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A Thorough QT/QTc Study of TAS5315 in Healthy Adult Subjects

A Thorough QT/QTc Study of TAS5315 in Healthy Adult Subjects

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Sex: There were 32 male subjects (66.7%) and 16 female subjects (33.3%) in the Treated Population, QT/QTc Evaluable Population, PK Evaluable Population, and QT/QTc and PK Evaluable Population. Age: The median age was 26.5 years, with a range from 20 to 39 years. BMI: The median BMI was 20.35, with a range from 18.0 to 24.4. Medical History: There were no subjects with a past medical history or complications.

Forty-eight subjects were enrolled in the study, all of whom received the investigational product. Dosing was discontinued in 2 subjects: 1 subject did not receive the investigational product during the TAS5315 4 mg dosing period, and 1 subject did not receive the investigational product during the placebo dosing period. However, all subjects were included in the QT/QTc Evaluable Population and PK Evaluable Population.

-The incidence of TEAE was 8.3% (4/48 subjects) in the TAS5315 8 mg group, 2.1% (1/47 subjects) in the TAS5315 4 mg group, 2.1% (1/48 subjects) in the moxifloxacin group, and 0% (0/47 subjects) in the placebo group. -The TEAEs were ventricular extrasystoles, sinusitis, muscle fatigue, and epistaxis, each at 2.1% (1/48 subjects) in the TAS5315 8 mg group, eosinophil count increased at 2.1% (1/47 subjects) in the TAS5315 4 mg group, and nausea and dermatitis contact, each at 2.1% (1/48 subjects) in the moxifloxacin group. All were mild in severity, and no TEAEs occurred in 2 or more subjects. A causal relationship to the investigational product was ruled out, except for nausea that occurred in the moxifloxacin group. -No deaths or other serious TEAEs were observed, and the only TEAEs that led to discontinuation of treatment in the next Period were sinusitis and ventricular extrasystoles, which occurred in 2.1% (1/48 subjects) each during the TAS5315 8 mg treatment period, in which sinusitis resolved after treatment with medication and ventricular extrasystoles resolved without treatment. The events were judged to have no causal relationship to the investigational product. -Regarding the AESI of 'bleeding-related events such as haemorrhage, petechiae, and ecchymosis,' epistaxis was observed in the TAS5315 8 mg group, but a causal relationship with the investigational product was ruled out and the subject recovered without treatment.

For the estimated clinical dose (4 mg) and the dose exceeding the clinical dose (8 mg) of TAS5315, the upper limit of the two-sided 90% confidence interval for the difference in delta-QTcF between TAS5315 and placebo was below 10 msec at all post-dose test time points.

-The effect on QT interval, pharmacokinetics, and safety of a single oral dose of TAS5315 at the estimated clinical dose (4 mg) and a dose exceeding the clinical dose (8 mg) were evaluated in healthy adult subjects. -A single dose of TAS5315 4 or 8 mg did not show clinically meaningful QTcF prolongation compared to placebo. There was no trend toward QTcF prolongation associated with increased plasma concentrations of TAS5315. -No safety concerns were observed when TAS5315 was administered at 4 and 8 mg.

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/jRCT2071220108

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

Mar. 15, 2023

Interventional

randomized controlled trial

double blind

placebo control

crossover 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) Vital signs 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 a history of torsade de pointes, unconsciousness of uncertain cause and convulsion of uncertain cause
3) Using pacemaker or implantable cardioverter defibrillator, or cardiac resynchronization device
4) Judged by the investigator to be ineligible as a participant of the clinical study based on the 12-lead ECG at the time of screening test (QT-interval corrected by Fridericia corrections [QTcF] is 450 msec or more, etc.)

Both

healthy adult males and females

Orally administration of TAS5315 (4mg or 8mg), placebo and Moxifloxacin

Difference between TAS5315 and placebo in change from baseline in QT-interval corrected by heart rate using Fridericia corrections [QTcF]

+81-92-283-7701

Feb. 09, 2023

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