Fibrostenotic Crohn's Disease
Conditions
Brief summary
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.
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.
Interventions
DRUGOntunisertib
Oral capsule
DRUG[14C]ontunisertib
IV infusion
Sponsors
Agomab Spain S.L.U.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Non-Randomized, open-label, two-parts Phase I study
Eligibility
Sex/Gender
MALE
Age
30 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute bioavailability of ontunisertib following oral and IV administration | Through study completion, an average of 8 days | Part 1: To determine the absolute oral bioavailability of ontunisertib |
| Cumulative amount of total radioactivity excreted in urine and feces | Through study completion, an average of 10 days | Part 2: To determine the mass balance recovery after a single oral dose of \[14C\]ontunisertib |
| 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 | Through study completion, an average of 10 days | Part 2: To characterize the metabolite profile in plasma and excreta (urine and/or feces) after a single oral dose of \[14C\]ontunisertib |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK parameter (AUClast) | Through study completion, an average of 8 days | Part 1: To characterize the IV PK (AUClast) of \[14C\]ontunisertib and total radioactivity in plasma |
| Cumulative amount of total radioactivity excreted in urine and feces following IV administration | Through study completion, an average of 8 days | Part 1: To determine the mass balance recovery after a single IV dose of \[14C\]ontunisertib |
| Whole blood-to-plasma concentration ratios for total radioactivity | Through study completion, an average of 10 days | Part 2: To evaluate the extent of distribution of total radioactivity into blood cells |
| Number of participants with adverse events (AEs) | Through study completion, an average of 18 days | Part 1 and Part 2: To assess the safety and tolerability of ontunisertib |
| Number of participants with abnormal physical examinations | Through study completion, an average of 18 days | Part 1 and Part 2: To assess the safety and tolerability of ontunisertib |
| Number of participants with abnormal vital signs | Through study completion, an average of 18 days | Part 1 and Part 2: To assess the safety and tolerability of ontunisertib |
| Number of participants with abnormal ECGs parameters | Through study completion, an average of 18 days | Part 1 and Part 2: To assess the safety and tolerability of ontunisertib |
| Number of participants with abnormal clinical laboratory safety tests | Through study completion, an average of 18 days | Part 1 and Part 2: To assess the safety and tolerability of ontunisertib |
| Chemical structure analysis of metabolites accounting for ≥10% | Through study completion, an average of 8 days | Part 1: To characterize the metabolites profile in plasma following an IV dose of \[14C\]ontunisertib |
Countries
United Kingdom
Contacts
CONTACTAgomab Clinical Operations
STUDY_DIRECTORSilke Hüttner, MD
Agomab Therapeutics
Outcome results
None listed