TAK-385 Phase I Absorption, Distribution, Metabolism, Excretion and Absolute Bioavailability Study

Takeda

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: TAK-385 Tablets; Drug: [14C]-TAK-385 Solution for Intravenous Infusion; Drug: [14C]-TAK-385 Oral Solution

Study type: Interventional

Funder types: Industry

Identifiers

NCT02252354

2014-001564-35 (EudraCT Number)

TAK-385-1009

14/WA/1087 (Registry Identifier)

U1111-1159-5663 (Registry Identifier)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 12 patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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12 participants in 2 patient groups

Part 1: [14C]-TAK-385

Experimental group

Description:

\[14C\]-TAK-385 80 mg, solution, orally, once on Day 1.

Treatment:

Drug: [14C]-TAK-385 Oral Solution

Part 2: TAK-385 + [14C]-TAK-385 IV

Experimental group

Description:

TAK-385 80 mg, tablets, orally, and \[14C\]-TAK-385 80 μg, infusion, intravenous once on Day 1.

Treatment:

Drug: [14C]-TAK-385 Solution for Intravenous Infusion

Drug: TAK-385 Tablets