Healthy Volunteers
Conditions
Brief summary
The objective of this study is to characterize the mass balance, absolute bioavailability, route and rates of elimination of RO7049839.
Interventions
DRUG[12C] RO7049389
Participants will receive oral \[12C\] RO7049389.
DRUG[13C] RO7049389
Participants will receive IV \[13C\] RO7049389.
DRUG[14C] RO7049389
Participants will receive an oral suspension of \[14C\] RO7049389.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Dose Excreted in Urine - MB Cohort | Up to Day 17 |
| Percentage of Dose Excreted in Feces - MB Cohort | Up to Day 17 |
| Percent Total Recovery (Urine + Feces) - MB Cohort | Up to Day 17 |
| Absolute Oral BA for RO7049389 - BA Cohort | Up to Day 4 of Periods 1 and 2 |
Secondary
| Measure | Time frame |
|---|---|
| Maximum Plasma Concentration (Cmax) of RO7049389 - MB Cohort | Up to Day 17 |
| Maximum Plasma Concentration (Cmax) of RO7049389 - BA Cohort | Up to Day 4 of Periods 1 and 2 |
| Time to Maximum Plasma Concentration (Tmax) of RO7049389 - MB Cohort | Up to Day 17 |
| Time to Maximum Plasma Concentration (Tmax) of RO7049389 - BA Cohort | Up to Day 4 of Periods 1 and 2 |
| Area Under Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7049389 - MB Cohort | Up to Day 4 |
| Area Under Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7049389 - BA Cohort | Up to Day 4 of Periods 1 and 2 |
| Clearance (CL) of RO7049389 - MB Cohort | Up to Day 17 |
| Area Under the Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of RO7049389 - BA Cohort | Up to Day 4 of Periods 1 and 2 |
| Apparent Clearance (CL/F) of RO7049389 - MB Cohort | Up to Day 4 |
| Apparent Clearance (CL/F) of RO7049389 - BA Cohort | Up to Day 4 |
| Renal Clearance (CLr) of RO7049389 - BA Cohort | Up to Day 4 of Periods 1 and 2 |
| Amount Excreted in Urine (Ae) of RO7049389 - BA Cohort | Up to Day 4 of Periods 1 and 2 |
| Percentage of Participants With Adverse Events (AEs) | Up to Day 29 (MB Cohort) or up to Day 29 of Period 2 (AB Cohort) |
| Area Under the Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of RO7049389 - MB Cohort | Up to Day 17 |
| Clearance (CL) of RO7049389 - BA Cohort | Up to Day 4 of Periods 1 and 2 |
| Half-Life (T1/2) of RO7049389 - MB Cohort | Up to Day 17 |
| Half-Life (T1/2) of RO7049389 - BA Cohort | Up to Day 4 of Periods 1 and 2 |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Absolute Bioavailability (BA) Cohort Period 1: Participants received 600 mg of oral \[12C\] RO7049389 under fasted conditions, followed by 100 ug of intravenous (IV) \[13C\] RO7049389 after a two-hour delay.
Period 2: After a 7-day washout period, participants received 1000 mg of oral \[12C\] RO7049389, followed by 100 ug of IV \[13C\] RO7049389 after a two-hour delay. | 16 |
| Mass Balance (MB) Cohort Participants received 600 mg of \[14C\] RO7049389 oral suspension under fasted conditions, followed by 100 ug of intravenous (IV) \[13C\] RO7049389 after a two-hour delay. (Note: \[14C\] RO7049389 was a combination of \[12C\]+\[14C\]-labeled RO7049389). | 6 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Lost to Follow-up | 1 | 0 |
| Period 1 | Subject unable to return for Period 2 | 3 | 0 |
Baseline characteristics
| Characteristic | Absolute Bioavailability (BA) Cohort | Mass Balance (MB) Cohort | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 6 Participants | 22 Participants |
| Age, Continuous | 29.4 years STANDARD_DEVIATION 5.9 | 50.5 years STANDARD_DEVIATION 7.7 | 35.2 years STANDARD_DEVIATION 11.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 6 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 0 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Female | 9 Participants | 0 Participants | 9 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 6 |
| other Total, other adverse events | 13 / 16 | 2 / 6 |
| serious Total, serious adverse events | 0 / 16 | 0 / 6 |
Outcome results
Primary
Absolute Oral BA for RO7049389 - BA Cohort
Time frame: Up to Day 4 of Periods 1 and 2
Population: All participants who have received at least one dose of study treatment and who have data from at least one post-dose sample were included in the PK analysis population. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which may influence the PK analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mass Balance (MB) Cohort | Absolute Oral BA for RO7049389 - BA Cohort | Asian participants - Period 1 | 41.7 Percentage | Geometric Coefficient of Variation 65.3 |
| Mass Balance (MB) Cohort | Absolute Oral BA for RO7049389 - BA Cohort | Caucasian participants - Period 1 | 30.6 Percentage | Geometric Coefficient of Variation 45.8 |
| Mass Balance (MB) Cohort | Absolute Oral BA for RO7049389 - BA Cohort | Asian participants - Period 2 | 61.4 Percentage | Geometric Coefficient of Variation 90.2 |
| Mass Balance (MB) Cohort | Absolute Oral BA for RO7049389 - BA Cohort | Caucasian participants - Period 2 | 40.7 Percentage | Geometric Coefficient of Variation 56 |
Primary
Percentage of Dose Excreted in Feces - MB Cohort
Time frame: Up to Day 17
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Mass Balance (MB) Cohort | Percentage of Dose Excreted in Feces - MB Cohort | 90.5 Percentage | Geometric Coefficient of Variation 4.9 |
Primary
Percentage of Dose Excreted in Urine - MB Cohort
Time frame: Up to Day 17
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Mass Balance (MB) Cohort | Percentage of Dose Excreted in Urine - MB Cohort | 3.81 Percentage | Geometric Coefficient of Variation 35.2 |
Primary
Percent Total Recovery (Urine + Feces) - MB Cohort
Time frame: Up to Day 17
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Mass Balance (MB) Cohort | Percent Total Recovery (Urine + Feces) - MB Cohort | 94.5 Percentage | Geometric Coefficient of Variation 5.5 |
Secondary
Amount Excreted in Urine (Ae) of RO7049389 - BA Cohort
Time frame: Up to Day 4 of Periods 1 and 2
Population: All participants who have received at least one dose of study treatment and who have data from at least one post-dose sample were included in the PK analysis population. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which may influence the PK analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mass Balance (MB) Cohort | Amount Excreted in Urine (Ae) of RO7049389 - BA Cohort | Asian participants - [12C] Period 1 | 3.4 mg | Standard Deviation 2.5 |
| Mass Balance (MB) Cohort | Amount Excreted in Urine (Ae) of RO7049389 - BA Cohort | Caucasian participants - [12C] Period 1 | 0.8 mg | Standard Deviation 0.8 |
| Mass Balance (MB) Cohort | Amount Excreted in Urine (Ae) of RO7049389 - BA Cohort | Asian participants - [12C] Period 2 | 5.9 mg | Standard Deviation 4.5 |
| Mass Balance (MB) Cohort | Amount Excreted in Urine (Ae) of RO7049389 - BA Cohort | Caucasian participants - [12C] Period 2 | 1.0 mg | Standard Deviation 1.2 |
Secondary
Apparent Clearance (CL/F) of RO7049389 - BA Cohort
Time frame: Up to Day 4
Population: All participants who have received at least one dose of study treatment and who have data from at least one post-dose sample were included in the PK analysis population. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which may influence the PK analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mass Balance (MB) Cohort | Apparent Clearance (CL/F) of RO7049389 - BA Cohort | Caucasian participants - [13C] Period 2 | 24.7 L/h | Geometric Coefficient of Variation 42.3 |
| Mass Balance (MB) Cohort | Apparent Clearance (CL/F) of RO7049389 - BA Cohort | Asian participants - [12C] Period 1 | 36.6 L/h | Geometric Coefficient of Variation 122.3 |
| Mass Balance (MB) Cohort | Apparent Clearance (CL/F) of RO7049389 - BA Cohort | Caucasian participants - [12C] Period 1 | 75.3 L/h | Geometric Coefficient of Variation 69.2 |
| Mass Balance (MB) Cohort | Apparent Clearance (CL/F) of RO7049389 - BA Cohort | Asian participants - [12C] Period 2 | 37.2 L/h | Geometric Coefficient of Variation 152.1 |
| Mass Balance (MB) Cohort | Apparent Clearance (CL/F) of RO7049389 - BA Cohort | Caucasian participants - [12C] Period 2 | 87.3 L/h | Geometric Coefficient of Variation 96.5 |
| Mass Balance (MB) Cohort | Apparent Clearance (CL/F) of RO7049389 - BA Cohort | Asian participants - [13C] Period 1 | 14.8 L/h | Geometric Coefficient of Variation 48.2 |
| Mass Balance (MB) Cohort | Apparent Clearance (CL/F) of RO7049389 - BA Cohort | Caucasian participants - [13C] Period 1 | 21.9 L/h | Geometric Coefficient of Variation 28.7 |
| Mass Balance (MB) Cohort | Apparent Clearance (CL/F) of RO7049389 - BA Cohort | Asian participants - [13C] Period 2 | 14.7 L/h | Geometric Coefficient of Variation 43.9 |
Secondary
Apparent Clearance (CL/F) of RO7049389 - MB Cohort
Time frame: Up to Day 4
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Mass Balance (MB) Cohort | Apparent Clearance (CL/F) of RO7049389 - MB Cohort | 100 L/h | Geometric Coefficient of Variation 71.4 |
Secondary
Area Under Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7049389 - BA Cohort
Time frame: Up to Day 4 of Periods 1 and 2
Population: All participants who have received at least one dose of study treatment and who have data from at least one post-dose sample were included in the PK analysis population. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which may influence the PK analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mass Balance (MB) Cohort | Area Under Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7049389 - BA Cohort | Asian participants - [12C] Period 1 | 16400 h*ng/mL | Geometric Coefficient of Variation 122.3 |
| Mass Balance (MB) Cohort | Area Under Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7049389 - BA Cohort | Caucasian participants - [12C] Period 1 | 7970 h*ng/mL | Geometric Coefficient of Variation 69.2 |
| Mass Balance (MB) Cohort | Area Under Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7049389 - BA Cohort | Asian participants - [13C] Period 1 | 6.8 h*ng/mL | Geometric Coefficient of Variation 48.2 |
| Mass Balance (MB) Cohort | Area Under Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7049389 - BA Cohort | Caucasian participants - [13C] Period 1 | 4.6 h*ng/mL | Geometric Coefficient of Variation 28.7 |
| Mass Balance (MB) Cohort | Area Under Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7049389 - BA Cohort | Asian participants - [12C] Period 2 | 26900 h*ng/mL | Geometric Coefficient of Variation 152.1 |
| Mass Balance (MB) Cohort | Area Under Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7049389 - BA Cohort | Caucasian participants - [12C] Period 2 | 11500 h*ng/mL | Geometric Coefficient of Variation 96.5 |
| Mass Balance (MB) Cohort | Area Under Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7049389 - BA Cohort | Asian participants - [13C] Period 2 | 6.8 h*ng/mL | Geometric Coefficient of Variation 43.9 |
| Mass Balance (MB) Cohort | Area Under Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7049389 - BA Cohort | Caucasian participants - [13C] Period 2 | 4.1 h*ng/mL | Geometric Coefficient of Variation 42.3 |
Secondary
Area Under Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7049389 - MB Cohort
Time frame: Up to Day 4
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mass Balance (MB) Cohort | Area Under Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7049389 - MB Cohort | [12C] RO7049389 | 5970 h*ng/mL | Geometric Coefficient of Variation 71.4 |
| Mass Balance (MB) Cohort | Area Under Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7049389 - MB Cohort | [13C] RO7049389 | 4.0 h*ng/mL | Geometric Coefficient of Variation 54.3 |
| Mass Balance (MB) Cohort | Area Under Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7049389 - MB Cohort | [14C] RO7049389 | 83700 h*ng/mL | Geometric Coefficient of Variation 39.6 |
Secondary
Area Under the Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of RO7049389 - BA Cohort
Time frame: Up to Day 4 of Periods 1 and 2
Population: All participants who have received at least one dose of study treatment and who have data from at least one post-dose sample were included in the PK analysis population. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which may influence the PK analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mass Balance (MB) Cohort | Area Under the Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of RO7049389 - BA Cohort | Caucasian participants - [13C] Period 1 | 4.4 h*ng/mL | Geometric Coefficient of Variation 27.2 |
| Mass Balance (MB) Cohort | Area Under the Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of RO7049389 - BA Cohort | Asian participants - [12C] Period 2 | 26800 h*ng/mL | Geometric Coefficient of Variation 152.2 |
| Mass Balance (MB) Cohort | Area Under the Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of RO7049389 - BA Cohort | Caucasian participants - [12C] Period 2 | 10100 h*ng/mL | Geometric Coefficient of Variation 96.9 |
| Mass Balance (MB) Cohort | Area Under the Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of RO7049389 - BA Cohort | Asian participants - [12C] Period 1 | 16300 h*ng/mL | Geometric Coefficient of Variation 123.1 |
| Mass Balance (MB) Cohort | Area Under the Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of RO7049389 - BA Cohort | Caucasian participants - [12C] Period 1 | 8110 h*ng/mL | Geometric Coefficient of Variation 63.7 |
| Mass Balance (MB) Cohort | Area Under the Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of RO7049389 - BA Cohort | Asian participants - [13C] Period 1 | 6.5 h*ng/mL | Geometric Coefficient of Variation 45.9 |
| Mass Balance (MB) Cohort | Area Under the Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of RO7049389 - BA Cohort | Asian participants - [13C] Period 2 | 7.2 h*ng/mL | Geometric Coefficient of Variation 41.1 |
| Mass Balance (MB) Cohort | Area Under the Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of RO7049389 - BA Cohort | Caucasian participants - [13C] Period 2 | 4.3 h*ng/mL | Geometric Coefficient of Variation 38.1 |
Secondary
Area Under the Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of RO7049389 - MB Cohort
Time frame: Up to Day 17
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Mass Balance (MB) Cohort | Area Under the Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of RO7049389 - MB Cohort | 8280 h*ng/mL | Geometric Coefficient of Variation 129.7 |
Secondary
Clearance (CL) of RO7049389 - BA Cohort
Time frame: Up to Day 4 of Periods 1 and 2
Population: All participants who have received at least one dose of study treatment and who have data from at least one post-dose sample were included in the PK analysis population. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which may influence the PK analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mass Balance (MB) Cohort | Clearance (CL) of RO7049389 - BA Cohort | Caucasian participants - [12C] Period 2 | 87.3 L/h | Geometric Coefficient of Variation 96.5 |
| Mass Balance (MB) Cohort | Clearance (CL) of RO7049389 - BA Cohort | Asian participants - [13C] Period 2 | 14.7 L/h | Geometric Coefficient of Variation 43.9 |
| Mass Balance (MB) Cohort | Clearance (CL) of RO7049389 - BA Cohort | Caucasian participants - [13C] Period 2 | 24.7 L/h | Geometric Coefficient of Variation 42.3 |
| Mass Balance (MB) Cohort | Clearance (CL) of RO7049389 - BA Cohort | Asian participants - [12C] Period 1 | 36.6 L/h | Geometric Coefficient of Variation 122.3 |
| Mass Balance (MB) Cohort | Clearance (CL) of RO7049389 - BA Cohort | Caucasian participants - [12C] Period 1 | 75.3 L/h | Geometric Coefficient of Variation 69.2 |
| Mass Balance (MB) Cohort | Clearance (CL) of RO7049389 - BA Cohort | Asian participants - [13C] Period 1 | 14.8 L/h | Geometric Coefficient of Variation 48.2 |
| Mass Balance (MB) Cohort | Clearance (CL) of RO7049389 - BA Cohort | Caucasian participants - [13C] Period 1 | 21.9 L/h | Geometric Coefficient of Variation 28.7 |
| Mass Balance (MB) Cohort | Clearance (CL) of RO7049389 - BA Cohort | Asian participants - [12C] Period 2 | 37.2 L/h | Geometric Coefficient of Variation 152.1 |
Secondary
Clearance (CL) of RO7049389 - MB Cohort
Time frame: Up to Day 17
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mass Balance (MB) Cohort | Clearance (CL) of RO7049389 - MB Cohort | [12C] RO7049389 | 100 L/h | Geometric Coefficient of Variation 71.4 |
| Mass Balance (MB) Cohort | Clearance (CL) of RO7049389 - MB Cohort | [13C] RO7049389 | 25.3 L/h | Geometric Coefficient of Variation 54.3 |
Secondary
Half-Life (T1/2) of RO7049389 - BA Cohort
Time frame: Up to Day 4 of Periods 1 and 2
Population: All participants who have received at least one dose of study treatment and who have data from at least one post-dose sample were included in the PK analysis population. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which may influence the PK analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mass Balance (MB) Cohort | Half-Life (T1/2) of RO7049389 - BA Cohort | Asian participants - [12C] Period 1 | 8.3 Hours | Geometric Coefficient of Variation 35.4 |
| Mass Balance (MB) Cohort | Half-Life (T1/2) of RO7049389 - BA Cohort | Caucasian participants - [12C] Period 1 | 7.6 Hours | Geometric Coefficient of Variation 31.1 |
| Mass Balance (MB) Cohort | Half-Life (T1/2) of RO7049389 - BA Cohort | Asian participants - [13C] Period 1 | 1.6 Hours | Geometric Coefficient of Variation 32.8 |
| Mass Balance (MB) Cohort | Half-Life (T1/2) of RO7049389 - BA Cohort | Caucasian participants - [13C] Period 1 | 1.3 Hours | Geometric Coefficient of Variation 46 |
| Mass Balance (MB) Cohort | Half-Life (T1/2) of RO7049389 - BA Cohort | Asian participants - [12C] Period 2 | 6.7 Hours | Geometric Coefficient of Variation 83.6 |
| Mass Balance (MB) Cohort | Half-Life (T1/2) of RO7049389 - BA Cohort | Caucasian participants - [12C] Period 2 | 11.1 Hours | Geometric Coefficient of Variation 34.6 |
| Mass Balance (MB) Cohort | Half-Life (T1/2) of RO7049389 - BA Cohort | Asian participants - [13C] Period 2 | 1.6 Hours | Geometric Coefficient of Variation 36.7 |
| Mass Balance (MB) Cohort | Half-Life (T1/2) of RO7049389 - BA Cohort | Caucasian participants - [13C] Period 2 | 1.1 Hours | Geometric Coefficient of Variation 46.7 |
Secondary
Half-Life (T1/2) of RO7049389 - MB Cohort
Time frame: Up to Day 17
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mass Balance (MB) Cohort | Half-Life (T1/2) of RO7049389 - MB Cohort | [12C] RO7049389 | 8.1 Hours | Geometric Coefficient of Variation 24.6 |
| Mass Balance (MB) Cohort | Half-Life (T1/2) of RO7049389 - MB Cohort | [13C] RO7049389 | 1.9 Hours | Geometric Coefficient of Variation 23.6 |
| Mass Balance (MB) Cohort | Half-Life (T1/2) of RO7049389 - MB Cohort | [14C] RO7049389 | 11.4 Hours | Geometric Coefficient of Variation 35.3 |
Secondary
Maximum Plasma Concentration (Cmax) of RO7049389 - BA Cohort
Time frame: Up to Day 4 of Periods 1 and 2
Population: All participants who have received at least one dose of study treatment and who have data from at least one post-dose sample were included in the PK analysis population. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which may influence the PK analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mass Balance (MB) Cohort | Maximum Plasma Concentration (Cmax) of RO7049389 - BA Cohort | Asian participants - [13C] Period 1 | 8.2 ng/mL | Geometric Coefficient of Variation 21.4 |
| Mass Balance (MB) Cohort | Maximum Plasma Concentration (Cmax) of RO7049389 - BA Cohort | Asian participants - [12C] Period 1 | 6390 ng/mL | Geometric Coefficient of Variation 118 |
| Mass Balance (MB) Cohort | Maximum Plasma Concentration (Cmax) of RO7049389 - BA Cohort | Caucasian participants - [12C] Period 1 | 3000 ng/mL | Geometric Coefficient of Variation 112.9 |
| Mass Balance (MB) Cohort | Maximum Plasma Concentration (Cmax) of RO7049389 - BA Cohort | Caucasian participants - [13C] Period 1 | 7.7 ng/mL | Geometric Coefficient of Variation 13.5 |
| Mass Balance (MB) Cohort | Maximum Plasma Concentration (Cmax) of RO7049389 - BA Cohort | Asian participants - [12C] Period 2 | 9470 ng/mL | Geometric Coefficient of Variation 110.7 |
| Mass Balance (MB) Cohort | Maximum Plasma Concentration (Cmax) of RO7049389 - BA Cohort | Caucasian participants - [12C] Period 2 | 3570 ng/mL | Geometric Coefficient of Variation 109.3 |
| Mass Balance (MB) Cohort | Maximum Plasma Concentration (Cmax) of RO7049389 - BA Cohort | Asian participants - [13C] Period 2 | 8.7 ng/mL | Geometric Coefficient of Variation 13.3 |
| Mass Balance (MB) Cohort | Maximum Plasma Concentration (Cmax) of RO7049389 - BA Cohort | Caucasian participants - [13C] Period 2 | 7.7 ng/mL | Geometric Coefficient of Variation 14.1 |
Secondary
Maximum Plasma Concentration (Cmax) of RO7049389 - MB Cohort
Time frame: Up to Day 17
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mass Balance (MB) Cohort | Maximum Plasma Concentration (Cmax) of RO7049389 - MB Cohort | [12C] RO7049389 | 3820 ng/mL | Geometric Coefficient of Variation 144.8 |
| Mass Balance (MB) Cohort | Maximum Plasma Concentration (Cmax) of RO7049389 - MB Cohort | [13C] RO7049389 | 7.6 ng/mL | Geometric Coefficient of Variation 16.9 |
| Mass Balance (MB) Cohort | Maximum Plasma Concentration (Cmax) of RO7049389 - MB Cohort | [14C] RO7049389 | 6390 ng/mL | Geometric Coefficient of Variation 89.7 |
Secondary
Percentage of Participants With Adverse Events (AEs)
Time frame: Up to Day 29 (MB Cohort) or up to Day 29 of Period 2 (AB Cohort)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mass Balance (MB) Cohort | Percentage of Participants With Adverse Events (AEs) | 81.3 Percentage of participants |
| Mass Balance (MB) Cohort | Percentage of Participants With Adverse Events (AEs) | 33.3 Percentage of participants |
Secondary
Renal Clearance (CLr) of RO7049389 - BA Cohort
Time frame: Up to Day 4 of Periods 1 and 2
Population: All participants who have received at least one dose of study treatment and who have data from at least one post-dose sample were included in the PK analysis population. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which may influence the PK analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mass Balance (MB) Cohort | Renal Clearance (CLr) of RO7049389 - BA Cohort | Asian participants - [12C] Period 1 | 2.7 mL/min | Geometric Coefficient of Variation 42.6 |
| Mass Balance (MB) Cohort | Renal Clearance (CLr) of RO7049389 - BA Cohort | Caucasian participants - [12C] Period 1 | 1.1 mL/min | Geometric Coefficient of Variation 61.1 |
| Mass Balance (MB) Cohort | Renal Clearance (CLr) of RO7049389 - BA Cohort | Asian participants - [12C] Period 2 | 2.5 mL/min | Geometric Coefficient of Variation 22.9 |
| Mass Balance (MB) Cohort | Renal Clearance (CLr) of RO7049389 - BA Cohort | Caucasian participants - [12C] Period 2 | 0.8 mL/min | Geometric Coefficient of Variation 65.5 |
Secondary
Time to Maximum Plasma Concentration (Tmax) of RO7049389 - BA Cohort
Time frame: Up to Day 4 of Periods 1 and 2
Population: All participants who have received at least one dose of study treatment and who have data from at least one post-dose sample were included in the PK analysis population. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which may influence the PK analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mass Balance (MB) Cohort | Time to Maximum Plasma Concentration (Tmax) of RO7049389 - BA Cohort | Caucasian participants - [12C] Period 1 | 2.00 Hours |
| Mass Balance (MB) Cohort | Time to Maximum Plasma Concentration (Tmax) of RO7049389 - BA Cohort | Asian participants - [13C] Period 1 | 2.13 Hours |
| Mass Balance (MB) Cohort | Time to Maximum Plasma Concentration (Tmax) of RO7049389 - BA Cohort | Caucasian participants - [13C] Period 1 | 6.00 Hours |
| Mass Balance (MB) Cohort | Time to Maximum Plasma Concentration (Tmax) of RO7049389 - BA Cohort | Asian participants - [12C] Period 2 | 1.50 Hours |
| Mass Balance (MB) Cohort | Time to Maximum Plasma Concentration (Tmax) of RO7049389 - BA Cohort | Asian participants - [12C] Period 1 | 1.75 Hours |
| Mass Balance (MB) Cohort | Time to Maximum Plasma Concentration (Tmax) of RO7049389 - BA Cohort | Caucasian participants - [12C] Period 2 | 2.00 Hours |
| Mass Balance (MB) Cohort | Time to Maximum Plasma Concentration (Tmax) of RO7049389 - BA Cohort | Asian participants - [13C] Period 2 | 2.13 Hours |
| Mass Balance (MB) Cohort | Time to Maximum Plasma Concentration (Tmax) of RO7049389 - BA Cohort | Caucasian participants - [13C] Period 2 | 2.13 Hours |
Secondary
Time to Maximum Plasma Concentration (Tmax) of RO7049389 - MB Cohort
Time frame: Up to Day 17
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mass Balance (MB) Cohort | Time to Maximum Plasma Concentration (Tmax) of RO7049389 - MB Cohort | [12C] RO7049389 | 1.50 Hours |
| Mass Balance (MB) Cohort | Time to Maximum Plasma Concentration (Tmax) of RO7049389 - MB Cohort | [13C] RO7049389 | 2.13 Hours |
| Mass Balance (MB) Cohort | Time to Maximum Plasma Concentration (Tmax) of RO7049389 - MB Cohort | [14C] RO7049389 | 4.00 Hours |