Trial Outcomes & Findings for A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants (NCT NCT04475848)
NCT ID: NCT04475848
Last Updated: 2024-07-10
Results Overview
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
88 participants
Primary outcome timeframe
Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
Results posted on
2024-07-10
Participant Flow
This study was conducted at one centre in the United Kingdom.
Participant milestones
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
6
|
6
|
6
|
6
|
10
|
2
|
6
|
6
|
6
|
6
|
16
|
|
Overall Study
COMPLETED
|
6
|
6
|
6
|
6
|
6
|
6
|
10
|
2
|
6
|
6
|
6
|
6
|
16
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
Baseline characteristics by cohort
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
n=10 Participants
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
n=2 Participants
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
n=6 Participants
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
n=16 Participants
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
Total
n=88 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
39.0 Years
STANDARD_DEVIATION 9.9 • n=5 Participants
|
37.3 Years
STANDARD_DEVIATION 8.1 • n=7 Participants
|
37.5 Years
STANDARD_DEVIATION 4.3 • n=5 Participants
|
33.7 Years
STANDARD_DEVIATION 11.9 • n=4 Participants
|
40.3 Years
STANDARD_DEVIATION 10.3 • n=21 Participants
|
33.8 Years
STANDARD_DEVIATION 12.6 • n=8 Participants
|
34.1 Years
STANDARD_DEVIATION 9.7 • n=8 Participants
|
38.5 Years
STANDARD_DEVIATION 2.1 • n=24 Participants
|
32.5 Years
STANDARD_DEVIATION 7.4 • n=42 Participants
|
36.2 Years
STANDARD_DEVIATION 11.7 • n=42 Participants
|
38.7 Years
STANDARD_DEVIATION 12.9 • n=42 Participants
|
30.3 Years
STANDARD_DEVIATION 11.2 • n=42 Participants
|
33.6 Years
STANDARD_DEVIATION 10.6 • n=36 Participants
|
35.8 Years
STANDARD_DEVIATION 9.4 • n=36 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
6 Participants
n=8 Participants
|
10 Participants
n=8 Participants
|
2 Participants
n=24 Participants
|
6 Participants
n=42 Participants
|
6 Participants
n=42 Participants
|
6 Participants
n=42 Participants
|
6 Participants
n=42 Participants
|
16 Participants
n=36 Participants
|
88 Participants
n=36 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
4 Participants
n=36 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
5 Participants
n=8 Participants
|
9 Participants
n=8 Participants
|
2 Participants
n=24 Participants
|
6 Participants
n=42 Participants
|
6 Participants
n=42 Participants
|
6 Participants
n=42 Participants
|
6 Participants
n=42 Participants
|
16 Participants
n=36 Participants
|
83 Participants
n=36 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
1 Participants
n=36 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
2 Participants
n=42 Participants
|
4 Participants
n=36 Participants
|
10 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
3 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=36 Participants
|
8 Participants
n=36 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
6 Participants
n=8 Participants
|
9 Participants
n=8 Participants
|
2 Participants
n=24 Participants
|
6 Participants
n=42 Participants
|
4 Participants
n=42 Participants
|
2 Participants
n=42 Participants
|
4 Participants
n=42 Participants
|
10 Participants
n=36 Participants
|
65 Participants
n=36 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=36 Participants
|
5 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=36 Participants
|
PRIMARY outcome
Timeframe: Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeksPopulation: The safety population included all participants randomized to study treatment and who received at least one dose of the study treatment.
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
n=10 Participants
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
n=2 Participants
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
n=6 Participants
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
n=16 Participants
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts 1, 2 and 3: Percentage of Participants With Adverse Events
|
2 Participants
|
2 Participants
|
2 Participants
|
4 Participants
|
2 Participants
|
3 Participants
|
2 Participants
|
0 Participants
|
4 Participants
|
6 Participants
|
4 Participants
|
2 Participants
|
15 Participants
|
PRIMARY outcome
Timeframe: From randomization up to 8 weeksPopulation: The safety population included all participants randomized to study treatment and who received at least one dose of the study treatment.
The C-SSRS is a questionnaire that is used to assess a participant's suicidal ideation and behaviors. The categories in the questionnaire have binary responses (yes/no) and include: Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation or behavior is indicated by a "yes" answer to any of the listed categories. A score of 0 is assigned if no suicide risk is present. Categories with non-zero values are reported here.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part 2: Number of Participants With Post-baseline Suicide Risk, Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)
Highest Suicidal Ideation
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Number of Participants With Post-baseline Suicide Risk, Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)
Highest Suicidal Behavior
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Number of Participants With Post-baseline Suicide Risk, Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)
Suicidal Ideation or Behavior
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Number of Participants With Post-baseline Suicide Risk, Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)
Self-Injury Behavior w/o suicidal intent
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-14Population: The pharmacokinetic (PK) population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
n=6 Participants
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
n=6 Participants
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
n=16 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 1
|
70.3 Nanograms per Milliliter (ng/mL)
Standard Deviation 31.4
|
150 Nanograms per Milliliter (ng/mL)
Standard Deviation 34.2
|
299 Nanograms per Milliliter (ng/mL)
Standard Deviation 50.0
|
451 Nanograms per Milliliter (ng/mL)
Standard Deviation 30.7
|
932 Nanograms per Milliliter (ng/mL)
Standard Deviation 34.6
|
618 Nanograms per Milliliter (ng/mL)
Standard Deviation 47.4
|
866 Nanograms per Milliliter (ng/mL)
Standard Deviation 39.5
|
490 Nanograms per Milliliter (ng/mL)
Standard Deviation 25.0
|
1250 Nanograms per Milliliter (ng/mL)
Standard Deviation 49.7
|
1580 Nanograms per Milliliter (ng/mL)
Standard Deviation 21.8
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 10
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
194 Nanograms per Milliliter (ng/mL)
Standard Deviation 44.9
|
456 Nanograms per Milliliter (ng/mL)
Standard Deviation 68.3
|
528 Nanograms per Milliliter (ng/mL)
Standard Deviation 46.7
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 14
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
816 Nanograms per Milliliter (ng/mL)
Standard Deviation 42.1
|
—
|
—
|
|
Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
1850 Nanograms per Milliliter (ng/mL)
Standard Deviation 30.5
|
—
|
—
|
|
Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 10
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
490 Nanograms per Milliliter (ng/mL)
Standard Deviation 25.0
|
1250 Nanograms per Milliliter (ng/mL)
Standard Deviation 49.7
|
1580 Nanograms per Milliliter (ng/mL)
Standard Deviation 21.8
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 14
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
2120 Nanograms per Milliliter (ng/mL)
Standard Deviation 32.8
|
—
|
—
|
|
Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 1
|
61.3 Nanograms per Milliliter (ng/mL)
Standard Deviation 45.0
|
187 Nanograms per Milliliter (ng/mL)
Standard Deviation 41.0
|
480 Nanograms per Milliliter (ng/mL)
Standard Deviation 76.0
|
490 Nanograms per Milliliter (ng/mL)
Standard Deviation 18.8
|
819 Nanograms per Milliliter (ng/mL)
Standard Deviation 21.2
|
1230 Nanograms per Milliliter (ng/mL)
Standard Deviation 67.2
|
3.57 Nanograms per Milliliter (ng/mL)
Standard Deviation 28.3
|
1850 Nanograms per Milliliter (ng/mL)
Standard Deviation 21.6
|
677 Nanograms per Milliliter (ng/mL)
Standard Deviation 47.9
|
1100 Nanograms per Milliliter (ng/mL)
Standard Deviation 41.4
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
2890 Nanograms per Milliliter (ng/mL)
Standard Deviation 61.9
|
—
|
—
|
|
Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 10
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
1100 Nanograms per Milliliter (ng/mL)
Standard Deviation 41.4
|
3180 Nanograms per Milliliter (ng/mL)
Standard Deviation 76.7
|
6010 Nanograms per Milliliter (ng/mL)
Standard Deviation 65.3
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 14
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
5310 Nanograms per Milliliter (ng/mL)
Standard Deviation 66.7
|
—
|
—
|
|
Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 1
|
32.3 Nanograms per Milliliter (ng/mL)
Standard Deviation 29.6
|
77.3 Nanograms per Milliliter (ng/mL)
Standard Deviation 25.2
|
169 Nanograms per Milliliter (ng/mL)
Standard Deviation 36.9
|
272 Nanograms per Milliliter (ng/mL)
Standard Deviation 32.5
|
491 Nanograms per Milliliter (ng/mL)
Standard Deviation 29.1
|
1.69 Nanograms per Milliliter (ng/mL)
Standard Deviation 71.1
|
1.33 Nanograms per Milliliter (ng/mL)
Standard Deviation 42.4
|
171 Nanograms per Milliliter (ng/mL)
Standard Deviation 43.0
|
452 Nanograms per Milliliter (ng/mL)
Standard Deviation 31.5
|
629 Nanograms per Milliliter (ng/mL)
Standard Deviation 30.3
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
710 Nanograms per Milliliter (ng/mL)
Standard Deviation 34.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-14Population: The pharmacokinetic (PK) population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=16 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 1
|
69.97 ng/mL
Standard Deviation 33.67
|
194.92 ng/mL
Standard Deviation 116.77
|
293.36 ng/mL
Standard Deviation 146.13
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 3
|
—
|
—
|
—
|
341.71 ng/mL
Standard Deviation 165.07
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 10
|
76.29 ng/mL
Standard Deviation 38.08
|
230.74 ng/mL
Standard Deviation 169.20
|
272.07 ng/mL
Standard Deviation 204.45
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 14
|
—
|
—
|
—
|
428.80 ng/mL
Standard Deviation 303.11
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 1
|
81.47 ng/mL
Standard Deviation 28.35
|
279.87 ng/mL
Standard Deviation 163.45
|
496.48 ng/mL
Standard Deviation 128.30
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 3
|
—
|
—
|
—
|
531.60 ng/mL
Standard Deviation 276.14
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 10
|
87.96 ng/mL
Standard Deviation 26.59
|
283.22 ng/mL
Standard Deviation 141.49
|
410.99 ng/mL
Standard Deviation 161.04
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 14
|
—
|
—
|
—
|
646.81 ng/mL
Standard Deviation 453.67
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 1
|
407.07 ng/mL
Standard Deviation 185.06
|
1380.91 ng/mL
Standard Deviation 931.78
|
2987.02 ng/mL
Standard Deviation 1307.84
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 3
|
—
|
—
|
—
|
2305.32 ng/mL
Standard Deviation 1570.98
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 10
|
743.87 ng/mL
Standard Deviation 336.40
|
2759.37 ng/mL
Standard Deviation 2433.54
|
4822.34 ng/mL
Standard Deviation 2550.00
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 14
|
—
|
—
|
—
|
4552.31 ng/mL
Standard Deviation 3813.18
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-14Population: The pharmacokinetic (PK) population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
n=6 Participants
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
n=6 Participants
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
n=16 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 1
|
1.00 Hours (h)
Interval 0.5 to 2.0
|
1.00 Hours (h)
Interval 0.5 to 2.12
|
2.00 Hours (h)
Interval 1.0 to 3.0
|
2.00 Hours (h)
Interval 1.0 to 2.02
|
4.00 Hours (h)
Interval 2.0 to 5.0
|
2.00 Hours (h)
Interval 1.0 to 5.0
|
2.00 Hours (h)
Interval 0.5 to 3.0
|
2.53 Hours (h)
Interval 2.0 to 3.0
|
2.01 Hours (h)
Interval 1.0 to 3.02
|
3.00 Hours (h)
Interval 2.0 to 3.02
|
3.00 Hours (h)
Interval 2.0 to 5.08
|
—
|
—
|
|
Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
3.00 Hours (h)
Interval 2.0 to 5.08
|
—
|
—
|
|
Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 10
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
2.02 Hours (h)
Interval 1.0 to 3.0
|
2.04 Hours (h)
Interval 1.02 to 3.0
|
2.00 Hours (h)
Interval 1.0 to 3.0
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 1
|
2.00 Hours (h)
Interval 1.0 to 3.0
|
2.00 Hours (h)
Interval 2.0 to 6.0
|
5.50 Hours (h)
Interval 5.0 to 7.0
|
6.51 Hours (h)
Interval 5.0 to 10.0
|
5.50 Hours (h)
Interval 3.0 to 10.0
|
6.50 Hours (h)
Interval 2.0 to 48.02
|
7.01 Hours (h)
Interval 5.0 to 24.05
|
5.00 Hours (h)
Interval 3.0 to 6.03
|
3.02 Hours (h)
Interval 3.0 to 10.0
|
5.00 Hours (h)
Interval 3.0 to 7.0
|
6.02 Hours (h)
Interval 3.0 to 10.08
|
—
|
—
|
|
Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
5.08 Hours (h)
Interval 3.0 to 12.0
|
—
|
—
|
|
Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 10
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
5.02 Hours (h)
Interval 2.08 to 5.05
|
4.00 Hours (h)
Interval 3.0 to 7.0
|
4.01 Hours (h)
Interval 3.0 to 7.03
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 14
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
3.00 Hours (h)
Interval 2.0 to 5.0
|
—
|
—
|
|
Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 14
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
6.02 Hours (h)
Interval 3.0 to 10.08
|
—
|
—
|
|
Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 1
|
1.50 Hours (h)
Interval 1.0 to 3.0
|
2.00 Hours (h)
Interval 1.0 to 6.0
|
4.00 Hours (h)
Interval 2.02 to 6.0
|
5.00 Hours (h)
Interval 3.0 to 6.0
|
5.00 Hours (h)
Interval 2.0 to 7.0
|
4.00 Hours (h)
Interval 2.0 to 7.05
|
5.01 Hours (h)
Interval 3.0 to 10.0
|
4.00 Hours (h)
Interval 3.0 to 5.0
|
3.02 Hours (h)
Interval 3.0 to 5.0
|
4.08 Hours (h)
Interval 2.0 to 6.02
|
5.00 Hours (h)
Interval 3.0 to 10.03
|
—
|
—
|
|
Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
4.02 Hours (h)
Interval 2.05 to 6.02
|
—
|
—
|
|
Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 10
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
3.01 Hours (h)
Interval 2.08 to 5.02
|
3.04 Hours (h)
Interval 3.0 to 5.0
|
2.51 Hours (h)
Interval 2.0 to 6.03
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 14
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
5.00 Hours (h)
Interval 3.0 to 10.03
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-10Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
n=6 Participants
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State
RO6953958
|
3.88 ng/mL
Geometric Coefficient of Variation 63.7
|
4.42 ng/mL
Geometric Coefficient of Variation 71.6
|
5.98 ng/mL
Geometric Coefficient of Variation 82.4
|
6.75 ng/mL
Geometric Coefficient of Variation 98.2
|
11.1 ng/mL
Geometric Coefficient of Variation 130.4
|
8.99 ng/mL
Geometric Coefficient of Variation 97.7
|
10.6 ng/mL
Geometric Coefficient of Variation 67.1
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State
RO7021594
|
2.67 ng/mL
Geometric Coefficient of Variation 24.0
|
6.22 ng/mL
Geometric Coefficient of Variation 84.1
|
12.6 ng/mL
Geometric Coefficient of Variation 163.1
|
41.1 ng/mL
Geometric Coefficient of Variation 3.16
|
31.6 ng/mL
Geometric Coefficient of Variation 4.04
|
80.3 ng/mL
Geometric Coefficient of Variation 12.6
|
115.1 ng/mL
Geometric Coefficient of Variation 9.75
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State
RO7045755
|
5.64 ng/mL
Geometric Coefficient of Variation 53.3
|
7.48 ng/mL
Geometric Coefficient of Variation 55.7
|
6.52 ng/mL
Geometric Coefficient of Variation 78.2
|
84.4 ng/mL
Geometric Coefficient of Variation 7.71
|
116.6 ng/mL
Geometric Coefficient of Variation 6.70
|
59.3 ng/mL
Geometric Coefficient of Variation 6.15
|
60.7 ng/mL
Geometric Coefficient of Variation 6.25
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-10Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
n=6 Participants
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594
|
87.23 h
Geometric Coefficient of Variation 14.9
|
96.03 h
Geometric Coefficient of Variation 0.1
|
96.01 h
Geometric Coefficient of Variation 0.0
|
170.15 h
Geometric Coefficient of Variation 29.3
|
144.29 h
Geometric Coefficient of Variation 24.6
|
208.08 h
Geometric Coefficient of Variation 10.8
|
216.78 h
Geometric Coefficient of Variation 0.5
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958
|
9.44 h
Geometric Coefficient of Variation 25.0
|
16.47 h
Geometric Coefficient of Variation 43.8
|
21.40 h
Geometric Coefficient of Variation 28.9
|
51.37 h
Geometric Coefficient of Variation 16.6
|
24.00 h
Geometric Coefficient of Variation 0.0
|
70.14 h
Geometric Coefficient of Variation 22.3
|
88.77 h
Geometric Coefficient of Variation 32.1
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755
|
3.84 h
Geometric Coefficient of Variation 52.9
|
19.06 h
Geometric Coefficient of Variation 37.0
|
26.96 h
Geometric Coefficient of Variation 28.9
|
54.96 h
Geometric Coefficient of Variation 21.2
|
38.10 h
Geometric Coefficient of Variation 37.0
|
74.87 h
Geometric Coefficient of Variation 12.2
|
92.34 h
Geometric Coefficient of Variation 34.9
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-14Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
n=6 Participants
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
n=6 Participants
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
n=16 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 1
|
1.75 h
Geometric Coefficient of Variation 11.8
|
3.43 h
Geometric Coefficient of Variation 52.4
|
3.98 h
Geometric Coefficient of Variation 46.3
|
9.54 h
Geometric Coefficient of Variation 13.9
|
3.57 h
Geometric Coefficient of Variation 20.6
|
13.1 h
Geometric Coefficient of Variation 23.7
|
14.9 h
Geometric Coefficient of Variation 21.8
|
2.63 h
Geometric Coefficient of Variation 43.6
|
6.60 h
Geometric Coefficient of Variation 18.9
|
4.99 h
Geometric Coefficient of Variation 27.3
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
5.87 h
Geometric Coefficient of Variation 27.6
|
—
|
—
|
|
Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 10
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
3.43 h
Geometric Coefficient of Variation 42.7
|
7.90 h
Geometric Coefficient of Variation 51.0
|
6.29 h
Geometric Coefficient of Variation 15.6
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 14
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
6.20 h
Geometric Coefficient of Variation 56.2
|
—
|
—
|
|
Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 1
|
21.0 h
Geometric Coefficient of Variation 13.7
|
19.7 h
Geometric Coefficient of Variation 12.4
|
19.1 h
Geometric Coefficient of Variation 14.1
|
20.8 h
Geometric Coefficient of Variation 25.4
|
20.6 h
Geometric Coefficient of Variation 30.4
|
27.7 h
Geometric Coefficient of Variation 18.6
|
27.1 h
Geometric Coefficient of Variation 17.3
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 10
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
31.5 h
Geometric Coefficient of Variation 31.2
|
34.0 h
Geometric Coefficient of Variation 9.7
|
35.8 h
Geometric Coefficient of Variation 17.5
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 14
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
36.0 h
Geometric Coefficient of Variation 24.9
|
—
|
—
|
|
Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 1
|
3.84 h
Geometric Coefficient of Variation 52.9
|
4.54 h
Geometric Coefficient of Variation 31.9
|
4.82 h
Geometric Coefficient of Variation 26.0
|
10.3 h
Geometric Coefficient of Variation 15.7
|
5.25 h
Geometric Coefficient of Variation 13.1
|
13.5 h
Geometric Coefficient of Variation 22.8
|
12.7 h
Geometric Coefficient of Variation 20.6
|
3.89 h
Geometric Coefficient of Variation 42.9
|
5.38 h
Geometric Coefficient of Variation 33.6
|
6.21 h
Geometric Coefficient of Variation 15.2
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
5.33 h
Geometric Coefficient of Variation 28.0
|
—
|
—
|
|
Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 10
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
4.39 h
Geometric Coefficient of Variation 50.6
|
6.72 h
Geometric Coefficient of Variation 42.9
|
7.91 h
Geometric Coefficient of Variation 54.4
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 14
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
5.81 h
Geometric Coefficient of Variation 55.8
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-14Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=16 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 1
|
1830 h*ng/mL
Geometric Coefficient of Variation 44.7
|
5820 h*ng/mL
Geometric Coefficient of Variation 63.9
|
11600 h*ng/mL
Geometric Coefficient of Variation 27.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 3
|
—
|
—
|
—
|
11400 h*ng/mL
Geometric Coefficient of Variation 51.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 10
|
2010 h*ng/mL
Geometric Coefficient of Variation 38.4
|
6060 h*ng/mL
Geometric Coefficient of Variation 58.0
|
9180 h*ng/mL
Geometric Coefficient of Variation 44.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 14
|
—
|
—
|
—
|
14300 h*ng/mL
Geometric Coefficient of Variation 65.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 1
|
9040 h*ng/mL
Geometric Coefficient of Variation 43.8
|
27400 h*ng/mL
Geometric Coefficient of Variation 79.8
|
64000 h*ng/mL
Geometric Coefficient of Variation 62.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 3
|
—
|
—
|
—
|
47000 h*ng/mL
Geometric Coefficient of Variation 60.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 10
|
16400 h*ng/mL
Geometric Coefficient of Variation 47.9
|
51500 h*ng/mL
Geometric Coefficient of Variation 85.4
|
103000 h*ng/mL
Geometric Coefficient of Variation 59.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 14
|
—
|
—
|
—
|
153000 h*ng/mL
Geometric Coefficient of Variation 82.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 1
|
1450 h*ng/mL
Geometric Coefficient of Variation 74.0
|
3980 h*ng/mL
Geometric Coefficient of Variation 70.8
|
6290 h*ng/mL
Geometric Coefficient of Variation 56.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 3
|
—
|
—
|
—
|
7240 h*ng/mL
Geometric Coefficient of Variation 57.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 10
|
1550 h*ng/mL
Geometric Coefficient of Variation 79.6
|
4290 h*ng/mL
Geometric Coefficient of Variation 97.2
|
5120 h*ng/mL
Geometric Coefficient of Variation 88.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 14
|
—
|
—
|
—
|
9560 h*ng/mL
Geometric Coefficient of Variation 86.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-5Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
n=6 Participants
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part 1: Area Under the Plasma Concentration Versus Time Curve From Zero to 24h Postdose (AUC(0-24h)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755
|
238 h*ng/mL
Geometric Coefficient of Variation 53.2
|
707 h*ng/mL
Geometric Coefficient of Variation 45.3
|
1610 h*ng/mL
Geometric Coefficient of Variation 34.7
|
3870 h*ng/mL
Geometric Coefficient of Variation 28.3
|
5330 h*ng/mL
Geometric Coefficient of Variation 31.1
|
4340 h*ng/mL
Geometric Coefficient of Variation 70.4
|
6630 h*ng/mL
Geometric Coefficient of Variation 68.5
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 1: Area Under the Plasma Concentration Versus Time Curve From Zero to 24h Postdose (AUC(0-24h)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958
|
204 h*ng/mL
Geometric Coefficient of Variation 38.9
|
665 h*ng/mL
Geometric Coefficient of Variation 51.3
|
1740 h*ng/mL
Geometric Coefficient of Variation 26.8
|
4140 h*ng/mL
Geometric Coefficient of Variation 39.9
|
5330 h*ng/mL
Geometric Coefficient of Variation 38.9
|
6170 h*ng/mL
Geometric Coefficient of Variation 39.7
|
8720 h*ng/mL
Geometric Coefficient of Variation 70.9
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 1: Area Under the Plasma Concentration Versus Time Curve From Zero to 24h Postdose (AUC(0-24h)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594
|
829 h*ng/mL
Geometric Coefficient of Variation 38.4
|
2910 h*ng/mL
Geometric Coefficient of Variation 45.1
|
7410 h*ng/mL
Geometric Coefficient of Variation 81.6
|
9010 h*ng/mL
Geometric Coefficient of Variation 17.9
|
12500 h*ng/mL
Geometric Coefficient of Variation 24.7
|
22700 h*ng/mL
Geometric Coefficient of Variation 60.9
|
23100 h*ng/mL
Geometric Coefficient of Variation 28.9
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-10Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
n=6 Participants
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part 1: Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Measurable Concentration (AUC0-last) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594
|
1410 h*ng/mL
Geometric Coefficient of Variation 38.6
|
4940 h*ng/mL
Geometric Coefficient of Variation 48.7
|
12200 h*ng/mL
Geometric Coefficient of Variation 89.0
|
21000 h*ng/mL
Geometric Coefficient of Variation 42.0
|
21400 h*ng/mL
Geometric Coefficient of Variation 40.1
|
74000 h*ng/mL
Geometric Coefficient of Variation 79.2
|
78500 h*ng/mL
Geometric Coefficient of Variation 46.2
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 1: Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Measurable Concentration (AUC0-last) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958
|
188 h*ng/mL
Geometric Coefficient of Variation 38.7
|
651 h*ng/mL
Geometric Coefficient of Variation 52.4
|
1730 h*ng/mL
Geometric Coefficient of Variation 27.7
|
4990 h*ng/mL
Geometric Coefficient of Variation 46.1
|
5330 h*ng/mL
Geometric Coefficient of Variation 38.9
|
9470 h*ng/mL
Geometric Coefficient of Variation 31.6
|
14700 h*ng/mL
Geometric Coefficient of Variation 83.0
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 1: Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Measurable Concentration (AUC0-last) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755
|
208 h*ng/mL
Geometric Coefficient of Variation 56.0
|
684 h*ng/mL
Geometric Coefficient of Variation 50.5
|
1650 h*ng/mL
Geometric Coefficient of Variation 34.6
|
4970 h*ng/mL
Geometric Coefficient of Variation 32.3
|
5670 h*ng/mL
Geometric Coefficient of Variation 34.0
|
6740 h*ng/mL
Geometric Coefficient of Variation 63.6
|
11500 h*ng/mL
Geometric Coefficient of Variation 93.0
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-10Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
n=6 Participants
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958
|
206 h*ng/mL
Geometric Coefficient of Variation 39.7
|
676 h*ng/mL
Geometric Coefficient of Variation 52.2
|
1780 h*ng/mL
Geometric Coefficient of Variation 26.2
|
5120 h*ng/mL
Geometric Coefficient of Variation 46.5
|
5410 h*ng/mL
Geometric Coefficient of Variation 39.3
|
9710 h*ng/mL
Geometric Coefficient of Variation 31.3
|
15200 h*ng/mL
Geometric Coefficient of Variation 78.7
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594
|
1190 h*ng/mL
Geometric Coefficient of Variation 36.8
|
4160 h*ng/mL
Geometric Coefficient of Variation 46.5
|
10500 h*ng/mL
Geometric Coefficient of Variation 85.3
|
15300 h*ng/mL
Geometric Coefficient of Variation 28.3
|
18100 h*ng/mL
Geometric Coefficient of Variation 33.3
|
44800 h*ng/mL
Geometric Coefficient of Variation 68.5
|
45400 h*ng/mL
Geometric Coefficient of Variation 30.3
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755
|
249 h*ng/mL
Geometric Coefficient of Variation 57.3
|
738 h*ng/mL
Geometric Coefficient of Variation 48.8
|
1700 h*ng/mL
Geometric Coefficient of Variation 35.4
|
4880 h*ng/mL
Geometric Coefficient of Variation 31.3
|
5750 h*ng/mL
Geometric Coefficient of Variation 33.1
|
6140 h*ng/mL
Geometric Coefficient of Variation 65.8
|
9680 h*ng/mL
Geometric Coefficient of Variation 79.3
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-14Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
n=6 Participants
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
n=6 Participants
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
n=16 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958
Day 10
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
22.4 L/h
Geometric Coefficient of Variation 38.4
|
23.1 L/h
Geometric Coefficient of Variation 58.0
|
17.4 L/h
Geometric Coefficient of Variation 27.8
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958
Day 14
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
15.87 L/h
Geometric Coefficient of Variation 58.6
|
—
|
—
|
|
Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958
Day 1
|
24.3 L/h
Geometric Coefficient of Variation 39.7
|
22.2 L/h
Geometric Coefficient of Variation 52.2
|
25.2 L/h
Geometric Coefficient of Variation 26.2
|
17.6 L/h
Geometric Coefficient of Variation 46.5
|
16.6 L/h
Geometric Coefficient of Variation 39.3
|
18.5 L/h
Geometric Coefficient of Variation 31.3
|
23.7 L/h
Geometric Coefficient of Variation 78.7
|
24.6 L/h
Geometric Coefficient of Variation 44.7
|
22.0 L/h
Geometric Coefficient of Variation 66.7
|
17.2 L/h
Geometric Coefficient of Variation 26.4
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958
Day 3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
18.43 L/h
Geometric Coefficient of Variation 51.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-14Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
n=6 Participants
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
n=6 Participants
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
n=16 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958
Day 1
|
89.1 L
Geometric Coefficient of Variation 51.2
|
110 L
Geometric Coefficient of Variation 47.5
|
145 L
Geometric Coefficient of Variation 42.7
|
242 L
Geometric Coefficient of Variation 45.3
|
85.8 L
Geometric Coefficient of Variation 35.8
|
45.5 L
Geometric Coefficient of Variation 425
|
509 L
Geometric Coefficient of Variation 91.5
|
93.1 L
Geometric Coefficient of Variation 30.2
|
209 L
Geometric Coefficient of Variation 63.0
|
164 L
Geometric Coefficient of Variation 69.6
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958
Day 10
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
111 L
Geometric Coefficient of Variation 25.2
|
263 L
Geometric Coefficient of Variation 77.2
|
158 L
Geometric Coefficient of Variation 42.1
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958
Day 14
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
142 L
Geometric Coefficient of Variation 72.5
|
—
|
—
|
|
Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958
Day 3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
161 L
Geometric Coefficient of Variation 58.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 and 10Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
n=6 Participants
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
n=6 Participants
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts 1 and 2: Cumulative Amount of Unchanged Drug Excreted Into the Urine (Ae) of RO6953958
Day 1
|
0.0322 mg
Standard Deviation 0.00658
|
0.133 mg
Standard Deviation 0.0513
|
0.266 mg
Standard Deviation 0.0766
|
0.612 mg
Standard Deviation 0.245
|
0.321 mg
Standard Deviation 0.0831
|
0.675 mg
Standard Deviation 0.377
|
1.14 mg
Standard Deviation 0.465
|
0.192 mg
Standard Deviation 0.0814
|
0.525 mg
Standard Deviation 0.234
|
0.461 mg
Standard Deviation 0.203
|
—
|
—
|
—
|
|
Parts 1 and 2: Cumulative Amount of Unchanged Drug Excreted Into the Urine (Ae) of RO6953958
Day 10
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0.220 mg
Standard Deviation 0.111
|
0.562 mg
Standard Deviation 0.260
|
0.437 mg
Standard Deviation 0.311
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 and 10Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
n=6 Participants
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
n=6 Participants
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts 1 and 2: Fraction of the Administered Drug Excreted Into the Urine (Fe) of RO6953958
Day 1
|
0.644 mg
Standard Deviation 0.132
|
0.888 mg
Standard Deviation 0.342
|
0.592 mg
Standard Deviation 0.170
|
0.679 mg
Standard Deviation 0.272
|
0.356 mg
Standard Deviation 0.0923
|
0.375 mg
Standard Deviation 0.209
|
0.316 mg
Standard Deviation 0.129
|
0.426 mg
Standard Deviation 0.181
|
0.375 mg
Standard Deviation 0.167
|
0.220 mg
Standard Deviation 0.0965
|
—
|
—
|
—
|
|
Parts 1 and 2: Fraction of the Administered Drug Excreted Into the Urine (Fe) of RO6953958
Day 10
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0.490 mg
Standard Deviation 0.246
|
0.402 mg
Standard Deviation 0.186
|
0.208 mg
Standard Deviation 0.148
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 and 10Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
n=6 Participants
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
n=6 Participants
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts 1 and 2: Renal Clearance of the Drug From Urine (CLR) of RO6953958
Day 1
|
115 mg
Geometric Coefficient of Variation 139.3
|
142 mg
Geometric Coefficient of Variation 52.8
|
123 mg
Geometric Coefficient of Variation 65.9
|
116 mg
Geometric Coefficient of Variation 59.6
|
49.9 mg
Geometric Coefficient of Variation 60.7
|
56.2 mg
Geometric Coefficient of Variation 150.2
|
81.7 mg
Geometric Coefficient of Variation 66.0
|
97.3 mg
Geometric Coefficient of Variation 29.5
|
84.3 mg
Geometric Coefficient of Variation 50.7
|
36.5 mg
Geometric Coefficient of Variation 35.3
|
—
|
—
|
—
|
|
Parts 1 and 2: Renal Clearance of the Drug From Urine (CLR) of RO6953958
Day 10
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
91.4 mg
Geometric Coefficient of Variation 43.5
|
78.7 mg
Geometric Coefficient of Variation 51.0
|
37.3 mg
Geometric Coefficient of Variation 36.3
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1, 3, 10, 12, 13Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=16 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 1
|
0.473 ng/mL
Geometric Coefficient of Variation 1305.9
|
31.0 ng/mL
Geometric Coefficient of Variation 160.4
|
82.4 ng/mL
Geometric Coefficient of Variation 50.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 3
|
—
|
—
|
—
|
60.78 ng/mL
Geometric Coefficient of Variation 116.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 10
|
1.20 ng/mL
Geometric Coefficient of Variation 660.9
|
24.2 ng/mL
Geometric Coefficient of Variation 177.7
|
40.5 ng/mL
Geometric Coefficient of Variation 161.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 12
|
—
|
—
|
—
|
57.89 ng/mL
Geometric Coefficient of Variation 190.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 13
|
—
|
—
|
—
|
54.40 ng/mL
Geometric Coefficient of Variation 197.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 1
|
227 ng/mL
Geometric Coefficient of Variation 48.0
|
704 ng/mL
Geometric Coefficient of Variation 99.0
|
2130 ng/mL
Geometric Coefficient of Variation 60.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 3
|
—
|
—
|
—
|
1462.36 ng/mL
Geometric Coefficient of Variation 67.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 10
|
449 ng/mL
Geometric Coefficient of Variation 52.2
|
1390 ng/mL
Geometric Coefficient of Variation 98.8
|
3020 ng/mL
Geometric Coefficient of Variation 62.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 12
|
—
|
—
|
—
|
2566.84 ng/mL
Geometric Coefficient of Variation 95.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 13
|
—
|
—
|
—
|
2517.91 ng/mL
Geometric Coefficient of Variation 86.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 1
|
4.25 ng/mL
Geometric Coefficient of Variation 930.3
|
27.6 ng/mL
Geometric Coefficient of Variation 300.4
|
63.0 ng/mL
Geometric Coefficient of Variation 119.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 3
|
—
|
—
|
—
|
62.88 ng/mL
Geometric Coefficient of Variation 199.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 10
|
5.14 ng/mL
Geometric Coefficient of Variation 1196.9
|
33.6 ng/mL
Geometric Coefficient of Variation 232.9
|
31.7 ng/mL
Geometric Coefficient of Variation 429.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 12
|
—
|
—
|
—
|
73.42 ng/mL
Geometric Coefficient of Variation 283.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 13
|
—
|
—
|
—
|
63.54 ng/mL
Geometric Coefficient of Variation 276.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-14Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=16 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts 2 and 3: Accumulation Ratio Based on AUC (RAUC) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 10
|
1.10 Ratio of AUC
Geometric Coefficient of Variation 8.4
|
1.04 Ratio of AUC
Geometric Coefficient of Variation 15.9
|
0.794 Ratio of AUC
Geometric Coefficient of Variation 23.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Accumulation Ratio Based on AUC (RAUC) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 14
|
—
|
—
|
—
|
1.25 Ratio of AUC
Geometric Coefficient of Variation 24.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Accumulation Ratio Based on AUC (RAUC) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 10
|
1.81 Ratio of AUC
Geometric Coefficient of Variation 13.9
|
1.87 Ratio of AUC
Geometric Coefficient of Variation 22.3
|
1.60 Ratio of AUC
Geometric Coefficient of Variation 21.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Accumulation Ratio Based on AUC (RAUC) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 14
|
—
|
—
|
—
|
3.27 Ratio of AUC
Geometric Coefficient of Variation 52.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Accumulation Ratio Based on AUC (RAUC) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 10
|
1.07 Ratio of AUC
Geometric Coefficient of Variation 8.1
|
1.08 Ratio of AUC
Geometric Coefficient of Variation 23.4
|
0.814 Ratio of AUC
Geometric Coefficient of Variation 31.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Accumulation Ratio Based on AUC (RAUC) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 14
|
—
|
—
|
—
|
1.32 Ratio of AUC
Geometric Coefficient of Variation 35.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-14Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=16 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts 2 and 3: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 10
|
1.13 Ratio of Cmax
Geometric Coefficient of Variation 10.0
|
1.01 Ratio of Cmax
Geometric Coefficient of Variation 45.2
|
0.839 Ratio of Cmax
Geometric Coefficient of Variation 28.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 14
|
—
|
—
|
—
|
1.15 Ratio of Cmax
Geometric Coefficient of Variation 30.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 10
|
1.05 Ratio of Cmax
Geometric Coefficient of Variation 19.0
|
1.05 Ratio of Cmax
Geometric Coefficient of Variation 24.0
|
0.856 Ratio of Cmax
Geometric Coefficient of Variation 13.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO6953958 - Day 14
|
—
|
—
|
—
|
1.14 Ratio of Cmax
Geometric Coefficient of Variation 27.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 10
|
1.63 Ratio of Cmax
Geometric Coefficient of Variation 12.1
|
1.77 Ratio of Cmax
Geometric Coefficient of Variation 32.2
|
1.59 Ratio of Cmax
Geometric Coefficient of Variation 16.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts 2 and 3: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 14
|
—
|
—
|
—
|
1.84 Ratio of Cmax
Geometric Coefficient of Variation 38.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-14Population: The PK population included all participants who received active (RO6953958) treatment. No data were analyzed and this outcome measure was not conducted.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1-14Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
n=6 Participants
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
n=6 Participants
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
n=16 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts 1, 2 and 3: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Cmax of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 1
|
0.839 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 61.6
|
1.20 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 43.3
|
1.54 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 42.3
|
1.05 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 32.1
|
0.846 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 37.2
|
1.91 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 85.3
|
1.43 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 43.4
|
1.39 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 77.7
|
1.45 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 99.3
|
1.97 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 72.9
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Cmax of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 10
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
2.16 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 50.7
|
2.46 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 109.8
|
3.66 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 69.0
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Cmax of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
1.50 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 72.4
|
—
|
—
|
|
Parts 1, 2 and 3: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Cmax of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 14
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
2.41 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 62.8
|
—
|
—
|
|
Parts 1, 2 and 3: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Cmax of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 1
|
0.442 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 16.9
|
0.497 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 29.5
|
0.544 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 37.9
|
0.580 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 24.7
|
0.507 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 17.6
|
0.474 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 38.0
|
0.534 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 40.3
|
0.350 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 32.3
|
0.366 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 35.6
|
0.328 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 27.2
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Cmax of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0.369 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 24.8
|
—
|
—
|
|
Parts 1, 2 and 3: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Cmax of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 10
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0.380 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 37.3
|
0.352 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 29.4
|
0.321 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 38.1
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Cmax of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 14
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0.371 Metabolite Ratio for Cmax
Geometric Coefficient of Variation 33.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-14Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
n=6 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
n=6 Participants
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
n=6 Participants
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
n=6 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
n=16 Participants
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts 1, 2 and 3: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 1
|
1.17 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 27.9
|
1.05 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 36.2
|
0.918 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 41.6
|
0.962 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 19.8
|
1.03 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 10.4
|
0.683 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 53.1
|
0.744 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 31.6
|
0.761 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 36.0
|
0.657 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 46.4
|
0.523 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 37.9
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0.612 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 40.0
|
—
|
—
|
|
Parts 1, 2 and 3: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 10
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0.744 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 40.0
|
0.681 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 52.4
|
0.536 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 44.1
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 1
|
6.98 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 73.9
|
7.30 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 48.6
|
6.81 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 69.3
|
3.97 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 34.0
|
3.84 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 32.6
|
7.39 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 68.6
|
5.02 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 50.3
|
4.75 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 72.5
|
5.31 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 90.8
|
5.32 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 77.9
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0.612 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 40.0
|
—
|
—
|
|
Parts 1, 2 and 3: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 10
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
7.85 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 69.3
|
8.17 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 100.8
|
10.7 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 94.8
|
—
|
—
|
—
|
|
Parts 1, 2 and 3: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7021594 - Day 14
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0.645 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 44.2
|
—
|
—
|
|
Parts 1, 2 and 3: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
RO7045755 - Day 14
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0.645 Metabolite Ratio for AUC(0-t)
Geometric Coefficient of Variation 44.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-14Population: The PK population included all participants who received active (RO6953958) treatment.
A single IV dose of 100 ug midazolam was administered on Day 1 and Day 13. A single oral dose 300 ug of midazolam was administered on Day 2 and Day 14. RO6953958 was administrated once daily at 210 mg from Day 3 up to Day 14 so concomitantly with IV dose of midazolam on Day 13 and with oral dose of midazolam on Day 14.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=16 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part 3: Tmax of Midazolam
Day 1
|
0.08 Hour (h)
Interval 0.08 to 0.08
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: Tmax of Midazolam
Day 2
|
0.75 Hour (h)
Interval 0.5 to 1.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: Tmax of Midazolam
Day 13
|
0.08 Hour (h)
Interval 0.08 to 0.25
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: Tmax of Midazolam
Day 14
|
0.63 Hour (h)
Interval 0.5 to 1.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-14Population: The PK population included all participants who received active (RO6953958) treatment.
A single IV dose of 100 ug midazolam was administered on Day 1 and Day 13. A single oral dose 300 ug of midazolam was administered on Day 2 and Day 14. RO6953958 was administrated once daily at 210 mg from Day 3 up to Day 14 so concomitantly with IV dose of midazolam on Day 13 and with oral dose of midazolam on Day 14.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=16 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part 3: Cmax of Midazolam
Day 1
|
2410 ng/mL
Geometric Coefficient of Variation 22.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: Cmax of Midazolam
Day 2
|
1200 ng/mL
Geometric Coefficient of Variation 28.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: Cmax of Midazolam
Day 13
|
2030 ng/mL
Geometric Coefficient of Variation 24.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: Cmax of Midazolam
Day 14
|
1250 ng/mL
Geometric Coefficient of Variation 31.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-14Population: The PK population included all participants who received active (RO6953958) treatment.
A single IV dose of 100 ug midazolam was administered on Day 1 and Day 13. A single oral dose 300 ug of midazolam was administered on Day 2 and Day 14. RO6953958 was administrated once daily at 210 mg from Day 3 up to Day 14 so concomitantly with IV dose of midazolam on Day 13 and with oral dose of midazolam on Day 14.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=16 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part 3: T1/2 of Midazolam
Day 1
|
4.38 h
Geometric Coefficient of Variation 30.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: T1/2 of Midazolam
Day 2
|
4.44 h
Geometric Coefficient of Variation 27.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: T1/2 of Midazolam
Day 13
|
4.69 h
Geometric Coefficient of Variation 33.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: T1/2 of Midazolam
Day 14
|
4.55 h
Geometric Coefficient of Variation 26.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-14Population: The PK population included all participants who received active (RO6953958) treatment.
A single IV dose of 100 ug midazolam was administered on Day 1 and Day 13. A single oral dose 300 ug of midazolam was administered on Day 2 and Day 14. RO6953958 was administrated once daily at 210 mg from Day 3 up to Day 14 so concomitantly with IV dose of midazolam on Day 13 and with oral dose of midazolam on Day 14.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=16 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part 3: AUClast of Midazolam
Day 1
|
3550 h*ng/mL
Geometric Coefficient of Variation 22.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: AUClast of Midazolam
Day 2
|
4140 h*ng/mL
Geometric Coefficient of Variation 37.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: AUClast of Midazolam
Day 13
|
3790 h*ng/mL
Geometric Coefficient of Variation 25.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: AUClast of Midazolam
Day 14
|
4470 h*ng/mL
Geometric Coefficient of Variation 46.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1-14Population: The PK population included all participants who received active (RO6953958) treatment.
A single IV dose of 100 ug midazolam was administered on Day 1 and Day 13. A single oral dose 300 ug of midazolam was administered on Day 2 and Day 14. RO6953958 was administrated once daily at 210 mg from Day 3 up to Day 14 so concomitantly with IV dose of midazolam on Day 13 and with oral dose of midazolam on Day 14.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=16 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part 3: AUCinf of Midazolam
Day 1
|
3630 h*ng/mL
Geometric Coefficient of Variation 24.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: AUCinf of Midazolam
Day 2
|
4270 h*ng/mL
Geometric Coefficient of Variation 39.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: AUCinf of Midazolam
Day 13
|
3910 h*ng/mL
Geometric Coefficient of Variation 29.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: AUCinf of Midazolam
Day 14
|
4630 h*ng/mL
Geometric Coefficient of Variation 49.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 2-14Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=16 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part 3: VF of Oral Midazolam
Day 2
|
450 Litre (L)
Geometric Coefficient of Variation 32.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: VF of Oral Midazolam
Day 14
|
426 Litre (L)
Geometric Coefficient of Variation 32.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 13 and 14Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=16 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part 3: RAUC of Midazolam
Day 13
|
1.07 Ratio
Geometric Coefficient of Variation 10.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: RAUC of Midazolam
Day 14
|
1.08 Ratio
Geometric Coefficient of Variation 20.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 13 and 14Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=16 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part 3: RCmax of Midazolam
Day 13
|
0.844 Ratio
Geometric Coefficient of Variation 22.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: RCmax of Midazolam
Day 14
|
1.05 Ratio
Geometric Coefficient of Variation 22.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 13Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=16 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part 3: CL: Total Plasma Clearance of IV Midazolam
Day 1
|
27.6 L/h
Geometric Coefficient of Variation 24.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: CL: Total Plasma Clearance of IV Midazolam
Day 13
|
25.6 L/h
Geometric Coefficient of Variation 29.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 2 and 14Population: The PK population included all participants who received active (RO6953958) treatment.
F is stated as a fraction of 1.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=16 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part 3: Fraction Absorbed (F) of Midazolam
Day 2
|
0.391 Ratio
Geometric Coefficient of Variation 22.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: Fraction Absorbed (F) of Midazolam
Day 14
|
0.396 Ratio
Geometric Coefficient of Variation 23.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 3 and 14Population: The PK population included all participants who received active (RO6953958) treatment.
Outcome measures
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=16 Participants
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part 3: Volume of Distribution Under Steady-state Conditions (Vss) of Midazolam
Day 3
|
161 Liters
Geometric Coefficient of Variation 58.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 3: Volume of Distribution Under Steady-state Conditions (Vss) of Midazolam
Day 14
|
142 Liters
Geometric Coefficient of Variation 72.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Part 1 (SAD): RO6953958 5mg (Fasted)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Part 1 (SAD): RO6953958 15mg (Fasted)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Part 1 (SAD): RO6953958 45mg (Fasted)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Part 1 (SAD): RO6953958 180mg (Fasted)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Part 1 (SAD): RO6953958 360mg (Fasted)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Part 1 (SAD): Placebo (Fasted)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Part 1 (SAD): Placebo (Fed)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Part 2 (MAD): RO6953958 45mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Part 2 (MAD): RO6953958 140mg
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Part 2 (MAD): RO6953958 210mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Part 2 (MAD): Placebo
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Part 1 (SAD): RO6953958 5mg (Fasted)
n=6 participants at risk
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 15mg (Fasted)
n=6 participants at risk
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 45mg (Fasted)
n=6 participants at risk
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 90mg (Fasted or Fed)
n=6 participants at risk
Participants received a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
|
Part 1 (SAD): RO6953958 180mg (Fasted)
n=6 participants at risk
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): RO6953958 360mg (Fasted)
n=6 participants at risk
Participants received a single oral dose of RO6953958 while fasted.
|
Part 1 (SAD): Placebo (Fasted)
n=10 participants at risk
Participants received a single oral dose of a placebo while fasted.
|
Part 1 (SAD): Placebo (Fed)
n=2 participants at risk
Participants received a single oral dose of a placebo while fed.
|
Part 2 (MAD): RO6953958 45mg
n=6 participants at risk
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
|
Part 2 (MAD): RO6953958 140mg
n=6 participants at risk
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): RO6953958 210mg
n=6 participants at risk
Participants received a multiple oral dose of RO6953958 QD for 10 days.
|
Part 2 (MAD): Placebo
n=6 participants at risk
Participants received a multiple oral dose of a placebo QD for 10 days.
|
Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug
n=16 participants at risk
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
6.2%
1/16 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Gastrointestinal disorders
Dry Mouth
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Gastrointestinal disorders
Gastrointestinal Sounds Abnormal
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Gastrointestinal disorders
Gastrooesophageal Reflux Disease
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
6.2%
1/16 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
6.2%
1/16 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
18.8%
3/16 • Number of events 3 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
General disorders
Catheter Site Pain
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
6.2%
1/16 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
General disorders
Catheter Site Swelling
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
General disorders
Chills
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
6.2%
1/16 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
General disorders
Fatigue
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
18.8%
3/16 • Number of events 3 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
General disorders
Medical Device Site Dermatitis
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
33.3%
2/6 • Number of events 3 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
General disorders
Puncture Site Pain
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
33.3%
2/6 • Number of events 2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
33.3%
2/6 • Number of events 2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
General disorders
Pyrexia
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
6.2%
1/16 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
General disorders
Swelling
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Infections and infestations
Ear Infection
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
10.0%
1/10 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
12.5%
2/16 • Number of events 2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Injury, poisoning and procedural complications
Procedural Headache
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
33.3%
2/6 • Number of events 2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
6.2%
1/16 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Stiffness
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
6.2%
1/16 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Musculoskeletal and connective tissue disorders
Tendon Discomfort
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Nervous system disorders
Dizziness
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
6.2%
1/16 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Nervous system disorders
Dizziness Postural
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
10.0%
1/10 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Nervous system disorders
Headache
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
33.3%
2/6 • Number of events 2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
50.0%
3/6 • Number of events 3 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
33.3%
2/6 • Number of events 2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
50.0%
3/6 • Number of events 4 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
33.3%
2/6 • Number of events 3 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
43.8%
7/16 • Number of events 7 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Nervous system disorders
Lethargy
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Nervous system disorders
Presyncope
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Nervous system disorders
Somnolence
|
33.3%
2/6 • Number of events 2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
12.5%
2/16 • Number of events 2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Nervous system disorders
Syncope
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
33.3%
2/6 • Number of events 2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Psychiatric disorders
Abnormal Dreams
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
16.7%
1/6 • Number of events 1 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/16 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/10 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
0.00%
0/6 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
12.5%
2/16 • Number of events 2 • Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER