臨床研究等提出・公開システム

A Drug-Drug Interaction Study of TAS5315 with CYP3A inhibitor in Healthy Adult Subjects

A Drug-Drug Interaction Study of TAS5315 with CYP3A inhibitor in Healthy Adult Subjects

20

All subjects treated with the investigational product were Japanese males. Median age was 27.5 years old (range: 20-38 years old) and median BMI was 21.50 (range: 18.4-23.9). Two subjects had a medical history (acute appendicitis and left pneumothorax, 1 subject each), but none of the subjects had complications.

Twenty subjects were enrolled in the study. All subjects had received at least one dose of TAS5315 and itraconazole, and the number of All Treated Subjects, Itraconazole Treated Subjects, and PK Evaluable Subjects were all 20. One subject was excluded from DDI Evaluable Subjects due to discontinuation of treatment, resulting in a total of 19 subjects.

-There were no TEAEs that resulted in death or other serious TEAEs. In this study, 'bleeding-related events such as haemorrhage, petechiae, and ecchymosis' were specified as AEs of Special Interest (AESIs); 1 subject experienced petechiae during the period of TAS5315 plus itraconazole treatment, but it was judged to be of no clinical significance because the event was mild in severity and resolved without treatment. -The TEAE that led to discontinuation of treatment was pharyngitis in 1 subject (5.0%) during the period of itraconazole monotherapy, but was not a TRAE. -The number (percentage) of TEAEs was 4 subjects (20.0%) overall; 1 subject (5.0%) during the period of itraconazole monotherapy, and 3 subjects (15.8%) during the period of TAS5315 plus itraconazole treatment. No TEAEs occurred during the period of TAS5315 monotherapy. The severity of TEAEs developed was mild or moderate, and all recovered during the study period. -The number (percentage) of TRAEs was 1 subject (5.3%) for each of TAS5315 and itraconazole during the period of TAS5315 plus itraconazole treatment. The TRAEs for TAS5315 and itraconazole were petechiae and blood triglycerides increased, respectively.

-When 1 mg of TAS5315 was administered orally as a single dose in combination with 200 mg of itraconazole (repeated orally once daily for 6 days), AUClast and AUCinf of TAS5315 were increased by approximately 34% compared to TAS5315 alone, while Cmax was similar. -When 1 mg of TAS5315 was administered orally as a single dose in combination with 200 mg of itraconazole (repeated orally once daily for 6 days), the Tmax of TAS5315 was unaffected.

When 1 mg of TAS5315 was coadministered with 200 mg of itraconazole, the AUC of TAS5315 was increased by approximately 34%, however, the Cmax was similar. The Tmax of TAS5315 was unaffected. When 1 mg of TAS5315 was coadministered with 200 mg of itraconazole, there was no apparent increase in the frequency of adverse events compared with TAS5315 or itraconazole alone, and no safety concerns were observed.

No

IPD data will not be shared according to the Sponsor policy on data sharing. Taiho clinical trial information disclosure policy may be found at https://www.taiho.co.jp/en/science/policy/clinical_trial_information_disclosure_policy/index.html

https://jrct.mhlw.go.jp/latest-detail/jRCT2071220117

Nasermoaddeli Ali

Taiho Pharmaceutical Co., Ltd.

1-27 Kandanishiki-cho, Chiyoda-ku, Tokyo

th-tas5315_clinical@taiho.co.jp

Suto Kotaro

Taiho Pharmaceutical Co., Ltd.

1-27 Kandanishiki-cho, Chiyoda-ku, Tokyo

+81-3-3293-2455

th-tas5315_clinical@taiho.co.jp

Complete

May. 01, 2023

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1) Aged 18 or older and younger than 40 years at the time of consent
2) Weigh at least 45.0 kg at the time of screening tests with a body mass index (BMI, weight [kg]/[height {m}]2) ranging from 18.0 to < 25.0 kg/m2
3) Blood pressure and body temperature obtained in screening tests within the following ranges
a Systolic blood pressure (in supine position), 90 to 139 mmHg
b Diastolic blood pressure (in supine position), 40 to 89 mmHg
c Body temperature ranging from 35.0 to 37.4
4) Judged to be healthy by the investigator based on the examination findings (subjective symptoms and objective findings), blood pressure, pulse rate, body temperature, 12-lead ECG, and laboratory tests (hematology test, biochemistry test, and urinalysis) at the time of screening tests

1) Had any concurrent disease (including symptoms and signs; however, diseases that do not affect evaluations in the study such as asymptomatic pollinosis and wart are excluded)

2) Had any severe disease history that may recur during the study period.

Both

healthy adult males and females

Orally administration of TAS5315 (1mg) and Itraconazole (200mg)

Maximum observed plasma concentration (Cmax) of TAS5315, area under the plasma concentration-time curve from the time of dosing to the time of last quantifiable plasma concentration (AUClast) of TAS5315, area under the plasma concentration-time curve from the time of dosing extrapolated to infinity (AUCinf) of TAS5315

+81-92-283-7701

April. 13, 2023

none