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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (10)

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

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Другое

Центры проведения

Великобритания · 1 центр

• Quotient Sciences Limited — Nottingham

Идентификаторы

NCT: NCT07672574 · AGMB129-01-CL-105

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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