Phase I Open-label Study to Evaluate Pharmacokinetics of TAK-272 in Participants With Renal or Hepatic Impairment

NCT02367872 | Completed Phase 1 Results

• 3 other identifiers: TAK-272/CPH-012U1111-1166-3774JapicCTI-152790
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to examine the effects of renal and hepatic impairment on TAK-272 pharmacokinetics with a single oral administration of TAK-272 in participants with renal or hepatic impairment.

Conditions

Renal Impairment; Hepatic Impairment

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (12)

• AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Free Form of TAK-272 (TAK-272F) and Its Metabolite M-I

  Day 1: Pre-dose and at multiple time points (0.5, 1, 1.5, 2, 3, 4, 5, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 hours post dose; up to 120 hours) post-dose

• Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I

  Day 1: Pre-dose and at multiple time points (0.5, 1, 1.5, 2, 3, 4, 5, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 hours post dose; up to 120 hours) post-dose

• AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I

  Day 1: Pre-dose and at multiple time points (0.5, 1, 1.5, 2, 3, 4, 5, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 hours post dose; up to 120 hours) post-dose

• AUClast,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration for TAK-272F

  AUClast,u is the area under the concentration-time curve of the unbound drug in plasma over the time interval from 0 to time of last quantifiable post-dose of TAK-272.

  Day 1: Pre-dose and at multiple time points (0.5, 1, 1.5, 2, 3, 4, 5, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 hours post dose; up to 120 hours) post-dose

• Cmax,u: Maximum Unbound Plasma Concentration for TAK-272F

  Cmax,u is the peak unbound plasma concentration of a drug after administration, obtained directly from the unbound plasma concentration-time curve.

  Day 1: Pre-dose and at multiple time points (0.5, 1, 1.5, 2, 3, 4, 5, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 hours post dose; up to 120 hours) post-dose

• AUC∞,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F

  AUC∞,u is the area under the concentration-time curve of the unbound drug in plasma over the time interval from 0 to infinity of TAK-272.

  Day 1: Pre-dose and at multiple time points (0.5, 1, 1.5, 2, 3, 4, 5, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 hours post dose; up to 120 hours) post-dose

• Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I

  Day 1: Pre-dose and at multiple time points (0.5, 1, 1.5, 2, 3, 4, 5, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 hours post dose; up to 120 hours) post-dose

• Apparent Clearance (CL/F) for TAK-272F

  Day 1: Pre-dose and at multiple time points (0.5, 1, 1.5, 2, 3, 4, 5, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 hours post dose; up to 120 hours) post-dose

• CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for TAK-272F

  CLu/F is the apparent clearance for unbound drug after extravascular administration of TAK-272.

  Day 1: Pre-dose and at multiple time points (0.5, 1, 1.5, 2, 3, 4, 5, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 hours post dose; up to 120 hours) post-dose

• Cumulative Urinary Excretion Ratio of TAK-272F and Its Metabolite M-I From 0 to 72 Hours Post-dose in Cohorts 1R, 2R, 3R, 4R, 1H, 2H and 3H

  Urinary excretion ratio (percentage \[%\] of dose) of TAK-272 and its metabolite M-I in urine was calculated for each participant.

  Day 1: Pre-dose and at multiple time points (4, 8, 12, 24, 36, 48, 72 hours post dose; up to 72 hours) post-dose

• Plasma Protein Binding Rate of TAK-272F in Cohorts 1R, 2R, 3R, 4R, 5R, 1H, 2H and 3H

  Plasma protein binding rate was the percentage of unbound fraction of TAK-272F in plasma protein.

  Baseline

• Excretion Ratio of TAK-272F in Dialysate in Cohort 5R

  Excretion ratio (% of dose) of TAK-272F in dialysis fluid was calculated for each participant.

  Day 1: Pre-dose, up to 6 hours post-dose

Secondary Outcomes (5)

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

  Baseline up to Day 8 of each Cohort

• Number of Participants With TEAE Related to Vital Signs

  Baseline up to Day 8 of each Cohort

• Number of Participants With TEAE Related to Body Weight

  Baseline up to Day 8 of each Cohort

• Number of Participants With TEAE Related to 12-lead Electrocardiograms (ECG)

  Baseline up to Day 8 of each Cohort

• Number of Participants With TEAE Related to Laboratory Tests

  Baseline up to Day 8 of each Cohort

Study Arms (8)

Participants with normal renal function: TAK-272 40 mg

ACTIVE COMPARATOR

Fasted single oral administration of TAK-272 40 milligram (mg)

Drug: TAK-272

Participants with mild renal impairment: TAK-272 40 mg

EXPERIMENTAL

Fasted single oral administration of TAK-272 40 mg

Drug: TAK-272

Participants with moderate renal impairment: TAK-272 40 mg

EXPERIMENTAL

Fasted single oral administration of TAK-272 40 mg

Drug: TAK-272

Participants with severe renal impairment: TAK-272 40 mg

EXPERIMENTAL

Fasted single oral administration of TAK-272 40 mg

Drug: TAK-272

Hemodialysis participants: TAK-272 40 mg

EXPERIMENTAL

Fasted single oral administration of TAK-272 40 mg

Drug: TAK-272

Participants with normal hepatic function: TAK-272 40 mg

ACTIVE COMPARATOR

Fasted single oral administration of TAK-272 40 mg

Drug: TAK-272

Participants with mild hepatic impairment: TAK-272 40 mg

EXPERIMENTAL

Fasted single oral administration of TAK-272 40 mg

Drug: TAK-272

Participants with moderate hepatic impairment: TAK-272 40 mg

EXPERIMENTAL

Fasted single oral administration of TAK-272 40 mg

Drug: TAK-272

Interventions

TAK-272 DRUG

TAK-272 tablet

Hemodialysis participants: TAK-272 40 mg; Participants with mild hepatic impairment: TAK-272 40 mg; Participants with mild renal impairment: TAK-272 40 mg; Participants with moderate hepatic impairment: TAK-272 40 mg; Participants with moderate renal impairment: TAK-272 40 mg; Participants with normal hepatic function: TAK-272 40 mg; Participants with normal renal function: TAK-272 40 mg; Participants with severe renal impairment: TAK-272 40 mg

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants
• In the opinion of the investigator or subinvestigator, the participant is capable of understanding and complying with protocol requirements.
• Signs and dates a written, informed consent form prior to the initiation of any study procedures.
• Is either male or female and aged 20 to 85 years, inclusive, at the time of informed consent.
• Weighs at least 45 kilogram (kg) for males and 40 kg for females and have a body mass index (BMI) of less than (\<) 35.0 kilogram per square meter (kg/m\^2) at screening and Day 1.
• A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent until 12 weeks after study drug administration.
• A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from signing of informed consent until 1 month after the completion of the study.
• Participants with normal renal or hepatic function (Cohorts 1R and 1H)
• Estimated glomerular filtration rate (eGFR) is greater than or equal to (\>=) 90 milliliter per minute per 1.73 square meter (mL/min/1.73 m\^2) at screening.
• Based on the participant's medical history, clinical laboratory values, and physical examination findings, the investigator or subinvestigator judges the participant to be in good health (hypertension, type 2 diabetes, and hypercholesteremia or dyslipidemia are controlled, if present).
• Is within +/-10 years of the mean age and +/-20 percent (%) of the mean weight for the 24 participants with renal impairment and 12 participants with hepatic impairment administered the study drug.
• Participants with renal impairment (Cohorts 2R, 3R, 4R, 5R)
• Falls into any of the following categories:
• With mild renal impairment (Cohort 2R): eGFR \>=60 mL/min/1.73 m\^2 and \<90 mL/min/1.73 m\^2 at screening.
• With moderate renal impairment (Cohort 3R): eGFR \>=30 mL/min/1.73 m\^2 and \<60 mL/min/1.73 m\^2 at screening.

You may not qualify if:

• All participants
• Has received any investigational product within 16 weeks (112 days) prior to the start of study drug administration.
• Has received TAK-272 in a previous clinical study.
• Is an immediate family member, study site employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (example, spouse, parent, child, sibling) or may consent under duress.
• Has a history of cancer. This does not include individuals who have been in remission for at least 1 year prior to the start of screening and who are judged by the investigator or subinvestigator to have had no recurrence during the study.
• Has a known hypersensitivity or allergy to any component of the TAK-272 formulation or renin inhibitors.
• Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
• Has any positive urine drug test result at screening (including test for alcohol) if a non-hemodialysis participant.
• Has taken any excluded medication or food product listed in the Excluded Medications and Dietary Products section during the period in which excluded medication use is prohibited, or needs to take any excluded medication or food product during the study.
• Previously has undergone kidney or liver transplantation.
• Has poor peripheral venous access.
• Has undergone whole blood collection of 800 milliliter (mL) or more within 52 weeks (364 days) prior to the start of study drug administration.
• Has undergone whole blood collection of 200 mL or more within 4 weeks (28 days) or 400 mL or more within 12 weeks (84 days) for males and 16 weeks (112 days) for females prior to the start of study drug administration.
• Has undergone blood component collection within 2 weeks (14 days) prior to the start of study drug administration.
• Has onset of myocardial infarction or coronary revascularization within 6 months before screening.

Sponsors & Collaborators

• Takeda: lead

Study Sites (4)

Unknown Facility

Kurume, Fukuoka, Japan

Location

Unknown Facility

Moriya, Ibaragi, Japan

Location

Unknown Facility

Sagamihara, Kanagawa, Japan

Location

Unknown Facility

Shinagawa, Tokyo, Japan

Location

Related Publications (1)

• Shimasaki Y, Sakaki M, Itou M, Kobayashi T, Aso M, Kagawa T, Saiki T, Matsuno K, Sano Y, Shimizu K, Kuroda S, Koumura E. Pharmacokinetics and Safety After a Single Dose of Imarikiren in Subjects with Renal or Hepatic Impairment. Clin Drug Investig. 2018 Nov;38(11):1041-1051. doi: 10.1007/s40261-018-0695-4.

  PMID: 30194585 DERIVED

MeSH Terms

Conditions

Renal Insufficiency

Interventions

imarikiren hydrochloride

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• General Manager

  Takeda

  STUDY DIRECTOR

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2015
• First Posted: February 20, 2015
• Study Start: March 1, 2015
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: November 6, 2017
• Results First Posted: August 10, 2017

Record last verified: 2017-10

Locations

JP (4)