Absorption, disposition and metabolic pathway of amiselimod (MT-1303) in healthy volunteers in a mass balance study

Abstract

1. The absorption, metabolism and excretion of MT-1303 were investigated in healthy male subjects after a single oral dose of 0.4 mg [14C]-MT-1303 (ClinicalTrials.gov NCT02293967).

2. The MT-1303 concentration in the plasma reached a maximum at 12 h after administration. Thereafter, the concentration declined with a half-life of 451 h. At the final assessment on Day 57, 91.16% of the administered radioactivity was excreted, and the cumulative excretion in the urine and faeces was 35.32% and 55.84%, respectively.

3. The most abundant metabolite in plasma was MT-1303-P, which accounted for 42.6% of the area under the plasma concentration–time curve (AUC) of the total radioactivity. The major component excreted in urine was Human Urine (HU)4 (3066434), accounting for 28.1% of radioactivity in the sample (4.05% of the dose), whereas MT-1303 was a major component in the faeces, accounting for 89.8% of radioactivity in the sample (25.49% of the dose) up to 240 h after administration.

4. This study indicates that multiple metabolic pathways are involved in the elimination of MT-1303 from the human body and the excretion of MT-1303 and MT-1303-P via the kidney is low. Therefore, MT-1303 is unlikely to cause conspicuous drug interactions or alter pharmacokinetics in patients with renal impairment.

Trial registration: ClinicalTrials.gov identifier: NCT02293967.

Keywords:

• Amiselimod
• autoimmune
• mass balance study
• multiple sclerosis
• pharmacokinetics
• phase I
• safety
• sphingosine-1-phosphate 1 receptor modulator
• tolerability

Acknowledgements

We thank JL Croxford, PhD, from Edanz Medical Writing for providing editorial support.

Disclosure statement

TK, SI, MF, AK, TG, HK and BPM are employees of Mitsubishi Tanabe Pharma, which provided funding for this research. SM has no conflicts of interest to declare.

Additional information

Funding

This work was funded by Mitsubishi Tanabe Pharma Corporation.