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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02370615
Other study ID # TAK-272/CPH-011
Secondary ID U1111-1167-0017J
Status Completed
Phase Phase 1
First received February 18, 2015
Last updated July 29, 2015
Start date February 2015
Est. completion date April 2015

Study information

Verified date July 2015
Source Takeda
Contact n/a
Is FDA regulated No
Health authority Japan: Ministry of Health, Labor and Welfare
Study type Interventional

Clinical Trial Summary

The purpose of this study is to investigate the effect of repeated-dose administration of itraconazole on the pharmacokinetics of TAK-272 and the effect of repeated-dose administration of TAK-272 on the pharmacokinetics of digoxin and midazolam in healthy Japanese adult males.


Description:

In cohort 1, the pharmacokinetics of TAK-272 will be compared between subjects receiving TAK-272 alone and those receiving TAK-272 in combination with itraconazole to investigate the effect of repeated-dose administration of itraconazole on the pharmacokinetics of TAK-272. In cohort 2, the pharmacokinetics of digoxin or midazolam will be compared between subjects receiving digoxin and midazolam alone and those receiving either of the drugs in combination with TAK-272 to investigate the effect of repeated-dose administration of TAK-272 on the pharmacokinetics of digoxin and midazolam.


Recruitment information / eligibility

Status Completed
Enrollment 34
Est. completion date April 2015
Est. primary completion date April 2015
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Male
Age group 20 Years to 35 Years
Eligibility Inclusion Criteria:

- 1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.

2. The participant who can sign and date the informed consent form before the initiation of the study procedure.

3. Healthy Japanese adult male volunteer. 4. The participant whois 20 to 35 years of age at the time of informed consent 5. The participant who weighs 50 kg or more with a body mass index (BMI) of 18.5 to less than 25.0 kg/m2 at the screening test.

Exclusion Criteria:

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

2. The participant who has received TAK-272 in previous. 3. Employees of the study site, their family members, those who are in a dependency relationsip with employees of the study site involved in the conduct of the study (e.g., spouse, parents, children, brothers and sisters), or those who might be coerced to consent to participate in the study.

4. The participant 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. The participant who has a history of serious hepatic disease. 6. The participant who has atrioventricular block or sinoatrial block. 7. The participant with digitalis intoxication. 8. The participant with acute narrow-angle glaucoma. 9. The participant with myasthenia gravis. 10. The participant with hypersensitivity to TAK-272 or any other renin inhibitors.

11. The participant with hypersensitivity to itraconazole, digoxin, digitalis preparation, or midazolam.

12. The participant with allergy to cherries. 13. The participant with a positive to urine test for drug abuse at the screening.

14. The participant with 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. The participant who needs to use prohibited concomitant drugs,vitamins, or foods listed in the table of prohibited concomitant drugs and foods (see Section 7.3), and the participant who has used any of them during the period prohibiting the concomitant use (see Table 7.a for the prohibition period for each item).

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

17. The participant 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. The participant with 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. The participant who curently 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. The participant with a past history of cancer. 21. The participant who is postive 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. The participant who donated 200 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. The participant who 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. The participant who donated blood components within the 2 weeks (14 days) before starting the study drug administration.

26. The participant who shows clinically significant abnormalities in electrocardiogram at screeing or before the study drug administration.

27. The participant who shows laboratory test abnormalities suggestive of a clinically significant primary disease or who shows abnormal values in any of the following parameters at screeing 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. The participant 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 subinvestigator.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
TAK-272, Itraconazole
TAK-272, ITRIZOLE Oral Solution 1 percent
TAK-272, Digoxin, Midazolam
TAK-272, DIGOSIN, Midazolam HCl Syrup

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Takeda

Country where clinical trial is conducted

Japan, 

Outcome

Type Measure Description Time frame Safety issue
Primary Maximum observed plasma concentrations (Cmax) of TAK-272F and TAK-272 metabolite in cohort 1 Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Days 1-4 and days 10-13 No
Primary Area under the plasma concentration-time curve (AUC) of TAK-272F and TAK-272 metabolite in cohort 1 Area under the plasma concentration-time curve (AUC) during a dosing interval. Days 1-4 and days 10-13 No
Primary Urinary excretion rates of TAK-272F and TAK-272 metabolite in cohort 1 Urinary excretion rate of TAK-272F and TAK-272 metabolite M-I will be calculated from the urinary concentration and volume of each participant. Days 1-4 and days 10-13 No
Primary Maximum observed plasma concentrations (Cmax) of cohort digoxin in cohort 2 Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Days 1-3 and days 7-9 No
Primary Area under the plasma concentration-time curve (AUC) of digoxin in cohort 2 Area under the plasma concentration-time curve during a dosing interval. Days 1-3 and days 7-9 No
Primary Urinary excretion rates of digoxin in cohort 2 Urinary excretion rate of digoxin will be calculated from the urinary concentration and volume of each participant. Days 1-3 and days 7-9 No
Primary Maximum observed plasma concentrations (Cmax) of midazolam and its metabolite in cohort2 Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Days 1-2 and days 7-8 No
Primary Area under the plasma concentration-time curve (AUC) of midazolam and its metabolite in cohort 2 Area under the plasma concentration-time curve during a dosing interval. Days 1-2 and days 7-8 No
Primary Number of participants who experience at least 1 treatment-emergent adverse event in cohort 1 The types and seriousness of adverse events(by symptom) occurring after the start of treatment with the investigational product will be summarized in terms of frequency. An advers event is defined as any untoward or unintended sign, symptom, or illness that occurs with adoministration of a pharmaceutical regardless of whether it is causally related to study drug. up to 19 days Yes
Primary Number of participants who experience at least 1 treatment-emergent adverse event in cohort 2 The types and seriousness of adverse events(by symptom) occurring after the start of treatment with the investigational product will be summarized in terms of frequency. An advers event is defined as any untoward or unintended sign, symptom, or illness that occurs with adoministration of a pharmaceutical regardless of whether it is causally related to study drug. up to15 days Yes
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