Renal ImpairmentPhase 1NCT02367872

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

A Phase 1 study testing TAK-272 in people with Renal Impairment and Hepatic Impairment, run by Takeda at 4 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 20 to 85 years
Conditions the study is for: Renal Impairment, Hepatic Impairment
What is being tested?: TAK-272
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 48 participants
Where: 4 sitesJapan
Study dates: Mar 2015to Jun 2016
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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.
With severe renal impairment or end-stage renal failure (non-hemodialysis participants) (Cohort 4R): eGFR <30 mL/min/1.73 m^2 at screening.
Hemodialysis participants (Cohort 5R): with end-stage renal failure and little or no urine output who are undergoing hemodialysis 3 times weekly.
For non-hemodialysis participants, difference in eGFR obtained between 3 months and 7 days before screening from eGFR at screening is less than or equal to (<=) 30%.
Participants with hepatic impairment (Cohorts 2H, 3H)
In observations during the screening period, those diagnosed with hepatic impairment corresponding to any of the following Child-Pugh classes:
With mild hepatic impairment (Cohort 2H): Child-Pugh class A.
With moderate hepatic impairment (Cohort 3H): Child-Pugh class B.
Is diagnosed by the investigator or subinvestigator with hepatic impairment that has remained stable during the 3 months before screening.

Who cannot join

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.

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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.
Has a history of abdominal surgery (excluding laparoscopic cholecystectomy or appendectomy without complications) or chest or non-peripheral vascular surgery within 6 months before screening.
Has onset of acute disease (example, renal and urinary tract disease) within 30 days before screening.
Has clinically significant abnormal electrocardiogram (ECG) in the screening period or the pretreatment examination.
Has clinically significant hyperkalemia.
If female, the participant is pregnant or lactating or intending to become pregnant before, during or within 1 month after participating in this study, or intending to donate ova during such time period.
If male, the participant intends to donate sperm during the course of this study or for 12 weeks thereafter.
In the opinion of the investigator or subinvestigator, is unlikely to comply with protocol or is unsuitable for any other reason.
Participants with normal renal and hepatic function (Cohorts 1R and 1H)
Has uncontrolled, clinically significant hepatic, renal, neurologic, cardiovascular, blood, pulmonary, metabolic, gastrointestinal, urologic or endocrine disease, immune disease, infection or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results.
Has clinical laboratory results at screening suggestive of a clinically significant underlying disease other than controlled hypertension, type 2 diabetes, hypercholesteremia, or dyslipidemia.
Systolic blood pressure is <80 millimeter of mercury (mmHg) at screening, in the pretreatment examination, or in the examination prior to the start of study drug administration and has repeated instances of the findings listed below, suggesting the presence of hypotension:
Dizziness postural, facial pallor, cold sweats.
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is >2.0 times higher than the upper limit of normal at screening.
Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antigen/antibody, or serological reactions for syphilis at screening.
Participants with renal impairment (Cohorts 2R, 3R, 4R, 5R)
Has uncontrolled, clinically significant hepatic, neurologic, cardiovascular, blood, pulmonary, metabolic, gastrointestinal, urologic or endocrine disease, immune disease, infection or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results.
Sitting systolic blood pressure is <110 mmHg at screening, in the pretreatment examination, or in the examination before administration on Day 1.
ALT or AST is >2.0 times higher than the upper limit of normal at screening.
Has a positive test result for HBsAg, HCV antibody, HIV antigen/antibody, or serological reactions for syphilis at screening.
Participants with hepatic impairment (Cohorts 2H, 3H)
Has uncontrolled, clinically significant renal, neurologic, cardiovascular, blood, pulmonary, metabolic, gastrointestinal, urologic or endocrine disease, immune disease, infection or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results.
Has ascites requiring invasive treatment.
Systolic blood pressure is <80 mmHg at screening, in the pretreatment examination, or in the examination prior to the start of study drug administration and has repeated instances of the findings listed below, suggesting the presence of hypotension:
Dizziness postural, facial pallor, cold sweats.
eGFR is <60 mL/min/1.73 m^2 at screening.
Has a positive test result for HIV antigen/antibody or the participant has a positive test result for serological reactions for syphilis and syphilis is judged not to have been cured at screening.

Trial locations and contacts

4 sites in 1 country.

Japan4 sites

Study site
Kurume, Fukuoka
Study site
Moriya, Ibaragi
Study site
Sagamihara, Kanagawa
Study site
Shinagawa, Tokyo

Other trials in Japan

About this study

Official title: Phase I Open-label, Parallel-group, Comparative Study to Evaluate the Effects of Renal or Hepatic Impairment on TAK-272 Pharmacokinetics With a Single Oral Administration of TAK-272 in Patients With Renal or Hepatic Impairment

Read the detailed description

This study is a phase I, open-label, parallel-group, comparative study to evaluate the effects of renal or hepatic impairment on pharmacokinetics of TAK-272 with a single oral administration of TAK-272 in participants with renal or hepatic impairment as compared with participants with normal renal and hepatic function.

Conditions: Renal Impairment, Hepatic Impairment
Being tested: TAK-272
Keywords: Drug therapy
Medical subject headings: Renal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TAK-272Drug
TAK-272 tablet

Study groups in NCT02367872
Study group	Role	What they receive
Participants with normal renal function: TAK-272 40 mg	Active comparator	Fasted single oral administration of TAK-272 40 milligram (mg) Receives: Drug: TAK-272
Participants with mild renal impairment: TAK-272 40 mg	Experimental	Fasted single oral administration of TAK-272 40 mg Receives: Drug: TAK-272
Participants with moderate renal impairment: TAK-272 40 mg	Experimental	Fasted single oral administration of TAK-272 40 mg Receives: Drug: TAK-272
Participants with severe renal impairment: TAK-272 40 mg	Experimental	Fasted single oral administration of TAK-272 40 mg Receives: Drug: TAK-272
Hemodialysis participants: TAK-272 40 mg	Experimental	Fasted single oral administration of TAK-272 40 mg Receives: Drug: TAK-272
Participants with normal hepatic function: TAK-272 40 mg	Active comparator	Fasted single oral administration of TAK-272 40 mg Receives: Drug: TAK-272
Participants with mild hepatic impairment: TAK-272 40 mg	Experimental	Fasted single oral administration of TAK-272 40 mg Receives: Drug: TAK-272
Participants with moderate hepatic impairment: TAK-272 40 mg	Experimental	Fasted single oral administration of TAK-272 40 mg Receives: Drug: TAK-272

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Measured: Baseline up to Day 8 of each Cohort
Number of Participants With TEAE Related to Vital Signs
Number of participants with TEAE related to vital signs was reported in this outcome measure. The related event to report was only "Blood Pressure Decreased" throughout this study.
Measured: Baseline up to Day 8 of each Cohort
Number of Participants With TEAE Related to Body Weight
Number of participants with TEAE related to body weight was reported in this outcome measure. There were no events to report as TEAE related to body weight throughout this study.
Measured: Baseline up to Day 8 of each Cohort
Number of Participants With TEAE Related to 12-lead Electrocardiograms (ECG)
Number of participants with TEAE related to ECG was reported in this outcome measure. There were no events to report as TEAE related to ECG throughout this study.
Measured: Baseline up to Day 8 of each Cohort
Number of Participants With TEAE Related to Laboratory Tests
Number of participants with TEAE related to laboratory tests was reported in this outcome measure. The related event to report was only "Alanine Aminotransferase Increased" throughout this study.
Measured: Baseline up to Day 8 of each Cohort

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2015Jun 2016

First posted20 Feb 2015 (estimated)
Study startMar 2015
Primary completionJun 2016
Study completionJun 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Renal ImpairmentStudies of the same condition, open and under way.
More trials run by TakedaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 48 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02367872
Sponsor's protocol ID: TAK-272/CPH-012
Other IDs: U1111-1166-3774, JapicCTI-152790
Status last verified: Oct 2017
First submitted: 13 Feb 2015
Last updated: 6 Nov 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 30194585

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 6 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I Open-label, Parallel-group, Comparative Study to Evaluate the Effects of Renal or Hepatic Impairment on TAK-272 Pharmacokinetics With a Single Oral Administration of TAK-272 in Patients With Renal or Hepatic Impairment
ClinicalTrials.gov ID: NCT02367872
Acronym / sponsor ID: TAK-272/CPH-012
Conditions: Renal Impairment, Hepatic Impairment
Keywords: Drug therapy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 48 participants (actual)
Lead sponsor: TakedaIndustry (pharma, biotech, devices)
Study start: Mar 2015
Primary completion: Jun 2016 (actual)
Study completion: Jun 2016 (actual)
First posted: 20 Feb 2015 (estimated)
Results: Posted 10 Aug 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 8

Arm	Type	Receives
Participants with normal renal function: TAK-272 40 mg	Active comparator	Drug: TAK-272Fasted single oral administration of TAK-272 40 milligram (mg)
Participants with mild renal impairment: TAK-272 40 mg	Experimental	Drug: TAK-272Fasted single oral administration of TAK-272 40 mg
Participants with moderate renal impairment: TAK-272 40 mg	Experimental	Drug: TAK-272Fasted single oral administration of TAK-272 40 mg
Participants with severe renal impairment: TAK-272 40 mg	Experimental	Drug: TAK-272Fasted single oral administration of TAK-272 40 mg
Hemodialysis participants: TAK-272 40 mg	Experimental	Drug: TAK-272Fasted single oral administration of TAK-272 40 mg
Participants with normal hepatic function: TAK-272 40 mg	Active comparator	Drug: TAK-272Fasted single oral administration of TAK-272 40 mg
Participants with mild hepatic impairment: TAK-272 40 mg	Experimental	Drug: TAK-272Fasted single oral administration of TAK-272 40 mg
Participants with moderate hepatic impairment: TAK-272 40 mg	Experimental	Drug: TAK-272Fasted single oral administration of TAK-272 40 mg

Who may qualify

Ages: 20 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (23 listed)

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.

Key exclusion criteria (41 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TAK-272TAK-272 tablet	Drug	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

Primary outcome

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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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 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.
Cmax,u: Maximum Unbound Plasma Concentration for TAK-272F
Time frame: 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 is the peak unbound plasma concentration of a drug after administration, obtained directly from the unbound plasma concentration-time curve.
AUC∞,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F
Time frame: 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 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.
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I
Time frame: 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
Time frame: 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
Time frame: 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 is the apparent clearance for unbound drug after extravascular administration of TAK-272.
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
Time frame: 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
Urinary excretion ratio (percentage [%] of dose) of TAK-272 and its metabolite M-I in urine was calculated for each participant.
Plasma Protein Binding Rate of TAK-272F in Cohorts 1R, 2R, 3R, 4R, 5R, 1H, 2H and 3H
Time frame: Baseline
Plasma protein binding rate was the percentage of unbound fraction of TAK-272F in plasma protein.
Excretion Ratio of TAK-272F in Dialysate in Cohort 5R
Time frame: Day 1: Pre-dose, up to 6 hours post-dose
Excretion ratio (% of dose) of TAK-272F in dialysis fluid was calculated for each participant.

5 secondary outcomes

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE)
Time frame: Baseline up to Day 8 of each Cohort
Number of Participants With TEAE Related to Vital Signs
Time frame: Baseline up to Day 8 of each Cohort
Number of Participants With TEAE Related to Body Weight
Time frame: Baseline up to Day 8 of each Cohort
Number of Participants With TEAE Related to 12-lead Electrocardiograms (ECG)
Time frame: Baseline up to Day 8 of each Cohort
Number of Participants With TEAE Related to Laboratory Tests
Time frame: Baseline up to Day 8 of each Cohort

Results and safety

Results posted to the registry on 10 Aug 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1R: Normal Renal Function	6	6
Cohort 2R: Mild Renal Impairment	6	6
Cohort 3R: Moderate Renal Impairment	6	6
Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis)	6	6
Cohort 5R: End-stage Renal Failure (Hemodialysis)	6	6
Cohort 1H: Normal Hepatic Function	6	6
Cohort 2H: Mild Hepatic Impairment	6	6
Cohort 3H: Moderate Hepatic Impairment	6	6

Primary outcome: 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

Time frame: 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. Geometric mean (Standard Deviation). Unit: nanogram*hour per milliliter (ng*hr/mL)

Measure	Cohort 1R: Normal Renal Function n = 6	Cohort 2R: Mild Renal Impairment n = 6	Cohort 3R: Moderate Renal Impairment n = 6	Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) n = 6	Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) n = 6	Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) n = 6	Cohort 1H: Normal Hepatic Function n = 6	Cohort 2H: Mild Hepatic Impairment n = 6	Cohort 3H: Moderate Hepatic Impairment n = 6
TAK-272F	2951 (391.70)	1507 (952.72)	3481 (797.67)	8053 (2964.7)	4579 (1091.2)	5409 (1343.0)	2269 (366.43)	2307 (750.08)	3085 (1551.3)
M-I	50.66 (27.097)	31.58 (13.765)	47.22 (18.319)	138.9 (89.619)	104.3 (20.684)	132.3 (40.166)	33.95 (13.432)	38.18 (14.860)	60.01 (27.427)

Cohort 1R: Normal Renal Function vs Cohort 2R: Mild Renal Impairment: LS Mean Cohort Ratio (%): 51.08 (95% CI 35.22 to 74.08)
Cohort 1R: Normal Renal Function vs Cohort 3R: Moderate Renal Impairment: LS Mean Cohort Ratio (%): 117.95 (95% CI 81.32 to 171.07)
Cohort 1R: Normal Renal Function vs Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis): LS Mean Cohort Ratio (%): 272.87 (95% CI 188.14 to 395.76)

Population analysed: The plasma PK set included all participants treated with the study drug who had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for plasma PK.

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

Measure	Cohort 1R: Normal Renal Function n = 6	Cohort 2R: Mild Renal Impairment n = 6	Cohort 3R: Moderate Renal Impairment n = 6	Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) n = 6	Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) n = 6	Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) n = 6	Cohort 1H: Normal Hepatic Function n = 6	Cohort 2H: Mild Hepatic Impairment n = 6	Cohort 3H: Moderate Hepatic Impairment n = 6
TAK-272F	753.5 (211.81)	432.2 (248.57)	580.5 (312.90)	1555 (303.45)	1061 (222.54)	1078 (417.38)	522.8 (111.65)	446.0 (198.78)	688.1 (339.69)
M-I	20.08 (11.909)	14.13 (7.0952)	11.05 (7.9919)	25.30 (13.442)	19.86 (5.6056)	20.87 (3.5431)	12.45 (8.8158)	11.45 (6.2582)	17.34 (6.6026)

Cohort 1R: Normal Renal Function vs Cohort 2R: Mild Renal Impairment: LS Mean Cohort Ratio (%): 57.36 (95% CI 37.76 to 87.14)
Cohort 1R: Normal Renal Function vs Cohort 3R: Moderate Renal Impairment: LS Mean Cohort Ratio (%): 77.04 (95% CI 50.72 to 117.03)
Cohort 1R: Normal Renal Function vs Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis): LS Mean Cohort Ratio (%): 206.41 (95% CI 135.88 to 313.54)

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

Measure	Cohort 1R: Normal Renal Function n = 6	Cohort 2R: Mild Renal Impairment n = 6	Cohort 3R: Moderate Renal Impairment n = 6	Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) n = 6	Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) n = 6	Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) n = 6	Cohort 1H: Normal Hepatic Function n = 6	Cohort 2H: Mild Hepatic Impairment n = 6	Cohort 3H: Moderate Hepatic Impairment n = 6
TAK-272F	2971 (393.33)	1527 (953.59)	3519 (812.10)	8106 (3004.0)	4647 (1101.8)	5471 (1342.1)	2289 (368.39)	2326 (746.40)	3126 (1575.2)
M-I	62.32 (32.579)	36.87 (15.778)	60.47 (21.246)	162.0 (99.759)	129.6 (23.022)	198.8 (95.110)	38.84 (15.615)	50.52 (16.916)	74.82 (31.470)

Cohort 1R: Normal Renal Function vs Cohort 2R: Mild Renal Impairment: LS Mean Cohort Ratio (%): 51.39 (95% CI 35.45 to 74.49)
Cohort 1R: Normal Renal Function vs Cohort 3R: Moderate Renal Impairment: LS Mean Cohort Ratio (%): 118.43 (95% CI 81.70 to 171.68)
Cohort 1R: Normal Renal Function vs Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis): LS Mean Cohort Ratio (%): 272.83 (95% CI 188.21 to 395.50)

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

Measure	Cohort 1R: Normal Renal Function n = 6	Cohort 2R: Mild Renal Impairment n = 6	Cohort 3R: Moderate Renal Impairment n = 6	Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) n = 6	Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) n = 6	Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) n = 6	Cohort 1H: Normal Hepatic Function n = 6	Cohort 2H: Mild Hepatic Impairment n = 6	Cohort 3H: Moderate Hepatic Impairment n = 6
Value	138.7 (72.422)	83.51 (40.288)	135.0 (16.105)	154.7 (55.009)	162.9 (40.127)	192.4 (55.731)	107.7 (17.583)	145.5 (82.297)	348.5 (102.16)

Cohort 1R: Normal Renal Function vs Cohort 2R: Mild Renal Impairment: LS Mean Cohort Ratio (%): 60.22 (95% CI 40.05 to 90.56)
Cohort 1R: Normal Renal Function vs Cohort 3R: Moderate Renal Impairment: LS Mean Cohort Ratio (%): 97.39 (95% CI 64.77 to 146.46)
Cohort 1R: Normal Renal Function vs Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis): LS Mean Cohort Ratio (%): 111.60 (95% CI 74.21 to 167.82)

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment-emergent adverse events are adverse events that started after the first dose of study drug up to Day 8 of each Cohort. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1R: Normal Renal Function	0 of 6 (0%)	1 of 6 (16.7%)	Not reported
Cohort 2R: Mild Renal Impairment	0 of 6 (0%)	1 of 6 (16.7%)	Not reported
Cohort 3R: Moderate Renal Impairment	0 of 6 (0%)	1 of 6 (16.7%)	Not reported
Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis)	0 of 6 (0%)	2 of 6 (33.3%)	Not reported
Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis)	0 of 6 (0%)	2 of 6 (33.3%)	Not reported
Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis)	0 of 6 (0%)	1 of 6 (16.7%)	Not reported
Cohort 1H: Normal Hepatic Function	0 of 6 (0%)	1 of 6 (16.7%)	Not reported
Cohort 2H: Mild Hepatic Impairment	0 of 6 (0%)	1 of 6 (16.7%)	Not reported
Cohort 3H: Moderate Hepatic Impairment	0 of 6 (0%)	3 of 6 (50%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30194585Shimasaki 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

General Manager study director

Takeda

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TAK-272 in people with Renal Impairment and Hepatic Impairment, run by Takeda at 4 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 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). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02367872, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2017.