Clinical trial NCT02370615: Drug-Drug Interaction Study Between TAK-272 and Itraconazole, Digoxin or Midazolam
Official title: A Phase 1, Drug-Drug Interaction Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of TAK-272 and the Effect of TAK-272 on the Pharmacokinetics of Digoxin or Midazolam In the Healthy Adult Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Japanese Healthy Adult Males
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-02-25
Enrollment: 34
Sex: MALE
Minimum age (years): 20
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration for TAK 272F and TAK 272-Metabolite (M-I) in Cohort 1
timeFrame: Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole
measure: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK 272F and TAK 272-M-I in Cohort 1
timeFrame: Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole
measure: AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK 272F and TAK 272-M-I in Cohort 1
timeFrame: Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole
measure: Cumulative Urinary Excretion Ratio of TAK 272F and TAK 272-M-I From 0 to 72 Hours Postdose in Cohort 1
timeFrame: Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole
measure: Cmax: Maximum Observed Plasma Concentration for Digoxin in Cohort 2
timeFrame: Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272
measure: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Digoxin in Cohort 2
timeFrame: Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272
measure: AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Digoxin in Cohort 2
timeFrame: Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272
measure: Urinary Excretion Ratio of Digoxin From 0 to 48 Hours Postdose in Cohort 2
timeFrame: Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272
measure: Cmax: Maximum Observed Plasma Concentration for Midazolam and 1'Hydroxymidazolam in Cohort 2
timeFrame: Day 1 and Day 7: pre-dose and at multiple time-points (upto 24 hours) postdose; Day 1 for Cohort 2: Midazolam and Day 7 for Cohort 2: Midazolam + TAK-272
measure: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam and 1'Hydroxymidazolam in Cohort 2
timeFrame: Day 1 and Day 7: pre-dose and at multiple time-points (upto 24 hours) postdose; Day 1 for Cohort 2: Midazolam and Day 7 for Cohort 2: Midazolam + TAK-272
measure: AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Midazolam and 1'Hydroxymidazolam in Cohort 2
timeFrame: Day 1 and Day 7: pre-dose and at multiple time-points (upto 24 hours) postdose; Day 1 for Cohort 2: Midazolam and Day 7 for Cohort 2: Midazolam + TAK-272
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
timeFrame: Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15
measure: Number of Participants With TEAEs Related to Vital Signs
timeFrame: Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15
measure: Number of Participants With TEAEs Related to Body Weight
timeFrame: Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15
measure: Number of Participants Who Had Clinically Significant Changes From Baseline in 12-lead Electrocardiograms
timeFrame: Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15
measure: Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis
timeFrame: Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15
measure: Number of Participants With Clinically Significant Change From Baseline in Continuous Pulse Oximetry (SpO2) in Cohort 2
timeFrame: Cohort 2: Baseline up to Day 15
Secondary outcomes:
Other outcomes:
Locations:
city: Osaka-shi
country: Japan
state: Osaka
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_CHAIR
References: