Healthy Volunteers
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this 2 part study is to look at how TAK-385 is taken up, broken down and removed from the body when given as a radiolabelled oral solution (by mouth) or as an oral tablet (by mouth) followed by a radiolabelled intravenous (IV) infusion (into the arm vein).
Detailed description
The study will consist of 2 parts involving up to 12 healthy male participants. In Part 1, up to 6 participants will receive a single 80 mg dose of \[14C\]-TAK-385 administered as an oral solution. In Part 2, up to 6 participants will receive a single oral 80 mg dose of TAK-385 administered as two 40 mg tablets and an 80 μg intravenous (into a vein) dose of \[14C\]-TAK-385 (containing not more than 37.0kBq \[1000 nCi\] 14C). This single centre study will take place in the United Kingdom.
Interventions
DRUG[14C]-TAK-385 Oral Solution
TAK-385 oral radiolabelled solution
DRUGTAK-385 Tablets
TAK-385 tablets 2 X 40 mg
DRUG[14C]-TAK-385 Solution for Intravenous Infusion
TAK-385 intravenous (IV) radiolabelled solution
Sponsors
Takeda
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Signs a written, informed consent form prior to the initiation of any study procedures. 2. Is a healthy male, aged 18 to 55; inclusive on Day-1. 3. Is capable of understanding and complying with protocol requirements. 4. Weighs at least 50 kg and has a body mass index (BMI) between 18.0 and 35.0 kg/m\^2, inclusive at Screening or Day-1. 5. In the opinion of the investigator, is in good healthy condition on the basis of a pre-study physical examination, medical history, vital signs, electrocardiogram, and the results of blood biochemistry, hematology, and serology test and urinalysis at Screening and Day -1. 6. 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 throughout the duration of the study and for 90 days after last dose.
Exclusion criteria
1. Has received any investigational compound within 45 days prior to Day -1. 2. Has received TAK-385 in a previous clinical study. 3. Has a resting systolic blood pressure ≤90 mmHg or ≥140 mmHg and a resting diastolic blood pressure ≤50 mmHg or ≥90 mmHg in supine position at Screening or Day-1. 4. QTc (Fridericia's correction) is \>450 msec at Screening or at Day -1 as read on the printout of the ECG produced by the electrocardiogram (ECG) equipment and evaluated by the investigator 5. Has active liver disease or jaundice, or with alanine aminotransferase (ALT),aspartate aminotransferase (AST), or bilirubin (total bilirubin) \>1.5 times the upper limit of normal (ULN) in the clinical laboratory tests at VISIT 1 and 2. The participant has positive test results for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV) or known history of human immunodeficiency virus (HIV) at Screening. 6. Has a resting pulse and heart rate (as read on ECG) \<45 beats per minute (bpm) or \>100 bpm at Screening or Day -1. 7. Has had an acute, clinically significant illness within 30 days prior to Day -1. 8. Has a history or clinical manifestations of significant metabolic (including diabetes mellitus, hypercholesterolemia, or dyslipidemia), hematologic, pulmonary, cardiovascular,gastrointestinal, neurological, rheumatologic, skin and subcutaneous tissue disorders,infectious, hepatic, renal, urologic, immunologic, psychiatric or mood disorders (including any past history of suicide attempt), or history of lactose intolerance. 9. Has a family history of bleeding disorders. 10. Has current or recent (within 6 months) history of gastrointestinal disease that would be expected to influence the absorption of drugs (ie, history of malabsorption,esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent heartburn, or any surgical intervention). 11. Has irregular defecation patterns (less than one defecation per two days or excessive diarrhea) and/or has a history of changes in bowel habits with daily routine or environment changes. 12. Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 millisievert (mSv) in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 1999, shall participate in the study 13. Has a history of abdominal surgery (except laparoscopic cholecystectomy or uncomplicated appendectomy), thoracic or nonperipheral vascular surgery within 6 months prior to Day - 1. 14. Has a history of cancer, other than basal cell or Stage 1 squamous cell carcinoma of the skin that has not been in remission for at least 5 years prior to Day 1. 15. Has significant cardiovascular disease including, but not limited to, a history of myocardial infarction, coronary angioplasty or bypass graft, unstable angina pectoris, transient ischemic attacks, clinically significant abnormal ECGs, New York Heart Association (NYHA) Functional Classification III or IV, or documented cerebrovascular accident within 6 months prior to Day -1. 16. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within 1 year prior to the Screening Visit. 17. Has used any tobacco (ie, nicotine) products (including but not limited to cigarettes, pipe, cigar, chewing tobacco, nicotine patch, or nicotine gum) within 6 months prior to Day -1 or is unwilling to abstain from these products for the duration of the study or has a positive carbon monoxide test result at Screening or Day -1. 18. Has taken any medications, supplements or food products as described in the Excluded Medications section. A subject has a positive carbon monoxide test result on Day-1. 19. Has poor peripheral venous access. 20. Is unwilling or unable to comply with the protocol or scheduled appointments 21. Is unable to understand verbal and/or written English. 22. Is a study site employee, or is an immediate family member (ie, spouse, parent, child, and sibling) of a study site employee, involved in conduct of this study. 23. Has received or donated more than 400 mL of blood or blood products within the 45 days preceding the beginning of the study or plans to donate blood during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 72 Post-dose | Hour 72 post-dose | Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered. |
| Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 4 Post-dose | Hour 4 post-dose | Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered. |
| Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 8 Post-dose | Hour 8 post-dose | Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered. |
| Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 12 Post-dose | Hour 12 post-dose | Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered. |
| Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 24 Post-dose | Hour 24 post-dose | Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered. |
| Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 36 Post-dose | Hour 36 post-dose | Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered. |
| Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 48 Post-dose | Hour 48 post-dose | Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered. |
| Part 1: Time to Reach the Maximum Plasma and Whole Blood Radioactivity Concentration (Cmax) for [14C]-TAK-385 | Day 1 pre-dose and various time-points (up to 288 hours) post-dose | Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. Radioactivity corresponds to no more than (NMT) 4.7 millibecquerel (MBq) (127 microcurie \[mCi\]). Cmax was calculated as disintegration per minute per mL (DPM/mL). Total \[14C\]-TAK-385 determination of plasma and whole blood samples was determined by accelerator mass spectrometry (AMS) method. |
| Part 1: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-385 | Day 1 pre-dose and various time-points (up to 168 hours) post-dose | Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. Plasma concentrations of TAK-385 were measured by high-performance liquid chromatography with tandem mass spectrometry method (LC-MS/MS). Correction of the LC-MS/MS derived concentrations were based upon the specific activity of the administered radiolabelled drug product (\[14C\]-TAK-385). |
| Part 1: Cmax: Maximum Observed Plasma and Whole Blood Radioactivity Concentration for [14C]-TAK-385 | Day 1 pre-dose and various time-points (up to 288 hours) post-dose | Maximum observed concentration (Cmax) is the peak concentration of a drug after administration, obtained directly from the concentration-time curve. Radioactivity corresponds to NMT 4.7 MBq (127 mCi). Cmax was measured in nanogram equivalent per milliliter (ng eq/mL) and was calculated as disintegration per minute per mL (DPM/mL). Total \[14C\]-TAK-385 determination of plasma and whole blood samples was determined by AMS method. |
| Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-385 | Day 1 pre-dose and various time-points (up to 168 hours) post-dose | Maximum observed concentration (Cmax) is the peak concentration of a drug after administration, obtained directly from the concentration-time curve. Plasma concentrations of TAK-385 were measured by high-performance liquid chromatography with tandem mass spectrometry method (LC-MS/MS). Correction of the LC-MS/MS derived concentrations were based upon the specific activity of the administered radiolabelled drug product (\[14C\]-TAK-385). |
| Part 1: AUC(0-inf): Area Under the Plasma and Whole Blood Radioactivity Concentration-time Curve From Time 0 to Infinity for [14C]-TAK-385 | Day 1 pre-dose and various time-points (up to 288 hours) post-dose | AUC(0-inf) is measure of area under the curve from time 0 to infinity. Radioactivity corresponds to NMT 4.7 MBq (127 mCi). AUC(0-inf) was measured in nanogram equivalent\*hour per milliliter (ng eq\*hr/mL) and was calculated as disintegration per minute per mL (DPM/mL). Total \[14C\]-TAK-385 determination of plasma and whole blood samples was determined by AMS method. |
| Part 1: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-385 | Day 1 pre-dose and various time-points (up to 168 hours) post-dose | AUC(0-inf) is area under the concentration-time curve from time 0 to infinity. Plasma concentrations of TAK-385 were measured by high-performance liquid chromatography with tandem mass spectrometry method (LC-MS/MS). Correction of the LC-MS/MS derived concentrations were based upon the specific activity of the administered radiolabelled drug product (\[14C\]-TAK-385) . |
| Part 1: AUC(0-168): Area Under the Plasma and Whole Blood Radioactivity Concentration-Time Curve From Time 0 to 168 Hours Postdose for [14C]-TAK-385 | Day 1 pre-dose and various time-points (up to 288 hours) post-dose | AUC(0-168) is measure of area under the curve over the dosing interval (tau),where tau is the length of the dosing interval: 168 hours in this study (AUC(0-168\]). Radioactivity corresponds to NMT 4.7 MBq (127 mCi). It was calculated as disintegration per minute per mL (DPM/mL). Total \[14C\]-TAK-385 determination of plasma and whole blood samples was determined by AMS method. |
| Part 1: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for TAK-385 | Day 1 pre-dose and various time-points (up to 168 hours) post-dose | AUC(0-168) is measure of area under the curve over the dosing interval (tau) (AUC(0-tau\]), where tau is the length of the dosing interval -168 hours in this study). Plasma concentrations of TAK-385 were measured by high-performance liquid chromatography with tandem mass spectrometry method (LC-MS/MS). Correction of the LC-MS/MS derived concentrations were based upon the specific activity of the administered radiolabelled drug product (\[14C\]-TAK-385). |
| Part 1: Terminal Phase Elimination Half-Life (t1/2z) in Plasma and Whole Blood Radioactivity for [14C]-TAK-385 | Day 1 pre-dose and various time-points (up to 288 hours) post-dose | Terminal phase elimination half-life (t1/2z) is the time required for half of the drug to be eliminated from the blood. Radioactivity corresponds to NMT 4.7 MBq (127 mCi). It was calculated as disintegration per minute per mL (DPM/mL). Total \[14C\]-TAK-385 determination of plasma and whole blood samples was determined by AMS method. |
| Part 1: Terminal Phase Elimination Half-Life (t1/2z) in Plasma for TAK-385 | Day 1 pre-dose and various time-points (up to 168 hours) post-dose | Terminal phase elimination half-life (t1/2z) is the time required for half of the drug to be eliminated from the blood. Plasma concentrations of TAK-385 were measured by high-performance liquid chromatography with tandem mass spectrometry method (LC-MS/MS). Correction of the LC-MS/MS derived concentrations were based upon the specific activity of the administered radiolabelled drug product (\[14C\]-TAK-385). |
| Part 1: Overall Cumulative Percent Recovery of Total Dosed Radioactivity in Urine and Feces | Day 1 pre-dose and various time-points (up to Day 288) post-dose | Overall cumulative percent of radioactive dose recovered in urine and feces is the total radioactivity excreted in urine and feces divided by the amount of total radioactivity dosed for each participant. Total \[14-C\] determination of urine and feces samples were determined by Liquid Scintillation Counting (LSC). |
| Part 2: Tmax : Time to Reach the Maximum Plasma Radioactivity Concentration (Cmax) for [14C]-TAK-385 | Day 1 pre-dose and various time-points (up to 168 hours) post-dose | Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. Radioactivity corresponds to NMT 37.0 kilobecquerel (kBq) (1000 nanocurie \[nCi\]). Total radioactivity and \[14C\]-TAK-385 determination of plasma samples was determined by AMS. |
| Part 2: Tmax : Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-385 | Day 1 pre-dose and various time-points (up to 168 hours) post-dose | Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. |
| Part 2: Cmax: Maximum Observed Plasma Radioactivity Concentration for [14C]-TAK-385 | Day 1 pre-dose and various time-points (up to 168hours) post-dose | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Radioactivity corresponds to NMT 37.0 kBq (1000 nCi).Total radioactivity and \[14C\]-TAK-385 determination of plasma samples was determined by AMS. |
| Part 2: Cmax: Maximum Observed Plasma Radioactivity Concentration for TAK-385 | Day 1 pre-dose and various time-points (up to 168 hours) post-dose | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. |
| Part 2: AUC(0-inf): Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Infinity for [14C]-TAK-385 | Day 1 pre-dose and various sampling time-points (up to 168 hours) post-dose | AUC(0-inf) is measure of area under the curve from time 0 to Infinity. Radioactivity corresponds to NMT 37.0 kBq (1000 nCi).AUC(0-inf) was corrected according to Hamilton Pool result.Total radioactivity and \[14C\]-TAK-385 determination of plasma samples was determined by AMS. |
| Part 2: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-385 | Day 1 pre-dose and various time-points (up to 288 hours) post-dose | AUC(0-inf) is measure of area under the curve from time 0 to Infinity. |
| Part 2: AUC(0-168): Area Under the Plasma Radioactivity Concentration-Time Curve From Time 0 to 168 Hours Postdose for [14C]-TAK-385 | Day 1 pre-dose and various time-points (up to 168 hours) post-dose | AUC(0-168) is measure of area under the curve over the dosing interval (tau), where tau is the length of the dosing interval :168 hours in this study (AUC(0-tau\]). AUC(0-168) was corrected according to Hamilton Pool result.Radioactivity corresponds to NMT 37.0 kBq (1000 nCi).Total radioactivity and \[14C\]-TAK-385 determination of plasma samples was determined by AMS. |
| Part 2: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for TAK-385 | Day 1 pre-dose and various time-points (up to 168 hours) post-dose | AUC(0-168) is measure of area under the curve over the dosing interval (tau),where tau is the length of the dosing interval: 168 hours in this study (AUC(0-tau\]). AUC was corrected using the Hamilton Pool Data to get an AUC for TAK-385. |
| Part 2: Terminal Phase Elimination Half-Life (t1/2z) in Plasma Radioactivity for [14C]-TAK-385 | Day 1 pre-dose and various time-points (up to 168 hours) post-dose | Terminal phase elimination half-life (t1/2z) is the time required for half of the drug to be eliminated from the blood. Radioactivity corresponds to NMT 37.0 kBq (1000 nCi).Total radioactivity and \[14C\]-TAK-385 determination of plasma samples was determined by AMS. |
| Part 2: Terminal Phase Elimination Half-Life (t1/2z) in Plasma for TAK-385 | Day 1 pre-dose and various time-points (up to 168 hours) post-dose | Terminal phase elimination half-life (t1/2z) is the time required for half of the drug to be eliminated from the blood. |
| Part 2: Absolute Bioavailability for the Oral Tablet Formulation | Day 1 pre-dose and various time-points (up to 168 hours) post-dose | Absolute bioavailability, defined as the fraction or percentage of the unchanged, orally administered dose that is systemically available, relative to the total dose administered intravenously. AUC was corrected using the Hamilton Pool Data to get an AUC for TAK-385 |
| Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percent Radioactivity | 0 to 191 hours post-dose | Amount of total \[14\]C, TAK-385, metabolite A, B, and C, and others excreted from feces, calculated as percentage of recovered radioactivity, are reported. Others were calculated by subtraction of the sum of the values for TAK-385, Metabolite-A, Metabolite-B, and Metabolite-C from the value of the total radioactivity (total \[14\]C).Radioactivity corresponds to NMT 4.7 MBq (127 mCi). |
| Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percent Radioactivity | 0 to 144 hours post-dose | Amount of total \[14\]C, TAK-385, metabolite A, B, and C, and others excreted from urine, calculated as percentage of recovered radioactivity, are reported. Others were calculated by subtraction of the sum of the values for TAK-385, Metabolite-A, Metabolite-B, and Metabolite-C from the value of the total radioactivity (total \[14\]C).Radioactivity corresponds to NMT 4.7 MBq (127 mCi). |
| Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percentage of Dose | 0 to 191 hours post-dose | Amount of total \[14\]C, TAK-385, metabolite A, B, and C, and others excreted from feces, calculated as percentage of dose. Others were calculated by subtraction of the sum of the values for TAK-385, Metabolite-A, Metabolite-B, and Metabolite-C from the value of the total \[14\]C. |
| Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percentage of Dose | 0 to 144 hours post-dose | Amount of total \[14\]C, TAK-385, metabolite A, B, and C, and others excreted from urine, calculated as percentage of dose. Others were calculated by subtraction of the sum of the values for TAK-385, Metabolite-A, Metabolite-B, and Metabolite-C from the value of the total \[14\]C. |
| Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 1 Post-dose | Hour 1 post-dose | Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered. |
| Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 2 Post-dose | Hour 2 post-dose | Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Apparent Oral Clearance (CL/F) for TAK-385 | Day 1 pre-dose and various time-points (up to 168 hours) post-dose | CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided by AUC expressed in liters/hour (L/hr).CL which was calculated by correcting the \[14C\]TAK-385 AUC, following the intravenous dose with the hamilton pool result to get a true CL (L/h). |
| Part 1: Volume of Distribution (Vz/F) for TAK-385 | Day 1 pre-dose and various time-points (up to 168 hours) post-dose | Vz/F is the distribution of a drug between plasma and the rest of the body following oral administration, calculated as CL/F divided by the terminal elimination rate constant (λz). Plasma concentrations of TAK-385 were measured by high-performance liquid chromatography with tandem mass spectrometry method (LC-MS/MS). Correction of the LC-MS/MS derived concentrations were based upon the specific activity of the administered radiolabelled drug product. |
| Part 2: Volume of Distribution (Vz/F) for TAK-385 | Day 1 pre-dose and various time-points (up to 168 hours) post-dose | Vz/F is the distribution of a drug between plasma and the rest of the body following oral administration, calculated as CL/F divided by the terminal elimination rate constant (λz). |
| Part 2: Overall Cumulative Percent Recovery of Total Dosed Radioactivity in Urine and Feces | Day 1 pre-dose and various time-points (up to 72 hours) post-dose for urine; Day 1 pre-dose and various time-points (up to 48 hours) post-dose | Overall cumulative percent of radioactive dose recovered in urine and feces is the total radioactivity excreted in urine and feces divided by the amount of total radioactivity dosed for each participant. |
| Part 2: Clearance (CL) for [14C]-TAK-385 | Day 1 pre-dose and various time-points (up to 168 hours) post-dose | CL is clearance of the drug from the plasma, calculated as the drug dose divided by AUC expressed in L/hr. CL is a quantitative measure of the rate at which a drug substance is removed from the body. Radioactivity corresponds to NMT 37.0 kBq (1000 nCi). |
| Part 1: Apparent Oral Clearance (CL/F) for TAK-385 | Day 1 pre-dose and various time-points (up to 168 hours) post-dose | CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided by AUC expressed in liters/hour (L/hr). CL which was calculated by correcting the \[14C\]TAK-385 AUC, following the intravenous dose with the hamilton pool result to get a true CL (L/h). Plasma concentrations of TAK-385 were measured by high-performance liquid chromatography with tandem mass spectrometry method (LC-MS/MS). Correction of the LC-MS/MS derived concentrations were based upon the specific activity of the administered radiolabelled drug product. |
Countries
United Kingdom
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in United Kingdom from 29 September 2014 to 27 October 2014.
Pre-assignment details
Healthy cohort of male participants were enrolled in this 2 part study, in 1 of 2 treatment groups as follows : Part 1: \[14C\]-TAK-385 80 milligram (mg); Part 2:TAK-385 80 mg + \[14C\]-TAK-385 80 microgram (mcg)
Participants by arm
| Arm | Count |
|---|---|
| Part 1: [14C]-TAK-385 \[14C\]-TAK-385 80 mg, solution, orally, single dose on Day 1. | 6 |
| Part 2: TAK-385 + [14C]-TAK-385 IV TAK-385 80 mg, tablets, orally, and \[14C\]-TAK-385 80 mcg, infusion, intravenous single dose on Day 1. | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Total | Part 1: [14C]-TAK-385 | Part 2: TAK-385 + [14C]-TAK-385 IV |
|---|---|---|---|
| Age, Customized Greater than(>)17 to less than equal to(<=)64 | 12 Participants | 6 Participants | 6 Participants |
| Alcohol Classification The participant has never drunk | 1 Participants | 1 Participants | 0 Participants |
| Alcohol Classification The participant is a current drinker | 11 Participants | 5 Participants | 6 Participants |
| Alcohol Classification The participant is an ex-drinker | 0 Participants | 0 Participants | 0 Participants |
| Caffeine Consumption No | 2 Participants | 1 Participants | 1 Participants |
| Caffeine Consumption Yes | 10 Participants | 5 Participants | 5 Participants |
| Race/Ethnicity, Customized More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 11 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 6 Participants | 6 Participants |
| Smoking Classification Current smoker | 0 Participants | 0 Participants | 0 Participants |
| Smoking Classification Ex-smoker | 4 Participants | 1 Participants | 3 Participants |
| Smoking Classification Never smoked | 8 Participants | 5 Participants | 3 Participants |
| Xanthine Consumption No | 9 Participants | 4 Participants | 5 Participants |
| Xanthine Consumption Yes | 3 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 12 Post-dose
Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered.
Time frame: Hour 12 post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 12 Post-dose | Metabolite A and B | 3.8 percentage of dose | 0.7 |
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 12 Post-dose | Metabolite-C | 1.3 percentage of dose | — |
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 12 Post-dose | TAK-385 | 45.7 percentage of dose | 0.9 |
Primary
Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 1 Post-dose
Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered.
Time frame: Hour 1 post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 1 Post-dose | Metabolite A and B | 3 percentage of dose | 0.7 |
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 1 Post-dose | Metabolite-C | 1.5 percentage of dose | — |
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 1 Post-dose | TAK-385 | 55.3 percentage of dose | 0.9 |
Primary
Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 24 Post-dose
Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered.
Time frame: Hour 24 post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 24 Post-dose | Metabolite A and B | 2.6 percentage of dose | 0.7 |
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 24 Post-dose | Metabolite-C | 2.1 percentage of dose | — |
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 24 Post-dose | TAK-385 | 53 percentage of dose | 0.9 |
Primary
Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 2 Post-dose
Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered.
Time frame: Hour 2 post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 2 Post-dose | Metabolite A and B | 2.5 percentage of dose | 0.7 |
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 2 Post-dose | Metabolite-C | 1.2 percentage of dose | — |
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 2 Post-dose | TAK-385 | 68.2 percentage of dose | 0.9 |
Primary
Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 36 Post-dose
Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered.
Time frame: Hour 36 post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 36 Post-dose | Metabolite A and B | 2.2 percentage of dose | 0.7 |
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 36 Post-dose | Metabolite-C | 2.7 percentage of dose | — |
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 36 Post-dose | TAK-385 | 52.4 percentage of dose | 0.9 |
Primary
Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 48 Post-dose
Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered.
Time frame: Hour 48 post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 48 Post-dose | Metabolite A and B | 3.2 percentage of dose | 0.7 |
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 48 Post-dose | Metabolite-C | 4.5 percentage of dose | — |
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 48 Post-dose | TAK-385 | 48 percentage of dose | 0.9 |
Primary
Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 4 Post-dose
Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered.
Time frame: Hour 4 post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 4 Post-dose | Metabolite A and B | 2.2 percentage of dose | 0.7 |
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 4 Post-dose | Metabolite-C | 0.8 percentage of dose | — |
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 4 Post-dose | TAK-385 | 58.8 percentage of dose | 0.9 |
Primary
Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 72 Post-dose
Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered.
Time frame: Hour 72 post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 72 Post-dose | Metabolite A and B | 3.0 percentage of dose | 0.7 |
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 72 Post-dose | Metabolite-C | 3.2 percentage of dose | — |
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 72 Post-dose | TAK-385 | 45.9 percentage of dose | 0.9 |
Primary
Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 8 Post-dose
Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered.
Time frame: Hour 8 post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 8 Post-dose | Metabolite A and B | 3.2 percentage of dose | 0.7 |
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 8 Post-dose | Metabolite-C | 1.2 percentage of dose | — |
| Part 1: [14C]-TAK-385 | Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 8 Post-dose | TAK-385 | 41.5 percentage of dose | 0.9 |
Primary
Part 1: AUC(0-168): Area Under the Plasma and Whole Blood Radioactivity Concentration-Time Curve From Time 0 to 168 Hours Postdose for [14C]-TAK-385
AUC(0-168) is measure of area under the curve over the dosing interval (tau),where tau is the length of the dosing interval: 168 hours in this study (AUC(0-168\]). Radioactivity corresponds to NMT 4.7 MBq (127 mCi). It was calculated as disintegration per minute per mL (DPM/mL). Total \[14C\]-TAK-385 determination of plasma and whole blood samples was determined by AMS method.
Time frame: Day 1 pre-dose and various time-points (up to 288 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: AUC(0-168): Area Under the Plasma and Whole Blood Radioactivity Concentration-Time Curve From Time 0 to 168 Hours Postdose for [14C]-TAK-385 | Whole Blood Radioactivity | 756.5 ng eq*hr/mL | Standard Deviation 229.5 |
| Part 1: [14C]-TAK-385 | Part 1: AUC(0-168): Area Under the Plasma and Whole Blood Radioactivity Concentration-Time Curve From Time 0 to 168 Hours Postdose for [14C]-TAK-385 | Plasma Radioactivity | 982.7 ng eq*hr/mL | Standard Deviation 288.7 |
Primary
Part 1: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for TAK-385
AUC(0-168) is measure of area under the curve over the dosing interval (tau) (AUC(0-tau\]), where tau is the length of the dosing interval -168 hours in this study). Plasma concentrations of TAK-385 were measured by high-performance liquid chromatography with tandem mass spectrometry method (LC-MS/MS). Correction of the LC-MS/MS derived concentrations were based upon the specific activity of the administered radiolabelled drug product (\[14C\]-TAK-385).
Time frame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for TAK-385 | 357.5 ng*hr/mL | Standard Deviation 119 |
Primary
Part 1: AUC(0-inf): Area Under the Plasma and Whole Blood Radioactivity Concentration-time Curve From Time 0 to Infinity for [14C]-TAK-385
AUC(0-inf) is measure of area under the curve from time 0 to infinity. Radioactivity corresponds to NMT 4.7 MBq (127 mCi). AUC(0-inf) was measured in nanogram equivalent\*hour per milliliter (ng eq\*hr/mL) and was calculated as disintegration per minute per mL (DPM/mL). Total \[14C\]-TAK-385 determination of plasma and whole blood samples was determined by AMS method.
Time frame: Day 1 pre-dose and various time-points (up to 288 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: AUC(0-inf): Area Under the Plasma and Whole Blood Radioactivity Concentration-time Curve From Time 0 to Infinity for [14C]-TAK-385 | Whole Blood Radioactivity | 1521.5 ng eq*hr/mL | Standard Deviation 421.2 |
| Part 1: [14C]-TAK-385 | Part 1: AUC(0-inf): Area Under the Plasma and Whole Blood Radioactivity Concentration-time Curve From Time 0 to Infinity for [14C]-TAK-385 | Plasma Radioactivity | 1771.4 ng eq*hr/mL | Standard Deviation 476.5 |
Primary
Part 1: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-385
AUC(0-inf) is area under the concentration-time curve from time 0 to infinity. Plasma concentrations of TAK-385 were measured by high-performance liquid chromatography with tandem mass spectrometry method (LC-MS/MS). Correction of the LC-MS/MS derived concentrations were based upon the specific activity of the administered radiolabelled drug product (\[14C\]-TAK-385) .
Time frame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-385 | 382.2 nanogram hour per milliliter (ng*hr/mL) | Standard Deviation 128.2 |
Primary
Part 1: Cmax: Maximum Observed Plasma and Whole Blood Radioactivity Concentration for [14C]-TAK-385
Maximum observed concentration (Cmax) is the peak concentration of a drug after administration, obtained directly from the concentration-time curve. Radioactivity corresponds to NMT 4.7 MBq (127 mCi). Cmax was measured in nanogram equivalent per milliliter (ng eq/mL) and was calculated as disintegration per minute per mL (DPM/mL). Total \[14C\]-TAK-385 determination of plasma and whole blood samples was determined by AMS method.
Time frame: Day 1 pre-dose and various time-points (up to 288 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: Cmax: Maximum Observed Plasma and Whole Blood Radioactivity Concentration for [14C]-TAK-385 | Whole Blood Radioactivity | 45.6 ng eq/mL | Standard Deviation 24.2 |
| Part 1: [14C]-TAK-385 | Part 1: Cmax: Maximum Observed Plasma and Whole Blood Radioactivity Concentration for [14C]-TAK-385 | Plasma Radioactivity | 56.1 ng eq/mL | Standard Deviation 34.2 |
Primary
Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-385
Maximum observed concentration (Cmax) is the peak concentration of a drug after administration, obtained directly from the concentration-time curve. Plasma concentrations of TAK-385 were measured by high-performance liquid chromatography with tandem mass spectrometry method (LC-MS/MS). Correction of the LC-MS/MS derived concentrations were based upon the specific activity of the administered radiolabelled drug product (\[14C\]-TAK-385).
Time frame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-385 | 44.7 nanogram per milliliter (ng/mL) | Standard Deviation 29 |
Primary
Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percentage of Dose
Amount of total \[14\]C, TAK-385, metabolite A, B, and C, and others excreted from feces, calculated as percentage of dose. Others were calculated by subtraction of the sum of the values for TAK-385, Metabolite-A, Metabolite-B, and Metabolite-C from the value of the total \[14\]C.
Time frame: 0 to 191 hours post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percentage of Dose | Total 14[C] | 80.6 percentage of dose | Standard Deviation 5.7 |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percentage of Dose | TAK-385 | 4.2 percentage of dose | Standard Deviation 2.9 |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percentage of Dose | Metabolite-A | 0.3 percentage of dose | Standard Deviation 0.3 |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percentage of Dose | Metabolite-B | NA percentage of dose | — |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percentage of Dose | Metabolite-C | 40.6 percentage of dose | Standard Deviation 4.9 |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percentage of Dose | Others | 35.6 percentage of dose | Standard Deviation 7.3 |
Primary
Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percent Radioactivity
Amount of total \[14\]C, TAK-385, metabolite A, B, and C, and others excreted from feces, calculated as percentage of recovered radioactivity, are reported. Others were calculated by subtraction of the sum of the values for TAK-385, Metabolite-A, Metabolite-B, and Metabolite-C from the value of the total radioactivity (total \[14\]C).Radioactivity corresponds to NMT 4.7 MBq (127 mCi).
Time frame: 0 to 191 hours post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percent Radioactivity | Total 14[C] | 100 percentage of recovered radioactivity | Standard Deviation 0 |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percent Radioactivity | TAK-385 | 5.1 percentage of recovered radioactivity | Standard Deviation 3.2 |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percent Radioactivity | Metabolite-A | 0.3 percentage of recovered radioactivity | Standard Deviation 0.4 |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percent Radioactivity | Metabolite-B | NA percentage of recovered radioactivity | — |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percent Radioactivity | Metabolite-C | 50.6 percentage of recovered radioactivity | Standard Deviation 7.5 |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percent Radioactivity | Others | 44.0 percentage of recovered radioactivity | Standard Deviation 8.1 |
Primary
Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percentage of Dose
Amount of total \[14\]C, TAK-385, metabolite A, B, and C, and others excreted from urine, calculated as percentage of dose. Others were calculated by subtraction of the sum of the values for TAK-385, Metabolite-A, Metabolite-B, and Metabolite-C from the value of the total \[14\]C.
Time frame: 0 to 144 hours post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percentage of Dose | Total 14[C] | 4.1 percentage of dose | Standard Deviation 0.7 |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percentage of Dose | TAK-385 | 2.2 percentage of dose | Standard Deviation 0.9 |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percentage of Dose | Metabolite-A | NA percentage of dose | — |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percentage of Dose | Metabolite-B | NA percentage of dose | — |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percentage of Dose | Metabolite-C | NA percentage of dose | — |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percentage of Dose | Others | 2.0 percentage of dose | Standard Deviation 0.9 |
Primary
Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percent Radioactivity
Amount of total \[14\]C, TAK-385, metabolite A, B, and C, and others excreted from urine, calculated as percentage of recovered radioactivity, are reported. Others were calculated by subtraction of the sum of the values for TAK-385, Metabolite-A, Metabolite-B, and Metabolite-C from the value of the total radioactivity (total \[14\]C).Radioactivity corresponds to NMT 4.7 MBq (127 mCi).
Time frame: 0 to 144 hours post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percent Radioactivity | Total 14[C] | 100 percentage of recovered radioactivity | Standard Deviation 0 |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percent Radioactivity | TAK-385 | 52.6 percentage of recovered radioactivity | Standard Deviation 19 |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percent Radioactivity | Metabolite-A | NA percentage of recovered radioactivity | — |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percent Radioactivity | Metabolite-B | NA percentage of recovered radioactivity | — |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percent Radioactivity | Metabolite-C | NA percentage of recovered radioactivity | — |
| Part 1: [14C]-TAK-385 | Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percent Radioactivity | Others | 47.4 percentage of recovered radioactivity | Standard Deviation 19 |
Primary
Part 1: Overall Cumulative Percent Recovery of Total Dosed Radioactivity in Urine and Feces
Overall cumulative percent of radioactive dose recovered in urine and feces is the total radioactivity excreted in urine and feces divided by the amount of total radioactivity dosed for each participant. Total \[14-C\] determination of urine and feces samples were determined by Liquid Scintillation Counting (LSC).
Time frame: Day 1 pre-dose and various time-points (up to Day 288) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: Overall Cumulative Percent Recovery of Total Dosed Radioactivity in Urine and Feces | Urine | 4.3 percent recovery of radioactivity | Standard Deviation 0.7 |
| Part 1: [14C]-TAK-385 | Part 1: Overall Cumulative Percent Recovery of Total Dosed Radioactivity in Urine and Feces | Feces | 82.7 percent recovery of radioactivity | Standard Deviation 6.3 |
Primary
Part 1: Terminal Phase Elimination Half-Life (t1/2z) in Plasma and Whole Blood Radioactivity for [14C]-TAK-385
Terminal phase elimination half-life (t1/2z) is the time required for half of the drug to be eliminated from the blood. Radioactivity corresponds to NMT 4.7 MBq (127 mCi). It was calculated as disintegration per minute per mL (DPM/mL). Total \[14C\]-TAK-385 determination of plasma and whole blood samples was determined by AMS method.
Time frame: Day 1 pre-dose and various time-points (up to 288 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: Terminal Phase Elimination Half-Life (t1/2z) in Plasma and Whole Blood Radioactivity for [14C]-TAK-385 | Whole Blood Radioactivity | 285.3 hours | Standard Deviation 32.9 |
| Part 1: [14C]-TAK-385 | Part 1: Terminal Phase Elimination Half-Life (t1/2z) in Plasma and Whole Blood Radioactivity for [14C]-TAK-385 | Plasma Radioactivity | 226.1 hours | Standard Deviation 22 |
Primary
Part 1: Terminal Phase Elimination Half-Life (t1/2z) in Plasma for TAK-385
Terminal phase elimination half-life (t1/2z) is the time required for half of the drug to be eliminated from the blood. Plasma concentrations of TAK-385 were measured by high-performance liquid chromatography with tandem mass spectrometry method (LC-MS/MS). Correction of the LC-MS/MS derived concentrations were based upon the specific activity of the administered radiolabelled drug product (\[14C\]-TAK-385).
Time frame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: Terminal Phase Elimination Half-Life (t1/2z) in Plasma for TAK-385 | 60.7 hours | Standard Deviation 6.6 |
Primary
Part 1: Time to Reach the Maximum Plasma and Whole Blood Radioactivity Concentration (Cmax) for [14C]-TAK-385
Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. Radioactivity corresponds to no more than (NMT) 4.7 millibecquerel (MBq) (127 microcurie \[mCi\]). Cmax was calculated as disintegration per minute per mL (DPM/mL). Total \[14C\]-TAK-385 determination of plasma and whole blood samples was determined by accelerator mass spectrometry (AMS) method.
Time frame: Day 1 pre-dose and various time-points (up to 288 hours) post-dose
Population: Pharmacokinetic (PK) set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: Time to Reach the Maximum Plasma and Whole Blood Radioactivity Concentration (Cmax) for [14C]-TAK-385 | Whole Blood Radioactivity | 2.0 hours | Full Range 1.4354 |
| Part 1: [14C]-TAK-385 | Part 1: Time to Reach the Maximum Plasma and Whole Blood Radioactivity Concentration (Cmax) for [14C]-TAK-385 | Plasma Radioactivity | 2.0 hours | Full Range 1.4354 |
Primary
Part 1: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-385
Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. Plasma concentrations of TAK-385 were measured by high-performance liquid chromatography with tandem mass spectrometry method (LC-MS/MS). Correction of the LC-MS/MS derived concentrations were based upon the specific activity of the administered radiolabelled drug product (\[14C\]-TAK-385).
Time frame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-385 | 1.2 hours | Full Range 1.4748 |
Primary
Part 2: Absolute Bioavailability for the Oral Tablet Formulation
Absolute bioavailability, defined as the fraction or percentage of the unchanged, orally administered dose that is systemically available, relative to the total dose administered intravenously. AUC was corrected using the Hamilton Pool Data to get an AUC for TAK-385
Time frame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 2: Absolute Bioavailability for the Oral Tablet Formulation | 11.6 percentage bioavailability | Standard Deviation 7.2 |
Primary
Part 2: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for TAK-385
AUC(0-168) is measure of area under the curve over the dosing interval (tau),where tau is the length of the dosing interval: 168 hours in this study (AUC(0-tau\]). AUC was corrected using the Hamilton Pool Data to get an AUC for TAK-385.
Time frame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 2: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for TAK-385 | 214.5 ng*hr/mL | Standard Deviation 106.3 |
Primary
Part 2: AUC(0-168): Area Under the Plasma Radioactivity Concentration-Time Curve From Time 0 to 168 Hours Postdose for [14C]-TAK-385
AUC(0-168) is measure of area under the curve over the dosing interval (tau), where tau is the length of the dosing interval :168 hours in this study (AUC(0-tau\]). AUC(0-168) was corrected according to Hamilton Pool result.Radioactivity corresponds to NMT 37.0 kBq (1000 nCi).Total radioactivity and \[14C\]-TAK-385 determination of plasma samples was determined by AMS.
Time frame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 2: AUC(0-168): Area Under the Plasma Radioactivity Concentration-Time Curve From Time 0 to 168 Hours Postdose for [14C]-TAK-385 | 3.2 ng eq*hr/mL | Standard Deviation 0.3 |
Primary
Part 2: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-385
AUC(0-inf) is measure of area under the curve from time 0 to Infinity.
Time frame: Day 1 pre-dose and various time-points (up to 288 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 2: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-385 | 225.2 ng*hr/mL | Standard Deviation 110.8 |
Primary
Part 2: AUC(0-inf): Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Infinity for [14C]-TAK-385
AUC(0-inf) is measure of area under the curve from time 0 to Infinity. Radioactivity corresponds to NMT 37.0 kBq (1000 nCi).AUC(0-inf) was corrected according to Hamilton Pool result.Total radioactivity and \[14C\]-TAK-385 determination of plasma samples was determined by AMS.
Time frame: Day 1 pre-dose and various sampling time-points (up to 168 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 2: AUC(0-inf): Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Infinity for [14C]-TAK-385 | 4.2 ng eq*hr/mL | Standard Deviation 0.6 |
Primary
Part 2: Cmax: Maximum Observed Plasma Radioactivity Concentration for [14C]-TAK-385
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Radioactivity corresponds to NMT 37.0 kBq (1000 nCi).Total radioactivity and \[14C\]-TAK-385 determination of plasma samples was determined by AMS.
Time frame: Day 1 pre-dose and various time-points (up to 168hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 2: Cmax: Maximum Observed Plasma Radioactivity Concentration for [14C]-TAK-385 | 2.6 ng eq/mL | Standard Deviation 0.3 |
Primary
Part 2: Cmax: Maximum Observed Plasma Radioactivity Concentration for TAK-385
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Time frame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 2: Cmax: Maximum Observed Plasma Radioactivity Concentration for TAK-385 | 24.6 ng/mL | Standard Deviation 13.2 |
Primary
Part 2: Terminal Phase Elimination Half-Life (t1/2z) in Plasma for TAK-385
Terminal phase elimination half-life (t1/2z) is the time required for half of the drug to be eliminated from the blood.
Time frame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 2: Terminal Phase Elimination Half-Life (t1/2z) in Plasma for TAK-385 | 50.6 hours | Standard Deviation 6 |
Primary
Part 2: Terminal Phase Elimination Half-Life (t1/2z) in Plasma Radioactivity for [14C]-TAK-385
Terminal phase elimination half-life (t1/2z) is the time required for half of the drug to be eliminated from the blood. Radioactivity corresponds to NMT 37.0 kBq (1000 nCi).Total radioactivity and \[14C\]-TAK-385 determination of plasma samples was determined by AMS.
Time frame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 2: Terminal Phase Elimination Half-Life (t1/2z) in Plasma Radioactivity for [14C]-TAK-385 | 110.5 hours | Standard Deviation 16.2 |
Primary
Part 2: Tmax : Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-385
Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.
Time frame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 2: Tmax : Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-385 | 2.2 hours | Full Range 2.0897 |
Primary
Part 2: Tmax : Time to Reach the Maximum Plasma Radioactivity Concentration (Cmax) for [14C]-TAK-385
Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. Radioactivity corresponds to NMT 37.0 kilobecquerel (kBq) (1000 nanocurie \[nCi\]). Total radioactivity and \[14C\]-TAK-385 determination of plasma samples was determined by AMS.
Time frame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 2: Tmax : Time to Reach the Maximum Plasma Radioactivity Concentration (Cmax) for [14C]-TAK-385 | 0.2 hours | Full Range 0.0455 |
Secondary
Part 1: Apparent Oral Clearance (CL/F) for TAK-385
CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided by AUC expressed in liters/hour (L/hr). CL which was calculated by correcting the \[14C\]TAK-385 AUC, following the intravenous dose with the hamilton pool result to get a true CL (L/h). Plasma concentrations of TAK-385 were measured by high-performance liquid chromatography with tandem mass spectrometry method (LC-MS/MS). Correction of the LC-MS/MS derived concentrations were based upon the specific activity of the administered radiolabelled drug product.
Time frame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: Apparent Oral Clearance (CL/F) for TAK-385 | 218.2 L/hr | Standard Deviation 66.7 |
Secondary
Part 1: Volume of Distribution (Vz/F) for TAK-385
Vz/F is the distribution of a drug between plasma and the rest of the body following oral administration, calculated as CL/F divided by the terminal elimination rate constant (λz). Plasma concentrations of TAK-385 were measured by high-performance liquid chromatography with tandem mass spectrometry method (LC-MS/MS). Correction of the LC-MS/MS derived concentrations were based upon the specific activity of the administered radiolabelled drug product.
Time frame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 1: Volume of Distribution (Vz/F) for TAK-385 | 18878.7 Liter (L) | Standard Deviation 5114.4 |
Secondary
Part 2: Apparent Oral Clearance (CL/F) for TAK-385
CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided by AUC expressed in liters/hour (L/hr).CL which was calculated by correcting the \[14C\]TAK-385 AUC, following the intravenous dose with the hamilton pool result to get a true CL (L/h).
Time frame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 2: Apparent Oral Clearance (CL/F) for TAK-385 | 382.9 L/hr | Standard Deviation 154.7 |
Secondary
Part 2: Clearance (CL) for [14C]-TAK-385
CL is clearance of the drug from the plasma, calculated as the drug dose divided by AUC expressed in L/hr. CL is a quantitative measure of the rate at which a drug substance is removed from the body. Radioactivity corresponds to NMT 37.0 kBq (1000 nCi).
Time frame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 2: Clearance (CL) for [14C]-TAK-385 | 29.4 L/hr | Standard Deviation 4.5 |
Secondary
Part 2: Overall Cumulative Percent Recovery of Total Dosed Radioactivity in Urine and Feces
Overall cumulative percent of radioactive dose recovered in urine and feces is the total radioactivity excreted in urine and feces divided by the amount of total radioactivity dosed for each participant.
Time frame: Day 1 pre-dose and various time-points (up to 72 hours) post-dose for urine; Day 1 pre-dose and various time-points (up to 48 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 2: Overall Cumulative Percent Recovery of Total Dosed Radioactivity in Urine and Feces | Urine | 13.3 percent recovery of radioactivity | Standard Deviation 3 |
| Part 1: [14C]-TAK-385 | Part 2: Overall Cumulative Percent Recovery of Total Dosed Radioactivity in Urine and Feces | Feces | 22.2 percent recovery of radioactivity | Standard Deviation 13.3 |
Secondary
Part 2: Volume of Distribution (Vz/F) for TAK-385
Vz/F is the distribution of a drug between plasma and the rest of the body following oral administration, calculated as CL/F divided by the terminal elimination rate constant (λz).
Time frame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
Population: PK set included all participants in the safety set with at least one measurable plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-TAK-385 | Part 2: Volume of Distribution (Vz/F) for TAK-385 | 28245.1 L | Standard Deviation 13011.8 |