Hepatic Impairment, Renal Impairment
Conditions
Keywords
Drug therapy
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.
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.
Interventions
DRUGTAK-272
TAK-272 tablet
Sponsors
Takeda
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
All participants 1. In the opinion of the investigator or subinvestigator, the participant is capable of understanding and complying with protocol requirements. 2. Signs and dates a written, informed consent form prior to the initiation of any study procedures. 3. Is either male or female and aged 20 to 85 years, inclusive, at the time of informed consent. 4. 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. 5. 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. 6. 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) 7. 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. 8. 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). 9. 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) 10. 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. 11. 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) 12. 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. 13. Is diagnosed by the investigator or subinvestigator with hepatic impairment that has remained stable during the 3 months before screening.
Exclusion criteria
All participants 1. Has received any investigational product within 16 weeks (112 days) prior to the start of study drug administration. 2. Has received TAK-272 in a previous clinical study. 3. 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. 4. 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. 5. Has a known hypersensitivity or allergy to any component of the TAK-272 formulation or renin inhibitors. 6. 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. 7. Has any positive urine drug test result at screening (including test for alcohol) if a non-hemodialysis participant. 8. 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. 9. Previously has undergone kidney or liver transplantation. 10. Has poor peripheral venous access. 11. Has undergone whole blood collection of 800 milliliter (mL) or more within 52 weeks (364 days) prior to the start of study drug administration. 12. 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. 13. Has undergone blood component collection within 2 weeks (14 days) prior to the start of study drug administration. 14. Has onset of myocardial infarction or coronary revascularization within 6 months before screening. 15. 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. 16. Has onset of acute disease (example, renal and urinary tract disease) within 30 days before screening. 17. Has clinically significant abnormal electrocardiogram (ECG) in the screening period or the pretreatment examination. 18. Has clinically significant hyperkalemia. 19. 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. 20. If male, the participant intends to donate sperm during the course of this study or for 12 weeks thereafter. 21. 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) 22. 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. 23. Has clinical laboratory results at screening suggestive of a clinically significant underlying disease other than controlled hypertension, type 2 diabetes, hypercholesteremia, or dyslipidemia. 24. 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. 25. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is \>2.0 times higher than the upper limit of normal at screening. 26. 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) 27. 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. 28. Sitting systolic blood pressure is \<110 mmHg at screening, in the pretreatment examination, or in the examination before administration on Day 1. 29. ALT or AST is \>2.0 times higher than the upper limit of normal at screening. 30. 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) 31. 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. 32. Has ascites requiring invasive treatment. 33. 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. 34. eGFR is \<60 mL/min/1.73 m\^2 at screening. 35. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Excretion Ratio of TAK-272F in Dialysate in Cohort 5R | 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. |
| 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 | 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 | 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 | Baseline | Plasma protein binding rate was the percentage of unbound fraction of TAK-272F in plasma protein. |
| 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With TEAE Related to Vital Signs | Baseline up to Day 8 of each Cohort | 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. |
| Number of Participants With TEAE Related to Body Weight | Baseline up to Day 8 of each Cohort | 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. |
| 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 ECG was reported in this outcome measure. There were no events to report as TEAE related to ECG throughout this study. |
| Number of Participants With TEAE Related to Laboratory Tests | Baseline up to Day 8 of each Cohort | 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. |
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | Baseline up to Day 8 of each Cohort | — |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 4 investigative sites in Japan from 1 March 2015 to 10 June 2016.
Pre-assignment details
Participants with normal renal (1R) and hepatic (1H) function; those who had historical diagnosis of renal (mild \[2R\], moderate \[3R\], severe or end-stage renal failure with no hemodialysis \[4R\], end-stage renal failure \[with hemodialysis\] \[5R\]); hepatic impairment (mild \[2H\] and moderate \[3H\]) were enrolled to receive TAK-272 40 milligram (mg).
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1R: Normal Renal Function Participants with normal renal function (eGFR\>=90 mL/min/1.73 m\^2) received TAK-272 40 mg, tablets, orally in fasted state, once on Day 1 of a 6-day treatment period with 2-day follow-up period. | 6 |
| Cohort 2R: Mild Renal Impairment Participants with mild renal impairment (eGFR \>=60,\< 90 mL/min/1.73 m\^2) received TAK-272 40 mg, tablets, orally in fasted state, once on Day 1 of a 6-day treatment period with 2-day follow-up period. | 6 |
| Cohort 3R: Moderate Renal Impairment Participants with moderate renal impairment (eGFR \>=30, \<60 mL/min/1.73 m\^2) received TAK-272 40 mg, tablets, orally in fasted state, once on Day 1 of a 6-day treatment period with 2-day follow-up period. | 6 |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) Participants with severe or end-stage renal failure undergoing no hemodialysis (eGFR \<30 mL/min/1.73 m\^2) received TAK-272 40 mg, tablets, orally in fasted state, once on Day 1 of a 6-day treatment period with 2-day follow-up period. | 6 |
| Cohort 5R: End-stage Renal Failure (Hemodialysis) Participants with hemodialysis received TAK-272 40 mg, tablets, orally in fasted state, once on Day 1 of a 6-day treatment period with 2-day follow-up period in Part 1 (dialysis on Day 1 after dosing). After Part 1 follow-up period, then the same participants received TAK-272 40 mg, tablets, orally in fasted state, once on Day 1 of a 6-day treatment period with 2-day follow-up period in Part 2 (non-dialysis on Day 1). Participants who completed Cohort 5R-Part 1 started Part 2 after completion of 2-day of follow up in Part 1. | 6 |
| Cohort 1H: Normal Hepatic Function Participants with normal hepatic function received TAK-272 40 mg, tablets, orally in fasted state, once on Day 1 of a 6-day treatment period with 2-day follow-up period. | 6 |
| Cohort 2H: Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh class A score of 5-6) received TAK-272 40 mg, tablets, orally in fasted state, once on Day 1 of a 6-day treatment period with 2-day follow-up period. The Child-Pugh classification assesses the severity of 5 hepatic parameters (total serum bilirubin, serum albumin, PT or INR, ascites and encephalopathy grade) on a scale of 1 (none) to 3 (moderate). Total hepatic impairment score ranges from 5 (mild) to 15 (severe) where higher score indicates more severity. | 6 |
| Cohort 3H: Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh class B score of 7-9) received TAK-272 40 mg, tablets, orally in fasted state, once on Day 1 of a 6-day treatment period with 2-day follow-up period. The Child-Pugh classification assesses the severity of 5 hepatic parameters (total serum bilirubin, serum albumin, PT or INR, ascites and encephalopathy grade) on a scale of 1 (none) to 3 (moderate). Total hepatic impairment score ranges from 5 (mild) to 15 (severe) where higher score indicates more severity. | 6 |
| Total | 48 |
Baseline characteristics
| Characteristic | Cohort 2R: Mild Renal Impairment | Cohort 3R: Moderate Renal Impairment | Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | Cohort 5R: End-stage Renal Failure (Hemodialysis) | Cohort 1H: Normal Hepatic Function | Cohort 2H: Mild Hepatic Impairment | Cohort 3H: Moderate Hepatic Impairment | Cohort 1R: Normal Renal Function | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 59.7 years STANDARD_DEVIATION 8.94 | 70.2 years STANDARD_DEVIATION 5.53 | 69.5 years STANDARD_DEVIATION 5.89 | 71.2 years STANDARD_DEVIATION 6.91 | 61.0 years STANDARD_DEVIATION 5.73 | 61.0 years STANDARD_DEVIATION 10.41 | 61.5 years STANDARD_DEVIATION 8.96 | 66.3 years STANDARD_DEVIATION 5.61 | 65.0 years STANDARD_DEVIATION 8.23 |
| Alcohol Classification Drinks a few days per month | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 7 Participants |
| Alcohol Classification Drinks a few days per week | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 9 Participants |
| Alcohol Classification Drinks every day | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 6 Participants |
| Alcohol Classification Never drinks | 2 Participants | 4 Participants | 3 Participants | 5 Participants | 2 Participants | 4 Participants | 4 Participants | 2 Participants | 26 Participants |
| Alpha1 Acid Glycoprotein (AGP) | 48.65 milligram per deciliter (mg/dL) STANDARD_DEVIATION 4.809 | 70.30 milligram per deciliter (mg/dL) STANDARD_DEVIATION 14.936 | 114.45 milligram per deciliter (mg/dL) STANDARD_DEVIATION 25.029 | 82.77 milligram per deciliter (mg/dL) STANDARD_DEVIATION 7.104 | 55.80 milligram per deciliter (mg/dL) STANDARD_DEVIATION 17.694 | 51.18 milligram per deciliter (mg/dL) STANDARD_DEVIATION 16.328 | 41.12 milligram per deciliter (mg/dL) STANDARD_DEVIATION 20.282 | 64.97 milligram per deciliter (mg/dL) STANDARD_DEVIATION 12.065 | 66.15 milligram per deciliter (mg/dL) STANDARD_DEVIATION 26.757 |
| Body Mass Index | 22.12 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.289 | 24.88 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.082 | 22.22 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.588 | 23.62 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.242 | 24.03 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.935 | 25.33 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.389 | 26.03 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.581 | 23.42 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.807 | 23.96 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.303 |
| Caffeine Classification No | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 4 Participants | 1 Participants | 10 Participants |
| Caffeine Classification Yes | 6 Participants | 5 Participants | 6 Participants | 5 Participants | 6 Participants | 3 Participants | 2 Participants | 5 Participants | 38 Participants |
| Estimated Glomerular Filtration Rate (eGFR) | 80.7 mL/min/1.73 m^2 STANDARD_DEVIATION 17.7 | 54.8 mL/min/1.73 m^2 STANDARD_DEVIATION 9.5 | 16.3 mL/min/1.73 m^2 STANDARD_DEVIATION 7.61 | 4.5 mL/min/1.73 m^2 STANDARD_DEVIATION 0.55 | 115.2 mL/min/1.73 m^2 STANDARD_DEVIATION 14.55 | 93.7 mL/min/1.73 m^2 STANDARD_DEVIATION 21.63 | 100.8 mL/min/1.73 m^2 STANDARD_DEVIATION 16.49 | 114.8 mL/min/1.73 m^2 STANDARD_DEVIATION 26.03 | 72.6 mL/min/1.73 m^2 STANDARD_DEVIATION 43.41 |
| Height | 163.7 centimeter (cm) STANDARD_DEVIATION 9.18 | 167.7 centimeter (cm) STANDARD_DEVIATION 5.32 | 159.0 centimeter (cm) STANDARD_DEVIATION 8.63 | 160.8 centimeter (cm) STANDARD_DEVIATION 5.56 | 161.2 centimeter (cm) STANDARD_DEVIATION 5.64 | 160.0 centimeter (cm) STANDARD_DEVIATION 10.2 | 161.5 centimeter (cm) STANDARD_DEVIATION 11.4 | 157.3 centimeter (cm) STANDARD_DEVIATION 10.91 | 161.4 centimeter (cm) STANDARD_DEVIATION 8.54 |
| Region of Enrollment Japan | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 48 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 14 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 3 Participants | 4 Participants | 4 Participants | 3 Participants | 34 Participants |
| Smoking Classification Current smoker | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants | 0 Participants | 10 Participants |
| Smoking Classification Ex-smoker | 1 Participants | 1 Participants | 4 Participants | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 4 Participants | 18 Participants |
| Smoking Classification Never smoked | 4 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 20 Participants |
| Weight | 59.80 kilogram (kg) STANDARD_DEVIATION 11.726 | 69.87 kilogram (kg) STANDARD_DEVIATION 5.654 | 56.48 kilogram (kg) STANDARD_DEVIATION 9.392 | 60.83 kilogram (kg) STANDARD_DEVIATION 6.982 | 62.25 kilogram (kg) STANDARD_DEVIATION 6.275 | 65.08 kilogram (kg) STANDARD_DEVIATION 11.76 | 69.73 kilogram (kg) STANDARD_DEVIATION 23.171 | 57.58 kilogram (kg) STANDARD_DEVIATION 6.328 | 62.70 kilogram (kg) STANDARD_DEVIATION 11.674 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 6 | 1 / 6 | 1 / 6 | 2 / 6 | 2 / 6 | 1 / 6 | 1 / 6 | 1 / 6 | 3 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1R: Normal Renal Function | Apparent Clearance (CL/F) for TAK-272F | 13.57 liter per hour (L/hr) | Standard Deviation 1.8565 |
| Cohort 2R: Mild Renal Impairment | Apparent Clearance (CL/F) for TAK-272F | 28.05 liter per hour (L/hr) | Standard Deviation 9.387 |
| Cohort 3R: Moderate Renal Impairment | Apparent Clearance (CL/F) for TAK-272F | 11.63 liter per hour (L/hr) | Standard Deviation 2.6246 |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | Apparent Clearance (CL/F) for TAK-272F | 5.290 liter per hour (L/hr) | Standard Deviation 2.3246 |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | Apparent Clearance (CL/F) for TAK-272F | 8.955 liter per hour (L/hr) | Standard Deviation 3.0987 |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | Apparent Clearance (CL/F) for TAK-272F | 7.535 liter per hour (L/hr) | Standard Deviation 2.143 |
| Cohort 1H: Normal Hepatic Function | Apparent Clearance (CL/F) for TAK-272F | 17.68 liter per hour (L/hr) | Standard Deviation 3.1682 |
| Cohort 2H: Mild Hepatic Impairment | Apparent Clearance (CL/F) for TAK-272F | 17.83 liter per hour (L/hr) | Standard Deviation 5.0433 |
| Cohort 3H: Moderate Hepatic Impairment | Apparent Clearance (CL/F) for TAK-272F | 13.70 liter per hour (L/hr) | Standard Deviation 5.1084 |
Primary
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
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1R: Normal Renal Function | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I | TAK-272F | 2971 ng*hr/mL | Standard Deviation 393.33 |
| Cohort 1R: Normal Renal Function | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I | M-I | 62.32 ng*hr/mL | Standard Deviation 32.579 |
| Cohort 2R: Mild Renal Impairment | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I | TAK-272F | 1527 ng*hr/mL | Standard Deviation 953.59 |
| Cohort 2R: Mild Renal Impairment | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I | M-I | 36.87 ng*hr/mL | Standard Deviation 15.778 |
| Cohort 3R: Moderate Renal Impairment | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I | TAK-272F | 3519 ng*hr/mL | Standard Deviation 812.1 |
| Cohort 3R: Moderate Renal Impairment | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I | M-I | 60.47 ng*hr/mL | Standard Deviation 21.246 |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I | TAK-272F | 8106 ng*hr/mL | Standard Deviation 3004 |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I | M-I | 162.0 ng*hr/mL | Standard Deviation 99.759 |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I | TAK-272F | 4647 ng*hr/mL | Standard Deviation 1101.8 |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I | M-I | 129.6 ng*hr/mL | Standard Deviation 23.022 |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I | M-I | 198.8 ng*hr/mL | Standard Deviation 95.11 |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I | TAK-272F | 5471 ng*hr/mL | Standard Deviation 1342.1 |
| Cohort 1H: Normal Hepatic Function | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I | M-I | 38.84 ng*hr/mL | Standard Deviation 15.615 |
| Cohort 1H: Normal Hepatic Function | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I | TAK-272F | 2289 ng*hr/mL | Standard Deviation 368.39 |
| Cohort 2H: Mild Hepatic Impairment | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I | TAK-272F | 2326 ng*hr/mL | Standard Deviation 746.4 |
| Cohort 2H: Mild Hepatic Impairment | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I | M-I | 50.52 ng*hr/mL | Standard Deviation 16.916 |
| Cohort 3H: Moderate Hepatic Impairment | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I | TAK-272F | 3126 ng*hr/mL | Standard Deviation 1575.2 |
| Cohort 3H: Moderate Hepatic Impairment | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F and Its Metabolite M-I | M-I | 74.82 ng*hr/mL | Standard Deviation 31.47 |
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 2R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [35.45, 74.49]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 3R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [81.7, 171.68]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 4R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [188.21, 395.5]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 5R-Part 2) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [127.02, 266.91]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 2H) and the reference group (Cohort 1H) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [69.04, 149.64]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 3H) and the reference group (Cohort 1H) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [92.78, 201.09]
Comparison: M-I: LS mean cohort ratios for the test groups (Cohort 2R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [33.99, 102.99]
Comparison: M-I: LS mean cohort ratios for the test groups (Cohort 3R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [55.75, 168.9]
Comparison: M-I: LS mean cohort ratios for the test groups (Cohort 4R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [149.39, 452.6]
Comparison: M-I: LS mean cohort ratios for the test groups (Cohort 5R-Part 2) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [183.31, 555.34]
Comparison: M-I: LS mean cohort ratios for the test groups (Cohort 2H) and the reference group (Cohort 1H) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [81.66, 207.18]
Comparison: M-I: LS mean cohort ratios for the test groups (Cohort 3H) and the reference group (Cohort 1H) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [120.94, 306.83]
Primary
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
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1R: Normal Renal Function | 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 | TAK-272F | 2951 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 391.7 |
| Cohort 1R: Normal Renal Function | 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 | M-I | 50.66 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 27.097 |
| Cohort 2R: Mild Renal Impairment | 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 | TAK-272F | 1507 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 952.72 |
| Cohort 2R: Mild Renal Impairment | 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 | M-I | 31.58 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 13.765 |
| Cohort 3R: Moderate Renal Impairment | 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 | TAK-272F | 3481 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 797.67 |
| Cohort 3R: Moderate Renal Impairment | 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 | M-I | 47.22 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 18.319 |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | 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 | TAK-272F | 8053 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 2964.7 |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | 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 | M-I | 138.9 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 89.619 |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | 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 | TAK-272F | 4579 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 1091.2 |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | 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 | M-I | 104.3 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 20.684 |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | 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 | M-I | 132.3 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 40.166 |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | 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 | TAK-272F | 5409 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 1343 |
| Cohort 1H: Normal Hepatic Function | 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 | M-I | 33.95 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 13.432 |
| Cohort 1H: Normal Hepatic Function | 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 | TAK-272F | 2269 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 366.43 |
| Cohort 2H: Mild Hepatic Impairment | 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 | TAK-272F | 2307 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 750.08 |
| Cohort 2H: Mild Hepatic Impairment | 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 | M-I | 38.18 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 14.86 |
| Cohort 3H: Moderate Hepatic Impairment | 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 | TAK-272F | 3085 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 1551.3 |
| Cohort 3H: Moderate Hepatic Impairment | 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 | M-I | 60.01 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 27.427 |
Comparison: TAK-272F: Least square mean (LS) mean cohort ratios for the test groups (Cohort 2R) and the reference group (Cohort 1R) with their 95 percent (%) confidence intervals (CI) were calculated using an analysis of variance (ANOVA) model for natural log-transformed data.95% CI: [35.22, 74.08]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 3R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [81.32, 171.07]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 4R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [188.14, 395.76]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 5R-Part 2) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [126.36, 265.81]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 2H) and the reference group (Cohort 1H) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [68.95, 149.9]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 3H) and the reference group (Cohort 1H) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [92.23, 200.5]
Comparison: M-I: LS mean cohort ratios for the test groups (Cohort 2R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [36.17, 107.45]
Comparison: M-I: LS mean cohort ratios for the test groups (Cohort 3R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [54.08, 160.64]
Comparison: M-I: LS mean cohort ratios for the test groups (Cohort 4R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [159.1, 472.63]
Comparison: M-I: LS mean cohort ratios for the test groups (Cohort 5R-Part 2) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [151.5, 450.05]
Comparison: M-I: LS mean cohort ratios for the test groups (Cohort 2H) and the reference group (Cohort 1H) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [69.34, 182.41]
Comparison: M-I: LS mean cohort ratios for the test groups (Cohort 3H) and the reference group (Cohort 1H) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [108.97, 286.67]
Primary
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.
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1R: Normal Renal Function | AUClast,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration for TAK-272F | 138.7 ng*hr/mL | Standard Deviation 72.422 |
| Cohort 2R: Mild Renal Impairment | AUClast,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration for TAK-272F | 83.51 ng*hr/mL | Standard Deviation 40.288 |
| Cohort 3R: Moderate Renal Impairment | AUClast,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration for TAK-272F | 135.0 ng*hr/mL | Standard Deviation 16.105 |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | AUClast,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration for TAK-272F | 154.7 ng*hr/mL | Standard Deviation 55.009 |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | AUClast,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration for TAK-272F | 162.9 ng*hr/mL | Standard Deviation 40.127 |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | AUClast,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration for TAK-272F | 192.4 ng*hr/mL | Standard Deviation 55.731 |
| Cohort 1H: Normal Hepatic Function | AUClast,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration for TAK-272F | 107.7 ng*hr/mL | Standard Deviation 17.583 |
| Cohort 2H: Mild Hepatic Impairment | AUClast,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration for TAK-272F | 145.5 ng*hr/mL | Standard Deviation 82.297 |
| Cohort 3H: Moderate Hepatic Impairment | AUClast,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration for TAK-272F | 348.5 ng*hr/mL | Standard Deviation 102.16 |
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 2R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [40.05, 90.56]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 3R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [64.77, 146.46]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 4R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [74.21, 167.82]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 5R-Part 2) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [92.29, 208.7]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 2H) and the reference group (Cohort 1H) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [87.91, 207.87]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 3H) and the reference group (Cohort 1H) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [210.54, 497.85]
Primary
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.
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1R: Normal Renal Function | AUC∞,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F | 139.3 ng*hr/mL | Standard Deviation 73.07 |
| Cohort 2R: Mild Renal Impairment | AUC∞,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F | 84.51 ng*hr/mL | Standard Deviation 40.355 |
| Cohort 3R: Moderate Renal Impairment | AUC∞,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F | 136.5 ng*hr/mL | Standard Deviation 16.537 |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | AUC∞,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F | 155.5 ng*hr/mL | Standard Deviation 56.099 |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | AUC∞,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F | 165.1 ng*hr/mL | Standard Deviation 39.885 |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | AUC∞,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F | 194.6 ng*hr/mL | Standard Deviation 55.238 |
| Cohort 1H: Normal Hepatic Function | AUC∞,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F | 108.5 ng*hr/mL | Standard Deviation 17.885 |
| Cohort 2H: Mild Hepatic Impairment | AUC∞,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F | 146.5 ng*hr/mL | Standard Deviation 82.8 |
| Cohort 3H: Moderate Hepatic Impairment | AUC∞,u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for TAK-272F | 352.9 ng*hr/mL | Standard Deviation 103.09 |
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 2R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [40.35, 91.27]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 3R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [65.17, 147.41]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 4R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [74.25, 167.96]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 5R-Part 2) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [92.88, 210.11]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 2H) and the reference group (Cohort 1H) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [87.75, 207.92]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 3H) and the reference group (Cohort 1H) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [211.32, 500.7]
Primary
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.
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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1R: Normal Renal Function | CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for TAK-272F | 315.7 L/hr | Standard Deviation 152.2 |
| Cohort 2R: Mild Renal Impairment | CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for TAK-272F | 500.8 L/hr | Standard Deviation 163.96 |
| Cohort 3R: Moderate Renal Impairment | CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for TAK-272F | 294.7 L/hr | Standard Deviation 34.938 |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for TAK-272F | 271.5 L/hr | Standard Deviation 100.55 |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for TAK-272F | 247.8 L/hr | Standard Deviation 60.579 |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for TAK-272F | 210.2 L/hr | Standard Deviation 46.94 |
| Cohort 1H: Normal Hepatic Function | CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for TAK-272F | 372.8 L/hr | Standard Deviation 66.949 |
| Cohort 2H: Mild Hepatic Impairment | CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for TAK-272F | 301.8 L/hr | Standard Deviation 139.68 |
| Cohort 3H: Moderate Hepatic Impairment | CLu/F: Apparent Clearance for Unbound Drug After Extravascular Administration for TAK-272F | 117.3 L/hr | Standard Deviation 33.417 |
Primary
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
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1R: Normal Renal Function | Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I | TAK-272F | 753.5 nanogram per milliliter (ng/mL) | Standard Deviation 211.81 |
| Cohort 1R: Normal Renal Function | Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I | M-I | 20.08 nanogram per milliliter (ng/mL) | Standard Deviation 11.909 |
| Cohort 2R: Mild Renal Impairment | Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I | TAK-272F | 432.2 nanogram per milliliter (ng/mL) | Standard Deviation 248.57 |
| Cohort 2R: Mild Renal Impairment | Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I | M-I | 14.13 nanogram per milliliter (ng/mL) | Standard Deviation 7.0952 |
| Cohort 3R: Moderate Renal Impairment | Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I | TAK-272F | 580.5 nanogram per milliliter (ng/mL) | Standard Deviation 312.9 |
| Cohort 3R: Moderate Renal Impairment | Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I | M-I | 11.05 nanogram per milliliter (ng/mL) | Standard Deviation 7.9919 |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I | TAK-272F | 1555 nanogram per milliliter (ng/mL) | Standard Deviation 303.45 |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I | M-I | 25.30 nanogram per milliliter (ng/mL) | Standard Deviation 13.442 |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I | TAK-272F | 1061 nanogram per milliliter (ng/mL) | Standard Deviation 222.54 |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I | M-I | 19.86 nanogram per milliliter (ng/mL) | Standard Deviation 5.6056 |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I | M-I | 20.87 nanogram per milliliter (ng/mL) | Standard Deviation 3.5431 |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I | TAK-272F | 1078 nanogram per milliliter (ng/mL) | Standard Deviation 417.38 |
| Cohort 1H: Normal Hepatic Function | Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I | M-I | 12.45 nanogram per milliliter (ng/mL) | Standard Deviation 8.8158 |
| Cohort 1H: Normal Hepatic Function | Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I | TAK-272F | 522.8 nanogram per milliliter (ng/mL) | Standard Deviation 111.65 |
| Cohort 2H: Mild Hepatic Impairment | Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I | TAK-272F | 446.0 nanogram per milliliter (ng/mL) | Standard Deviation 198.78 |
| Cohort 2H: Mild Hepatic Impairment | Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I | M-I | 11.45 nanogram per milliliter (ng/mL) | Standard Deviation 6.2582 |
| Cohort 3H: Moderate Hepatic Impairment | Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I | TAK-272F | 688.1 nanogram per milliliter (ng/mL) | Standard Deviation 339.69 |
| Cohort 3H: Moderate Hepatic Impairment | Cmax: Maximum Observed Plasma Concentration for TAK-272F and Its Metabolite M-I | M-I | 17.34 nanogram per milliliter (ng/mL) | Standard Deviation 6.6026 |
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 2H) and the reference group (Cohort 1H) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [51.03, 142.61]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 2R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [37.76, 87.14]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 3R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [50.72, 117.03]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 4R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [135.88, 313.54]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 5R-Part 2) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [94.21, 217.39]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 3H) and the reference group (Cohort 1H) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [78.74, 220.04]
Comparison: M-I: LS mean cohort ratios for the test groups (Cohort 2R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [40.42, 122.53]
Comparison: M-I: LS mean cohort ratios for the test groups (Cohort 3R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [31.61, 95.81]
Comparison: M-I: LS mean cohort ratios for the test groups (Cohort 4R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [72.35, 219.3]
Comparison: M-I: LS mean cohort ratios for the test groups (Cohort 5R-Part 2) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [59.7, 180.95]
Comparison: M-I: LS mean cohort ratios for the test groups (Cohort 2H) and the reference group (Cohort 1H) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [49.45, 171.06]
Comparison: M-I: LS mean cohort ratios for the test groups (Cohort 3H) and the reference group (Cohort 1H) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [74.91, 259.15]
Primary
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.
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1R: Normal Renal Function | Cmax,u: Maximum Unbound Plasma Concentration for TAK-272F | 35.38 ng/mL | Standard Deviation 20.053 |
| Cohort 2R: Mild Renal Impairment | Cmax,u: Maximum Unbound Plasma Concentration for TAK-272F | 23.92 ng/mL | Standard Deviation 12.222 |
| Cohort 3R: Moderate Renal Impairment | Cmax,u: Maximum Unbound Plasma Concentration for TAK-272F | 22.54 ng/mL | Standard Deviation 10.18 |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | Cmax,u: Maximum Unbound Plasma Concentration for TAK-272F | 29.88 ng/mL | Standard Deviation 5.8353 |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | Cmax,u: Maximum Unbound Plasma Concentration for TAK-272F | 37.76 ng/mL | Standard Deviation 11.566 |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | Cmax,u: Maximum Unbound Plasma Concentration for TAK-272F | 38.41 ng/mL | Standard Deviation 22.002 |
| Cohort 1H: Normal Hepatic Function | Cmax,u: Maximum Unbound Plasma Concentration for TAK-272F | 24.82 ng/mL | Standard Deviation 7.1225 |
| Cohort 2H: Mild Hepatic Impairment | Cmax,u: Maximum Unbound Plasma Concentration for TAK-272F | 28.11 ng/mL | Standard Deviation 17.659 |
| Cohort 3H: Moderate Hepatic Impairment | Cmax,u: Maximum Unbound Plasma Concentration for TAK-272F | 77.66 ng/mL | Standard Deviation 23.421 |
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 2R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [42.17, 108.39]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 3R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [39.73, 102.12]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 4R) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [52.67, 135.38]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 5R-Part 2) and the reference group (Cohort 1R) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [67.7, 174.01]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 2H) and the reference group (Cohort 1H) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [69.62, 184.24]
Comparison: TAK-272F: LS mean cohort ratios for the test groups (Cohort 3H) and the reference group (Cohort 1H) with their 95% CIs were calculated using an ANOVA model for natural log-transformed data.95% CI: [192.34, 509]
Primary
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.
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
Population: The urine PK analysis population where urinary excretion data on Day 1 was available. The urine 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 urine PK.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1R: Normal Renal Function | 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 | TAK-272F | 13.227 percentage of dose | Standard Deviation 1.3321 |
| Cohort 1R: Normal Renal Function | 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 | M-I | 0.558 percentage of dose | Standard Deviation 0.2596 |
| Cohort 2R: Mild Renal Impairment | 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 | TAK-272F | 10.710 percentage of dose | Standard Deviation 3.2216 |
| Cohort 2R: Mild Renal Impairment | 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 | M-I | 0.477 percentage of dose | Standard Deviation 0.2017 |
| Cohort 3R: Moderate Renal Impairment | 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 | TAK-272F | 12.820 percentage of dose | Standard Deviation 2.6621 |
| Cohort 3R: Moderate Renal Impairment | 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 | M-I | 0.284 percentage of dose | Standard Deviation 0.0598 |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | 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 | TAK-272F | 4.947 percentage of dose | Standard Deviation 3.3152 |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | 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 | M-I | 0.072 percentage of dose | Standard Deviation 0.0462 |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | 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 | TAK-272F | 13.980 percentage of dose | Standard Deviation 5.038 |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | 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 | M-I | 0.453 percentage of dose | Standard Deviation 0.1515 |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | 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 | TAK-272F | 15.205 percentage of dose | Standard Deviation 2.6194 |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | 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 | M-I | 0.557 percentage of dose | Standard Deviation 0.1672 |
| Cohort 1H: Normal Hepatic Function | 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 | TAK-272F | 21.222 percentage of dose | Standard Deviation 4.9429 |
| Cohort 1H: Normal Hepatic Function | 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 | M-I | 0.788 percentage of dose | Standard Deviation 0.3352 |
Primary
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.
Time frame: Day 1: Pre-dose, up to 6 hours post-dose
Population: The dialysate 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 dialysate PK.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1R: Normal Renal Function | Excretion Ratio of TAK-272F in Dialysate in Cohort 5R | 3.110 percentage of dose | Standard Deviation 0.8911 |
Primary
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.
Time frame: Baseline
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1R: Normal Renal Function | Plasma Protein Binding Rate of TAK-272F in Cohorts 1R, 2R, 3R, 4R, 5R, 1H, 2H and 3H | 5.298 % of unbound fraction of TAK-272F | Standard Deviation 3.1279 |
| Cohort 2R: Mild Renal Impairment | Plasma Protein Binding Rate of TAK-272F in Cohorts 1R, 2R, 3R, 4R, 5R, 1H, 2H and 3H | 5.597 % of unbound fraction of TAK-272F | Standard Deviation 0.8826 |
| Cohort 3R: Moderate Renal Impairment | Plasma Protein Binding Rate of TAK-272F in Cohorts 1R, 2R, 3R, 4R, 5R, 1H, 2H and 3H | 3.970 % of unbound fraction of TAK-272F | Standard Deviation 0.88091 |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | Plasma Protein Binding Rate of TAK-272F in Cohorts 1R, 2R, 3R, 4R, 5R, 1H, 2H and 3H | 1.948 % of unbound fraction of TAK-272F | Standard Deviation 0.35549 |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | Plasma Protein Binding Rate of TAK-272F in Cohorts 1R, 2R, 3R, 4R, 5R, 1H, 2H and 3H | 3.598 % of unbound fraction of TAK-272F | Standard Deviation 0.59734 |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | Plasma Protein Binding Rate of TAK-272F in Cohorts 1R, 2R, 3R, 4R, 5R, 1H, 2H and 3H | 4.800 % of unbound fraction of TAK-272F | Standard Deviation 0.77095 |
| Cohort 1H: Normal Hepatic Function | Plasma Protein Binding Rate of TAK-272F in Cohorts 1R, 2R, 3R, 4R, 5R, 1H, 2H and 3H | 7.177 % of unbound fraction of TAK-272F | Standard Deviation 4.0484 |
| Cohort 2H: Mild Hepatic Impairment | Plasma Protein Binding Rate of TAK-272F in Cohorts 1R, 2R, 3R, 4R, 5R, 1H, 2H and 3H | 12.82 % of unbound fraction of TAK-272F | Standard Deviation 6.5481 |
Primary
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
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1R: Normal Renal Function | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I | TAK-272F | 0.7500 hour |
| Cohort 1R: Normal Renal Function | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I | M-I | 0.7500 hour |
| Cohort 2R: Mild Renal Impairment | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I | TAK-272F | 0.5000 hour |
| Cohort 2R: Mild Renal Impairment | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I | M-I | 0.7500 hour |
| Cohort 3R: Moderate Renal Impairment | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I | TAK-272F | 1.000 hour |
| Cohort 3R: Moderate Renal Impairment | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I | M-I | 0.7500 hour |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I | TAK-272F | 1.000 hour |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I | M-I | 1.000 hour |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I | TAK-272F | 0.7250 hour |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I | M-I | 0.7250 hour |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I | M-I | 0.9250 hour |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I | TAK-272F | 0.9815 hour |
| Cohort 1H: Normal Hepatic Function | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I | M-I | 1.000 hour |
| Cohort 1H: Normal Hepatic Function | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I | TAK-272F | 1.000 hour |
| Cohort 2H: Mild Hepatic Impairment | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I | TAK-272F | 0.5170 hour |
| Cohort 2H: Mild Hepatic Impairment | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I | M-I | 1.000 hour |
| Cohort 3H: Moderate Hepatic Impairment | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I | TAK-272F | 0.5000 hour |
| Cohort 3H: Moderate Hepatic Impairment | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-272F and Its Metabolite M-I | M-I | 0.5000 hour |
Secondary
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE)
Time frame: Baseline up to Day 8 of each Cohort
Population: The safety analysis set included all participants who were treated with at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1R: Normal Renal Function | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 1 participants |
| Cohort 2R: Mild Renal Impairment | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 1 participants |
| Cohort 3R: Moderate Renal Impairment | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 1 participants |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 2 participants |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 2 participants |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 1 participants |
| Cohort 1H: Normal Hepatic Function | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 1 participants |
| Cohort 2H: Mild Hepatic Impairment | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 1 participants |
| Cohort 3H: Moderate Hepatic Impairment | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 3 participants |
Secondary
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.
Time frame: Baseline up to Day 8 of each Cohort
Population: The safety analysis set included all participants who were treated with at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1R: Normal Renal Function | Number of Participants With TEAE Related to 12-lead Electrocardiograms (ECG) | 0 participants |
| Cohort 2R: Mild Renal Impairment | Number of Participants With TEAE Related to 12-lead Electrocardiograms (ECG) | 0 participants |
| Cohort 3R: Moderate Renal Impairment | Number of Participants With TEAE Related to 12-lead Electrocardiograms (ECG) | 0 participants |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | Number of Participants With TEAE Related to 12-lead Electrocardiograms (ECG) | 0 participants |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | Number of Participants With TEAE Related to 12-lead Electrocardiograms (ECG) | 0 participants |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | Number of Participants With TEAE Related to 12-lead Electrocardiograms (ECG) | 0 participants |
| Cohort 1H: Normal Hepatic Function | Number of Participants With TEAE Related to 12-lead Electrocardiograms (ECG) | 0 participants |
| Cohort 2H: Mild Hepatic Impairment | Number of Participants With TEAE Related to 12-lead Electrocardiograms (ECG) | 0 participants |
| Cohort 3H: Moderate Hepatic Impairment | Number of Participants With TEAE Related to 12-lead Electrocardiograms (ECG) | 0 participants |
Secondary
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.
Time frame: Baseline up to Day 8 of each Cohort
Population: The safety analysis set included all participants who were treated with at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1R: Normal Renal Function | Number of Participants With TEAE Related to Body Weight | 0 participants |
| Cohort 2R: Mild Renal Impairment | Number of Participants With TEAE Related to Body Weight | 0 participants |
| Cohort 3R: Moderate Renal Impairment | Number of Participants With TEAE Related to Body Weight | 0 participants |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | Number of Participants With TEAE Related to Body Weight | 0 participants |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | Number of Participants With TEAE Related to Body Weight | 0 participants |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | Number of Participants With TEAE Related to Body Weight | 0 participants |
| Cohort 1H: Normal Hepatic Function | Number of Participants With TEAE Related to Body Weight | 0 participants |
| Cohort 2H: Mild Hepatic Impairment | Number of Participants With TEAE Related to Body Weight | 0 participants |
| Cohort 3H: Moderate Hepatic Impairment | Number of Participants With TEAE Related to Body Weight | 0 participants |
Secondary
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.
Time frame: Baseline up to Day 8 of each Cohort
Population: The safety analysis set included all participants who were treated with at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1R: Normal Renal Function | Number of Participants With TEAE Related to Laboratory Tests | 0 participants |
| Cohort 2R: Mild Renal Impairment | Number of Participants With TEAE Related to Laboratory Tests | 1 participants |
| Cohort 3R: Moderate Renal Impairment | Number of Participants With TEAE Related to Laboratory Tests | 0 participants |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | Number of Participants With TEAE Related to Laboratory Tests | 0 participants |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | Number of Participants With TEAE Related to Laboratory Tests | 0 participants |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | Number of Participants With TEAE Related to Laboratory Tests | 0 participants |
| Cohort 1H: Normal Hepatic Function | Number of Participants With TEAE Related to Laboratory Tests | 1 participants |
| Cohort 2H: Mild Hepatic Impairment | Number of Participants With TEAE Related to Laboratory Tests | 0 participants |
| Cohort 3H: Moderate Hepatic Impairment | Number of Participants With TEAE Related to Laboratory Tests | 0 participants |
Secondary
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.
Time frame: Baseline up to Day 8 of each Cohort
Population: The safety analysis set included all participants who were treated with at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1R: Normal Renal Function | Number of Participants With TEAE Related to Vital Signs | 0 participants |
| Cohort 2R: Mild Renal Impairment | Number of Participants With TEAE Related to Vital Signs | 0 participants |
| Cohort 3R: Moderate Renal Impairment | Number of Participants With TEAE Related to Vital Signs | 0 participants |
| Cohort 4R: Severe or End-stage Renal Failure(Non-hemodialysis) | Number of Participants With TEAE Related to Vital Signs | 1 participants |
| Cohort 5R-Part 1: End-stage Renal Failure (Hemodialysis) | Number of Participants With TEAE Related to Vital Signs | 1 participants |
| Cohort 5R-Part 2: End-stage Renal Failure (Hemodialysis) | Number of Participants With TEAE Related to Vital Signs | 0 participants |
| Cohort 1H: Normal Hepatic Function | Number of Participants With TEAE Related to Vital Signs | 0 participants |
| Cohort 2H: Mild Hepatic Impairment | Number of Participants With TEAE Related to Vital Signs | 0 participants |
| Cohort 3H: Moderate Hepatic Impairment | Number of Participants With TEAE Related to Vital Signs | 1 participants |