants, with the most common TEAEs being lentigo (52.8%) and skin hyperpigmentation (50.0%) after multiple doses. Systemic exposure to dersimelagon in plasma (based on AUC0-∞ and Cmax) increased in a slightly more than dose-proportional manner over the 1- to 600-mg single-dose range. Following multiple doses, dersimelagon was rapidly absorbed (median Tmax ranging from 4 to 5 h postdose on days 1 and 14). Mean t1/2 ranged from 10.56 to 18.97 h on day 14, and the steady state of plasma concentration was generally reached by 5 days of multiple dosing. There were no observable effects of age or race on the PK profile of dersimelagon or its metabolite dersimelagon glucuronide. No treatment-related effects on melanin density (MD) were observed following single doses of dersimelagon; however, after multiple doses, increases in MD were observed in participants receiving 150 and 300 mg dersimelagon. Conclusion: Our study results indicate that dersimelagon is generally well tolerated and demonstrates a generally consistent PK profile across diverse subgroups. Treatment-related increases in MD warrant further investigation in a larger study population and in patients with EPP and XLP. Trial registration: A Study to Investigate the Safety, Tolerability and Pharmacokinetics of MT-7117 in Healthy Subjects, NCT02834442, https://clinicaltrials.gov/ct2/show/NCT02834442, registration began July 2016.
- Subjects
SKIN diseases; X-linked genetic disorders; DRUG tolerance; MELANINS; ORAL drug administration; CELL receptors; METABOLIC disorders; RANDOMIZED controlled trials; DOSE-effect relationship in pharmacology; DESCRIPTIVE statistics; RESEARCH funding; STATISTICAL sampling; PATIENT safety; DISEASE complications
- Publication
European Journal of Clinical Pharmacology, 2023, Vol 79, Issue 6, p801
- ISSN
0031-6970
- Publication type
Article
- DOI
10.1007/s00228-023-03476-6