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

NCT02370615 | Completed Phase 1 Results

• 3 other identifiers: TAK-272/CPH-011U1111-1167-0017JapicCTI-152810
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Japanese Healthy Adult Males

Outcome Measures

Primary Outcomes (17)

• Cmax: Maximum Observed Plasma Concentration for TAK 272F and TAK 272-Metabolite (M-I) in Cohort 1

  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

• 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

  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

• 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

  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

• Cumulative Urinary Excretion Ratio of TAK 272F and TAK 272-M-I From 0 to 72 Hours Postdose in Cohort 1

  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

• Cmax: Maximum Observed Plasma Concentration for Digoxin in Cohort 2

  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

• AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Digoxin in Cohort 2

  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

• 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

  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

• Urinary Excretion Ratio of Digoxin From 0 to 48 Hours Postdose in Cohort 2

  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

• Cmax: Maximum Observed Plasma Concentration for Midazolam and 1'Hydroxymidazolam in Cohort 2

  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

• AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam and 1'Hydroxymidazolam in Cohort 2

  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

• 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

  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

• Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

  Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15

• Number of Participants With TEAEs Related to Vital Signs

  Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15

• Number of Participants With TEAEs Related to Body Weight

  Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15

• Number of Participants Who Had Clinically Significant Changes From Baseline in 12-lead Electrocardiograms

  Number of participants who had ECG findings changed from "within normal limit" or "abnormal, clinically significant" to "abnormal and clinically significant" after study drug administration.

  Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15

• Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis

  Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15

• Number of Participants With Clinically Significant Change From Baseline in Continuous Pulse Oximetry (SpO2) in Cohort 2

  Cohort 2: Baseline up to Day 15

Study Arms (2)

Cohort 1: TAK-272 + Itraconazole

EXPERIMENTAL

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.

Drug: TAK-272; Drug: Itraconazole

Cohort 2: Midazolam + Digoxin + TAK-272

EXPERIMENTAL

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.

Drug: TAK-272; Drug: Digoxin; Drug: Midazolam

Interventions

TAK-272 DRUG

TAK-272 tablet.

Cohort 1: TAK-272 + Itraconazole; Cohort 2: Midazolam + Digoxin + TAK-272

Digoxin DRUG

Digoxin tablet.

Cohort 2: Midazolam + Digoxin + TAK-272

Itraconazole DRUG

Itraconazole oral solution

Cohort 1: TAK-272 + Itraconazole

Midazolam DRUG

Midazolam syrup.

Cohort 2: Midazolam + Digoxin + TAK-272

Eligibility Criteria

• Age: 20 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Is capable of understanding and complying with protocol requirements.
• Who can sign and date the informed consent form before the initiation of the study procedure.
• Healthy Japanese adult male volunteer.
• Is of 20 to 35 years of age at the time of informed consent
• 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.
• 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.

You may not qualify if:

• Who was administered any investigational product within 16 weeks (112 days) prior to the initial drug administration.
• Who has received TAK-272 in previous.
• 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.
• 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.
• Who has a history of serious hepatic disease.
• Who has atrioventricular block or sinoatrial block.
• Has digitalis intoxication.
• Has acute narrow-angle glaucoma.
• Has myasthenia gravis.
• Has hypersensitivity to TAK-272 or any other renin inhibitors.
• Has hypersensitivity to itraconazole, digoxin, digitalis preparation, or midazolam.
• Has allergy to cherries.
• Has a positive to urine test for drug abuse at the screening.
• 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.
• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Unknown Facility

Osaka, Osaka, Japan

Location

MeSH Terms

Interventions

imarikiren hydrochloride; Digoxin; Itraconazole; Midazolam

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2015
• First Posted: February 25, 2015
• Study Start: February 1, 2015
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: May 23, 2016
• Results First Posted: May 23, 2016

Record last verified: 2016-04

Locations

JP (1)