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Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Oral Doses of S-001000 by dose-titration method in Japanese Healthy Adult Male Subjects(twice-daily oral administration)

Phase I Clinical Study of S-001000 Multiple Doses(twice-daily oral administration)

12

All subjects were healthy adult male subjects. Regarding other characteristics of subjects in the S-001000 (9 subjects) and placebo (3 subjects) groups, ages (mean, hereafter) at consent were 28.4 and 33.3 years; heights were 174.51 and 168.23 cm; weights were 69.16 and 67.50 kg; and BMIs were 22.66 and 23.83 kg/m2, respectively, with no significant bias among the treatment groups. The populations for pharmacokinetics and pharmacodynamics analyses were also same to that for safety analysis, and there was no significant bias in subject background between treatment groups.

Of the 33 subjects who gave consent, 12 subjects were randomly assigned to receive the study drugs, excluding total 21 subjects who were screen failure, i.e. inclusion criteria violation before receiving the study drugs, or reserved subjects. All 12 subjects who received the study drugs (9 in the S-001000 and 3 in placebo groups) completed the study.

Adverse events were observed in 2 (stomatitis, diarrhea) out of 9 subjects (22.2%) in the S-001000 group and in 1 (headache) out of 3 subjects (33.3%) in placebo group. These events were mild and recovered without treatment. Of these, adverse events judged to be causally related to the study drug, i.e. adverse drug reaction, were observed in 1 (stomatitis) out of 9 subjects (11.1%) in the S-001000 group and in 1 (headache) out of 3 subjects (33.3%) in placebo group. Adverse events leading to discontinuation of study drug administration, deaths or serious adverse events were not observed in either treatment group.

Primary evaluation (Safety): Refer to the above item of adverse events for safety information. Secondary evaluation (Pharmacokinetics): During each dosing periods of S-001000 30 to 120 mg/day, Cmax and AUC on the first and last dosing days of each dose level increased in proportion to the dose and their linearity were observed. Ctrough was nearly constant after the second dosing day of each dose level at any of the repeated doses from S-001000 30 to 120 mg/day, and steady state was considered to have been reached at least on the second dosing day of each dose level. The cumulative coefficient (R, 0-12 hr) for each dose level ranged from 0.9521 to 1.132, indicated no accumulation. Secondary evaluation (Pharmacodynamics): During the dosing period of S-001000 30 to 120 mg/day, serum uric acid levels decreased significantly (predose on Day 20, mean: 1.59 mg/dL) from the level at predose on Day 1 (Mean: 6.52 mg/dL) and showed dose-dependent decrease over time. During the dosing period of S-001000 30 to 120 mg/day, calculated values of uric acid clearance and FEUA increased significantly compared to placebo in almost all urine storage intervals.

No problem was observed in the safety and tolerability of repeated oral administration of S-001000 30 to 120 mg/day twice daily for total 20 days by a dose-escalation method. Cmax and AUC increased in proportion to the dose and their linearity were observed. Steady state was almost reached after the second dosing day of each dose level and no accumulation was observed based on pharmacokinetics such as Ctrough and R. The reduction in serum uric acid levels was maintained in terms of pharmacodynamics.

Mar. 13, 2023

No

https://jrct.niph.go.jp/latest-detail/jRCT2071210091

Tsubouchi Ichiro

Sato Pharmaceutical Co., Ltd.

1-5-27, Motoakasaka, Minato-Ku, Tokyo

clinicaltrials-info@sato-seiyaku.co.jp

Clinical Trials Information Desk

Sato Pharmaceutical Co., Ltd.

1-5-27, Motoakasaka, Minato-Ku, Tokyo

+81-3-5412-7329

clinicaltrials-info@sato-seiyaku.co.jp

Complete

Oct. 21, 2021

Interventional

randomized controlled trial

single blind

placebo control

parallel assignment

treatment purpose

(1) Japanese healthy male aged >= 20 and <= 45 years at the time of informed consent.
(2) Subjects with screening body mass index (BMI) >= 18.5 kg/m2 to < 28.0 kg/m2.
(3) Subjects considered healthy by the investigator/subinvestigator based on the results of screening examination, and medical examination and all tests performed after admission and before study drug administration.
(4) Subjects who are fully informed of the study objectives, contents, and study drug, and voluntarily provide a written consent to participate in the study.

(1)Subjects with a current or past history of a clinically concerned gastrointestinal, hepatic, musculoskeletal, respiratory, cerebrovascular or cardiovascular, hematological, oncological, endocrine, immunological, psychiatric, neurological, or urogenital disease, or any condition that, in the opinion of the investigator/subinvestigator, would compromise the subject's safety or interfere with this study results.
(2)Subjects with a current or past history of urinary calculus.
(3)Subjects with a history of surgery or a current internal medical condition that, in the opinion of the investigator/subinvestigator, may interfere with drug absorption, distribution, metabolism, or excretion.
(4)Otherwise, subjects who are judged by the investigator/subinvestigator to be ineligible for the study.

Male

Gout and Hyperuricemia

The drugs of S-001000 or S-001000 placebo were administrated by a multiple oral dose twice-daily

Safety Endpoints
(1) AEs and adverse drug reactions (ADRs)
(2) Laboratory values (hematology, clinical chemistry, and urinalysis)
(3) Vital signs (blood pressure, pulse rate, and body temperature)
(4) 12-lead ECG

Pharmacokinetic Endpoints
Each PK parameter of unchanged S-001000 and its metabolites will be calculated from the plasma or urine drug concentration.

+81-92-283-7701

Oct. 15, 2021

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