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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ontunisertib | Experimental | Participants will receive single oral dose of ontunisertib |
|
| [14C]ontunisertib solution for infusion | Experimental | Participants will receive single IV dose of [14C]ontunisertib |
|
| [14C]ontunisertib | Experimental | Participants will receive single oral dose of [14C]ontunisertib |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ontunisertib | Drug | Oral capsule |
|
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
Only males are eligible to participate.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Agomab Clinical Operations | Contact | 0032 3318 91 70 | clinicalstudies@agomab.com |
| Name | Affiliation | Role |
|---|---|---|
| Silke Hüttner, MD | Agomab Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Quotient Sciences Limited | Nottingham | NG11 6JS | United Kingdom |
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Non-Randomized, open-label, two-parts Phase I study
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| [14C]ontunisertib | Drug | IV infusion |
|
| [14C]ontunisertib | Drug | Oral capsule |
|
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 |