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A study to evaluate the effects on QT/QTc Interval of TS-142 in Healthy Adult Subjects

A QT/QTc Evaluation Study of TS-142 in Healthy Adult Subjects

59

Age(years):Mean+-SD 25.7+-4.8, Body Weight(kg):Mean+-SD 56.24+-7.44, Sex(%):Male 42.4 Female 57.6

59 subjects were randomized and allocated to 4 sequences, then received investigational product more than once. 6 subjects were discontinued. 54 subjects in each of Placebo group, TS-142 10 mg group and TS-142 30 mg group, and 55 subjects in moxifloxacin group completed this study.

The adverse events were observed in 3 of 56 subjects (5.4%) in Placebo group, 5 of 55 subjects (9.1%) in TS-142 10 mg group, 3 of 56 subjects (5.4%) in TS-142 30 mg group, 2 of 56 subjects (3.6%) in moxifloxacin group.

QTcF (delta delta QTcF) was set as a primary endpoint. In both TS-142 groups, all one-sided 95% confidential interval of delta delta QTcF were less than 10 msec (threshold) in any time point post-dose of TS-142. That indicated TS-142 did not have any effects on QTcF prolongation.

The effects on QT/QTc interval were evaluated following a single oral dose of TS-142 10 mg and 30 mg in Japanese healthy adults. No QTcF prolongation was shown and no clinically relevant safety concerns were observed in TS-142 groups.

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2071210018

Mita Seiji

Taisho Pharmaceutical Co., LTD.

3-24,1, Takada, Toshima-Ku, Tokyo

shu_chiken@taisho.co.jp

Development Headquarters Development Management

Taisho Pharmaceutical Co., LTD.

3-24,1, Takada, Toshima-Ku, Tokyo

+81-3-3985-1118

shu_chiken@taisho.co.jp

Complete

May. 31, 2021

Interventional

randomized controlled trial

double blind

active control

crossover assignment

other

1. Japanese Males or females aged 20 years or older but less than 40 years at the time of informed consent
2. those with a BMI of 18.5 in male (17.6 in female) or more and less than 25.0 and a body weight of 40.0 kg or more at screening test
3. those whose pulse rate measured by standard 12-lead ECG is 50 beats/min or more but no more than 90 beats/min at screening test and at the time before administration of investigational drug in period 1
4. those who are judged eligible to participate in the study by the principal investigator or sub-investigator based on the results of screening test and test conducted before administration of investigational drug in period 1. However, if who showed abnormal findings but not clinically significant, they can be enrolled in clinical trials based on comprehensive consideration of medical viewpoints by the principal investigator or subinvestigator.
5. those who are able to receive the explanation before participating in the study, understand the content of the study, and provide written informed consent by the subjects themselves.

1. Subjects who have any disease and are not considered healthy subjects based on the medical judgment of the principal investigator or sub-investigator.
2. Subjects with a medical history considered inappropriate for participation in the study, including respiratory, cardiovascular, gastrointestinal, hepatic, renal, urological, endocrine, metabolic, hematological, immune, skin, neurological, and psychiatric diseases.
3. Subjects with a history of drug allergy or food allergy.
4. Subjects with a history of hypersensitivity to moxifloxacin or other quinolone antimicrobials
5. Subjects with risk factors or with a history of risk factors for aortic aneurysm, aortic dissection (such as Marfan syndrome)
6. Subjects with significant allergic predisposition (such as asthma requiring medical treatment)
7. Subjects with congenital disease, heart disease, or a history of heart disease
8. Subjects with risk factors or with a history of risk factors for torsade de pointes (TdP) (heart failure, hypokalemia, family history of long QT syndrome, etc.)
9. Subjects with a history of unconscious seizures suspected of involving TdP.
10. Subjects with waveforms difficult to assess for QTc interval prolongation in standard 12-lead ECG at screening and the timing before administration of investigational product in period 1 (drift, electromyography contamination, T-wave geometry, marked sinus arrhythmia, frequent premature beats, etc.)
11. Subjects with QTcF(Fridericia correction method) of at least 450 msec in men and at least 470 msec in women in standard-12-lead ECG at screening test and at the time before administration of investigational product in period 1.
12. Subjects with suicidal ideation, suicide attempt on the Colombian Suicide Assessment Scale (C-SSRS) on Day-1 or a history of suicide attempt within the previous 5 years.

Both

Insomnia

Drug (Single dose of TS-142 10 mg, TS-142 30 mg, TS-142 placebo or moxifloxacin 400 mg in the morning under fasting in each period), Holter ECGs

QTcF:QT-interval corrected by Fridericia corrections in Holter ECGs
[Difference in change from baseline in QTc interval at each time point in each group compared with the placebo group]

+81-92-283-7701

May. 28, 2021

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