Clinical trial NCT04729309: Mass Balance and Absolute Bioavailability Study of RO7049389 in Healthy Volunteers
Official title: Open-Label Study to Investigate the Mass Balance and Absolute Bioavailability of a Single Oral Dose of [14C]-Labeled RO7049389 or RO7049389 and an Intravenous Micro-Dose of [13C]-Labeled RO7049389 in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2021-01-28
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The objective of this study is to characterize the mass balance, absolute bioavailability, route and rates of elimination of RO7049839.


Eligibility criteria: Inclusion Criteria:

* Caucasian (must have Caucasian parents and grandparents) or East Asian (must have Chinese, Korean, or Japanese parents and grandparents)
* Body mass index between 18 to 30 kg/m\^2 (inclusive) and a weight range of 50 kg to 100 kg (inclusive) at screening
* For women of childbearing potential: agree to use two methods of contraception, with at least one method considered as highly effective during the study and for at least 90 days after the last dose of study drug
* For men: agree to remain abstinent (refrain from heterosexual intercourse) or agree to use contraceptive measures, and agree to refrain from donating sperm during the treatment period and for at least 90 days after the last dose of study drug

Exclusion Criteria:

* Pregnant or lactating women, and male participants with partners who are pregnant or lactating
* History or symptoms of any clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, oncologic, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study treatment; or of interfering with the interpretation of data
* Personal history or family history of congenital long QT interval (QT) syndrome and/or cardiac sudden death
* History of Gilbert syndrome
* Participants who have had significant acute infection, e.g. influenza, local infection, acute gastrointestinal (GI) symptoms, or any other clinically significant illness within two weeks of dose administration
* Any confirmed significant reactions (urticaria or anaphylaxis) against any drug, or multiple drug allergies
* Any clinically significant concomitant diseases or conditions that could interfere with the conduct of the study, or in the opinion of the Investigator, would pose an unacceptable risk to the participant in this study
* Taking any herbal medications or substances, supplements (including vitamins), traditional Chinese medicines, prescription medicine, or over-the-counter medications within 14 days of first dosing or within 5 times the elimination half-life of the medication prior to first dosing, whichever is longer
* History of having received any systemic anti-neoplastic (including radiation) or immune-modulatory treatment (including systemic oral or inhaled corticosteroids) 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study
* Are currently enrolled in or have participated in any other clinical study involving an investigational product or in any other type of medical research within the last 90 days (or within 5 half-lives of the investigational product, whichever is longer)
* Donation or loss of blood or blood products in excess of 500 mL within 3 months of screening
* Evidence of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
* Hepatitis A, B, C, D, or E or HIV infection
* History of drug or alcohol abuse in the past 2 years
* Regular alcohol consumption in males \> 21 units per week and in females \> 14 units per week (1 unit = 1/2 pint of beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type)
* Use of \> 5 cigarettes or equivalent nicotine-containing product per day prior to screening

Exclusion Criteria for Mass Balance Cohorts

* Regular work with ionizing radiation or radioactive material
* Radiation exposure, including that from the present study, 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, as defined in the Ionising Radiation Regulations 2017, shall participate in the study
* Exposure to radiation for diagnostic reasons (except dental X-rays and plain X-rays of thorax and bony skeleton \[excluding spinal column\]), during work, or during participation in a medical trial in the previous year
* History of gastrointestinal (GI) surgery

Primary outcomes:
measure: Percentage of Dose Excreted in Urine - MB Cohort
timeFrame: Up to Day 17
measure: Percentage of Dose Excreted in Feces - MB Cohort
timeFrame: Up to Day 17
measure: Percent Total Recovery (Urine + Feces) - MB Cohort
timeFrame: Up to Day 17
measure: Absolute Oral BA for RO7049389 - BA Cohort
timeFrame: Up to Day 4 of Periods 1 and 2
Secondary outcomes:
measure: Clearance (CL) of RO7049389 - MB Cohort
timeFrame: Up to Day 17
measure: Clearance (CL) of RO7049389 - BA Cohort
timeFrame: Up to Day 4 of Periods 1 and 2
measure: Half-Life (T1/2) of RO7049389 - MB Cohort
timeFrame: Up to Day 17
measure: Half-Life (T1/2) of RO7049389 - BA Cohort
timeFrame: Up to Day 4 of Periods 1 and 2
measure: Maximum Plasma Concentration (Cmax) of RO7049389 - MB Cohort
timeFrame: Up to Day 17
measure: Maximum Plasma Concentration (Cmax) of RO7049389 - BA Cohort
timeFrame: Up to Day 4 of Periods 1 and 2
measure: Time to Maximum Plasma Concentration (Tmax) of RO7049389 - MB Cohort
timeFrame: Up to Day 17
measure: Time to Maximum Plasma Concentration (Tmax) of RO7049389 - BA Cohort
timeFrame: Up to Day 4 of Periods 1 and 2
measure: Area Under Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7049389 - MB Cohort
timeFrame: Up to Day 4
measure: Area Under Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7049389 - BA Cohort
timeFrame: Up to Day 4 of Periods 1 and 2
measure: Area Under the Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of RO7049389 - MB Cohort
timeFrame: Up to Day 17
measure: Area Under the Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of RO7049389 - BA Cohort
timeFrame: Up to Day 4 of Periods 1 and 2
measure: Apparent Clearance (CL/F) of RO7049389 - MB Cohort
timeFrame: Up to Day 4
measure: Apparent Clearance (CL/F) of RO7049389 - BA Cohort
timeFrame: Up to Day 4
measure: Renal Clearance (CLr) of RO7049389 - BA Cohort
timeFrame: Up to Day 4 of Periods 1 and 2
measure: Amount Excreted in Urine (Ae) of RO7049389 - BA Cohort
timeFrame: Up to Day 4 of Periods 1 and 2
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Up to Day 29 (MB Cohort) or up to Day 29 of Period 2 (AB Cohort)
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Quotient Sciences
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: