A Study to Investigate the Safety, Tolerability, Pharmaco... | NCT04475848 | Trialant
NCT04475848
Sponsor
Hoffmann-La Roche
Status
Completed
Last Update Posted
Jul 10, 2024Actual
Enrollment
88Actual
Phase
Phase 1
Conditions
Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Mental Disorders
Neurodevelopmental Disorders
Interventions
RO6953958
Placebo
Midazolam
Countries
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT04475848
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
BP41695
Secondary IDs
ID
Type
Description
Link
2019-004486-41
EudraCT Number
Brief Title
A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
Official Title
A Randomized, Investigator- /Subject-blind, Single- and Multiple-ascending Dose, Placebo-controlled Study to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 (Including RO6953958 Effect on Midazolam) Following Oral Administration in Healthy Male Participants
Acronym
Not provided
Organization
Hoffmann-La RocheINDUSTRY
Status Module
Record Verification Date
Jul 2024
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jul 15, 2020Actual
Primary Completion Date
Feb 6, 2022Actual
Completion Date
Feb 6, 2022Actual
First Submitted Date
Jul 13, 2020
First Submission Date that Met QC Criteria
Jul 15, 2020
First Posted Date
Jul 17, 2020Actual
Results Waived
Not provided
Results First Submitted Date
Jan 30, 2023
Results First Submitted that Met QC Criteria
Jul 8, 2024
Results First Posted Date
Jul 10, 2024Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Jul 8, 2024
Last Update Posted Date
Jul 10, 2024Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Hoffmann-La RocheINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
No
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
Detailed Description
Not provided
Conditions Module
Conditions
Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Mental Disorders
Neurodevelopmental Disorders
Keywords
Autism Spectrum Disorder
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
88Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Part 1: SAD/FE
Experimental
There will be 7 cohorts in this study. In each cohort, participants will receive a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort will return to receive the same single oral dose of RO6953958 repeated in the fed state.
Drug: RO6953958
Part 1: SAD placebo
Placebo Comparator
There will be 7 cohorts in this study. In each cohort, participants will receive a single oral dose of a placebo while fasted/fed.
Drug: Placebo
Part 2: MAD
Experimental
A maximum of 5 dose levels are anticipated. For each dose level, a minimum of 8 and a maximum of 16 participants will receive a multiple oral dose of RO6953958 once daily (QD) for 10 days.
Drug: RO6953958
Part 2: MAD placebo
Placebo Comparator
A maximum of 5 dose levels are anticipated. For each dose level, a minimum of 8 and a maximum of 16 participants will receive a multiple oral dose of palcebo QD for 10 days.
Drug: Placebo
Part 3: DDI
Experimental
RO6953958 will be administered at the maximum dose QD that was tested in the ongoing Part 2 (MAD).
Participants will also be administered midazolam.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
RO6953958
Drug
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).
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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.
Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
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.
From randomization up to 8 weeks
Secondary Outcomes
Measure
Description
Time Frame
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
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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
Accepts Healthy Volunteers
Yes
Sex
Male
Sex/Gender Based
Yes
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
55 Years
Standard Ages
Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Clinical Trials
Hoffmann-La Roche
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Hammersmith Medicines Research; Central Middlesex Hospital
This study was conducted at one centre in the United Kingdom.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
FG001
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot_SAP
Yes
Yes
No
Study Protocol and Statistical Analysis Plan
Nov 5, 2021
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
Drug: RO6953958
Drug: Midazolam
Part 1: SAD/FE
Part 2: MAD
Part 3: DDI
Placebo
Drug
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.
Part 1: SAD placebo
Part 2: MAD placebo
Midazolam
Drug
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.
Part 3: DDI
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
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.
Day 1-14
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.
Day 1-14
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.
Day 1-14
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.
Day 1-14
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.
Day 1-14
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
F is stated as a fraction of 1.
Days 2 and 14
Part 3: Volume of Distribution Under Steady-state Conditions (Vss) of Midazolam
Days 3 and 14
FG002
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
FG003
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.
FG004
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
FG005
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
FG006
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
FG007
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
FG008
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
FG009
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
FG010
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
FG011
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
FG0006 subjects
FG0016 subjects
FG0026 subjects
FG0036 subjects
FG0046 subjects
FG0056 subjects
FG00610 subjects
FG0072 subjects
FG0086 subjects
FG0096 subjects
FG0106 subjects
FG0116 subjects
FG01216 subjects
COMPLETED
FG0006 subjects
FG0016 subjects
FG0026 subjects
FG0036 subjects
FG0046 subjects
FG0056 subjects
FG00610 subjects
FG0072 subjects
FG0086 subjects
FG0096 subjects
FG0106 subjects
FG0116 subjects
FG01216 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
BG001
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
BG002
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
BG003
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.
BG004
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
BG005
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
BG006
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
BG007
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
BG008
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
BG009
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
BG010
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
BG011
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
BG013
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0006
BG0016
BG0026
BG0036
BG0046
BG0056
BG00610
BG0072
BG0086
BG0096
BG0106
BG0116
BG01216
BG01388
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00039.0± 9.9
BG00137.3± 8.1
BG00237.5± 4.3
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0000
BG0010
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0001
BG0011
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
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.
The safety population included all participants randomized to study treatment and who received at least one dose of the study treatment.
Posted
Count of Participants
Participants
Part 1: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort). Parts 2 and 3: From randomization up to 8 weeks
ID
Title
Description
OG000
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG001
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG002
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG003
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.
OG004
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG005
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG006
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
OG007
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
OG008
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
OG009
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
OG010
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
OG011
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG0002
OG0012
OG0022
OG003
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.
The safety population included all participants randomized to study treatment and who received at least one dose of the study treatment.
Posted
Count of Participants
Participants
From randomization up to 8 weeks
ID
Title
Description
OG000
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
OG001
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
Secondary
Parts 1, 2 and 3: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
The pharmacokinetic (PK) population included all participants who received active (RO6953958) treatment.
Posted
Mean
Standard Deviation
Nanograms per Milliliter (ng/mL)
Day 1-14
ID
Title
Description
OG000
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG001
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG002
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG003
Part 1 (SAD): RO6953958 90mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG004
Part 1 (SAD): RO6953958 90mg (Fed)
Secondary
Parts 2 and 3: Average Plasma Concentration (Cavg) of RO6953958 and Its Metabolites RO7021594 and RO7045755
The pharmacokinetic (PK) population included all participants who received active (RO6953958) treatment.
Posted
Mean
Standard Deviation
ng/mL
Day 1-14
ID
Title
Description
OG000
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
OG001
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
OG002
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Secondary
Parts 1, 2 and 3: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
The pharmacokinetic (PK) population included all participants who received active (RO6953958) treatment.
Posted
Median
Full Range
Hours (h)
Day 1-14
ID
Title
Description
OG000
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG001
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG002
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG003
Part 1 (SAD): RO6953958 90mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG004
Part 1 (SAD): RO6953958 90mg (Fed)
Secondary
Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and Its Metabolites RO7021594 and RO7045755 in Fasted and Fed State
The PK population included all participants who received active (RO6953958) treatment.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Day 1-10
ID
Title
Description
OG000
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG001
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG002
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG003
Part 1 (SAD): RO6953958 90mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG004
Part 1 (SAD): RO6953958 90mg (Fed)
Secondary
Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and Its Metabolites RO7021594 and RO7045755
The PK population included all participants who received active (RO6953958) treatment.
Posted
Geometric Mean
Geometric Coefficient of Variation
h
Day 1-10
ID
Title
Description
OG000
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG001
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG002
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG003
Part 1 (SAD): RO6953958 90mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG004
Part 1 (SAD): RO6953958 90mg (Fed)
Secondary
Parts 1, 2 and 3: Terminal Elimination Phase Half-Life (t1/2) of RO6953958 and Its Metabolites RO7021594 and RO7045755
The PK population included all participants who received active (RO6953958) treatment.
Posted
Geometric Mean
Geometric Coefficient of Variation
h
Day 1-14
ID
Title
Description
OG000
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG001
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG002
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG003
Part 1 (SAD): RO6953958 90mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG004
Part 1 (SAD): RO6953958 90mg (Fed)
Secondary
Parts 2 and 3: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and Its Metabolites RO7021594 and RO7045755
The PK population included all participants who received active (RO6953958) treatment.
Posted
Geometric Mean
Geometric Coefficient of Variation
h*ng/mL
Day 1-14
ID
Title
Description
OG000
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
OG001
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
OG002
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
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
The PK population included all participants who received active (RO6953958) treatment.
Posted
Geometric Mean
Geometric Coefficient of Variation
h*ng/mL
Day 1-5
ID
Title
Description
OG000
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG001
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG002
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG003
Part 1 (SAD): RO6953958 90mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG004
Part 1 (SAD): RO6953958 90mg (Fed)
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
The PK population included all participants who received active (RO6953958) treatment.
Posted
Geometric Mean
Geometric Coefficient of Variation
h*ng/mL
Day 1-10
ID
Title
Description
OG000
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG001
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG002
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG003
Part 1 (SAD): RO6953958 90mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG004
Part 1 (SAD): RO6953958 90mg (Fed)
Secondary
Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO6953958 and Its Metabolites RO7021594 and RO7045755
The PK population included all participants who received active (RO6953958) treatment.
Posted
Geometric Mean
Geometric Coefficient of Variation
h*ng/mL
Day 1-10
ID
Title
Description
OG000
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG001
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG002
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG003
Part 1 (SAD): RO6953958 90mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG004
Part 1 (SAD): RO6953958 90mg (Fed)
Secondary
Parts 1, 2 and 3: Apparent Clearance (CL/F) of RO6953958
The PK population included all participants who received active (RO6953958) treatment.
Posted
Geometric Mean
Geometric Coefficient of Variation
L/h
Day 1-14
ID
Title
Description
OG000
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG001
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG002
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG003
Part 1 (SAD): RO6953958 90mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG004
Part 1 (SAD): RO6953958 90mg (Fed)
Secondary
Parts 1, 2 and 3: Apparent Volume of Distribution (V/F) of RO6953958
The PK population included all participants who received active (RO6953958) treatment.
Posted
Geometric Mean
Geometric Coefficient of Variation
L
Day 1-14
ID
Title
Description
OG000
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG001
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG002
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG003
Part 1 (SAD): RO6953958 90mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG004
Part 1 (SAD): RO6953958 90mg (Fed)
Secondary
Parts 1 and 2: Cumulative Amount of Unchanged Drug Excreted Into the Urine (Ae) of RO6953958
The PK population included all participants who received active (RO6953958) treatment.
Posted
Mean
Standard Deviation
mg
Day 1 and 10
ID
Title
Description
OG000
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG001
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG002
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG003
Part 1 (SAD): RO6953958 90mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG004
Part 1 (SAD): RO6953958 90mg (Fed)
Secondary
Parts 1 and 2: Fraction of the Administered Drug Excreted Into the Urine (Fe) of RO6953958
The PK population included all participants who received active (RO6953958) treatment.
Posted
Mean
Standard Deviation
mg
Day 1 and 10
ID
Title
Description
OG000
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG001
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG002
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG003
Part 1 (SAD): RO6953958 90mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG004
Part 1 (SAD): RO6953958 90mg (Fed)
Secondary
Parts 1 and 2: Renal Clearance of the Drug From Urine (CLR) of RO6953958
The PK population included all participants who received active (RO6953958) treatment.
Posted
Geometric Mean
Geometric Coefficient of Variation
mg
Day 1 and 10
ID
Title
Description
OG000
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG001
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG002
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG003
Part 1 (SAD): RO6953958 90mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG004
Part 1 (SAD): RO6953958 90mg (Fed)
Secondary
Parts 2 and 3: Trough Plasma Concentration (Ctrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755
The PK population included all participants who received active (RO6953958) treatment.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Day 1, 3, 10, 12, 13
ID
Title
Description
OG000
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
OG001
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
OG002
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Secondary
Parts 2 and 3: Accumulation Ratio Based on AUC (RAUC) of RO6953958 and Its Metabolites RO7021594 and RO7045755
The PK population included all participants who received active (RO6953958) treatment.
Posted
Geometric Mean
Geometric Coefficient of Variation
Ratio of AUC
Day 1-14
ID
Title
Description
OG000
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
OG001
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
OG002
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Secondary
Parts 2 and 3: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and Its Metabolites RO7021594 and RO7045755
The PK population included all participants who received active (RO6953958) treatment.
Posted
Geometric Mean
Geometric Coefficient of Variation
Ratio of Cmax
Day 1-14
ID
Title
Description
OG000
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
OG001
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
OG002
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Secondary
Parts 2 and 3: Accumulation Ratio Based on Ctrough (RCtrough) of RO6953958 and Its Metabolites RO7021594 and RO7045755
The PK population included all participants who received active (RO6953958) treatment. No data were analyzed and this outcome measure was not conducted.
Posted
Day 1-14
ID
Title
Description
OG000
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
OG001
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
OG002
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Secondary
Parts 1, 2 and 3: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Cmax of RO6953958 and Its Metabolites RO7021594 and RO7045755
The PK population included all participants who received active (RO6953958) treatment.
Posted
Geometric Mean
Geometric Coefficient of Variation
Metabolite Ratio for Cmax
Day 1-14
ID
Title
Description
OG000
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG001
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG002
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG003
Part 1 (SAD): RO6953958 90mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG004
Part 1 (SAD): RO6953958 90mg (Fed)
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
The PK population included all participants who received active (RO6953958) treatment.
Posted
Geometric Mean
Geometric Coefficient of Variation
Metabolite Ratio for AUC(0-t)
Day 1-14
ID
Title
Description
OG000
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG001
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG002
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG003
Part 1 (SAD): RO6953958 90mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG004
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.
The PK population included all participants who received active (RO6953958) treatment.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Units
Counts
Participants
OG000
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.
The PK population included all participants who received active (RO6953958) treatment.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Units
Counts
Participants
OG000
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.
The PK population included all participants who received active (RO6953958) treatment.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Units
Counts
Participants
OG000
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.
The PK population included all participants who received active (RO6953958) treatment.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Units
Counts
Participants
OG000
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.
The PK population included all participants who received active (RO6953958) treatment.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Units
Counts
Participants
OG000
Secondary
Part 3: VF of Oral Midazolam
The PK population included all participants who received active (RO6953958) treatment.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Units
Counts
Participants
OG00016
Secondary
Part 3: RAUC of Midazolam
The PK population included all participants who received active (RO6953958) treatment.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Units
Counts
Participants
OG00016
Secondary
Part 3: RCmax of Midazolam
The PK population included all participants who received active (RO6953958) treatment.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Units
Counts
Participants
OG00016
Secondary
Part 3: CL: Total Plasma Clearance of IV Midazolam
The PK population included all participants who received active (RO6953958) treatment.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Units
Counts
Participants
OG00016
Secondary
Part 3: Fraction Absorbed (F) of Midazolam
F is stated as a fraction of 1.
The PK population included all participants who received active (RO6953958) treatment.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Units
Counts
Participants
OG00016
Secondary
Part 3: Volume of Distribution Under Steady-state Conditions (Vss) of Midazolam
The PK population included all participants who received active (RO6953958) treatment.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Units
Counts
Participants
OG00016
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
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Part 1 (SAD): RO6953958 5mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
0
6
0
6
2
6
EG001
Part 1 (SAD): RO6953958 15mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
0
6
0
6
2
6
EG002
Part 1 (SAD): RO6953958 45mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
0
6
0
6
2
6
EG003
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.
0
6
0
6
4
6
EG004
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
0
6
0
6
2
6
EG005
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
0
6
0
6
3
6
EG006
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
0
10
0
10
2
10
EG007
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
0
2
0
2
0
2
EG008
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
0
6
0
6
4
6
EG009
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
0
6
0
6
6
6
EG010
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
0
6
0
6
4
6
EG011
Part 2 (MAD): Placebo
Participants received a multiple oral dose of a placebo QD for 10 days.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
0
16
0
16
10
16
Serious Adverse Events
Not provided
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Abdominal Pain Upper
Gastrointestinal disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0051 events1 affected6 at risk
EG0060 events0 affected10 at risk
EG0072 at risk
EG0080 events0 affected6 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
EG0110 events0 affected6 at risk
EG0120 events0 affected16 at risk
Constipation
Gastrointestinal disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dry Mouth
Gastrointestinal disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Gastrointestinal Sounds Abnormal
Gastrointestinal disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Gastrooesophageal Reflux Disease
Gastrointestinal disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Catheter Site Pain
General disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Catheter Site Swelling
General disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Chills
General disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Fatigue
General disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Medical Device Site Dermatitis
General disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Puncture Site Pain
General disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Pyrexia
General disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Swelling
General disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Ear Infection
Infections and infestations
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Upper Respiratory Tract Infection
Infections and infestations
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Procedural Headache
Injury, poisoning and procedural complications
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Back Pain
Musculoskeletal and connective tissue disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Musculoskeletal Pain
Musculoskeletal and connective tissue disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Musculoskeletal Stiffness
Musculoskeletal and connective tissue disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Tendon Discomfort
Musculoskeletal and connective tissue disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dizziness
Nervous system disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dizziness Postural
Nervous system disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Headache
Nervous system disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0012 events2 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Lethargy
Nervous system disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Presyncope
Nervous system disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Somnolence
Nervous system disorders
MedDRA v25.0
Systematic Assessment
EG0002 events2 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Syncope
Nervous system disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Abnormal Dreams
Psychiatric disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Oropharyngeal Pain
Respiratory, thoracic and mediastinal disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Sneezing
Respiratory, thoracic and mediastinal disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dry Skin
Skin and subcutaneous tissue disorders
MedDRA v25.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
OG0076
OG0086
OG0096
OG01016
Title
Denominators
Categories
RO6953958 - Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0036
ParticipantsOG0046
ParticipantsOG0056
ParticipantsOG0066
ParticipantsOG0076
ParticipantsOG0086
ParticipantsOG0096
ParticipantsOG0100
Title
Measurements
OG00070.3± 31.4
OG001150± 34.2
OG002299± 50.0
OG003
RO6953958 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO6953958 - Day 10
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO6953958 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7021594 - Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0036
RO7021594 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7021594 - Day 10
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7021594 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7045755 - Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0036
RO7045755 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7045755 - Day 10
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7045755 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Units
Counts
Participants
OG0006
OG0016
OG0026
OG00316
Title
Denominators
Categories
RO6953958 - Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
Title
Measurements
OG00081.47± 28.35
OG001279.87± 163.45
OG002496.48± 128.30
RO6953958 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO6953958 - Day 10
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
RO6953958 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO7021594 - Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
RO7021594 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO7021594 - Day 10
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
RO7021594 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO7045755 - Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
RO7045755 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO7045755 - Day 10
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
RO7045755 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
OG005
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG006
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG007
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
OG008
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
OG009
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
OG0076
OG0086
OG0096
OG01016
Title
Denominators
Categories
RO6953958 - Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0036
ParticipantsOG0046
ParticipantsOG0056
ParticipantsOG0066
ParticipantsOG0076
ParticipantsOG0086
ParticipantsOG0096
ParticipantsOG01016
Title
Measurements
OG0001.00(0.50 to 2.00)
OG0011.00(0.50 to 2.12)
OG0022.00(1.00 to 3.00)
OG003
RO6953958 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO6953958 - Day 10
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO6953958 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7021594 - Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0036
RO7021594 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7021594 - Day 10
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7021594 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7045755 - Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0036
RO7045755 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7045755 - Day 10
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7045755 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
OG005
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG006
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG007
Part 1 (SAD): Placebo (Fasted)
Participants received a single oral dose of a placebo while fasted.
OG008
Part 1 (SAD): Placebo (Fed)
Participants received a single oral dose of a placebo while fed.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
OG0070
OG0080
Title
Denominators
Categories
RO6953958
Title
Measurements
OG0003.88± 63.7
OG0014.42± 71.6
OG0025.98± 82.4
OG0036.75± 98.2
OG00411.1± 130.4
OG0058.99± 97.7
OG00610.6± 67.1
RO7021594
Title
Measurements
OG0002.67± 24.0
OG0016.22± 84.1
OG00212.6± 163.1
OG003
RO7045755
Title
Measurements
OG0005.64± 53.3
OG0017.48± 55.7
OG0026.52± 78.2
OG003
Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
OG005
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG006
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
Title
Denominators
Categories
RO6953958
Title
Measurements
OG0009.44± 25.0
OG00116.47± 43.8
OG00221.40± 28.9
OG00351.37± 16.6
OG00424.00± 0.0
OG00570.14± 22.3
OG00688.77± 32.1
RO7021594
Title
Measurements
OG00087.23± 14.9
OG00196.03± 0.1
OG00296.01± 0.0
OG003
RO7045755
Title
Measurements
OG0003.84± 52.9
OG00119.06± 37.0
OG00226.96± 28.9
OG003
Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
OG005
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG006
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG007
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
OG008
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
OG009
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
OG0076
OG0086
OG0096
OG01016
Title
Denominators
Categories
RO6953958 - Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0036
ParticipantsOG0046
ParticipantsOG0056
ParticipantsOG0066
ParticipantsOG0076
ParticipantsOG0085
ParticipantsOG0093
ParticipantsOG0100
Title
Measurements
OG0001.75± 11.8
OG0013.43± 52.4
OG0023.98± 46.3
OG003
RO6953958 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO6953958 - Day 10
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO6953958 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7021594 - Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0036
RO7021594 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7021594 - Day 10
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7021594 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7045755 - Day 1
ParticipantsOG0003
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0036
RO7045755 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7045755 - Day 10
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7045755 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Units
Counts
Participants
OG0006
OG0016
OG0026
OG00316
Title
Denominators
Categories
RO6953958 - Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
Title
Measurements
OG0001830± 44.7
OG0015820± 63.9
OG00211600± 27.5
RO6953958 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO6953958 - Day 10
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
RO6953958 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO7021594 - Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
RO7021594 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO7021594 - Day 10
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
RO7021594 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO7045755 - Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
RO7045755 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO7045755 - Day 10
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
RO7045755 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
OG005
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG006
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
Title
Denominators
Categories
RO6953958
Title
Measurements
OG000204± 38.9
OG001665± 51.3
OG0021740± 26.8
OG0034140± 39.9
OG0045330± 38.9
OG0056170± 39.7
OG0068720± 70.9
RO7021594
Title
Measurements
OG000829± 38.4
OG0012910± 45.1
OG0027410± 81.6
OG003
RO7045755
Title
Measurements
OG000238± 53.2
OG001707± 45.3
OG0021610± 34.7
OG003
Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
OG005
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG006
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
Title
Denominators
Categories
RO6953958
Title
Measurements
OG000188± 38.7
OG001651± 52.4
OG0021730± 27.7
OG0034990± 46.1
OG0045330± 38.9
OG0059470± 31.6
OG00614700± 83.0
RO7021594
Title
Measurements
OG0001410± 38.6
OG0014940± 48.7
OG00212200± 89.0
OG003
RO7045755
Title
Measurements
OG000208± 56.0
OG001684± 50.5
OG0021650± 34.6
OG003
Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
OG005
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG006
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
Title
Denominators
Categories
RO6953958
Title
Measurements
OG000206± 39.7
OG001676± 52.2
OG0021780± 26.2
OG0035120± 46.5
OG0045410± 39.3
OG0059710± 31.3
OG00615200± 78.7
RO7021594
Title
Measurements
OG0001190± 36.8
OG0014160± 46.5
OG00210500± 85.3
OG003
RO7045755
Title
Measurements
OG000249± 57.3
OG001738± 48.8
OG0021700± 35.4
OG003
Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
OG005
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG006
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG007
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
OG008
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
OG009
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
OG0076
OG0086
OG0096
OG01016
Title
Denominators
Categories
Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0036
ParticipantsOG0046
ParticipantsOG0056
ParticipantsOG0066
ParticipantsOG0076
ParticipantsOG0085
ParticipantsOG0095
ParticipantsOG0100
Title
Measurements
OG00024.3± 39.7
OG00122.2± 52.2
OG00225.2± 26.2
OG003
Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Day 10
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state
OG005
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG006
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG007
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
OG008
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
OG009
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
OG0076
OG0086
OG0096
OG01016
Title
Denominators
Categories
Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0036
ParticipantsOG0046
ParticipantsOG0056
ParticipantsOG0066
ParticipantsOG0076
ParticipantsOG0086
ParticipantsOG0096
ParticipantsOG0100
Title
Measurements
OG00089.1± 51.2
OG001110± 47.5
OG002145± 42.7
OG003
Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Day 10
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state
OG005
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG006
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG007
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
OG008
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
OG009
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
OG0076
OG0086
OG0096
Title
Denominators
Categories
Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0036
ParticipantsOG0046
ParticipantsOG0056
ParticipantsOG0066
ParticipantsOG0076
ParticipantsOG0086
ParticipantsOG0096
Title
Measurements
OG0000.0322± 0.00658
OG0010.133± 0.0513
OG0020.266± 0.0766
OG003
Day 10
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state
OG005
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG006
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG007
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
OG008
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
OG009
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
OG0076
OG0086
OG0096
Title
Denominators
Categories
Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0036
ParticipantsOG0046
ParticipantsOG0056
ParticipantsOG0066
ParticipantsOG0076
ParticipantsOG0086
ParticipantsOG0096
Title
Measurements
OG0000.644± 0.132
OG0010.888± 0.342
OG0020.592± 0.170
OG003
Day 10
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state
OG005
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG006
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG007
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
OG008
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
OG009
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
OG0076
OG0086
OG0096
Title
Denominators
Categories
Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0036
ParticipantsOG0046
ParticipantsOG0056
ParticipantsOG0066
ParticipantsOG0076
ParticipantsOG0086
ParticipantsOG0096
Title
Measurements
OG000115± 139.3
OG001142± 52.8
OG002123± 65.9
OG003
Day 10
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Units
Counts
Participants
OG0006
OG0016
OG0026
OG00316
Title
Denominators
Categories
RO6953958 - Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
Title
Measurements
OG0000.473± 1305.9
OG00131.0± 160.4
OG00282.4± 50.2
RO6953958 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO6953958 - Day 10
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
RO6953958 - Day 12
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO6953958 - Day 13
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO7021594 - Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
RO7021594 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO7021594 - Day 10
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
RO7021594 - Day 12
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO7021594 - Day 13
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO7045755 - Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
RO7045755 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO7045755 - Day 10
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
RO7045755 - Day 12
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO7045755 - Day 13
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
Units
Counts
Participants
OG0006
OG0016
OG0026
OG00316
Title
Denominators
Categories
RO6953958 - Day 10
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
Title
Measurements
OG0001.10± 8.4
OG0011.04± 15.9
OG0020.794± 23.9
RO6953958 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO7021594 - Day 10
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
RO7021594 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO7045755 - Day 10
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
RO7045755 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
Units
Counts
Participants
OG0006
OG0016
OG0026
OG00316
Title
Denominators
Categories
RO6953958 - Day 10
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
Title
Measurements
OG0001.05± 19.0
OG0011.05± 24.0
OG0020.856± 13.6
RO6953958 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO7021594 - Day 10
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
RO7021594 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
RO7045755 - Day 10
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0030
RO7045755 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG00316
Units
Counts
Participants
OG0000
OG0010
OG0020
OG0030
Title
Denominators
Categories
RO6953958
RO7021594
RO7045755
Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
OG005
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG006
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG007
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
OG008
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
OG009
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
OG0076
OG0086
OG0096
OG01016
Title
Denominators
Categories
RO7021594 - Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0036
ParticipantsOG0046
ParticipantsOG0056
ParticipantsOG0066
ParticipantsOG0076
ParticipantsOG0086
ParticipantsOG0096
ParticipantsOG0100
Title
Measurements
OG0000.839± 61.6
OG0011.20± 43.3
OG0021.54± 42.3
OG003
RO7021594 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7021594 - Day 10
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7021594 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7045755 - Day 1
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0036
RO7045755 - Day 3
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7045755 - Day 10
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
RO7045755 - Day 14
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Part 1 (SAD): RO6953958 90mg (Fed)
Participants in the fed (FE) cohort returned to receive the same single oral dose of RO6953958 repeated in the fed state.
OG005
Part 1 (SAD): RO6953958 180mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG006
Part 1 (SAD): RO6953958 360mg (Fasted)
Participants received a single oral dose of RO6953958 while fasted.
OG007
Part 2 (MAD): RO6953958 45mg
Participants received a multiple oral dose of RO6953958 once daily (QD) for 10 days.
OG008
Part 2 (MAD): RO6953958 140mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
OG009
Part 2 (MAD): RO6953958 210mg
Participants received a multiple oral dose of RO6953958 QD for 10 days.
Participants were administered RO6953958 at the maximum dose QD that was tested in the ongoing Part 2 (MAD). Participants were also administered midazolam.