Drug-Drug Interaction Study Between TAK-272 and Itraconazole, Digoxin or Midazolam

NCT ID: NCT02370615

Last Updated: 2016-05-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2015-04-30

Brief Summary

The purpose of this study is to evaluate the effect of repeated-dose administration of itraconazole on the pharmacokinetics of TAK-272, as well as the effect of repeated-dose administration of TAK-272 on the pharmacokinetics of digoxin or midazolam in healthy Japanese adult males.

Detailed Description

In Cohort 1, the effect of repeated-dose administration of itraconazole on the pharmacokinetics of TAK-272 was evaluated by comparing between participants receiving TAK-272 alone and those receiving TAK-272 in combination with itraconazole. In Cohort 2, the effect of repeated-dose administration of TAK-272 on the pharmacokinetics of digoxin or midazolam was evaluated by comparing between participants receiving digoxin or midazolam alone and those receiving either of the drugs in combination with TAK-272.

Conditions

Japanese Healthy Adult Males

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: TAK-272 + Itraconazole

TAK-272 40 mg, tablet, orally, once on Day 1 and 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.

Group Type: EXPERIMENTAL

TAK-272

Intervention Type: DRUG

TAK-272 tablet.

Itraconazole

Intervention Type: DRUG

Itraconazole oral solution

Cohort 2: Midazolam + Digoxin + TAK-272

Midazolam 2 mg, syrup, and Digoxin 0.25 mg, tablet, orally, once on Day 1 and 7, followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8.

Group Type: EXPERIMENTAL

TAK-272

Intervention Type: DRUG

TAK-272 tablet.

Digoxin

Intervention Type: DRUG

Digoxin tablet.

Midazolam

Intervention Type: DRUG

Midazolam syrup.

Interventions

TAK-272

TAK-272 tablet.

Intervention Type: DRUG

Digoxin

Digoxin tablet.

Intervention Type: DRUG

Itraconazole

Itraconazole oral solution

Intervention Type: DRUG

Midazolam

Midazolam syrup.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Is capable of understanding and complying with protocol requirements.

2. Who can sign and date the informed consent form before the initiation of the study procedure.

3. Healthy Japanese adult male volunteer.

4. Is of 20 to 35 years of age at the time of informed consent

5. Weighs 50 kilogram (kg) or more with a body mass index (BMI) of 18.5 to less than 25.0 kilogram per square meter (kg/m^2) at the screening test.

6. Male participant who was nonsterilized and sexually active with a female partner of childbearing potential had to agree to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after the completion of the study.

Exclusion Criteria

1. Who was administered any investigational product within 16 weeks (112 days) prior to the initial drug administration.

2. Who has received TAK-272 in previous.

3. Employees of the study site, their family members, those who are in a dependency relationship with employees of the study site involved in the conduct of the study (example, spouse, parents, children, brothers and sisters), or those who might be coerced to consent to participate in the study.

4. Who has poorly controlled, clinically significant abnormalities of the nervous system, cardiovascular system, lungs, liver, kidneys, metabolism, gastrointestinal system, urinary system, endocrinological system or other organs or systems, and which may possibly affect study participation or study results.

5. Who has a history of serious hepatic disease.

6. Who has atrioventricular block or sinoatrial block.

7. Has digitalis intoxication.

8. Has acute narrow-angle glaucoma.

9. Has myasthenia gravis.

10. Has hypersensitivity to TAK-272 or any other renin inhibitors.

11. Has hypersensitivity to itraconazole, digoxin, digitalis preparation, or midazolam.

12. Has allergy to cherries.

13. Has a positive to urine test for drug abuse at the screening.

14. Has a history of drug abuse (defined as illegal drug use) or alcohol addiction within 1 year prior to the screening visit, and those who are not willing to give up alcohol or drugs during the study period.

15. Who needs to use prohibited concomitant drugs, vitamins, or foods listed in the table of prohibited concomitant drugs and foods, and the participant who has used any of them during the period prohibiting the concomitant use.

16. Male participants who plans to donate sperm during the study period or up to 12 weeks after the end of the study.

17. Who currently has cardiovascular, central nervous, hepatic, or hematopoietic disease, renal insufficiency, metabolic or endocrinological disorder, serious allergy, asthma, hypoxemia, hypertension, convulsions, or allergic rash.

18. Has a disease history, examination findings, or clinical test findings related to safety that reasonably suggest a disease for which TAK 272 or related renin inhibitors in the same class, itraconazole, digoxin, or midazolam is contraindicated or a disease that may affect the study conduct (which includes, for example, peptic ulcer disease, convulsive disorder, and arrhythmia).

19. Who currently has or recently had (within the past 6 months) gastrointestinal disease that may affect drug absorption (malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent [at least once a week] heartburn, surgical intervension [e.g., cholecystectomy]).

20. Has past history of cancer.

21. Who is positive for any of the following at screening: hepatitis B virus surface antigen (HBs), antibody against hepatitis C virus (HCV), human immunodeficiency virus (HIV) antigen, anti-HIV antibody, or serological tests for syphilis.

22. The participant with difficulty having blood collected from a peripheral vein.

23. Who has donated 200 milliliter (mL) or more whole blood within the 4 weeks (28 days) or 400 mL or more whole blood within the 12 weeks (84 days) before starting the study drug administration.

24. Who has donated a total of 800 mL or more of whole blood within the 52 weeks (364 days) before the day of starting the study drug administration.

25. Who has donated blood components within the 2 weeks (14 days) before starting the study drug administration.

26. Who shows clinically significant abnormalities in electrocardiogram at screening or before the study drug administration.

27. Who shows laboratory test abnormalities suggestive of a clinically significant primary disease or who shows abnormal values in any of the following parameters at screening or before the study drug administration: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) exceeding 1.5 times the upper limit of the normal range.

28. Who is unlikely to comply with the study protocol or is ineligible for the study for any other reason, as considered by the investigator or sub investigator.

29. Who had systolic blood pressure under 80 millimeter of mercury(mmHg) at Screening, pretreatment examination, and before the start of study drug administration, and who had suspected hypotension with 2 or more of the following symptoms and findings through physical examinations: dizziness postural, facial pallor, cold sweat.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_CHAIR

Takeda

Locations

Osaka, Osaka, Japan

Countries

Japan

Other Identifiers

U1111-1167-0017

Identifier Type: REGISTRY

Identifier Source: secondary_id

JapicCTI-152810

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-272/CPH-011

Identifier Type: -

Identifier Source: org_study_id