Study to Assess Absolute Bioavailability of TAK-935 (OV935) and to Characterize Mass Balance, Pharmacokinetics, Metabolism, and Excretion of [14C]TAK-935 (OV935) in Healthy Male Participants

NCT ID: NCT04992442

Last Updated: 2021-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-09
• Study Completion Date: 2020-08-18

Brief Summary

The purpose of this study is to determine absolute bioavailability (ABA) of TAK-935 (F) following a single microdose intravenous (IV) administration of 50 microgram (μg) (approximately 1 microcurie [μCi]) [14C]TAK-935 and a single oral administration of 3×100 mg milligram (mg) TAK-935 tablets in Treatment Period 1, and to assess the mass balance, characterize the pharmacokinetics (PK) of TAK-935 and metabolite [M-I (N-oxide)] in plasma and urine, and total radioactivity concentration equivalents in plasma and whole blood following a single oral administration of 300 mg (approximately 100 μCi) [14C]TAK-935 in Treatment Period 2.

Detailed Description

The drug being tested in this study is called TAK-935 (also known as soticlestat/OV935). The study determines ABA in Treatment Period 1, and the absorption, metabolism, excretion, and mass balance of TAK-935 after single oral administration in Treatment Period 2 in healthy adult male participants, by collecting plasma, urine, and feces samples for drug concentration analysis, and plasma, whole blood, urine, and fecal samples for total radioactivity analysis and metabolic profiling.

The study will enroll approximately 6 healthy adult male participants. The study is designed to consist of 2 periods: Treatment Period 1 (ABA Study Period) and Treatment Period 2 (Absorption, Distribution, Metabolism, and Elimination [ADME] Study Period). In Treatment Period 1, all participants will receive a single unlabelled oral dose of TAK-935 as 3×100 mg tablets and a microdose IV infusion of 50 μg (approximately 1 μCi) [14C]TAK-935, followed by a Washout Period of 7 days before the dose in Treatment Period 2. In Treatment Period 2, all participants will receive a single dose of 300 mg (approximately 100 μCi) [14C]TAK-935 as an oral solution.

This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 65 days including Screening Period. Participants will be contacted approximately 30 days after the last dose of study drug for a follow-up assessment. This compound was transferred to Takeda and acquired on 29 March 2021. This registration is retrospective due to the transfer of ownership.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

TAK-935 300 mg + [14C]TAK-935 50 μg + [14C]TAK-935 300 mg

TAK-935 3×100 mg, tablets, orally, once on Day 1, followed by \[14C\]TAK-935 50 micrograms (μg) \[approximately 1 μCi\], IV infusion, once on Day 1 of Treatment Period 1, followed by a Washout Period of 7 days, further followed by \[14C\]TAK-935 300 mg (approximately 100 μCi) solution, orally, once on Day 1 of Treatment Period 2.

Group Type: EXPERIMENTAL

TAK-935 Oral Tablet

Intervention Type: DRUG

TAK-935 tablet

[14C]TAK-935 IV Infusion

Intervention Type: DRUG

\[14C\]TAK-935 IV infusion

[14C]TAK-935 Oral Solution

Intervention Type: DRUG

\[14C\]TAK-935 oral solution

Interventions

TAK-935 Oral Tablet

TAK-935 tablet

Intervention Type: DRUG

[14C]TAK-935 IV Infusion

\[14C\]TAK-935 IV infusion

Intervention Type: DRUG

[14C]TAK-935 Oral Solution

\[14C\]TAK-935 oral solution

Intervention Type: DRUG

Other Intervention Names

OV935; Soticlestat; OV935; OV935

Eligibility Criteria

Inclusion Criteria

1. Weighs at least 50 kg and body mass index (BMI) ≥18.0 and ˂32.0 kg/m^2 at Screening Visit.

2. Continuous nonsmoker who has not used nicotine-containing products (including vaping) for at least 3 months prior to the first dosing and throughout the study, based on participant self-reporting.

3. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the Investigator or designee.

Exclusion Criteria

1. History or presence of cataracts or other clinically significant vision disturbances.

2. Abnormal and clinically significant ECG abnormality at Screening visit:

• QT interval with Fridericia's correction method (QTcF) >450 milliseconds (ms) confirmed with one repeat testing.

3. History or presence of gastritis, gastrointestinal tract, gastric bypass surgery, or hepatic disorder or other clinical condition which, in the opinion of the Investigator or designee, may affect the absorption, distribution, metabolism, or elimination of study drug.

4. Has a risk of suicide according to the Investigator's clinical judgment [e.g., per Columbia-Suicide Severity Rating Scale (C-SSRS)] or has made a suicide attempt in the previous year prior to Screening Visit.

5. Positive urine drug or alcohol results at screening or first check-in.

6. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) or novel coronavirus 2019 (COVID-19).

7. Seated blood pressure is less than 90/40 millimeter of mercury (mmHg) or greater than 140/90 mmHg at Screening.

8. Seated HR is lower than 40 beats per minute (bpm) or higher than 99 bpm at Screening Visit.

9. Estimated creatinine clearance <80 mL/min at Screening Visit.

10. Has tattoo(s) or scarring at or near the site of IV infusion or any other condition which may interfere with infusion site examination, in the opinion of the Investigator.

11. Has infrequent bowel movements (less than approximately once per day) within 30 days prior to first dosing.

12. Recent history of abnormal bowel movements, such as diarrhea, loose stools, or constipation, within 2 weeks prior to first dosing.

13. Has received radiolabeled substances or has been exposed to radiation sources within 12 months of first dosing or is likely to receive radiation exposure or radioisotopes within 12 months of first dosing such that participation in this study would increase their total exposure beyond the recommended levels considered safe [i.e., weighted annual limit recommended by the International Commission on Radiological Protection (ICRP) of 3000 milli roentgen equivalent man (mrem)].

14. Unable to refrain from or anticipates the use of:

1. Any drug, including prescription and nonprescription medications, herbal remedies, or vitamin supplements within 14 days prior to the first dosing and throughout the study, including the Follow-up Period. Thyroid hormone replacement medication may be permitted if the participant has been on the same stable dose for the immediate 3 months prior to first study drug administration. After the first dose of study drug, ibuprofen (up to 1.2 g per 24 hours) may be administered at the discretion of the Investigator or designee. Milk of Magnesia (i.e., magnesium hydroxide) (≤60 mL per day) may be administered to ensure defecation, at discretion of the Investigator or designee.

2. Any drugs known to be significant inducers of cytochrome P450 (CYP)3A4, CYP2C19 or uridine diphosphate glucuronosyltransferase (UGT), including St. John's Wort, within 28 days prior to the first dosing and throughout the study, including the Follow-up Period. Appropriate sources (e.g., Flockhart Table^TM) will be consulted to confirm lack of PK/pharmacodynamic interaction with study drug(s).

3. Alcohol

15. Has been on a diet incompatible with the on-study diet, in the opinion of the Investigator or designee, within the 30 days prior to the first dosing and throughout the study.

16. Donation of blood or significant blood loss within 56 days prior to the first dosing.

17. Plasma donation within 7 days prior to the first dosing.

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Celerion

Lincoln, Nebraska, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

TAK-935-1008

Identifier Type: -

Identifier Source: org_study_id