Phase 1 Completed N=34 Treatment

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

Japanese Healthy Adult Males

Source: ClinicalTrials.gov NCT02370615 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

May 2016

Primary outcomePrimary: Cmax: Maximum Observed Plasma Concentration for TAK 272F and TAK 272-Metabolite (M-I) in Cohort 1 — 387.8; 780.3; 10.02; 0.9550 nanogram per milliliter (ng/mL)

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.

Outcome Measures

Outcome	Result	p-value
PRIMARY Cmax: Maximum Observed Plasma Concentration for TAK 272F and TAK 272-Metabolite (M-I) in Cohort 1	387.8; 780.3; 10.02; 0.9550	—
PRIMARY 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	1861; 9098; 46.53; 9.373	—
PRIMARY 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	1842; 8659; 38.34; 0.9092	—
PRIMARY Cumulative Urinary Excretion Ratio of TAK 272F and TAK 272-M-I From 0 to 72 Hours Postdose in Cohort 1	11.523; 37.803; 0.556; 0.071	—
PRIMARY Cmax: Maximum Observed Plasma Concentration for Digoxin in Cohort 2	1.212; 1.635	—
PRIMARY AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Digoxin in Cohort 2	15.49; 15.79	—
PRIMARY 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	9.191; 10.61	—
PRIMARY Urinary Excretion Ratio of Digoxin From 0 to 48 Hours Postdose in Cohort 2	31.391; 35.983	—
PRIMARY Cmax: Maximum Observed Plasma Concentration for Midazolam and 1'Hydroxymidazolam in Cohort 2	10.02; 12.37; 4.813; 4.270	—
PRIMARY AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam and 1'Hydroxymidazolam in Cohort 2	27.11; 38.55; 13.00; 14.06	—
PRIMARY 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	26.77; 38.16; 12.49; 13.25	—
PRIMARY Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	10; 7	—
PRIMARY Number of Participants With TEAEs Related to Vital Signs	1; 0; 2; 0; 0; 1	—
PRIMARY Number of Participants With TEAEs Related to Body Weight	0; 0	—
PRIMARY Number of Participants Who Had Clinically Significant Changes From Baseline in 12-lead Electrocardiograms	0; 0	—
PRIMARY Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis	2; 1; 1; 0; 0; 1	—
PRIMARY Number of Participants With Clinically Significant Change From Baseline in Continuous Pulse Oximetry (SpO2) in Cohort 2	—	—

Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

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.
Male participants who plans to donate sperm during the study period or up to 12 weeks after the end of the study.
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.
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).
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]).
Has past history of cancer.
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.
The participant with difficulty having blood collected from a peripheral vein.
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.
Who has donated a total o

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02370615). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.