Phase 1
N=12
TAK-385 Phase I Absorption, Distribution, Metabolism, Excretion and Absolute Bioavailability Study
Healthy Volunteers
Bottom Line
View on ClinicalTrials.gov: NCT02252354 ↗Enrolled (actual)
12
Serious AEs
0.0%
Results posted
Dec 2015
Primary outcome: Primary: Part 1: Time to Reach the Maximum Plasma and Whole Blood Radioactivity Concentration (Cmax) for [14C]-TAK-385 — 2.0; 2.0 hours
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- [14C]-TAK-385 Oral Solution (Drug); TAK-385 Tablets (Drug); [14C]-TAK-385 Solution for Intravenous Infusion (Drug)
- Age
- Adult · 18+ yrs
- Sex
- Male
- Sponsor
- Takeda
- Primary completion
- Oct 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Time to Reach the Maximum Plasma and Whole Blood Radioactivity Concentration (Cmax) for [14C]-TAK-385 |
2.0; 2.0 | — |
| PRIMARY Part 1: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-385 |
1.2 | — |
| PRIMARY Part 1: Cmax: Maximum Observed Plasma and Whole Blood Radioactivity Concentration for [14C]-TAK-385 |
45.6; 56.1 | — |
| PRIMARY Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-385 |
44.7 | — |
| 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 |
1521.5; 1771.4 | — |
| PRIMARY Part 1: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-385 |
382.2 | — |
| 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 |
756.5; 982.7 | — |
| PRIMARY Part 1: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for TAK-385 |
357.5 | — |
| PRIMARY Part 1: Terminal Phase Elimination Half-Life (t1/2z) in Plasma and Whole Blood Radioactivity for [14C]-TAK-385 |
285.3; 226.1 | — |
| PRIMARY Part 1: Terminal Phase Elimination Half-Life (t1/2z) in Plasma for TAK-385 |
60.7 | — |
| PRIMARY Part 1: Overall Cumulative Percent Recovery of Total Dosed Radioactivity in Urine and Feces |
4.3; 82.7 | — |
| PRIMARY Part 2: Tmax : Time to Reach the Maximum Plasma Radioactivity Concentration (Cmax) for [14C]-TAK-385 |
0.2 | — |
| PRIMARY Part 2: Tmax : Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-385 |
2.2 | — |
| PRIMARY Part 2: Cmax: Maximum Observed Plasma Radioactivity Concentration for [14C]-TAK-385 |
2.6 | — |
| PRIMARY Part 2: Cmax: Maximum Observed Plasma Radioactivity Concentration for TAK-385 |
24.6 | — |
| PRIMARY Part 2: AUC(0-inf): Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Infinity for [14C]-TAK-385 |
4.2 | — |
| PRIMARY Part 2: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-385 |
225.2 | — |
| 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 |
3.2 | — |
| PRIMARY Part 2: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for TAK-385 |
214.5 | — |
| PRIMARY Part 2: Terminal Phase Elimination Half-Life (t1/2z) in Plasma Radioactivity for [14C]-TAK-385 |
110.5 | — |
| PRIMARY Part 2: Terminal Phase Elimination Half-Life (t1/2z) in Plasma for TAK-385 |
50.6 | — |
| PRIMARY Part 2: Absolute Bioavailability for the Oral Tablet Formulation |
11.6 | — |
| PRIMARY Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percent Radioactivity |
100; 5.1; 0.3; NA; 50.6; 44.0 | — |
| PRIMARY Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percent Radioactivity |
100; 52.6; NA; NA; NA; 47.4 | — |
| PRIMARY Part 1: Excretion of TAK-385 and Its Metabolites in Human Feces as Percentage of Dose |
80.6; 4.2; 0.3; NA; 40.6; 35.6 | — |
| PRIMARY Part 1: Excretion of TAK-385 and Its Metabolites in Human Urine as Percentage of Dose |
4.1; 2.2; NA; NA; NA; 2.0 | — |
| PRIMARY Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 1 Post-dose |
3; 1.5; 55.3 | — |
| PRIMARY Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 2 Post-dose |
2.5; 1.2; 68.2 | — |
| PRIMARY Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 4 Post-dose |
2.2; 0.8; 58.8 | — |
| PRIMARY Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 8 Post-dose |
3.2; 1.2; 41.5 | — |
| PRIMARY Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 12 Post-dose |
3.8; 1.3; 45.7 | — |
| PRIMARY Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 24 Post-dose |
2.6; 2.1; 53 | — |
| PRIMARY Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 36 Post-dose |
2.2; 2.7; 52.4 | — |
| PRIMARY Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 48 Post-dose |
3.2; 4.5; 48 | — |
| PRIMARY Part 1: [14]C Distribution Profile From TAK-385 and Metabolites A, B, and C in Plasma Pools at Hour 72 Post-dose |
3.0; 3.2; 45.9 | — |
| SECONDARY Part 1: Apparent Oral Clearance (CL/F) for TAK-385 |
218.2 | — |
| SECONDARY Part 2: Apparent Oral Clearance (CL/F) for TAK-385 |
382.9 | — |
| SECONDARY Part 1: Volume of Distribution (Vz/F) for TAK-385 |
18878.7 | — |
| SECONDARY Part 2: Volume of Distribution (Vz/F) for TAK-385 |
28245.1 | — |
| SECONDARY Part 2: Overall Cumulative Percent Recovery of Total Dosed Radioactivity in Urine and Feces |
13.3; 22.2 | — |
| SECONDARY Part 2: Clearance (CL) for [14C]-TAK-385 |
29.4 | — |
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).
Eligibility Criteria
Inclusion Criteria
- Signs a written, informed consent form prior to the initiation of any study procedures.
- Is a healthy male, aged 18 to 55; inclusive on Day-1.
- Is capable of understanding and complying with protocol requirements.
- 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.
- 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.
- 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
- Has received any investigational compound within 45 days prior to Day -1.
- Has received TAK-385 in a previous clinical study.
- 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.
- 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
- 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.
- Has a resting pulse and heart rate (as read on ECG) 100 bpm at Screening or Day -1.
- Has had an acute, clinically significant illness within 30 days prior to Day -1.
- 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.
- Has a family history of bleeding disorders.
- 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).
- 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.
- 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
- Has a history of abdominal surgery (except laparoscopic cholecystectomy or uncomplicated appendectomy), thoracic or nonperipheral vascular surgery within 6 months prior to Day - 1.
- 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.
- 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 a
Data sourced from ClinicalTrials.gov (NCT02252354). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.