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A Phase I Open-Label Study to Evaluate the Mass Balance and Pharmacokinetics of [14C]DS-1001b Following Single Oral Administration to Healthy Adult Male Subjects

A Mass Balance Study of [14C]DS-1001b

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All 8 participants enrolled were Japanese male. The mean (standard deviation; SD) age at the time informed consent was obtained was 37.5 (11.11) years. The mean (SD) BMI was 21.925 (1.6787) kg/m^2. UGT1A1 gene polymorphism status was as follows: 6 participants had wild type (-/-) (extensive metabolizer: EM), and 2 had homozygous mutations (1 each in *6/*6 and *28/*28) (poor metabolizer: PM).

Eight healthy adult male were enrolled in the study, received the study drug (approx. 250 mg/1MBq), and completed the study. All participants were included in the safety analysis set and the PK analysis set.

No adverse events (AE) were reported, and there were no clinically significant changes in clinical laboratory results, vital signs, body weight, and 12-lead electrocardiograms.

<Pharmacokinetic> The mean (SD) total recovery of radioactivity up to 288 hours after administration was 96.0% (1.0%), with 7.5% (1.5%) and 88.4% (1.9%) excreted in urine and feces, respectively. The mean (SD) t1/2 of total radioactivity in whole blood and plasma was 102 (18.9) hours and 101 (14.8) hours, respectively. DS-1001a in plasma reached Cmax with a median Tmax (minimum, maximum) of 3.00 (2.00, 4.00) hours and was eliminated with a t1/2 of 6.18 (1.17) hours. The mean (SD) of exposure ratios of DS-1001a to total radioactivity in plasma were 0.609 (0.108) for Cmax and 0.387 (0.0519) for AUCinf. The formation of the glucuronide metabolite was minimal, and the Tmax and t1/2 of the glucuronide of DS-1001a were similar to those of DS-1001a. The exposure of UGT1A1 PM participants (n=2) to DS-1001a was approximately 1.5-fold higher than EM participants (n=6), but a definitive conclusion cannot be drawn because of the small number of participants in each genotype subgroup. <Safety> Refer to "Adverse events" section.

Ninety-six percent of the radioactivity was recovered within 288 hours after administration, with 7.5% in urine and 88.4% excreted in feces. Fecal excretion was found to be the primary route of excretion. No AE were reported, and there were no clinically significant changes in clinical laboratory results, vital signs, body weight, and 12-lead electrocardiograms.

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2071240033

Inoguchi Akihiro

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

dsclinicaltrial_jp@daiichisankyo.com

Contact for Clinical Trial Information

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial_jp@daiichisankyo.com

Complete

Aug. 07, 2024

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

Subjects who meet all of the following criteria are eligible for the study.
1. Healthy Japanese adult males
2. Aged 18 to 55 years (both inclusive) at the time of informed consent
3. A body mass index (BMI) >=18.5 and <25.0 kg/m^2 at the time of screening test
4. UGT1A1 EM (having no mutation of *6 and *28), or UGT1A1 PM (having either of *6/*6, *6/*28, or *28/*28)

1. Having a history of stomach or intestinal surgery or disease that would potentially alter absorption and/or excretion of orally administered drugs (however, appendectomy and repair of pyloric stenosis are allowed)
2. Having 3 days or less with at least one spontaneous defecation (bowel movement without purgative medicine, enema or stool extraction) during the 7 days prior to the screening test
3. Having a history of hypersensitivity or being idiosyncratic (e.g., having penicillin allergy) to any drug
4. Underwent administration of radiolabeled substances or exposure to diagnostic/therapeutic radiation (e.g., gastric X ray, computed tomography [CT] scans, positron emission tomography [PET], etc.) during the period from 12 months before study drug administration and until completion of the post-study examination or follow-up examination (however, chest X ray and dental radiography are allowed)

Male

Healthy adult male

Administer a single oral dose of suspension of DS-1001b containing [14C]DS-1001b to the subjects in the fasted state.

Mass balance and pharmacokinetics

Pharmacokinetics of parent drug and its metabolite, safety

+81-92-283-7701

July. 11, 2024

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