Mass Balance and Absolute Bioavailability Study of RO7049389 in Healthy Volunteers

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: [13C] RO7049389; Drug: [14C] RO7049389; Drug: [12C] RO7049389

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom, NG11 6JS
    • Quotient Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mass Balance (MB) Cohort; Participants will receive oral [14C] RO7049389 under fasted conditions, followed by intravenous IV [13C] after a two-hour period.	Drug: [13C] RO7049389; Participants will receive IV [13C] RO7049389.; Drug: [14C] RO7049389; Participants will receive an oral suspension of [14C] RO7049389.
Experimental: Absolute Bioavailability (BA) Cohort; 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: [13C] RO7049389; Participants will receive IV [13C] RO7049389.; Drug: [12C] RO7049389; Participants will receive oral [12C] RO7049389.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2021
• Primary Completion (Actual): June 14, 2021
• Study Completion (Actual): June 14, 2021

Study Registration Dates

• First Submitted: January 26, 2021
• First Submitted That Met QC Criteria: January 26, 2021
• First Posted (Actual): January 28, 2021

Study Record Updates

• Last Update Posted (Actual): July 22, 2021
• Last Update Submitted That Met QC Criteria: July 21, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: BP41811

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No