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

Official title

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

Overview

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

• Drug Ontunisertib
  Oral capsule
• Drug [14C]ontunisertib
  IV infusion
• Drug [14C]ontunisertib
  Oral capsule

Primary outcome measures

• Absolute bioavailability of ontunisertib following oral and IV administration [Time frame: Through study completion, an average of 8 days]
• Cumulative amount of total radioactivity excreted in urine and feces [Time frame: 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 [Time frame: Through study completion, an average of 10 days]

Secondary outcome measures (10)

• PK parameter (AUClast) [Time frame: Through study completion, an average of 8 days]
• Cumulative amount of total radioactivity excreted in urine and feces following IV administration [Time frame: Through study completion, an average of 8 days]
• PK parameter (AUClast) [Time frame: Through study completion, an average of 18 days]
• Whole blood-to-plasma concentration ratios for total radioactivity [Time frame: Through study completion, an average of 10 days]
• Number of participants with adverse events (AEs) [Time frame: Through study completion, an average of 18 days]
• Number of participants with abnormal physical examinations [Time frame: Through study completion, an average of 18 days]
• Number of participants with abnormal vital signs [Time frame: Through study completion, an average of 18 days]
• Number of participants with abnormal ECGs parameters [Time frame: Through study completion, an average of 18 days]
• Number of participants with abnormal clinical laboratory safety tests [Time frame: Through study completion, an average of 18 days]
• Chemical structure analysis of metabolites accounting for ≥10% [Time frame: Through study completion, an average of 8 days]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Other

Study locations

United Kingdom · 1 center

• Quotient Sciences Limited — Nottingham

Identifiers

NCT: NCT07672574 · AGMB129-01-CL-105

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗