Autism Spectrum Disorder, Autistic Disorder, Child Development Disorders, Pervasive, Mental Disorders, Neurodevelopmental Disorders
Conditions
Keywords
Autism Spectrum Disorder
Brief summary
This study will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single- and multiple-ascending doses (SAD (Part 1) and MAD (Part 2)) and food effect (FE) of RO6953958 following oral administration in healthy male participants. Part 3 (Drug-drug interaction (DDI)) will assess the safety, tolerability, and effect of RO6953958 on the PK of the cytochrome P450 (CYP) 3A substrate midazolam.
Interventions
DRUGRO6953958
Part 1: RO6953958 will be administered in an adaptive manner. The starting dose is planned to be 5 milligrams (mg). Part 2: The starting dose is planned to be 45 mg. Part 3: RO6953958 will be administered QD following a standardized breakfast on Day 3 to Day 14 at the maximum dose QD that was tested in the ongoing Part 2 (MAD).
DRUGPlacebo
Part 1: A placebo will be administered in an adaptive manner. The starting dose is planned to be 5 mg. Part 2: The starting dose is planned to be 45 mg.
DRUGMidazolam
Midazolam will be administered as single intervenous (IV) bolus injection of 100 micrograms (ug) on Day 1 and Day 13, and as single oral dose of 300 ug on Day 2 and Day 14.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Body mass index (BMI) within 18 to 31 kg/m2 * During treatment and for at least 14 days after the last dose to remain abstinent * Refrain from donating sperm for at least 14 days after last dose * Part 2 (MAD) only - Participants must be prepared to collect a sleep log and wear an actigraphy device the week before participation in the study. Participants must also have scored 5 or less on the Pittsburgh Sleep Quality Index (PSQI), less than 13 on the Epworth sleepiness scale (ESS), and not be considered an extreme morning or evening type according to the morningness-eveningness questionnaire (MEQ) at screening to be eligible.
Exclusion criteria
* History or evidence of any medical condition potentially altering the absorption, metabolism, or elimination of drugs * History of any clinically significant gastrointestinal, renal, hepatic, bronchopulmonary, neurological, psychiatric, cardiovascular, endocrinological, hematological, or allergic disease, sleep disorders (Part 2 \[MAD\] only), unexplained syncope (within 12 months prior to screening), metabolic disorder, cancer, or cirrhosis * Use of any psychoactive medication, or medications known to have effects on central nervous system (CNS), or blood flow * History of convulsions * History of clinically significant hypersensitivity (e.g., drugs, excipients) or allergic reactions * Abnormal blood pressure (BP) and pulse rate * Presence of orthostatic hypotension * History or presence of clinically significant ECG abnormalities or cardiovascular disease * Current or chronic history of liver disease or known hepatic or biliary abnormalities * Known active or any major episode of infection within 4 weeks prior to the start of drug administration * Participants who test positive for acute respiratory syndrome coronavirus 2 (SARS-CoV-2) * Have used or intend to use over-the-counter (OTC) or prescription medication including herbal medications within 30 days prior to dosing * Positive test for drugs, abuse of alcohol, human immunodeficiency virus (HIV), hepatitis B or hepatitis C virus (HCV), presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C antibody test * Inability or unwillingness to fully consume standardized breakfast at Day 1 * Part 2 (MAD) only - Participants who have issues sleeping or participants who have travelled across 2 or more time zones in the past month. * Part 2 (MAD) only - Participants who cannot produce sufficient saliva for study assessments * Participants who have donated more than 500 mL of blood or blood products or had significant blood loss within 3 months prior to screening * Have a history of clinically significant back pain, back pathology, and/or back injury that may predispose to complications from, or technical difficulty with, lumbar puncture * Complications that would lead to difficulty in obtaining a lumbar puncture * Part 3 (DDI) only - History of hypersensitivity to benzodiazepines (including midazolam) or its formulation ingredients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Parts 1, 2 and 3: Percentage of Participants With Adverse Events | Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks | 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. |
| Part 2: Number of Participants With Post-baseline Suicide Risk, Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) | From randomization up to 8 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | Day 1-14 | — |
| Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | Day 1-14 | — |
| Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | Day 1-14 | — |
| Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State | Day 1-10 | — |
| Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | Day 1-10 | — |
| Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | Day 1-14 | — |
| Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | Day 1-14 | — |
| 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 | Day 1-5 | — |
| 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 | Day 1-10 | — |
| Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | Day 1-10 | — |
| Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958 | Day 1-14 | — |
| Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958 | Day 1-14 | — |
| Parts 1 and 2: Cumulative Amount of Unchanged Drug Excreted Into the Urine (Ae) of RO6953958 | Day 1 and 10 | — |
| Parts 1 and 2: Fraction of the Administered Drug Excreted Into the Urine (Fe) of RO6953958 | Day 1 and 10 | — |
| Parts 1 and 2: Renal Clearance of the Drug From Urine (CLR) of RO6953958 | Day 1 and 10 | — |
| Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | Day 1, 3, 10, 12, 13 | — |
| Parts 2 and 3: Accumulation Ratio Based on AUC (RAUC) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | Day 1-14 | — |
| Parts 2 and 3: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | Day 1-14 | — |
| Parts 2 and 3: Accumulation Ratio Based on Ctrough (RCtrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | Day 1-14 | — |
| Parts 1, 2 and 3: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Cmax of RO6953958 and Its Metabolites RO7021594 and RO7045755 | Day 1-14 | — |
| 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 | Day 1-14 | — |
| Part 3: Tmax of Midazolam | Day 1-14 | 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. |
| Part 3: Cmax of Midazolam | Day 1-14 | 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. |
| Part 3: T1/2 of Midazolam | Day 1-14 | 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. |
| Part 3: AUClast of Midazolam | Day 1-14 | 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. |
| Part 3: AUCinf of Midazolam | Day 1-14 | 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. |
| Part 3: VF of Oral Midazolam | Day 2-14 | — |
| Part 3: RAUC of Midazolam | Days 13 and 14 | — |
| Part 3: RCmax of Midazolam | Days 13 and 14 | — |
| Part 3: CL: Total Plasma Clearance of IV Midazolam | Days 1 and 13 | — |
| Part 3: Fraction Absorbed (F) of Midazolam | Days 2 and 14 | F is stated as a fraction of 1. |
| Part 3: Volume of Distribution Under Steady-state Conditions (Vss) of Midazolam | Days 3 and 14 | — |
Countries
United Kingdom
Participant flow
Recruitment details
This study was conducted at one centre in the United Kingdom.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) Participants received a single oral dose of RO6953958 while fasted. | 6 |
| Part 1 (SAD): RO6953958 15mg (Fasted) Participants received a single oral dose of RO6953958 while fasted. | 6 |
| Part 1 (SAD): RO6953958 45mg (Fasted) Participants received a single oral dose of RO6953958 while fasted. | 6 |
| 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. | 6 |
| Part 1 (SAD): RO6953958 180mg (Fasted) Participants received a single oral dose of RO6953958 while fasted. | 6 |
| Part 1 (SAD): RO6953958 360mg (Fasted) Participants received a single oral dose of RO6953958 while fasted. | 6 |
| Part 1 (SAD): Placebo (Fasted) Participants received a single oral dose of a placebo while fasted. | 10 |
| Part 1 (SAD): Placebo (Fed) Participants received a single oral dose of a placebo while fed. | 2 |
| Part 2 (MAD): RO6953958 45mg Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days. | 6 |
| Part 2 (MAD): RO6953958 140mg Participants received a multiple oral dose of RO6953958 QD for 10 days. | 6 |
| Part 2 (MAD): RO6953958 210mg Participants received a multiple oral dose of RO6953958 QD for 10 days. | 6 |
| Part 2 (MAD): Placebo Participants received a multiple oral dose of a placebo QD for 10 days. | 6 |
| 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. | 16 |
| Total | 88 |
Baseline characteristics
| Characteristic | Part 1 (SAD): RO6953958 5mg (Fasted) | Part 1 (SAD): RO6953958 15mg (Fasted) | Part 1 (SAD): RO6953958 45mg (Fasted) | Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Part 1 (SAD): RO6953958 180mg (Fasted) | Part 1 (SAD): RO6953958 360mg (Fasted) | Part 1 (SAD): Placebo (Fasted) | Part 1 (SAD): Placebo (Fed) | Part 2 (MAD): RO6953958 45mg | Part 2 (MAD): RO6953958 140mg | Part 2 (MAD): RO6953958 210mg | Part 2 (MAD): Placebo | Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 39.0 Years STANDARD_DEVIATION 9.9 | 37.3 Years STANDARD_DEVIATION 8.1 | 37.5 Years STANDARD_DEVIATION 4.3 | 33.7 Years STANDARD_DEVIATION 11.9 | 40.3 Years STANDARD_DEVIATION 10.3 | 33.8 Years STANDARD_DEVIATION 12.6 | 34.1 Years STANDARD_DEVIATION 9.7 | 38.5 Years STANDARD_DEVIATION 2.1 | 32.5 Years STANDARD_DEVIATION 7.4 | 36.2 Years STANDARD_DEVIATION 11.7 | 38.7 Years STANDARD_DEVIATION 12.9 | 30.3 Years STANDARD_DEVIATION 11.2 | 33.6 Years STANDARD_DEVIATION 10.6 | 35.8 Years STANDARD_DEVIATION 9.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 5 Participants | 5 Participants | 6 Participants | 6 Participants | 5 Participants | 9 Participants | 2 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 16 Participants | 83 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 4 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 5 Participants | 6 Participants | 5 Participants | 6 Participants | 9 Participants | 2 Participants | 6 Participants | 4 Participants | 2 Participants | 4 Participants | 10 Participants | 65 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 10 Participants | 2 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 16 Participants | 88 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 16 |
| other Total, other adverse events | 2 / 6 | 2 / 6 | 2 / 6 | 4 / 6 | 2 / 6 | 3 / 6 | 2 / 10 | 0 / 2 | 4 / 6 | 6 / 6 | 4 / 6 | 2 / 6 | 10 / 16 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 16 |
Outcome results
Primary
Part 2: Number of Participants With Post-baseline Suicide Risk, Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)
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.
Time frame: From randomization up to 8 weeks
Population: The safety population included all participants randomized to study treatment and who received at least one dose of the study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
Primary
Parts 1, 2 and 3: Percentage of Participants With Adverse Events
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.
Time frame: Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
Population: The safety population included all participants randomized to study treatment and who received at least one dose of the study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | Parts 1, 2 and 3: Percentage of Participants With Adverse Events | 2 Participants |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 1, 2 and 3: Percentage of Participants With Adverse Events | 2 Participants |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 1, 2 and 3: Percentage of Participants With Adverse Events | 2 Participants |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Parts 1, 2 and 3: Percentage of Participants With Adverse Events | 4 Participants |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Parts 1, 2 and 3: Percentage of Participants With Adverse Events | 2 Participants |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Parts 1, 2 and 3: Percentage of Participants With Adverse Events | 3 Participants |
| Part 1 (SAD): Placebo (Fasted) | Parts 1, 2 and 3: Percentage of Participants With Adverse Events | 2 Participants |
| Part 1 (SAD): Placebo (Fed) | Parts 1, 2 and 3: Percentage of Participants With Adverse Events | 0 Participants |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Percentage of Participants With Adverse Events | 4 Participants |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Percentage of Participants With Adverse Events | 6 Participants |
| Part 2 (MAD): RO6953958 210mg | Parts 1, 2 and 3: Percentage of Participants With Adverse Events | 4 Participants |
| Part 2 (MAD): Placebo | Parts 1, 2 and 3: Percentage of Participants With Adverse Events | 2 Participants |
| Part 3 (DDI): RO6953958 210mg, Midazolam Injection 100ug, Midazolam Oral 330ug | Parts 1, 2 and 3: Percentage of Participants With Adverse Events | 15 Participants |
Secondary
Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755
Time frame: Day 1-10
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 | 4160 h*ng/mL | Geometric Coefficient of Variation 46.5 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 | 676 h*ng/mL | Geometric Coefficient of Variation 52.2 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 | 738 h*ng/mL | Geometric Coefficient of Variation 48.8 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 | 1700 h*ng/mL | Geometric Coefficient of Variation 35.4 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 | 1780 h*ng/mL | Geometric Coefficient of Variation 26.2 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 | 10500 h*ng/mL | Geometric Coefficient of Variation 85.3 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 | 15300 h*ng/mL | Geometric Coefficient of Variation 28.3 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 | 5120 h*ng/mL | Geometric Coefficient of Variation 46.5 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 | 4880 h*ng/mL | Geometric Coefficient of Variation 31.3 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 | 18100 h*ng/mL | Geometric Coefficient of Variation 33.3 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 | 5410 h*ng/mL | Geometric Coefficient of Variation 39.3 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 | 5750 h*ng/mL | Geometric Coefficient of Variation 33.1 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 | 9710 h*ng/mL | Geometric Coefficient of Variation 31.3 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 | 6140 h*ng/mL | Geometric Coefficient of Variation 65.8 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 | 44800 h*ng/mL | Geometric Coefficient of Variation 68.5 |
| Part 1 (SAD): Placebo (Fasted) | Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 | 9680 h*ng/mL | Geometric Coefficient of Variation 79.3 |
| Part 1 (SAD): Placebo (Fasted) | Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 | 45400 h*ng/mL | Geometric Coefficient of Variation 30.3 |
| Part 1 (SAD): Placebo (Fasted) | Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 | 15200 h*ng/mL | Geometric Coefficient of Variation 78.7 |
Secondary
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
Time frame: Day 1-5
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | 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 | 665 h*ng/mL | Geometric Coefficient of Variation 51.3 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | 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 | 707 h*ng/mL | Geometric Coefficient of Variation 45.3 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | 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 | 2910 h*ng/mL | Geometric Coefficient of Variation 45.1 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | 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 | 1610 h*ng/mL | Geometric Coefficient of Variation 34.7 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | 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 | 1740 h*ng/mL | Geometric Coefficient of Variation 26.8 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | 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 | 7410 h*ng/mL | Geometric Coefficient of Variation 81.6 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 | 4140 h*ng/mL | Geometric Coefficient of Variation 39.9 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 | 3870 h*ng/mL | Geometric Coefficient of Variation 28.3 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 | 9010 h*ng/mL | Geometric Coefficient of Variation 17.9 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | 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 | 5330 h*ng/mL | Geometric Coefficient of Variation 31.1 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | 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 | 5330 h*ng/mL | Geometric Coefficient of Variation 38.9 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | 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 | 12500 h*ng/mL | Geometric Coefficient of Variation 24.7 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | 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 | 4340 h*ng/mL | Geometric Coefficient of Variation 70.4 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | 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 | 6170 h*ng/mL | Geometric Coefficient of Variation 39.7 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | 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 | 22700 h*ng/mL | Geometric Coefficient of Variation 60.9 |
| Part 1 (SAD): Placebo (Fasted) | 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 | 8720 h*ng/mL | Geometric Coefficient of Variation 70.9 |
| Part 1 (SAD): Placebo (Fasted) | 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 | 23100 h*ng/mL | Geometric Coefficient of Variation 28.9 |
| Part 1 (SAD): Placebo (Fasted) | 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 | 6630 h*ng/mL | Geometric Coefficient of Variation 68.5 |
Secondary
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
Time frame: Day 1-10
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | 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 | 4940 h*ng/mL | Geometric Coefficient of Variation 48.7 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | 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 | 684 h*ng/mL | Geometric Coefficient of Variation 50.5 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | 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 | 651 h*ng/mL | Geometric Coefficient of Variation 52.4 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | 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 | 1650 h*ng/mL | Geometric Coefficient of Variation 34.6 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | 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 | 1730 h*ng/mL | Geometric Coefficient of Variation 27.7 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | 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 | 12200 h*ng/mL | Geometric Coefficient of Variation 89 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 | 21000 h*ng/mL | Geometric Coefficient of Variation 42 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 | 4970 h*ng/mL | Geometric Coefficient of Variation 32.3 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 | 4990 h*ng/mL | Geometric Coefficient of Variation 46.1 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | 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 | 5330 h*ng/mL | Geometric Coefficient of Variation 38.9 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | 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 | 21400 h*ng/mL | Geometric Coefficient of Variation 40.1 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | 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 | 5670 h*ng/mL | Geometric Coefficient of Variation 34 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | 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 | 9470 h*ng/mL | Geometric Coefficient of Variation 31.6 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | 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 | 6740 h*ng/mL | Geometric Coefficient of Variation 63.6 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | 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 | 74000 h*ng/mL | Geometric Coefficient of Variation 79.2 |
| Part 1 (SAD): Placebo (Fasted) | 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 | 78500 h*ng/mL | Geometric Coefficient of Variation 46.2 |
| Part 1 (SAD): Placebo (Fasted) | 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 | 14700 h*ng/mL | Geometric Coefficient of Variation 83 |
| Part 1 (SAD): Placebo (Fasted) | 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 | 11500 h*ng/mL | Geometric Coefficient of Variation 93 |
Secondary
Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State
Time frame: Day 1-10
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State | RO7021594 | 6.22 ng/mL | Geometric Coefficient of Variation 84.1 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State | RO6953958 | 4.42 ng/mL | Geometric Coefficient of Variation 71.6 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State | RO7045755 | 7.48 ng/mL | Geometric Coefficient of Variation 55.7 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State | RO7045755 | 6.52 ng/mL | Geometric Coefficient of Variation 78.2 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State | RO6953958 | 5.98 ng/mL | Geometric Coefficient of Variation 82.4 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State | RO7021594 | 12.6 ng/mL | Geometric Coefficient of Variation 163.1 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State | RO7021594 | 41.1 ng/mL | Geometric Coefficient of Variation 3.16 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State | RO6953958 | 6.75 ng/mL | Geometric Coefficient of Variation 98.2 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State | RO7045755 | 84.4 ng/mL | Geometric Coefficient of Variation 7.71 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State | RO7021594 | 31.6 ng/mL | Geometric Coefficient of Variation 4.04 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State | RO6953958 | 11.1 ng/mL | Geometric Coefficient of Variation 130.4 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State | RO7045755 | 116.6 ng/mL | Geometric Coefficient of Variation 6.7 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State | RO6953958 | 8.99 ng/mL | Geometric Coefficient of Variation 97.7 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State | RO7045755 | 59.3 ng/mL | Geometric Coefficient of Variation 6.15 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State | RO7021594 | 80.3 ng/mL | Geometric Coefficient of Variation 12.6 |
| Part 1 (SAD): Placebo (Fasted) | Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State | RO7045755 | 60.7 ng/mL | Geometric Coefficient of Variation 6.25 |
| Part 1 (SAD): Placebo (Fasted) | Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State | RO7021594 | 115.1 ng/mL | Geometric Coefficient of Variation 9.75 |
| Part 1 (SAD): Placebo (Fasted) | Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State | RO6953958 | 10.6 ng/mL | Geometric Coefficient of Variation 67.1 |
Secondary
Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755
Time frame: Day 1-10
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 | 96.03 h | Geometric Coefficient of Variation 0.1 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 | 19.06 h | Geometric Coefficient of Variation 37 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 | 16.47 h | Geometric Coefficient of Variation 43.8 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 | 26.96 h | Geometric Coefficient of Variation 28.9 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 | 21.40 h | Geometric Coefficient of Variation 28.9 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 | 96.01 h | Geometric Coefficient of Variation 0 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 | 54.96 h | Geometric Coefficient of Variation 21.2 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 | 51.37 h | Geometric Coefficient of Variation 16.6 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 | 170.15 h | Geometric Coefficient of Variation 29.3 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 | 144.29 h | Geometric Coefficient of Variation 24.6 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 | 38.10 h | Geometric Coefficient of Variation 37 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 | 24.00 h | Geometric Coefficient of Variation 0 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 | 74.87 h | Geometric Coefficient of Variation 12.2 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 | 70.14 h | Geometric Coefficient of Variation 22.3 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 | 208.08 h | Geometric Coefficient of Variation 10.8 |
| Part 1 (SAD): Placebo (Fasted) | Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 | 88.77 h | Geometric Coefficient of Variation 32.1 |
| Part 1 (SAD): Placebo (Fasted) | Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 | 216.78 h | Geometric Coefficient of Variation 0.5 |
| Part 1 (SAD): Placebo (Fasted) | Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 | 92.34 h | Geometric Coefficient of Variation 34.9 |
Secondary
Part 3: AUCinf of Midazolam
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.
Time frame: Day 1-14
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: AUCinf of Midazolam | Day 1 | 3630 h*ng/mL | Geometric Coefficient of Variation 24.4 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: AUCinf of Midazolam | Day 2 | 4270 h*ng/mL | Geometric Coefficient of Variation 39.9 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: AUCinf of Midazolam | Day 13 | 3910 h*ng/mL | Geometric Coefficient of Variation 29.2 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: AUCinf of Midazolam | Day 14 | 4630 h*ng/mL | Geometric Coefficient of Variation 49.6 |
Secondary
Part 3: AUClast of Midazolam
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.
Time frame: Day 1-14
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: AUClast of Midazolam | Day 14 | 4470 h*ng/mL | Geometric Coefficient of Variation 46 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: AUClast of Midazolam | Day 1 | 3550 h*ng/mL | Geometric Coefficient of Variation 22.8 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: AUClast of Midazolam | Day 2 | 4140 h*ng/mL | Geometric Coefficient of Variation 37.4 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: AUClast of Midazolam | Day 13 | 3790 h*ng/mL | Geometric Coefficient of Variation 25.8 |
Secondary
Part 3: CL: Total Plasma Clearance of IV Midazolam
Time frame: Days 1 and 13
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: CL: Total Plasma Clearance of IV Midazolam | Day 1 | 27.6 L/h | Geometric Coefficient of Variation 24.4 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: CL: Total Plasma Clearance of IV Midazolam | Day 13 | 25.6 L/h | Geometric Coefficient of Variation 29.2 |
Secondary
Part 3: Cmax of Midazolam
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.
Time frame: Day 1-14
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: Cmax of Midazolam | Day 1 | 2410 ng/mL | Geometric Coefficient of Variation 22.8 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: Cmax of Midazolam | Day 2 | 1200 ng/mL | Geometric Coefficient of Variation 28.5 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: Cmax of Midazolam | Day 13 | 2030 ng/mL | Geometric Coefficient of Variation 24.1 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: Cmax of Midazolam | Day 14 | 1250 ng/mL | Geometric Coefficient of Variation 31.2 |
Secondary
Part 3: Fraction Absorbed (F) of Midazolam
F is stated as a fraction of 1.
Time frame: Days 2 and 14
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: Fraction Absorbed (F) of Midazolam | Day 2 | 0.391 Ratio | Geometric Coefficient of Variation 22 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: Fraction Absorbed (F) of Midazolam | Day 14 | 0.396 Ratio | Geometric Coefficient of Variation 23.9 |
Secondary
Part 3: RAUC of Midazolam
Time frame: Days 13 and 14
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: RAUC of Midazolam | Day 13 | 1.07 Ratio | Geometric Coefficient of Variation 10.3 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: RAUC of Midazolam | Day 14 | 1.08 Ratio | Geometric Coefficient of Variation 20.7 |
Secondary
Part 3: RCmax of Midazolam
Time frame: Days 13 and 14
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: RCmax of Midazolam | Day 13 | 0.844 Ratio | Geometric Coefficient of Variation 22.8 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: RCmax of Midazolam | Day 14 | 1.05 Ratio | Geometric Coefficient of Variation 22.5 |
Secondary
Part 3: T1/2 of Midazolam
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.
Time frame: Day 1-14
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: T1/2 of Midazolam | Day 1 | 4.38 h | Geometric Coefficient of Variation 30 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: T1/2 of Midazolam | Day 2 | 4.44 h | Geometric Coefficient of Variation 27.2 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: T1/2 of Midazolam | Day 13 | 4.69 h | Geometric Coefficient of Variation 33.8 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: T1/2 of Midazolam | Day 14 | 4.55 h | Geometric Coefficient of Variation 26.6 |
Secondary
Part 3: Tmax of Midazolam
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.
Time frame: Day 1-14
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: Tmax of Midazolam | Day 1 | 0.08 Hour (h) |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: Tmax of Midazolam | Day 2 | 0.75 Hour (h) |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: Tmax of Midazolam | Day 13 | 0.08 Hour (h) |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: Tmax of Midazolam | Day 14 | 0.63 Hour (h) |
Secondary
Part 3: VF of Oral Midazolam
Time frame: Day 2-14
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: VF of Oral Midazolam | Day 2 | 450 Litre (L) | Geometric Coefficient of Variation 32 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: VF of Oral Midazolam | Day 14 | 426 Litre (L) | Geometric Coefficient of Variation 32.1 |
Secondary
Part 3: Volume of Distribution Under Steady-state Conditions (Vss) of Midazolam
Time frame: Days 3 and 14
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: Volume of Distribution Under Steady-state Conditions (Vss) of Midazolam | Day 3 | 161 Liters | Geometric Coefficient of Variation 58.3 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | Part 3: Volume of Distribution Under Steady-state Conditions (Vss) of Midazolam | Day 14 | 142 Liters | Geometric Coefficient of Variation 72.5 |
Secondary
Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958
Time frame: Day 1-14
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958 | Day 1 | 24.3 L/h | Geometric Coefficient of Variation 39.7 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958 | Day 1 | 22.2 L/h | Geometric Coefficient of Variation 52.2 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958 | Day 1 | 25.2 L/h | Geometric Coefficient of Variation 26.2 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958 | Day 1 | 17.6 L/h | Geometric Coefficient of Variation 46.5 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958 | Day 1 | 16.6 L/h | Geometric Coefficient of Variation 39.3 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958 | Day 1 | 18.5 L/h | Geometric Coefficient of Variation 31.3 |
| Part 1 (SAD): Placebo (Fasted) | Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958 | Day 1 | 23.7 L/h | Geometric Coefficient of Variation 78.7 |
| Part 1 (SAD): Placebo (Fed) | Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958 | Day 1 | 24.6 L/h | Geometric Coefficient of Variation 44.7 |
| Part 1 (SAD): Placebo (Fed) | Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958 | Day 10 | 22.4 L/h | Geometric Coefficient of Variation 38.4 |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958 | Day 10 | 23.1 L/h | Geometric Coefficient of Variation 58 |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958 | Day 1 | 22.0 L/h | Geometric Coefficient of Variation 66.7 |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958 | Day 1 | 17.2 L/h | Geometric Coefficient of Variation 26.4 |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958 | Day 10 | 17.4 L/h | Geometric Coefficient of Variation 27.8 |
| Part 2 (MAD): RO6953958 210mg | Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958 | Day 3 | 18.43 L/h | Geometric Coefficient of Variation 51.2 |
| Part 2 (MAD): RO6953958 210mg | Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958 | Day 14 | 15.87 L/h | Geometric Coefficient of Variation 58.6 |
Secondary
Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958
Time frame: Day 1-14
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958 | Day 1 | 89.1 L | Geometric Coefficient of Variation 51.2 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958 | Day 1 | 110 L | Geometric Coefficient of Variation 47.5 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958 | Day 1 | 145 L | Geometric Coefficient of Variation 42.7 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958 | Day 1 | 242 L | Geometric Coefficient of Variation 45.3 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958 | Day 1 | 85.8 L | Geometric Coefficient of Variation 35.8 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958 | Day 1 | 45.5 L | Geometric Coefficient of Variation 425 |
| Part 1 (SAD): Placebo (Fasted) | Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958 | Day 1 | 509 L | Geometric Coefficient of Variation 91.5 |
| Part 1 (SAD): Placebo (Fed) | Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958 | Day 1 | 93.1 L | Geometric Coefficient of Variation 30.2 |
| Part 1 (SAD): Placebo (Fed) | Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958 | Day 10 | 111 L | Geometric Coefficient of Variation 25.2 |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958 | Day 10 | 263 L | Geometric Coefficient of Variation 77.2 |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958 | Day 1 | 209 L | Geometric Coefficient of Variation 63 |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958 | Day 1 | 164 L | Geometric Coefficient of Variation 69.6 |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958 | Day 10 | 158 L | Geometric Coefficient of Variation 42.1 |
| Part 2 (MAD): RO6953958 210mg | Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958 | Day 3 | 161 L | Geometric Coefficient of Variation 58.3 |
| Part 2 (MAD): RO6953958 210mg | Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958 | Day 14 | 142 L | Geometric Coefficient of Variation 72.5 |
Secondary
Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
Time frame: Day 1-14
Population: The pharmacokinetic (PK) population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 187 Nanograms per Milliliter (ng/mL) | Standard Deviation 41 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 77.3 Nanograms per Milliliter (ng/mL) | Standard Deviation 25.2 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 150 Nanograms per Milliliter (ng/mL) | Standard Deviation 34.2 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 480 Nanograms per Milliliter (ng/mL) | Standard Deviation 76 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 169 Nanograms per Milliliter (ng/mL) | Standard Deviation 36.9 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 299 Nanograms per Milliliter (ng/mL) | Standard Deviation 50 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 272 Nanograms per Milliliter (ng/mL) | Standard Deviation 32.5 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 451 Nanograms per Milliliter (ng/mL) | Standard Deviation 30.7 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 490 Nanograms per Milliliter (ng/mL) | Standard Deviation 18.8 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 932 Nanograms per Milliliter (ng/mL) | Standard Deviation 34.6 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 819 Nanograms per Milliliter (ng/mL) | Standard Deviation 21.2 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 491 Nanograms per Milliliter (ng/mL) | Standard Deviation 29.1 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 1230 Nanograms per Milliliter (ng/mL) | Standard Deviation 67.2 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 1.69 Nanograms per Milliliter (ng/mL) | Standard Deviation 71.1 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 618 Nanograms per Milliliter (ng/mL) | Standard Deviation 47.4 |
| Part 1 (SAD): Placebo (Fasted) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 3.57 Nanograms per Milliliter (ng/mL) | Standard Deviation 28.3 |
| Part 1 (SAD): Placebo (Fasted) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 866 Nanograms per Milliliter (ng/mL) | Standard Deviation 39.5 |
| Part 1 (SAD): Placebo (Fasted) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 1.33 Nanograms per Milliliter (ng/mL) | Standard Deviation 42.4 |
| Part 1 (SAD): Placebo (Fed) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 171 Nanograms per Milliliter (ng/mL) | Standard Deviation 43 |
| Part 1 (SAD): Placebo (Fed) | 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 |
| Part 1 (SAD): Placebo (Fed) | 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 |
| Part 1 (SAD): Placebo (Fed) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 1850 Nanograms per Milliliter (ng/mL) | Standard Deviation 21.6 |
| Part 1 (SAD): Placebo (Fed) | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 490 Nanograms per Milliliter (ng/mL) | Standard Deviation 25 |
| Part 1 (SAD): Placebo (Fed) | 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 |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 1250 Nanograms per Milliliter (ng/mL) | Standard Deviation 49.7 |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 10 | 3180 Nanograms per Milliliter (ng/mL) | Standard Deviation 76.7 |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 677 Nanograms per Milliliter (ng/mL) | Standard Deviation 47.9 |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 10 | 1250 Nanograms per Milliliter (ng/mL) | Standard Deviation 49.7 |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 10 | 456 Nanograms per Milliliter (ng/mL) | Standard Deviation 68.3 |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 452 Nanograms per Milliliter (ng/mL) | Standard Deviation 31.5 |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 629 Nanograms per Milliliter (ng/mL) | Standard Deviation 30.3 |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 1580 Nanograms per Milliliter (ng/mL) | Standard Deviation 21.8 |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 10 | 1580 Nanograms per Milliliter (ng/mL) | Standard Deviation 21.8 |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 1100 Nanograms per Milliliter (ng/mL) | Standard Deviation 41.4 |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 10 | 6010 Nanograms per Milliliter (ng/mL) | Standard Deviation 65.3 |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 10 | 528 Nanograms per Milliliter (ng/mL) | Standard Deviation 46.7 |
| Part 2 (MAD): RO6953958 210mg | 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 |
| Part 2 (MAD): RO6953958 210mg | 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 |
| Part 2 (MAD): RO6953958 210mg | 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 |
| Part 2 (MAD): RO6953958 210mg | 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 |
| Part 2 (MAD): RO6953958 210mg | 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 |
| Part 2 (MAD): RO6953958 210mg | 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 |
Secondary
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
Time frame: Day 1-14
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | 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 | 7.30 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 48.6 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | 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 | 1.05 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 36.2 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | 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 | 0.918 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 41.6 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | 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 | 6.81 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 69.3 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 | 0.962 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 19.8 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 | 3.97 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 34 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | 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 | 3.84 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 32.6 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | 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 | 1.03 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 10.4 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | 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 | 7.39 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 68.6 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | 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 | 0.683 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 53.1 |
| Part 1 (SAD): Placebo (Fasted) | 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 | 5.02 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 50.3 |
| Part 1 (SAD): Placebo (Fasted) | 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 | 0.744 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 31.6 |
| Part 1 (SAD): Placebo (Fed) | 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 |
| Part 1 (SAD): Placebo (Fed) | 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 |
| Part 1 (SAD): Placebo (Fed) | 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 | 0.761 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 36 |
| Part 1 (SAD): Placebo (Fed) | 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 | 4.75 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 72.5 |
| Part 2 (MAD): RO6953958 45mg | 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 | 8.17 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 100.8 |
| Part 2 (MAD): RO6953958 45mg | 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 | 0.681 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 52.4 |
| Part 2 (MAD): RO6953958 45mg | 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 | 5.31 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 90.8 |
| Part 2 (MAD): RO6953958 45mg | 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 | 0.657 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 46.4 |
| Part 2 (MAD): RO6953958 140mg | 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 | 5.32 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 77.9 |
| Part 2 (MAD): RO6953958 140mg | 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 | 0.536 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 44.1 |
| Part 2 (MAD): RO6953958 140mg | 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 | 0.523 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 37.9 |
| Part 2 (MAD): RO6953958 140mg | 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 | 10.7 Metabolite Ratio for AUC(0-t) | Geometric Coefficient of Variation 94.8 |
| Part 2 (MAD): RO6953958 210mg | 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 |
| Part 2 (MAD): RO6953958 210mg | 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 |
| Part 2 (MAD): RO6953958 210mg | 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 |
| Part 2 (MAD): RO6953958 210mg | 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 |
Secondary
Parts 1, 2 and 3: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Cmax of RO6953958 and Its Metabolites RO7021594 and RO7045755
Time frame: Day 1-14
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | 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 | 1.20 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 43.3 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | 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 | 0.497 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 29.5 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | 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 | 1.54 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 42.3 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | 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 | 0.544 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 37.9 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 | 1.05 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 32.1 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 | 0.580 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 24.7 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | 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 | 0.507 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 17.6 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | 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 | 0.846 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 37.2 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | 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 | 1.91 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 85.3 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | 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 | 0.474 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 38 |
| Part 1 (SAD): Placebo (Fasted) | 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 | 1.43 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 43.4 |
| Part 1 (SAD): Placebo (Fasted) | 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 | 0.534 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 40.3 |
| Part 1 (SAD): Placebo (Fed) | 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 | 1.39 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 77.7 |
| Part 1 (SAD): Placebo (Fed) | 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 |
| Part 1 (SAD): Placebo (Fed) | 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 | 0.350 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 32.3 |
| Part 1 (SAD): Placebo (Fed) | 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 |
| Part 2 (MAD): RO6953958 45mg | 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 | 0.352 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 29.4 |
| Part 2 (MAD): RO6953958 45mg | 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 | 0.366 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 35.6 |
| Part 2 (MAD): RO6953958 45mg | 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 | 2.46 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 109.8 |
| Part 2 (MAD): RO6953958 45mg | 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 | 1.45 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 99.3 |
| Part 2 (MAD): RO6953958 140mg | 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 | 3.66 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 69 |
| Part 2 (MAD): RO6953958 140mg | 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 | 1.97 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 72.9 |
| Part 2 (MAD): RO6953958 140mg | 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 | 0.321 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 38.1 |
| Part 2 (MAD): RO6953958 140mg | 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 | 0.328 Metabolite Ratio for Cmax | Geometric Coefficient of Variation 27.2 |
| Part 2 (MAD): RO6953958 210mg | 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 |
| Part 2 (MAD): RO6953958 210mg | 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 |
| Part 2 (MAD): RO6953958 210mg | 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 |
| Part 2 (MAD): RO6953958 210mg | 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 |
Secondary
Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755
Time frame: Day 1-14
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 19.7 h | Geometric Coefficient of Variation 12.4 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 3.43 h | Geometric Coefficient of Variation 52.4 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 4.54 h | Geometric Coefficient of Variation 31.9 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 19.1 h | Geometric Coefficient of Variation 14.1 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 4.82 h | Geometric Coefficient of Variation 26 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 3.98 h | Geometric Coefficient of Variation 46.3 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 20.8 h | Geometric Coefficient of Variation 25.4 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 9.54 h | Geometric Coefficient of Variation 13.9 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 10.3 h | Geometric Coefficient of Variation 15.7 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 3.57 h | Geometric Coefficient of Variation 20.6 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 20.6 h | Geometric Coefficient of Variation 30.4 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 5.25 h | Geometric Coefficient of Variation 13.1 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 13.1 h | Geometric Coefficient of Variation 23.7 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 27.7 h | Geometric Coefficient of Variation 18.6 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 13.5 h | Geometric Coefficient of Variation 22.8 |
| Part 1 (SAD): Placebo (Fasted) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 14.9 h | Geometric Coefficient of Variation 21.8 |
| Part 1 (SAD): Placebo (Fasted) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 27.1 h | Geometric Coefficient of Variation 17.3 |
| Part 1 (SAD): Placebo (Fasted) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 12.7 h | Geometric Coefficient of Variation 20.6 |
| Part 1 (SAD): Placebo (Fed) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 3.89 h | Geometric Coefficient of Variation 42.9 |
| Part 1 (SAD): Placebo (Fed) | 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 |
| Part 1 (SAD): Placebo (Fed) | 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 |
| Part 1 (SAD): Placebo (Fed) | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 2.63 h | Geometric Coefficient of Variation 43.6 |
| Part 1 (SAD): Placebo (Fed) | 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 |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 10 | 7.90 h | Geometric Coefficient of Variation 51 |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 10 | 34.0 h | Geometric Coefficient of Variation 9.7 |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 6.60 h | Geometric Coefficient of Variation 18.9 |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 5.38 h | Geometric Coefficient of Variation 33.6 |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 10 | 6.72 h | Geometric Coefficient of Variation 42.9 |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 10 | 35.8 h | Geometric Coefficient of Variation 17.5 |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 10 | 7.91 h | Geometric Coefficient of Variation 54.4 |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 10 | 6.29 h | Geometric Coefficient of Variation 15.6 |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 4.99 h | Geometric Coefficient of Variation 27.3 |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 6.21 h | Geometric Coefficient of Variation 15.2 |
| Part 2 (MAD): RO6953958 210mg | 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 |
| Part 2 (MAD): RO6953958 210mg | 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 |
| Part 2 (MAD): RO6953958 210mg | 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 |
| Part 2 (MAD): RO6953958 210mg | 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 |
| Part 2 (MAD): RO6953958 210mg | 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
Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
Time frame: Day 1-14
Population: The pharmacokinetic (PK) population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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) |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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) |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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) |
| Part 1 (SAD): RO6953958 15mg (Fasted) | 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) |
| Part 1 (SAD): RO6953958 15mg (Fasted) | 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) |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 2.00 Hours (h) |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 5.50 Hours (h) |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 4.00 Hours (h) |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 2.00 Hours (h) |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 5.00 Hours (h) |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 2.00 Hours (h) |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 6.51 Hours (h) |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 5.50 Hours (h) |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 5.00 Hours (h) |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 4.00 Hours (h) |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 6.50 Hours (h) |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 2.00 Hours (h) |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 4.00 Hours (h) |
| Part 1 (SAD): Placebo (Fasted) | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 5.01 Hours (h) |
| Part 1 (SAD): Placebo (Fasted) | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 2.00 Hours (h) |
| Part 1 (SAD): Placebo (Fasted) | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 7.01 Hours (h) |
| Part 1 (SAD): Placebo (Fed) | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 2.53 Hours (h) |
| Part 1 (SAD): Placebo (Fed) | 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) |
| Part 1 (SAD): Placebo (Fed) | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 5.00 Hours (h) |
| Part 1 (SAD): Placebo (Fed) | 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) |
| Part 1 (SAD): Placebo (Fed) | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 4.00 Hours (h) |
| Part 1 (SAD): Placebo (Fed) | 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) |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 10 | 4.00 Hours (h) |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 10 | 2.04 Hours (h) |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 3.02 Hours (h) |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 10 | 3.04 Hours (h) |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 3.02 Hours (h) |
| Part 2 (MAD): RO6953958 45mg | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 2.01 Hours (h) |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 10 | 2.51 Hours (h) |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 10 | 4.01 Hours (h) |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 10 | 2.00 Hours (h) |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 3.00 Hours (h) |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 4.08 Hours (h) |
| Part 2 (MAD): RO6953958 140mg | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 5.00 Hours (h) |
| Part 2 (MAD): RO6953958 210mg | 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) |
| Part 2 (MAD): RO6953958 210mg | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 6.02 Hours (h) |
| Part 2 (MAD): RO6953958 210mg | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 5.00 Hours (h) |
| Part 2 (MAD): RO6953958 210mg | 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) |
| Part 2 (MAD): RO6953958 210mg | 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) |
| Part 2 (MAD): RO6953958 210mg | 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) |
| Part 2 (MAD): RO6953958 210mg | Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 3.00 Hours (h) |
| Part 2 (MAD): RO6953958 210mg | 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) |
| Part 2 (MAD): RO6953958 210mg | 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) |
Secondary
Parts 1 and 2: Cumulative Amount of Unchanged Drug Excreted Into the Urine (Ae) of RO6953958
Time frame: Day 1 and 10
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 1 and 2: Cumulative Amount of Unchanged Drug Excreted Into the Urine (Ae) of RO6953958 | Day 1 | 0.133 mg | Standard Deviation 0.0513 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 1 and 2: Cumulative Amount of Unchanged Drug Excreted Into the Urine (Ae) of RO6953958 | Day 1 | 0.266 mg | Standard Deviation 0.0766 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Parts 1 and 2: Cumulative Amount of Unchanged Drug Excreted Into the Urine (Ae) of RO6953958 | Day 1 | 0.612 mg | Standard Deviation 0.245 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Parts 1 and 2: Cumulative Amount of Unchanged Drug Excreted Into the Urine (Ae) of RO6953958 | Day 1 | 0.321 mg | Standard Deviation 0.0831 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Parts 1 and 2: Cumulative Amount of Unchanged Drug Excreted Into the Urine (Ae) of RO6953958 | Day 1 | 0.675 mg | Standard Deviation 0.377 |
| Part 1 (SAD): Placebo (Fasted) | Parts 1 and 2: Cumulative Amount of Unchanged Drug Excreted Into the Urine (Ae) of RO6953958 | Day 1 | 1.14 mg | Standard Deviation 0.465 |
| Part 1 (SAD): Placebo (Fed) | Parts 1 and 2: Cumulative Amount of Unchanged Drug Excreted Into the Urine (Ae) of RO6953958 | Day 1 | 0.192 mg | Standard Deviation 0.0814 |
| Part 1 (SAD): Placebo (Fed) | 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 |
| Part 2 (MAD): RO6953958 45mg | Parts 1 and 2: Cumulative Amount of Unchanged Drug Excreted Into the Urine (Ae) of RO6953958 | Day 1 | 0.525 mg | Standard Deviation 0.234 |
| Part 2 (MAD): RO6953958 45mg | Parts 1 and 2: Cumulative Amount of Unchanged Drug Excreted Into the Urine (Ae) of RO6953958 | Day 10 | 0.562 mg | Standard Deviation 0.26 |
| Part 2 (MAD): RO6953958 140mg | Parts 1 and 2: Cumulative Amount of Unchanged Drug Excreted Into the Urine (Ae) of RO6953958 | Day 1 | 0.461 mg | Standard Deviation 0.203 |
| Part 2 (MAD): RO6953958 140mg | Parts 1 and 2: Cumulative Amount of Unchanged Drug Excreted Into the Urine (Ae) of RO6953958 | Day 10 | 0.437 mg | Standard Deviation 0.311 |
Secondary
Parts 1 and 2: Fraction of the Administered Drug Excreted Into the Urine (Fe) of RO6953958
Time frame: Day 1 and 10
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 1 and 2: Fraction of the Administered Drug Excreted Into the Urine (Fe) of RO6953958 | Day 1 | 0.888 mg | Standard Deviation 0.342 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 1 and 2: Fraction of the Administered Drug Excreted Into the Urine (Fe) of RO6953958 | Day 1 | 0.592 mg | Standard Deviation 0.17 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Parts 1 and 2: Fraction of the Administered Drug Excreted Into the Urine (Fe) of RO6953958 | Day 1 | 0.679 mg | Standard Deviation 0.272 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Parts 1 and 2: Fraction of the Administered Drug Excreted Into the Urine (Fe) of RO6953958 | Day 1 | 0.356 mg | Standard Deviation 0.0923 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Parts 1 and 2: Fraction of the Administered Drug Excreted Into the Urine (Fe) of RO6953958 | Day 1 | 0.375 mg | Standard Deviation 0.209 |
| Part 1 (SAD): Placebo (Fasted) | Parts 1 and 2: Fraction of the Administered Drug Excreted Into the Urine (Fe) of RO6953958 | Day 1 | 0.316 mg | Standard Deviation 0.129 |
| Part 1 (SAD): Placebo (Fed) | Parts 1 and 2: Fraction of the Administered Drug Excreted Into the Urine (Fe) of RO6953958 | Day 1 | 0.426 mg | Standard Deviation 0.181 |
| Part 1 (SAD): Placebo (Fed) | 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 |
| Part 2 (MAD): RO6953958 45mg | Parts 1 and 2: Fraction of the Administered Drug Excreted Into the Urine (Fe) of RO6953958 | Day 1 | 0.375 mg | Standard Deviation 0.167 |
| Part 2 (MAD): RO6953958 45mg | Parts 1 and 2: Fraction of the Administered Drug Excreted Into the Urine (Fe) of RO6953958 | Day 10 | 0.402 mg | Standard Deviation 0.186 |
| Part 2 (MAD): RO6953958 140mg | Parts 1 and 2: Fraction of the Administered Drug Excreted Into the Urine (Fe) of RO6953958 | Day 1 | 0.220 mg | Standard Deviation 0.0965 |
| Part 2 (MAD): RO6953958 140mg | Parts 1 and 2: Fraction of the Administered Drug Excreted Into the Urine (Fe) of RO6953958 | Day 10 | 0.208 mg | Standard Deviation 0.148 |
Secondary
Parts 1 and 2: Renal Clearance of the Drug From Urine (CLR) of RO6953958
Time frame: Day 1 and 10
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | Parts 1 and 2: Renal Clearance of the Drug From Urine (CLR) of RO6953958 | Day 1 | 115 mg | Geometric Coefficient of Variation 139.3 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 1 and 2: Renal Clearance of the Drug From Urine (CLR) of RO6953958 | Day 1 | 142 mg | Geometric Coefficient of Variation 52.8 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 1 and 2: Renal Clearance of the Drug From Urine (CLR) of RO6953958 | Day 1 | 123 mg | Geometric Coefficient of Variation 65.9 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | Parts 1 and 2: Renal Clearance of the Drug From Urine (CLR) of RO6953958 | Day 1 | 116 mg | Geometric Coefficient of Variation 59.6 |
| Part 1 (SAD): RO6953958 180mg (Fasted) | Parts 1 and 2: Renal Clearance of the Drug From Urine (CLR) of RO6953958 | Day 1 | 49.9 mg | Geometric Coefficient of Variation 60.7 |
| Part 1 (SAD): RO6953958 360mg (Fasted) | Parts 1 and 2: Renal Clearance of the Drug From Urine (CLR) of RO6953958 | Day 1 | 56.2 mg | Geometric Coefficient of Variation 150.2 |
| Part 1 (SAD): Placebo (Fasted) | Parts 1 and 2: Renal Clearance of the Drug From Urine (CLR) of RO6953958 | Day 1 | 81.7 mg | Geometric Coefficient of Variation 66 |
| Part 1 (SAD): Placebo (Fed) | 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 |
| Part 1 (SAD): Placebo (Fed) | Parts 1 and 2: Renal Clearance of the Drug From Urine (CLR) of RO6953958 | Day 1 | 97.3 mg | Geometric Coefficient of Variation 29.5 |
| Part 2 (MAD): RO6953958 45mg | Parts 1 and 2: Renal Clearance of the Drug From Urine (CLR) of RO6953958 | Day 10 | 78.7 mg | Geometric Coefficient of Variation 51 |
| Part 2 (MAD): RO6953958 45mg | Parts 1 and 2: Renal Clearance of the Drug From Urine (CLR) of RO6953958 | Day 1 | 84.3 mg | Geometric Coefficient of Variation 50.7 |
| Part 2 (MAD): RO6953958 140mg | Parts 1 and 2: Renal Clearance of the Drug From Urine (CLR) of RO6953958 | Day 1 | 36.5 mg | Geometric Coefficient of Variation 35.3 |
| Part 2 (MAD): RO6953958 140mg | Parts 1 and 2: Renal Clearance of the Drug From Urine (CLR) of RO6953958 | Day 10 | 37.3 mg | Geometric Coefficient of Variation 36.3 |
Secondary
Parts 2 and 3: Accumulation Ratio Based on AUC (RAUC) of RO6953958 and Its Metabolites RO7021594 and RO7045755
Time frame: Day 1-14
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Accumulation Ratio Based on AUC (RAUC) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 10 | 1.04 Ratio of AUC | Geometric Coefficient of Variation 15.9 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Accumulation Ratio Based on AUC (RAUC) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 10 | 1.08 Ratio of AUC | Geometric Coefficient of Variation 23.4 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Accumulation Ratio Based on AUC (RAUC) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 10 | 1.87 Ratio of AUC | Geometric Coefficient of Variation 22.3 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Accumulation Ratio Based on AUC (RAUC) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 10 | 1.60 Ratio of AUC | Geometric Coefficient of Variation 21.8 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Accumulation Ratio Based on AUC (RAUC) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 10 | 0.794 Ratio of AUC | Geometric Coefficient of Variation 23.9 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Accumulation Ratio Based on AUC (RAUC) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 10 | 0.814 Ratio of AUC | Geometric Coefficient of Variation 31.2 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
Secondary
Parts 2 and 3: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
Time frame: Day 1-14
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | 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 24 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 10 | 1.01 Ratio of Cmax | Geometric Coefficient of Variation 45.2 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 10 | 1.77 Ratio of Cmax | Geometric Coefficient of Variation 32.2 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 10 | 1.59 Ratio of Cmax | Geometric Coefficient of Variation 16.8 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 10 | 0.856 Ratio of Cmax | Geometric Coefficient of Variation 13.6 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 10 | 0.839 Ratio of Cmax | Geometric Coefficient of Variation 28.1 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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
Parts 2 and 3: Accumulation Ratio Based on Ctrough (RCtrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755
Time frame: Day 1-14
Population: The PK population included all participants who received active (RO6953958) treatment. No data were analyzed and this outcome measure was not conducted.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Parts 2 and 3: Accumulation Ratio Based on Ctrough (RCtrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 | — |
| Unknown | Parts 2 and 3: Accumulation Ratio Based on Ctrough (RCtrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 | — |
| Unknown | Parts 2 and 3: Accumulation Ratio Based on Ctrough (RCtrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 | — |
Secondary
Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
Time frame: Day 1-14
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 10 | 4290 h*ng/mL | Geometric Coefficient of Variation 97.2 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 10 | 51500 h*ng/mL | Geometric Coefficient of Variation 85.4 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 5820 h*ng/mL | Geometric Coefficient of Variation 63.9 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 27400 h*ng/mL | Geometric Coefficient of Variation 79.8 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 10 | 6060 h*ng/mL | Geometric Coefficient of Variation 58 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 3980 h*ng/mL | Geometric Coefficient of Variation 70.8 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 10 | 9180 h*ng/mL | Geometric Coefficient of Variation 44.9 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 64000 h*ng/mL | Geometric Coefficient of Variation 62 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 10 | 103000 h*ng/mL | Geometric Coefficient of Variation 59.3 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 10 | 5120 h*ng/mL | Geometric Coefficient of Variation 88.8 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 6290 h*ng/mL | Geometric Coefficient of Variation 56.5 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 11600 h*ng/mL | Geometric Coefficient of Variation 27.5 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
Secondary
Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755
Time frame: Day 1-14
Population: The pharmacokinetic (PK) population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 336.4 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 10 | 230.74 ng/mL | Standard Deviation 169.2 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 10 | 2759.37 ng/mL | Standard Deviation 2433.54 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 279.87 ng/mL | Standard Deviation 163.45 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 1380.91 ng/mL | Standard Deviation 931.78 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 10 | 283.22 ng/mL | Standard Deviation 141.49 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 194.92 ng/mL | Standard Deviation 116.77 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 10 | 410.99 ng/mL | Standard Deviation 161.04 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 2987.02 ng/mL | Standard Deviation 1307.84 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 10 | 4822.34 ng/mL | Standard Deviation 2550 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 10 | 272.07 ng/mL | Standard Deviation 204.45 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 293.36 ng/mL | Standard Deviation 146.13 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 496.48 ng/mL | Standard Deviation 128.3 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
Secondary
Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755
Time frame: Day 1, 3, 10, 12, 13
Population: The PK population included all participants who received active (RO6953958) treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 5mg (Fasted) | 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 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 27.6 ng/mL | Geometric Coefficient of Variation 300.4 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 31.0 ng/mL | Geometric Coefficient of Variation 160.4 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 10 | 1390 ng/mL | Geometric Coefficient of Variation 98.8 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 10 | 33.6 ng/mL | Geometric Coefficient of Variation 232.9 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 704 ng/mL | Geometric Coefficient of Variation 99 |
| Part 1 (SAD): RO6953958 15mg (Fasted) | Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 10 | 24.2 ng/mL | Geometric Coefficient of Variation 177.7 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 10 | 40.5 ng/mL | Geometric Coefficient of Variation 161.4 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 1 | 2130 ng/mL | Geometric Coefficient of Variation 60.4 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 10 | 31.7 ng/mL | Geometric Coefficient of Variation 429.6 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7021594 - Day 10 | 3020 ng/mL | Geometric Coefficient of Variation 62.9 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO7045755 - Day 1 | 63.0 ng/mL | Geometric Coefficient of Variation 119.7 |
| Part 1 (SAD): RO6953958 45mg (Fasted) | Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755 | RO6953958 - Day 1 | 82.4 ng/mL | Geometric Coefficient of Variation 50.2 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |
| Part 1 (SAD): RO6953958 90mg (Fasted or Fed) | 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 |