Human Mass Balance Study of [14C] Ontunisertib in Healthy Volunteers

An Open-label, Two-part Trial to Assess the Mass-balance Recovery, Metabolite Profile, Metabolite Identification and Absolute Bioavailability of [14C] Ontunisertib in Healthy Male Participants

This is an open, two-part study in healthy male volunteers, aged 30-65 years.

This trial aims to understand how the human body absorbs, distributes, metabolizes and eliminates ontunisertib after a single oral dose of radiolabelled test medicine ([14C]ontunisertib) and determine the routes and rates of elimination of the test medicine.

Study Overview

• Status: Not yet recruiting
• Conditions: Fibrostenotic Crohn's Disease
• Intervention / Treatment: Drug: Ontunisertib; Drug: [14C]ontunisertib; Drug: [14C]ontunisertib

Detailed Description

This is an open, two-part study in healthy male volunteers, aged 30-65 years with the trial duration of approximately 7 weeks.

In Part 1 of this study, healthy volunteers will be given a dose of test medicine orally followed by an intravenous injection of a very small dose of radiolabelled test medicine that contains a tiny amount of radioactivity (called carbon-14) so that the test medicine can be traced in the blood.

In Part 2, single doses of test medicine will be administered orally to find out how the body breaks down and gets rid of the test medicine. The test medicine will be 'radiolabelled' - it will contain a small amount of radioactivity (Carbon-14) - so that it can be traced in the body.

Participants will take part in both study parts and will remain resident in the clinic for up to 10 days after their final dose of Investigation Medicinal Product (IMP). After the participants have left the clinic, they may have to collect their urine and faeces at home until mass balance criteria has been met.

Over a period of at least 8 days in Part 1 and 10 days in Part 2, many blood samples will be taken, and volunteers will collect all their urine and faeces so that the amount of test medicine and its breakdown products can be measured/analysed.

A blood sample will be taken from volunteers between admission and first dose for pharmacogenetic testing.

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Agomab Clinical Operations; Phone Number: 0032 3318 91 70; Email: clinicalstudies@agomab.com

Study Locations

• United Kingdom
  • Nottingham, United Kingdom, NG11 6JS
    • Quotient Sciences Limited

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Males aged 30 to 65 years inclusive at the time of signing informed consent
• Must agree to the use of an adequate method of contraception for up to 93 days post-final dose
• Healthy male participants according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs, 12-lead ECG, and laboratory safety tests without any clinically significant abnormalities.
• Body mass index of 18.0 to 29.9 kg/m2

Exclusion Criteria:

• Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients
• History of clinically significant renal, hepatic, respiratory, particularly GI disease, especially peptic ulceration, clinically significant GI bleeding, ulcerative colitis, Crohn's Disease or Irritable Bowel Syndrome, and neurological or psychiatric disorder
• History of GI surgery (with the exception of appendectomy or hernia repair unless it was performed within the previous 12 months)
• Clinically significant abnormal clinical chemistry, hematology, coagulation or urinalysis as judged by the investigator at screening.
• Radiation exposure, including that from the present trial, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker shall participate in the trial
• Participants who have been administered IMP in an ADME trial or any trial involving administration of 14C radioactivity in the last 12 months
• Male participants with pregnant or lactating partners

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ontunisertib; Participants will receive single oral dose of ontunisertib	Drug: Ontunisertib; Oral capsule; Other Names: AGMB-129
Experimental: [14C]ontunisertib solution for infusion; Participants will receive single IV dose of [14C]ontunisertib	Drug: [14C]ontunisertib; IV infusion; Drug: [14C]ontunisertib; Oral capsule
Experimental: [14C]ontunisertib; Participants will receive single oral dose of [14C]ontunisertib	Drug: [14C]ontunisertib; IV infusion; Drug: [14C]ontunisertib; Oral capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute bioavailability of ontunisertib following oral and IV administration	Part 1: To determine the absolute oral bioavailability of ontunisertib	Through study completion, an average of 8 days
Cumulative amount of total radioactivity excreted in urine and feces	Part 2: To determine the mass balance recovery after a single oral dose of [14C]ontunisertib	Through study completion, an average of 10 days
Chemical structure of each metabolite accounting for ≥10% of circulating total radioactivity and Metabolite profiling accounting for >80% of total radioactivity recovered in urine and/or feces	Part 2: To characterize the metabolite profile in plasma and excreta (urine and/or feces) after a single oral dose of [14C]ontunisertib	Through study completion, an average of 10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameter (AUClast)	Part 1: To characterize the IV PK (AUClast) of [14C]ontunisertib and total radioactivity in plasma	Through study completion, an average of 8 days
Cumulative amount of total radioactivity excreted in urine and feces following IV administration	Part 1: To determine the mass balance recovery after a single IV dose of [14C]ontunisertib	Through study completion, an average of 8 days
PK parameter (AUClast)	Part 1 and Part 2: To characterize the plasma PK (AUClast) of ontunisertib and metabolites and total radioactivity (Part 2 only) following a single oral dose	Through study completion, an average of 18 days
Whole blood-to-plasma concentration ratios for total radioactivity	Part 2: To evaluate the extent of distribution of total radioactivity into blood cells	Through study completion, an average of 10 days
Number of participants with adverse events (AEs)	Part 1 and Part 2: To assess the safety and tolerability of ontunisertib	Through study completion, an average of 18 days
Number of participants with abnormal physical examinations	Part 1 and Part 2: To assess the safety and tolerability of ontunisertib	Through study completion, an average of 18 days
Number of participants with abnormal vital signs	Part 1 and Part 2: To assess the safety and tolerability of ontunisertib	Through study completion, an average of 18 days
Number of participants with abnormal ECGs parameters	Part 1 and Part 2: To assess the safety and tolerability of ontunisertib	Through study completion, an average of 18 days
Number of participants with abnormal clinical laboratory safety tests	Part 1 and Part 2: To assess the safety and tolerability of ontunisertib	Through study completion, an average of 18 days
Chemical structure analysis of metabolites accounting for ≥10%	Part 1: To characterize the metabolites profile in plasma following an IV dose of [14C]ontunisertib	Through study completion, an average of 8 days

Collaborators and Investigators

• Sponsor: Agomab Spain S.L.U.
• Investigators: Study Director: Silke Hüttner, MD, Agomab Therapeutics

Study record dates

Study Major Dates

• Study Start (Estimated): July 20, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: June 12, 2026
• First Submitted That Met QC Criteria: June 22, 2026
• First Posted (Actual): June 29, 2026

Study Record Updates

• Last Update Posted (Actual): June 29, 2026
• Last Update Submitted That Met QC Criteria: June 22, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: AGMB129-01-CL-105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No