Mass Balance and Absolute Bioavailability Study of RO7049389 in Healthy Volunteers

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

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: [12C] RO7049389
* Drug: [13C] RO7049389
* Drug: [14C] RO7049389


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mass Balance (MB) Cohort<br>Participants will receive oral [14C] RO7049389 under fasted conditions, followed by intravenous IV [13C] after a two-hour period. | Drug: [13C] RO7049389<br>* Participants will receive IV [13C] RO7049389.<br>Drug: [14C] RO7049389<br>* Participants will receive an oral suspension of [14C] RO7049389.<br>|
| Experimental: Absolute Bioavailability (BA) Cohort<br>In Periods 1 and 2, participants will receive oral [12C] RO7049389 under fasted conditions, followed by IV [13C] RO7049389. There is a minimum 7-day washout between periods. | Drug: [12C] RO7049389<br>* Participants will receive oral [12C] RO7049389.<br>Drug: [13C] RO7049389<br>* Participants will receive IV [13C] RO7049389.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Dose Excreted in Urine |  | Up to Day 17 | 
| Percentage of Dose Excreted in Feces |  | Up to Day 17 | 
| Absolute Oral BA for RO7049389 |  | Up to Day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) of RO7049389 |  | Up to Day 4 | 
| Area Under the Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUClast) of RO7049389 |  | Up to Day 4 | 
| Area Under Concentration-Time Curve from Time Zero to Infinity (AUC0-inf) of RO7049389 |  | Up to Day 4 | 
| Time to Maximum Plasma Concentration (Tmax) of RO7049389 |  | Up to Day 4 | 
| Apparent Clearance (CL/F) of RO7049389 |  | Up to Day 4 | 
| Clearance (CL) of RO7049389 |  | Up to Day 4 | 
| Renal Clearance (CLr) of RO7049389 |  | Up to Day 4 | 
| Amount Excreted in Urine (Ae) of RO7049389 |  | Up to Day 4 | 
| Half-Life (T1/2) of RO7049389 |  | Up to Day 4 | 
| Percentage of Participants with Adverse Events (AEs) |  | Up to Day 29 |