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Phase 1 Study of DS-3201b to Assess the Effects of Multiple Oral Administration of Rifampicin on the Pharmacokinetics of Single Oral Administration of DS-3201b Tablets in Healthy Japanese Subjects

Phase 1 Study of DS-3201b to Assess the Effects of Multiple Oral Administration of Rifampicin on the Pharmacokinetics of Single Oral Administration of DS-3201b Tablets in Healthy Japanese Subjects

20

The mean (range) age of the subjects was 30.5 (20 to 45) years, the mean weight was 57.30 kg, and the mean BMI was 20.77 kg/m2. The demographic and other baseline characteristics of the pharmacokinetic analysis set were identical to those of the safety analysis set.

Of the 47 subjects enrolled, 20 were registered for and completed the study.

The overall incidence of TEAEs was 25.0% (5/20 subjects): no TEAEs after administration of DS-3201b alone (from Day 1 to 8), 5.0% (1 subject) after administration of rifampicin alone (from Day 8 to 16), and 10.0% (2 subjects) after coadministration of DS-3201b and rifampicin (from Day 16 to 23), and 10.0% (2 subjects) after discharge (Day 23). The TEAEs that occurred in 2 or more subjects were alanine aminotransferase increased and aspartate aminotransferase increased, reported in 1 subject each after administration of rifampicin and after discharge (Day 23). All TEAEs reported were Grade 1 and resolved without any actions taken. One TEAE, laryngeal pain, reported after coadministration of DS-3201b and rifampicin was considered to be related to the study drug. No other TEAEs were considered to be related to the study drug. No deaths, serious TEAEs, TEAEs resulting in study withdrawal, or TEAEs of Grade 2 or higher were reported in the study.

- PK The geometric least square mean ratios (90% CIs) of the Cmax, AUClast, and AUCinf of total DS-3201a estimated by analysis of variance (ANOVA) were 0.417 (0.319, 0.545), 0.288 (0.226, 0.366), and 0.286 (0.225, 0.364), respectively, for coadministration of DS-3201b and rifampicin compared with administration of DS-3201b alone. Coadministration of DS-3201b and rifampicin decreased the Cmax of total DS-3201a by approximately 60% and the AUCs of total DS-3201a by approximately 70%.

- PK The geometric least square mean ratios (90% CIs) of the Cmax, AUClast, and AUCinf for CALZ-1809a estimated by ANOVA were 1.287 (1.036 to 1.600), 0.716 (0.574, 0.894), and 0.713 (0.573, 0.886), respectively, for coadministration of DS-3201b and rifampicin compared with administration of DS-3201b alone. Coadministration of DS-3201b and rifampicin increased the Cmax of CALZ-1809a by approximately 30% and decreased the AUCs of CALZ-1809a by approximately 30%. - Safety Refer to "Adverse events" section.

Coadministration of DS-3201b and rifampicin resulted in an approximately 60% and 70% decrease in the Cmax and AUCs of DS-3201a, respectively, compared with the administration of DS-3201b alone. No new safety concerns were found when DS-3201b was coadministered with rifampicin.

No

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Inoguchi Akihiro

Daiichi Sankyo Co., Ltd.

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

dsclinicaltrial@daiichisankyo.co.jp

Contact for Clinical Trial Information

Daiichi Sankyo Co., Ltd.

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

+81-3-6225-1111

dsclinicaltrial@daiichisankyo.co.jp

completed

July. 29, 2020

Interventional

A single-center,, open-label, 1 sequence crossover study

other

1

1. Gender: Japanese males or females
2. Age: >=20 and =<45 years (at the time of informed consent)
3. Body mass index (BMI) = Body weight (kg) / (Height [m])2: >=18.5 and <25.0 (at screening)

1. Having a history of hypersensitivity to any drugs or substances including rifampicin, or being idiosyncratic (eg, having penicillin allergy)
2. Having alcohol or drug dependence etc.

Both

Healthy volunteers

investigational material(s)
Generic name etc : DS-3201b
INN of investigational material : valemetostat
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : Oral administration

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -

pharmacokinetics
- Pharmacokinetic parameters of plasma concentration of total DS-3201a:
Cmax, AUClast, AUCinf

safety
Pharmacokinetic:
- Pharmacokinetic parameters of plasma concentration of total DS-3201a:
Tmax, Kel, t1/2, CL/F, Vz/F
- Pharmacokinetic parameters of plasma concentrations of unbound DS-3201a:
Cmax, AUClast, AUCinf, Tmax, Kel, t1/2
- Pharmacokinetic parameters of plasma concentration of total CALZ-1809a:
Cmax, AUClast, AUCinf, Tmax, Kel, t1/2
Safety:
Adverse events, laboratory tests, body weight, vital signs (blood pressure, pulse rate, body temperature), and 12-lead electrocardiogram

June. 19, 2020