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

NCT04992442 | Completed Phase 1 Results FDA Drug

• 1 other identifier: TAK-935-1008
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (28)

• Period 1: Percent Absolute Bioavailability (%F) for TAK-935

  Bioavailability is defined as the proportion of a drug which enters the circulation when introduced into the body and so is able to have an active effect. Percent absolute bioavailability, calculated for plasma TAK-935 as \[Actual Dose (IV) x Area Under the Concentration-time Curve from Time 0 to Infinity {AUCinf} (oral)\] / \[Actual Dose (oral) x AUCinf (IV)\] x 100.

  Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1

• Period 2: Total Radioactivity Expressed as Cumulative Percentage of Dose of [14C]TAK-935 Excreted in Urine and Feces Combined [Combined Cum%Dose]

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Urine (CumAe[u])

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Feces (CumAe[f])

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Urine and Feces Combined (Combined CumAe)

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-935 Excreted in Urine (Cum%Dose[u])

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-935 Excreted in Feces (Cum%Dose[f])

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: Cmax: Maximum Observed Plasma Concentration of TAK-935

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-935

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: t(1/2)z: Terminal Disposition Phase Half-life of TAK-935 in Plasma

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-935

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-935

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-935

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: Cmax: Maximum Observed Plasma Radioactivity Concentration

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: Tmax: Time to Reach the Maximum Plasma Radioactivity Concentration (Cmax)

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Plasma Radioactivity Concentration

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: AUC0-inf: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Infinity

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: AUC0-t: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Time t

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: AUC0-last: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: Cmax: Maximum Observed Whole Blood Radioactivity Concentration

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: Tmax: Time to Reach the Maximum Whole Blood Radioactivity Concentration (Cmax)

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Whole Blood Radioactivity Concentration

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: AUC0-inf: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to Infinity

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: AUC0-t: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to t

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: AUC0-last: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: CLR: Renal Clearance for TAK-935 in Urine

  Renal clearance (CLr) is the volume of plasma entering the kidney that is completely cleared of drug per unit of time.

  Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

• Period 2: Aet1-t2: Amount of TAK-935 Excreted in the Urine in Each Collection Interval

  0-12, 12-24, 24-48, 48-72, 72-96, 96-120 hours post-dose in Treatment Period 2

• Period 2: Whole Blood to Plasma Partitioning Ratio: Change From Baseline in Percentage of [14C]TAK-935 Radioactivity in Whole Blood Relative to Plasma

  0.17, 0.42, 0.75, 1.5, 2.5, 4.5, 8, 12, and 24 hours post-dose in Treatment Period 2

Secondary Outcomes (22)

• Period 1: Ceoi: Plasma Concentration at the End of Infusion for [14C]TAK-935

  Day 1: At the end of infusion (at 15 minutes post dose) in Treatment Period 1

• Period 1: Cmax: Maximum Observed Plasma Concentration for TAK-935 After Oral Administration

  Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1

• Period 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-935 After Oral Administration

  Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1

• Period 1: AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-935 After Oral Administration

  Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1

• Period 1: AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for [14C]TAK-935 After IV Administration

  Day 1 pre-dose and at multiple time points (up to 47.5 hours) post-dose in Treatment Period 1

Study Arms (1)

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

EXPERIMENTAL

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.

Drug: TAK-935 Oral Tablet; Drug: [14C]TAK-935 IV Infusion; Drug: [14C]TAK-935 Oral Solution

Interventions

TAK-935 Oral Tablet DRUG

TAK-935 tablet

Also known as: OV935, Soticlestat

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

[14C]TAK-935 IV Infusion DRUG

\[14C\]TAK-935 IV infusion

Also known as: OV935

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

[14C]TAK-935 Oral Solution DRUG

\[14C\]TAK-935 oral solution

Also known as: OV935

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

Eligibility Criteria

• Age: 19 Years - 55 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Weighs at least 50 kg and body mass index (BMI) ≥18.0 and ˂32.0 kg/m\^2 at Screening Visit.
• 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.
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the Investigator or designee.

You may not qualify if:

• History or presence of cataracts or other clinically significant vision disturbances.
• 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.
• 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.
• 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.
• Positive urine drug or alcohol results at screening or first check-in.
• Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) or novel coronavirus 2019 (COVID-19).
• Seated blood pressure is less than 90/40 millimeter of mercury (mmHg) or greater than 140/90 mmHg at Screening.
• Seated HR is lower than 40 beats per minute (bpm) or higher than 99 bpm at Screening Visit.
• Estimated creatinine clearance \<80 mL/min at Screening Visit.
• 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.
• Has infrequent bowel movements (less than approximately once per day) within 30 days prior to first dosing.
• Recent history of abnormal bowel movements, such as diarrhea, loose stools, or constipation, within 2 weeks prior to first dosing.
• 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 \[i.e., weighted annual limit recommended by the International Commission on Radiological Protection (ICRP) of 3000 milli roentgen equivalent man (mrem)\].
• Unable to refrain from or anticipates the use of:

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Celerion

Lincoln, Nebraska, 68502, United States

Location

MeSH Terms

Interventions

soticlestat

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2021
• First Posted: August 5, 2021
• Study Start: July 9, 2020
• Primary Completion: August 18, 2020
• Study Completion: August 18, 2020
• Last Updated: October 4, 2021
• Results First Posted: October 4, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (1)