Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02370615
Recruitment Status : Completed
First Posted : February 25, 2015
Results First Posted : May 23, 2016
Last Update Posted : May 23, 2016
Sponsor:
Information provided by (Responsible Party):
Takeda

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.

Condition or disease Intervention/treatment Phase
Japanese Healthy Adult Males Drug: TAK-272 Drug: Digoxin Drug: Itraconazole Drug: Midazolam Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : February 2015
Actual Primary Completion Date : April 2015
Actual Study Completion Date : April 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions

Arm Intervention/treatment
Experimental: 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.
Drug: TAK-272
TAK-272 tablet.

Drug: Itraconazole
Itraconazole oral solution

Experimental: 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.
Drug: TAK-272
TAK-272 tablet.

Drug: Digoxin
Digoxin tablet.

Drug: Midazolam
Midazolam syrup.




Primary Outcome Measures :
  1. Cmax: Maximum Observed Plasma Concentration for TAK 272F and TAK 272-Metabolite (M-I) in Cohort 1 [ Time Frame: 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 ]
  2. 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 [ Time Frame: 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 ]
  3. 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 [ Time Frame: 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 ]
  4. Cumulative Urinary Excretion Ratio of TAK 272F and TAK 272-M-I From 0 to 72 Hours Postdose in Cohort 1 [ Time Frame: 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 ]
  5. Cmax: Maximum Observed Plasma Concentration for Digoxin in Cohort 2 [ Time Frame: 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 ]
  6. AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Digoxin in Cohort 2 [ Time Frame: 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 ]
  7. 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 [ Time Frame: 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 ]
  8. Urinary Excretion Ratio of Digoxin From 0 to 48 Hours Postdose in Cohort 2 [ Time Frame: 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 ]
  9. Cmax: Maximum Observed Plasma Concentration for Midazolam and 1'Hydroxymidazolam in Cohort 2 [ Time Frame: 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 ]
  10. AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam and 1'Hydroxymidazolam in Cohort 2 [ Time Frame: 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 ]
  11. 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 [ Time Frame: 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 ]
  12. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15 ]
  13. Number of Participants With TEAEs Related to Vital Signs [ Time Frame: Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15 ]
  14. Number of Participants With TEAEs Related to Body Weight [ Time Frame: Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15 ]
  15. Number of Participants Who Had Clinically Significant Changes From Baseline in 12-lead Electrocardiograms [ Time Frame: Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15 ]
    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.

  16. Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis [ Time Frame: Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15 ]
  17. Number of Participants With Clinically Significant Change From Baseline in Continuous Pulse Oximetry (SpO2) in Cohort 2 [ Time Frame: Cohort 2: Baseline up to Day 15 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02370615


Locations
Layout table for location information
Japan
Osaka-shi, Osaka, Japan
Sponsors and Collaborators
Takeda
Investigators
Layout table for investigator information
Study Chair: Medical Director Takeda

Layout table for additonal information
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02370615     History of Changes
Other Study ID Numbers: TAK-272/CPH-011
U1111-1167-0017 ( Registry Identifier: WHO )
JapicCTI-152810 ( Registry Identifier: JapicCTI )
First Posted: February 25, 2015    Key Record Dates
Results First Posted: May 23, 2016
Last Update Posted: May 23, 2016
Last Verified: April 2016

Additional relevant MeSH terms:
Layout table for MeSH terms
Itraconazole
Hydroxyitraconazole
Midazolam
Digoxin
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Cytochrome P-450 CYP3A Inhibitors
Anti-Arrhythmia Agents
Cardiotonic Agents
Protective Agents