Clinical trial NCT02252354: TAK-385 Phase I Absorption, Distribution, Metabolism, Excretion and Absolute Bioavailability Study
Official title: An Open-Label, Single-Centre,Two Part Phase I Mass Balance Study to Assess the Absorption, Distribution, Metabolism, Excretion and Absolute Bioavailability of Orally Administered [14C]-TAK-385 in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2014-09-30
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Time to Reach the Maximum Plasma and Whole Blood Radioactivity Concentration (Cmax) for [14C]-TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 288 hours) post-dose
measure: Part 1: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
measure: Part 1: Cmax: Maximum Observed Plasma and Whole Blood Radioactivity Concentration for [14C]-TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 288 hours) post-dose
measure: Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
measure: 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
timeFrame: Day 1 pre-dose and various time-points (up to 288 hours) post-dose
measure: Part 1: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
measure: 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
timeFrame: Day 1 pre-dose and various time-points (up to 288 hours) post-dose
measure: Part 1: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
measure: Part 1: Terminal Phase Elimination Half-Life (t1/2z) in Plasma and Whole Blood Radioactivity for [14C]-TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 288 hours) post-dose
measure: Part 1: Terminal Phase Elimination Half-Life (t1/2z) in Plasma for TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
measure: Part 1: Overall Cumulative Percent Recovery of Total Dosed Radioactivity in Urine and Feces
timeFrame: Day 1 pre-dose and various time-points (up to Day 288) post-dose
measure: Part 2: Tmax : Time to Reach the Maximum Plasma Radioactivity Concentration (Cmax) for [14C]-TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
measure: Part 2: Tmax : Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
measure: Part 2: Cmax: Maximum Observed Plasma Radioactivity Concentration for [14C]-TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 168hours) post-dose
measure: Part 2: Cmax: Maximum Observed Plasma Radioactivity Concentration for TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
measure: Part 2: AUC(0-inf): Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Infinity for [14C]-TAK-385
timeFrame: Day 1 pre-dose and various sampling time-points (up to 168 hours) post-dose
measure: Part 2: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 288 hours) post-dose
measure: Part 2: AUC(0-168): Area Under the Plasma Radioactivity Concentration-Time Curve From Time 0 to 168 Hours Postdose for [14C]-TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
measure: Part 2: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
measure: Part 2: Terminal Phase Elimination Half-Life (t1/2z) in Plasma Radioactivity for [14C]-TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
measure: Part 2: Terminal Phase Elimination Half-Life (t1/2z) in Plasma for TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
measure: Part 2: Absolute Bioavailability for the Oral Tablet Formulation
timeFrame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
measure: Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percent Radioactivity
timeFrame: 0 to 191 hours post-dose
measure: Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percent Radioactivity
timeFrame: 0 to 144 hours post-dose
measure: Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percentage of Dose
timeFrame: 0 to 191 hours post-dose
measure: Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percentage of Dose
timeFrame: 0 to 144 hours post-dose
measure: Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 1 Post-dose
timeFrame: Hour 1 post-dose
measure: Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 2 Post-dose
timeFrame: Hour 2 post-dose
measure: Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 4 Post-dose
timeFrame: Hour 4 post-dose
measure: Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 8 Post-dose
timeFrame: Hour 8 post-dose
measure: Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 12 Post-dose
timeFrame: Hour 12 post-dose
measure: Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 24 Post-dose
timeFrame: Hour 24 post-dose
measure: Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 36 Post-dose
timeFrame: Hour 36 post-dose
measure: Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 48 Post-dose
timeFrame: Hour 48 post-dose
measure: Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 72 Post-dose
timeFrame: Hour 72 post-dose
Secondary outcomes:
measure: Part 1: Apparent Oral Clearance (CL/F) for TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
measure: Part 2: Apparent Oral Clearance (CL/F) for TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
measure: Part 1: Volume of Distribution (Vz/F) for TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
measure: Part 2: Volume of Distribution (Vz/F) for TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
measure: Part 2: Overall Cumulative Percent Recovery of Total Dosed Radioactivity in Urine and Feces
timeFrame: 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
measure: Part 2: Clearance (CL) for [14C]-TAK-385
timeFrame: Day 1 pre-dose and various time-points (up to 168 hours) post-dose
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References: