NCT04992442

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

Completed Phase 1 Results posted Last updated 4 October 2021

What this trial tests

Phase 1 trial testing TAK-935 Oral Tablet in Healthy Volunteers in 6 participants. Completed in 18 August 2020.

Timeline

9 July 2020

Primary endpoint
18 August 2020

18 August 2020

Quick facts

Lead sponsor	Takeda
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	other
Enrollment	6
Start date	9 July 2020
Primary completion	18 August 2020
Estimated completion	18 August 2020
Sites	1 location across United States

Drugs / interventions tested

• TAK-935 Oral Tablet
• [14C]TAK-935 IV Infusion — full drug profile →
• [14C]TAK-935 Oral Solution — full drug profile →

Conditions studied

• Healthy Volunteers — all drugs for Healthy Volunteers →

Sponsor

Takeda — full company profile →

Who can join

Adults 19 to 55, male only, with Healthy Volunteers. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Period 1: Percent Absolute Bioavailability (%F) for TAK-935 Primary · Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Treatment Period 1

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.

Group	Value	95% CI
TAK-935 300 mg + [14C]TAK-935 50 μg	12.57	± 75.1

Period 2: Total Radioactivity Expressed as Cumulative Percentage of Dose of [14C]TAK-935 Excreted in Urine and Feces Combined [Combined Cum%Dose] Primary · Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Group	Value	95% CI
[14C]TAK-935 300 mg	97.55	± 0.5

Period 2: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Urine (CumAe[u]) Primary · Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Group	Value	95% CI
[14C]TAK-935 300 mg	292.3	± 1.4

Period 2: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Feces (CumAe[f]) Primary · Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Group	Value	95% CI
[14C]TAK-935 300 mg	9.429	± 48.2

Period 2: Total Radioactivity Expressed as Amount of [14C]TAK-935 Excreted in Urine and Feces Combined (Combined CumAe) Primary · Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Group	Value	95% CI
[14C]TAK-935 300 mg	300.7	± 0.5

Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-935 Excreted in Urine (Cum%Dose[u]) Primary · Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Group	Value	95% CI
[14C]TAK-935 300 mg	94.81	± 1.4

Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-935 Excreted in Feces (Cum%Dose[f]) Primary · Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Group	Value	95% CI
[14C]TAK-935 300 mg	3.058	± 48.2

Period 2: Cmax: Maximum Observed Plasma Concentration of TAK-935 Primary · Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Group	Value	95% CI
[14C]TAK-935 300 mg	1352	± 61.3

Period 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-935 Primary · Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Group	Value	95% CI
[14C]TAK-935 300 mg	0.42	0.42 – 0.42

Period 2: t(1/2)z: Terminal Disposition Phase Half-life of TAK-935 in Plasma Primary · Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Group	Value	95% CI
[14C]TAK-935 300 mg	4.374	3.51 – 10.55

Period 2: AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-935 Primary · Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Group	Value	95% CI
[14C]TAK-935 300 mg	1805	± 40.4

Period 2: AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-935 Primary · Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose in Treatment Period 2

Group	Value	95% CI
[14C]TAK-935 300 mg	1547	± 40.8

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose up to 30±2 days after last dose of study drug (up to approximately 40 days). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

TAK-935 300 mg + [14C]TAK-935 50 μg

Serious: 0/6 (0%)

Deaths: 0/6

[14C]TAK-935 300 mg

Serious: 0/6 (0%)

Deaths: 0/6

Other adverse events (1 terms — click to expand)

Reaction	System	TAK-935 300 mg + [14C]TAK-…	[14C]TAK-935 300 mg
Headache	Nervous system disorders	—	—

Data from ClinicalTrials.gov NCT04992442 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.