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ONO-2808-05:An Open-label, Phase I, Single-dose Study to Investigate the Mass Balance of ONO-2808 after Oral Administration of 14C-ONO-2808 in Japanese Healthy Adult Male Subjects

ONO-2808-05:A Study to Investigate the Mass Balance of ONO-2808 in Japanese Healthy Adult Male Subjects

6

Japanese healthy adult male subjects (age: 21 to 45 years)

This study was an open-label, single-dose study to investigate the mass balance of ONO-2808 after oral administration of 14C-ONO-2808. The study consists of a screening period and a treatment period (16 days and 15 nights), and 14C-ONO-2808 was administered as a single oral dose on Day 1. A total of 6 healthy adult male subjects were enrolled in the study, and all subjects completed the study. No subjects were excluded from analysis, and the analysis population for pharmacokinetic and safety endpoints included all subjects.

No deaths or other SAEs (serious adverse events) were reported in the study. Of the 6 subjects, 1 subject (16.7%) experienced abdominal pain upper as an adverse event, which was classified as mild and considered as not related to study treatment. No clinically relevant changes were observed throughout the study in clinical laboratory tests, vital signs, and 12-lead ECGs.

After a single oral dose of 14C-ONO-2808 in Japanese healthy adult males, the mean cumulative excretion rate of 14C-radioactivity in urine+feces at Day 17 (384-hour postdose), when data were available for all 6 subjects, was 89.3% with 71.5% of 14C-radioactivity excreted in urine and 17.8% in feces, and the major route of elimination of 14C-radioactivity would be the urine. At 24 and 72 hours after administration, the mean cumulative 14C-radioactivity excretion rates in urine+feces were 23.6% and 56.8%, respectively, which suggested slow elimination of ONO-2808. At the last evaluation time point of each subject, the mean cumulative excretion rate of 14C-radioactivity in urine+feces was 89.6%, and in the majority of subjects (4/6 subjects), the cumulative recovery of 14C-radioactivity in urine+feces was over 90%. The whole blood and plasma concentrations of 14C-radioactivity rapidly increased immediately after administration of 14C-ONO-2808, and the peak concentration was achieved within about 1 hour after dosing. And then, the whole blood and plasma concentrations of 14C-radioactivity slowly decreased. The mean concentrations of 14C-radioactivity in whole blood and plasma ran in parallel over time, and the ratios of whole blood to plasma concentration of 14C-radioactivity were 0.64 to 0.88 by Day 17 (384-hour postdose), which suggested that blood cell distribution of 14C-radioactivity might be low. For PK parameters of 14C-radioactivity in whole blood and plasma, mean Cmax values were 348 and 449 ng eq./mL, median Tmax values were 0.750 and 0.500 hours, mean AUClast values were 13600 and 19200 ng eq.*h/mL, mean AUCinf values were 13800 and 19500 ng eq.*h/mL, and mean T1/2 values were 104 and 75.1 hours, respectively. The plasma concentrations of ONO-2808 rapidly increased immediately after administration of 14C-ONO-2808, and the peak concentration was achieved within about 1 hour after dosing. And then, the plasma concentrations of ONO-2808 slowly decreased. For PK parameters of plasma ONO-2808, mean Cmax value was 424 ng/mL, median Tmax value was 0.750 hours, mean AUClast value was 13500 ng*h/mL, mean AUCinf value was 13700 ng*h/mL, mean T1/2 value was 94.8 hours, and mean CL/F value was 1.50 L/h. The mean plasma concentrations of ONO-2808 and 14C-radioactivity nearly ran in parallel over time, and the plasma concentrations of 14C-radioactivity were higher than those of ONO-2808 at all time points. The mean Cmax values of plasma ONO-2808 and 14C-radioactivity were similar, but the mean AUCinf values of 14C-radioactivity were approximately 1.4-fold higher than those of ONO-2808.

After a single oral dose of 14C-ONO-2808 in Japanese healthy adult males, the mean cumulative excretion rate of 14C-radioactivity in urine+feces at Day 17 was 89.3% with 71.5% of 14C-radioactivity excreted in urine, and the major route of elimination of ONO-2808 and its metabolites would be the urine. In this study, no deaths or other SAEs were reported, and safety was favorable.

May. 15, 2026

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2071240057

Hirashima Yoshinori

Ono Pharmaceutical Co.,LTD

1-8-2 Kyutaromachi, Chuo-ku Osaka-shi, Osaka-fu Japan

clinical_trial@ono-pharma.com

JP Clinical Trial Support Desk

Ono Pharmaceutical Co.,LTD

1-8-2 Kyutaromachi, Chuo-ku Osaka-shi, Osaka-fu Japan

+81-120-278-120

clinical_trial@ono-pharma.com

Complete

Oct. 11, 2024

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1) Healthy Japanese adult males
2) The subject is aged 18 to 45 years, inclusive, at the time of signing the informed consent form
3) The subject has a BMI of 18.5 kg/m2 or more and less than 25.0 kg/m2 (rounded down to 2 decimal places) at screening

1) Subjects who are on a treatment for or with a history of respiratory, cardiovascular, psychiatric, neurologic,
gastrointestinal, immunologic, hepatic, renal, hematopoietic or endocrine and/or other disease
2) Subjects with current or with a history of severe allergy to drugs or foods
3) The subject who is judged by the investigator or subinvestigator to be inappropriate as a subject of this study based on the results of screening tests

Male

Healthy Volunteers

Subjects receive a single oral dose of 20 mg(1 MBq) 14C-ONO-2808

Urinary and fecal excretion rates of radioactivity and cumulative excretion rates of radioactivity

Adverse events that occurred after administration of investigational product until the end of final examination

+81-92-283-7701

Oct. 11, 2024

none