A Study to Investigate the Efficacy and Safety of Balovap... | NCT02901431 | Trialant
NCT02901431
Sponsor
Hoffmann-La Roche
Status
Terminated
Last Update Posted
Feb 8, 2021Actual
Enrollment
339Actual
Phase
Phase 2
Conditions
Autism Spectrum Disorder
Interventions
Placebo
RO5285119
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT02901431
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
BP30153
Secondary IDs
Not provided
Brief Title
A Study to Investigate the Efficacy and Safety of Balovaptan (RO5285119) in Participants With Autism Spectrum Disorder (ASD)
Official Title
A Phase II Multi-Center, Randomized, Double-Blind, 24-Week, Parallel Group, Placebo-Controlled Study to Investigate the Efficacy and Safety of Balovaptan (RO5285119) in Children and Adolescents Age 5-17 With Autism Spectrum Disorder (ASD)
Acronym
Not provided
Organization
Hoffmann-La RocheINDUSTRY
Status Module
Record Verification Date
Jan 2021
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
The 24-week analysis indicated no clinical or statistical benefit for the primary endpoint for the overall study population. No new safety concerns identified.
Expanded Access Info
No
Start Date
Nov 21, 2016Actual
Primary Completion Date
Apr 15, 2020Actual
Completion Date
Jun 30, 2020Actual
First Submitted Date
Sep 12, 2016
First Submission Date that Met QC Criteria
Sep 12, 2016
First Posted Date
Sep 15, 2016Estimated
Results Waived
Not provided
Results First Submitted Date
Dec 7, 2020
Results First Submitted that Met QC Criteria
Jan 14, 2021
Results First Posted Date
Feb 8, 2021Actual
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
Jan 14, 2021
Last Update Posted Date
Feb 8, 2021Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Hoffmann-La RocheINDUSTRY
Collaborators
Not provided
Oversight Module
No data available
No data is available for this block.
Description Module
Brief Summary
For participants enrolled prior to Version 6 of the protocol: This was a Phase II multi-center, randomized, double-blind, 24-week, 3-arm, parallel group, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of balovaptan in children and adolescents aged 5-17 years with ASD who are high functioning (intelligence quotient [IQ] greater than or equal to [>=] 70).
For participants enrolled according to Version 6 of the protocol: This was a Phase II multi-center, randomized, double-blind, 24-week, parallel group, placebo-controlled, 2-arm study with participants assigned either to a 10 milligram (mg) or equivalent dose of balovaptan, or placebo. All other study parameters remained as stated above.
There are three parts to this study: PK Part (Study part 1) included up to 8 weeks of treatment, Main Treatment Part (Study part 2) included 24 week of treatment, and the Open Label Extension Part (Study part 3) included Week 24 to Week 76 of treatment.
All participants that completed the 24-week treatment period were eligible to participate in an optional 52-week open-label extension (OLE) during which they received balovaptan treatment.
Detailed Description
Not provided
Conditions Module
Conditions
Autism Spectrum Disorder
Keywords
Not provided
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 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
339Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Placebo
Placebo Comparator
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
Drug: Placebo
Balovaptan (RO5285119) 10 mg/d equivalent
Experimental
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks (up to 52 additional weeks for those enrolled in the OLE).
Drug: RO5285119
Balovaptan (RO5285119) 4 mg/d equivalent
Experimental
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 mg/d of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks. This arm is open only to those participants enrolled prior to Version 6 of the study protocol.
Drug: RO5285119
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Placebo
Drug
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
Placebo
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Change From Baseline in Vineland™-II Adaptive Behavior Scale Two Domain Composite (2DC) Score at Week 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
Vineland™-II Adaptive Behavior Scales 2-Domain Composite (2DC) Score is defined as mean of the Communication domain standard score & Socialization domain standard score. If any of the 2 individual domain standard scores is missing 2DC score is not computed. Vineland™-II is an instrument that measures communication, daily living skills, socialization, motor skills and maladaptive behavior of individuals with developmental disabilities. Survey Interview Form will be administered to a subject's reliable caregiver in this study, during which the rater or clinician will ask to the caregiver open ended questions relating to the subject's activities and behavior. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning. Mixed model with repeated measures (MMRM) was used for analysis with assessments at baseline, week 12 and week 24.
Baseline, Week 24
Secondary Outcomes
Measure
Description
Time Frame
Change From Baseline in Vineland™-II Composite Standard Score After 12 Weeks and 24 Weeks of Treatment for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
The Vineland™-II is an instrument that measures communication, daily living skills, socialization, motor skills (only in children up to 6 years) and maladaptive (not assessed in this study) behavior of individuals with developmental disabilities. The Survey Interview Form (i.e., semi -structured interview) will be administered to a subject's reliable caregiver in this study, during which the rater or clinician will ask to the caregiver open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, Daily Living Skills, and motor skills (up to 6 years only) and used to calculate the Vineland-II Adaptive Behavior Composite score. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Fluent in English
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for ASD or International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD10) criteria for Autism diagnosis confirmed by Autism Diagnostic Observational Schedule (ADOS-2) criteria
Social Responsiveness Scale, second edition (SRS-2) (T-score) >= 66
Clinical Global Impressions of Severity (CGI-S) >= 4 (moderately ill) at screening
IQ >= 70 as assessed by Wechsler Abbreviated Scale of Intelligence Scale: Second Edition (WASI-II) or Wechsler Preschool and Primary Scale of Intelligence: Fourth Edition (WPPSI-IV) intelligence test
Language, hearing, and vision compatible with the study measurements as judged by the investigator
Inclusion Criteria for the OLE:
Have completed the blinded treatment phase of the study OR were required to stop dosing at or before Week 8
Have no adverse events that would prohibit starting the OLE
Exclusion Criteria:
Initiation of a major change in psychosocial intervention (including investigational) within 4 weeks prior to screening
Unstable or uncontrolled clinically significant psychiatric and/or neurological disorder that may interfere with the safety or efficacy endpoints
Known personal or family history of cerebral aneurysm
Risk of suicidal behavior
Seizure within the past 6 months
Medical history of alcohol or substance abuse/dependence
Concurrent cardio-vascular disease not considered well controlled by the Investigator
Clinically significant abnormality on electrocardiogram at screening
Concomitant disease or condition (pulmonary, gastro-intestinal, hepatic, renal, metabolic, immunological system, or obesity that could interfere with the conduct of the study
Evidence for current gastro-intestinal bleeding, e.g., active stomach ulcer disease
History of coagulopathies, bleeding disorders, or blood dyscrasias
Positive serology for hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) 1, or HIV 2
Confirmed clinically significant abnormality in parameters of hematology, clinical chemistry, coagulation, or urinalysis
Medical history of malignancy if not considered cured
Participation in an investigational drug study within 90 days or 5 times the half-life of the investigational molecule (whichever is longer) prior to randomization
Loss of blood over 250 milliliters within three months prior to screening
Allowed medications have not been stable since 4 weeks before screening, and allowed medications for treatment of epilepsy have not been stable since 3 months before screening
Use of prohibited medications within 2 weeks prior to screening visit or 5 times the half-life prior to randomization (whichever is longer)
Hollander E, Jacob S, Jou R, McNamara N, Sikich L, Tobe R, Smith J, Sanders K, Squassante L, Murtagh L, Gleissl T, Wandel C, Veenstra-VanderWeele J. Balovaptan vs Placebo for Social Communication in Childhood Autism Spectrum Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2022 Aug 1;79(8):760-769. doi: 10.1001/jamapsychiatry.2022.1717.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
PK review revealed that age-adjusted doses of 4 and 10 mg in 5-17 year olds were not equivalent to target exposure. For the Main Study Part, data was summarised by exposure ranges (tertiles) based on individual participants PK exposure at Week 12, estimated as the average plasma concentration since treatment start. To allow clear analysis by exposure tertiles, participants with dose adjustment were excluded from analysis by tertiles.
Recruitment Details
A total of 339 participants were enrolled from 44 sites in the United States.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
PK Part - Placebo
Participants received a matching placebo orally. Approximate treatment duration was up to 8 weeks.
FG001
PK Part - Balovaptan (RO5285119) 4 mg/d Equivalent
Periods
Title
Milestones
Reasons Not Completed
PK Part
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
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
Yes
No
No
Study Protocol
Dec 19, 2018
Dec 7, 2020
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
No data available
No data is available for this block.
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
RO5285119
Drug
Participants received age-adjusted total daily oral dose approximately equivalent to the adult doses of either 4 mg/d or 10 mg/d of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks (up to 52 additional weeks for those enrolled in the OLE).
Balovaptan (RO5285119) 10 mg/d equivalent
Balovaptan (RO5285119) 4 mg/d equivalent
Baseline, Weeks 12 and 24
Change From Baseline in Vineland™-II Adaptive Behavior Scale Communication, Socialization, and Daily Living Skills Domain Standard Scores at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
The Vineland™-II is an instrument that measures communication, daily living skills, socialization, motor skills (only in children up to 6 years) and maladaptive (not assessed in this study) behavior of individuals with developmental disabilities. The Survey Interview Form (i.e., semi -structured interview) will be administered to a subject's reliable caregiver in this study, during which the rater or clinician will ask to the caregiver open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, and Daily Living Skills. Standardized scores on the domains range from 20-160 with higher scores indicating better functioning. Measure Type is Adjusted least-squares means.
Baseline, Weeks 12 and 24
Proportion of Subjects With >=6 Points Improvement in the Vineland-II 2DC Score for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
Vineland™-II Adaptive Behavior Scales 2-Domain Composite (2DC) Score is defined as mean of the Communication domain standard score & Socialization domain standard score. If any of the 2 individual domain standard scores is missing 2DC score is not computed. Vineland™-II is an instrument that measures communication, daily living skills, socialization, motor skills and maladaptive behavior of individuals with developmental disabilities. Survey Interview Form will be administered to a subject's reliable caregiver in this study, during which the rater or clinician will ask to the caregiver open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, Daily Living Skills, and motor skills and used to calculate the Vineland™-II Adaptive Behavior Composite score. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning.
Baseline, Weeks 12 and 24
Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
The CGI-S reflects the rater's impression of the subject's current autism severity on a 7-point scale ranging from no symptoms (1) to very severe symptoms (7). Changes in CGI-S score were calculated as increase or decrease in absolute CGI-S scores between Baseline and Weeks 12 and 24.
Baseline, Weeks 12 and 24
Change From Baseline in Ohio Autism Clinical Impressions Scale-Severity (OACIS-S) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
The OACIS-S is a 10-item, clinician-completed measures based upon interview and/or observation. The OACIS-S assess severity and improvement, respectively, in social interaction, aberrant behavior, repetitive or ritualistic behavior, verbal communication, nonverbal communication skills, hyperactivity and inattention, anxiety and fearfulness, sensory sensitivities, restricted and narrow interests, and a global rating of autism. Each item of the OACIS-S is rated on a 7-point scale ranging from no symptoms (1) to very severe symptoms (7). Changes in CGI-S score were calculated as increase or decrease in absolute CGI-S scores between Baseline and Weeks 12 and 24.
Baseline, Weeks 12 and 24
Clinical Global Impressions- Improvement (CGI-I) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
The CGI rating scales are tools used to evaluate both the severity of illness and change from baseline. The CGI-I is used to assess the clinical change as compared to symptoms at baseline using a 7-point scale, ranging from very much improved (1) to very much worse (7). For this study modified versions will be used.
Weeks 12 and 24
Ohio Autism Clinical Impressions Scale- Improvement (OACIS-I) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
The OACIS-I is a 10-item, clinician-completed measures based upon interview and/or observation. The OACIS-I assess severity and improvement, respectively, in social interaction, aberrant behavior, repetitive or ritualistic behavior, verbal communication, nonverbal communication skills, hyperactivity and inattention, anxiety and fearfulness, sensory sensitivities, restricted and narrow interests, and a global rating of autism. The OACIS-I is used to assess the clinical change as compared to symptoms at baseline using a 7-point scale, ranging from very much improved (1) to very much worse (7).
Weeks 12 and 24
Change From Baseline in Patient-Reported Pediatric Quality of Life (PedsQL) v4.0 Generic Core Scale After 12 Weeks and 24 Weeks of Treatment for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
The Pediatric Quality of Life Inventory PedsQL™4.0 Generic Core Scale assessment consists of a 23 item questionnaire encompassing 4 core scale domains: Physical Functioning (8 items); Emotional Functioning (5 items); Social Functioning (5 items); and School Functioning (5 items). For children aged 8 years and above, the PedsQL items are scored on a 5 point Likert-type response scale (0=never a problem; 1=almost never a problem; 2=sometimes a problem; 3=often a problem; and 4=almost always a problem). For children aged 5-7 years, scoring is based on a three-point scale (0=Not at all, 2=Sometimes, 4=A lot). Once scored, items will be reverse scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0), so that higher scores indicate better health-related quality of life.
Baseline, Weeks 12 and 24
Change From Baseline in Vineland-II Composite Standard Score in Adolescents and Children Independently at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
The Vineland-II is an instrument that measures communication, daily living skills, socialization, motor skills (only in children up to 6 years) and maladaptive (not assessed in this study) behavior of individuals with developmental disabilities. The Survey Interview Form (i.e., semi -structured interview) will be administered to a subject's reliable caregiver in this study, during which the rater or clinician will ask to the caregiver open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, Daily Living Skills, and motor skills (up to 6 years only) and used to calculate the Vineland-II Adaptive Behavior Composite score. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning.
Baseline, Weeks 12 and 24
Change From Baseline in Vineland-II Adaptive Behavior Scale 2DC Score at Week 12 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
The Vineland-II is an instrument that measures communication, daily living skills, socialization, motor skills (only in children up to 6 years) and maladaptive (not assessed in this study) behavior of individuals with developmental disabilities. The Survey Interview Form (i.e., semi -structured interview) will be administered to a subject's reliable caregiver in this study, during which the rater or clinician will ask to the caregiver open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, Daily Living Skills, and motor skills (up to 6 years only) and used to calculate the Vineland-II Adaptive Behavior Composite score. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning. Mixed model with repeated measures (MMRM) was used for analysis.
Baseline, Week 12
Percentage of Participants With Adverse Events for Treatment With Balovaptan
PK review revealed that age-adjusted doses of 4 and 10 mg in 5-17 year olds were not equivalent to target exposure. For the Main Study Part, data was summarised by exposure ranges (tertiles) based on individual participants PK exposure at Week 12, estimated as the average plasma concentration since treatment start. To allow clear analysis by exposure tertiles, participants with dose adjustment were excluded from analysis by tertiles.
Baseline to Week 24 and up to Week 76
Phoenix
Arizona
85006
United States
NRC Research Institute
Orange
California
92868
United States
PCSD Feighner Research
San Diego
California
92108
United States
University of California at San Francisco
San Francisco
California
94115
United States
Children's Hospital of Colorado
Aurora
Colorado
80045
United States
DBA IMMUNOe Int'l Res Center
Centennial
Colorado
80112
United States
Yale University / Yale-New Haven Hospital
New Haven
Connecticut
06519-1124
United States
Sarkis Clinical Trials
Gainesville
Florida
32607
United States
Segal trials
North Miami
Florida
33161
United States
Medical Research Group of Central Florida
Orange City
Florida
32763
United States
APG- Advanced Psychiatric Group
Orlando
Florida
32803
United States
USF Rothman Center
St. Petersburg
Florida
33701
United States
Rush University Medical Center
Chicago
Illinois
60612
United States
Capstone Clinical Research
Libertyville
Illinois
60048
United States
Kennedy Krieger Institute
Baltimore
Maryland
21205
United States
Massachusetts General Hospital
Boston
Massachusetts
02114
United States
Boston Childrens Hospital
Boston
Massachusetts
02115
United States
Massachusetts General Hospital; Lurie Center for Autism
Lexington
Massachusetts
02421
United States
UMASS Medical School
Worcester
Massachusetts
01655
United States
University of Minnesota; Clin. Neuro Research Unit
Minneapolis
Minnesota
55414
United States
St. Charles Psychiatric Associates
Saint Charles
Missouri
63304
United States
Midwest Childrens Health Research Institute
Lincoln
Nebraska
68516
United States
Center for Autism and the Developing Brain
New York
New York
10032
United States
Nathan S. Kline Institute for Psychiatric Research
Orangeburg
New York
10962
United States
University of Rochester
Rochester
New York
14627 0001
United States
Richmond Behavioral Associates
Staten Island
New York
10312
United States
Albert Einstein College of Medicine
The Bronx
New York
10461
United States
DUKE SCHOOL OF MEDICINE;Duke Center for Autism and Brain Development
Durham
North Carolina
27705
United States
Cincinnati Children's Hospital Medical Center
Cincinnati
Ohio
45229
United States
University Hospitals
Cleveland
Ohio
44106
United States
Ohio State University
Columbus
Ohio
43210
United States
Cutting Edge Research Group
Oklahoma City
Oklahoma
73116
United States
Suburban Research Associates
Media
Pennsylvania
19063
United States
Children's Hospital of Philadelphia;Allergy/Immunology Department
Philadelphia
Pennsylvania
19104
United States
UPMC Western Psychiatric Institute and Clinic
Pittsburgh
Pennsylvania
15203
United States
Vanderbilt University Medical Center
Nashville
Tennessee
37232
United States
BioBehavioral Research of Austin, PC
Austin
Texas
78759
United States
Relaro Medical Trials
Dallas
Texas
75243
United States
Red Oak Psychiatry Associates, PA
Houston
Texas
77090
United States
Road Runner Research
San Antonio
Texas
78249
United States
Northwest Clinical Research Center
Bellevue
Washington
98007
United States
Pacific Institute of Medical Sciences
Bothell
Washington
98011
United States
Core Clinical Research
Everett
Washington
98201
United States
Seattle Children's Research Institute; Psychiatry and Behavioral Medicine
Seattle
Washington
98121
United States
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 8 weeks.
FG002
PK Part - Balovaptan (RO5285119) 10 mg/d Equivalent
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 8 weeks.
FG003
Main Study Part - Placebo
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks in Main Study Part.
FG004
Main Study Part - Low Exposure Tertile
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 or 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks in Main Study Part.
FG005
Main Study Part - Medium Exposure Tertile
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 or 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks in Main Study Part.
FG006
Main Study Part - High Exposure Tertile
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 or 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks in Main Study Part.
FG007
Main Study Part - Dose Adjusters
Participants with dose adjustment who were excluded from the analysis by tertiles. Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 or 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks in Main Study Part.
FG008
Open Label Extension Part - Placebo
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 52 weeks in Open Label Extension Part.
FG009
Open Label Extension Part - Low Exposure Tertile
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 52 weeks in Open Label Extension Part.
FG010
Open Label Extension Part - Medium Exposure Tertile
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 52 weeks in Open Label Extension Part.
FG011
Open Label Extension Part - High Exposure Tertile
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 52 weeks in Open Label Extension Part.
FG012
Open Label Extension Part - Dose-Adjusters
Participants with dose adjustment who were excluded from the analysis by tertiles. Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 52 weeks in Open Label Extension Part.
FG00012 subjects
FG00111 subjects
FG00215 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
COMPLETED
FG0005 subjects
FG0015 subjects
FG0026 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
NOT COMPLETED
FG0007 subjects
FG0016 subjects
FG0029 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Pending IMC/SOC Dose Confirmation
FG0002 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Pending dose confirmation
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
8 weeks of treatment ran out
FG0002 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Stopped treatment after 8 weeks
FG0001 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Stopped on Sponsor instruction pending dose confirmation
FG0001 subjects
FG0010 subjects
FG0024 subjects
FG0030 subjects
Discontinued per Sponsor
FG0000 subjects
FG0013 subjects
FG0020 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0001 subjects
FG0011 subjects
FG0023 subjects
FG0030 subjects
FG004
Main Treatment Part
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003112 subjects
FG00457 subjects
FG00566 subjects
FG00666 subjects
FG0077 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00386 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00326 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Open Label Part
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG00868 subjects
FG00935 subjects
FG01040 subjects
FG01146 subjects
FG0125 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
PK Part & Main Part reported separately. 7 patients ("re-starters") are counted twice. PK review revealed age-adjusted doses of 4 & 10 mg in 5-17 year olds weren't equivalent to target exposure. For Main Study Part, data was summarised by exposure ranges (tertiles) based on individual patients PK exposure at Week 12, estimated as average plasma concentration since treatment start. To allow clear analysis by exposure tertiles, patients with dose adjustment were excluded from analysis by tertiles.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
PK Part (Study Part 1) - Placebo
Participants received a matching placebo orally. Approximate treatment duration was up to 8 weeks.
BG001
PK Part (Study Part 1) - Balovaptan (RO5285119) 4 mg/d Equivalent
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 8 weeks.
BG002
PK Part (Study Part 1) - Balovaptan (RO5285119) 10 mg/d Equivalent
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 mg/d of balovaptan (RO5285119). Approximate treatment duration was up to 8 weeks.
BG003
Main Study Part (Study Part 2) - Placebo
Participants in the Main Study Part received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
BG004
Main Study Part (Study Part 2) - Low Exposure Tertile
Participants in the Main Study Part in the Low Exposure Tertile received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 or 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
BG005
Main Study Part (Study Part 2) - Medium Exposure Tertile
Participants in the Main Study Part in the Medium Exposure Tertile received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 or 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
BG006
Main Study Part (Study Part 2) - High Exposure Tertile
Participants in the Main Study Part in the High Exposure Tertile received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 or 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
BG007
Main Study Part (Study Part 2) - Dose-Adjusters
Participants with dose adjustment who were excluded from the analysis by tertiles. Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 or 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks in Main Study Part.
BG008
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00012
BG00111
BG00215
BG003112
BG00457
BG00566
BG00666
BG0077
BG008346
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Participants in the PK part of the study.
Participants in the PK part of the study.
Mean
Standard Deviation
Years
Title
Denominators
Categories
ParticipantsBG00012
ParticipantsBG00111
ParticipantsBG00215
ParticipantsBG003
Age, Continuous
Participants in the Main part of the study.
Mean
Standard Deviation
Years
Title
Denominators
Categories
ParticipantsBG0000
ParticipantsBG0010
ParticipantsBG002
Sex: Female, Male
Participants in the PK part of the study.
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00012
ParticipantsBG00111
ParticipantsBG002
Sex: Female, Male
Participants in Main Part of study.
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0000
ParticipantsBG0010
ParticipantsBG002
Ethnicity (NIH/OMB)
Participants in the PK part of the study.
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00012
ParticipantsBG00111
ParticipantsBG002
Ethnicity (NIH/OMB)
Participants in the main part of the study.
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0000
ParticipantsBG0010
ParticipantsBG002
Race (NIH/OMB)
Participants in PK part of the study.
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00012
ParticipantsBG00111
ParticipantsBG002
Race (NIH/OMB)
Participants in Main Part of study
Participants in Main Part of study.
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0000
ParticipantsBG0010
ParticipantsBG002
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
Change From Baseline in Vineland™-II Adaptive Behavior Scale Two Domain Composite (2DC) Score at Week 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
Vineland™-II Adaptive Behavior Scales 2-Domain Composite (2DC) Score is defined as mean of the Communication domain standard score & Socialization domain standard score. If any of the 2 individual domain standard scores is missing 2DC score is not computed. Vineland™-II is an instrument that measures communication, daily living skills, socialization, motor skills and maladaptive behavior of individuals with developmental disabilities. Survey Interview Form will be administered to a subject's reliable caregiver in this study, during which the rater or clinician will ask to the caregiver open ended questions relating to the subject's activities and behavior. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning. Mixed model with repeated measures (MMRM) was used for analysis with assessments at baseline, week 12 and week 24.
Efficacy Inferential Population included participants that were divided by randomized treatment and included participants taking balovaptan 10 mg equivalent dose and participants from the concurrently randomized placebo group in the corresponding randomization stage. Participants with dose adjustments or interruptions, or who were on a different dose than the final dose for their age group, were excluded.
Posted
Least Squares Mean
Standard Error
Score on a scale
Baseline, Week 24
ID
Title
Description
OG000
Placebo
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
OG001
Balovaptan (RO5285119) 10 mg/d Equivalent
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
Units
Counts
Participants
OG00081
OG00186
Title
Denominators
Categories
Title
Measurements
OG0002.34± 1.15
OG0012.17± 1.11
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Mixed Models Analysis
0.911
Difference in Adjusted LSMeans
-0.16
2-Sided
90
-2.56
2.23
Superiority
Secondary
Change From Baseline in Vineland™-II Composite Standard Score After 12 Weeks and 24 Weeks of Treatment for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
The Vineland™-II is an instrument that measures communication, daily living skills, socialization, motor skills (only in children up to 6 years) and maladaptive (not assessed in this study) behavior of individuals with developmental disabilities. The Survey Interview Form (i.e., semi -structured interview) will be administered to a subject's reliable caregiver in this study, during which the rater or clinician will ask to the caregiver open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, Daily Living Skills, and motor skills (up to 6 years only) and used to calculate the Vineland-II Adaptive Behavior Composite score. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning.
Efficacy Inferential Population included participants that were divided by randomized treatment and included participants taking balovaptan 10 mg equivalent dose and participants from the concurrently randomized placebo group in the corresponding randomization stage. Participants with dose adjustments or interruptions, or who were on a different dose than the final dose for their age group, were excluded.
Posted
Least Squares Mean
Standard Error
Score on a scale
Baseline, Weeks 12 and 24
ID
Title
Description
OG000
Placebo
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
Secondary
Change From Baseline in Vineland™-II Adaptive Behavior Scale Communication, Socialization, and Daily Living Skills Domain Standard Scores at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
The Vineland™-II is an instrument that measures communication, daily living skills, socialization, motor skills (only in children up to 6 years) and maladaptive (not assessed in this study) behavior of individuals with developmental disabilities. The Survey Interview Form (i.e., semi -structured interview) will be administered to a subject's reliable caregiver in this study, during which the rater or clinician will ask to the caregiver open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, and Daily Living Skills. Standardized scores on the domains range from 20-160 with higher scores indicating better functioning. Measure Type is Adjusted least-squares means.
Efficacy Inferential Population included participants that were divided by randomized treatment and included participants taking balovaptan 10 mg equivalent dose and participants from the concurrently randomized placebo group in the corresponding randomization stage. Participants with dose adjustments or interruptions, or who were on a different dose than the final dose for their age group, were excluded.
Posted
Least Squares Mean
Standard Error
Score on a scale
Baseline, Weeks 12 and 24
ID
Title
Description
OG000
Placebo
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
Secondary
Proportion of Subjects With >=6 Points Improvement in the Vineland-II 2DC Score for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
Vineland™-II Adaptive Behavior Scales 2-Domain Composite (2DC) Score is defined as mean of the Communication domain standard score & Socialization domain standard score. If any of the 2 individual domain standard scores is missing 2DC score is not computed. Vineland™-II is an instrument that measures communication, daily living skills, socialization, motor skills and maladaptive behavior of individuals with developmental disabilities. Survey Interview Form will be administered to a subject's reliable caregiver in this study, during which the rater or clinician will ask to the caregiver open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, Daily Living Skills, and motor skills and used to calculate the Vineland™-II Adaptive Behavior Composite score. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning.
Efficacy Inferential Population included participants that were divided by randomized treatment and included participants taking balovaptan 10 mg equivalent dose and participants from the concurrently randomized placebo group in the corresponding randomization stage. Participants with dose adjustments or interruptions, or who were on a different dose than the final dose for their age group, were excluded.
Posted
Number
Percentage of participants
Baseline, Weeks 12 and 24
ID
Title
Description
OG000
Placebo
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
Secondary
Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
The CGI-S reflects the rater's impression of the subject's current autism severity on a 7-point scale ranging from no symptoms (1) to very severe symptoms (7). Changes in CGI-S score were calculated as increase or decrease in absolute CGI-S scores between Baseline and Weeks 12 and 24.
Efficacy Inferential Population included participants that were divided by randomized treatment and included participants taking balovaptan 10 mg equivalent dose and participants from the concurrently randomized placebo group in the corresponding randomization stage. Participants with dose adjustments or interruptions, or who were on a different dose than the final dose for their age group, were excluded.
Posted
Number
Percentage of participants
Baseline, Weeks 12 and 24
ID
Title
Description
OG000
Placebo
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
OG001
Balovaptan (RO5285119) 10 mg/d Equivalent
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
Secondary
Change From Baseline in Ohio Autism Clinical Impressions Scale-Severity (OACIS-S) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
The OACIS-S is a 10-item, clinician-completed measures based upon interview and/or observation. The OACIS-S assess severity and improvement, respectively, in social interaction, aberrant behavior, repetitive or ritualistic behavior, verbal communication, nonverbal communication skills, hyperactivity and inattention, anxiety and fearfulness, sensory sensitivities, restricted and narrow interests, and a global rating of autism. Each item of the OACIS-S is rated on a 7-point scale ranging from no symptoms (1) to very severe symptoms (7). Changes in CGI-S score were calculated as increase or decrease in absolute CGI-S scores between Baseline and Weeks 12 and 24.
Efficacy Inferential Population included participants that were divided by randomized treatment and included participants taking balovaptan 10 mg equivalent dose and participants from the concurrently randomized placebo group in the corresponding randomization stage. Participants with dose adjustments or interruptions, or who were on a different dose than the final dose for their age group, were excluded.
Posted
Number
Percentage of participants
Baseline, Weeks 12 and 24
ID
Title
Description
OG000
Placebo
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
OG001
Balovaptan (RO5285119) 10 mg/d Equivalent
Secondary
Clinical Global Impressions- Improvement (CGI-I) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
The CGI rating scales are tools used to evaluate both the severity of illness and change from baseline. The CGI-I is used to assess the clinical change as compared to symptoms at baseline using a 7-point scale, ranging from very much improved (1) to very much worse (7). For this study modified versions will be used.
Efficacy Inferential Population included participants that were divided by randomized treatment and included participants taking balovaptan 10 mg equivalent dose and participants from the concurrently randomized placebo group in the corresponding randomization stage. Participants with dose adjustments or interruptions, or who were on a different dose than the final dose for their age group, were excluded.
Posted
Number
Percentage of participants
Weeks 12 and 24
ID
Title
Description
OG000
Placebo
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
OG001
Balovaptan (RO5285119) 10 mg/d Equivalent
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
Secondary
Ohio Autism Clinical Impressions Scale- Improvement (OACIS-I) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
The OACIS-I is a 10-item, clinician-completed measures based upon interview and/or observation. The OACIS-I assess severity and improvement, respectively, in social interaction, aberrant behavior, repetitive or ritualistic behavior, verbal communication, nonverbal communication skills, hyperactivity and inattention, anxiety and fearfulness, sensory sensitivities, restricted and narrow interests, and a global rating of autism. The OACIS-I is used to assess the clinical change as compared to symptoms at baseline using a 7-point scale, ranging from very much improved (1) to very much worse (7).
Efficacy Inferential Population included participants that were divided by randomized treatment and included participants taking balovaptan 10 mg equivalent dose and participants from the concurrently randomized placebo group in the corresponding randomization stage. Participants with dose adjustments or interruptions, or who were on a different dose than the final dose for their age group, were excluded.
Posted
Number
Percentage of participants
Weeks 12 and 24
ID
Title
Description
OG000
Placebo
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
OG001
Balovaptan (RO5285119) 10 mg/d Equivalent
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
Secondary
Change From Baseline in Patient-Reported Pediatric Quality of Life (PedsQL) v4.0 Generic Core Scale After 12 Weeks and 24 Weeks of Treatment for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
The Pediatric Quality of Life Inventory PedsQL™4.0 Generic Core Scale assessment consists of a 23 item questionnaire encompassing 4 core scale domains: Physical Functioning (8 items); Emotional Functioning (5 items); Social Functioning (5 items); and School Functioning (5 items). For children aged 8 years and above, the PedsQL items are scored on a 5 point Likert-type response scale (0=never a problem; 1=almost never a problem; 2=sometimes a problem; 3=often a problem; and 4=almost always a problem). For children aged 5-7 years, scoring is based on a three-point scale (0=Not at all, 2=Sometimes, 4=A lot). Once scored, items will be reverse scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0), so that higher scores indicate better health-related quality of life.
Efficacy Inferential Population included participants that were divided by randomized treatment and included participants taking balovaptan 10 mg equivalent dose and participants from the concurrently randomized placebo group in the corresponding randomization stage. Participants with dose adjustments or interruptions, or who were on a different dose than the final dose for their age group, were excluded.
Posted
Least Squares Mean
Standard Error
Score on scale
Baseline, Weeks 12 and 24
ID
Title
Description
OG000
Placebo
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
Secondary
Change From Baseline in Vineland-II Composite Standard Score in Adolescents and Children Independently at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
The Vineland-II is an instrument that measures communication, daily living skills, socialization, motor skills (only in children up to 6 years) and maladaptive (not assessed in this study) behavior of individuals with developmental disabilities. The Survey Interview Form (i.e., semi -structured interview) will be administered to a subject's reliable caregiver in this study, during which the rater or clinician will ask to the caregiver open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, Daily Living Skills, and motor skills (up to 6 years only) and used to calculate the Vineland-II Adaptive Behavior Composite score. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning.
Efficacy Inferential Population included participants that were divided by randomized treatment and included participants taking balovaptan 10 mg equivalent dose and participants from the concurrently randomized placebo group in the corresponding randomization stage. Participants with dose adjustments or interruptions, or who were on a different dose than the final dose for their age group, were excluded.
Posted
Mean
Standard Deviation
Score on scale
Baseline, Weeks 12 and 24
ID
Title
Description
OG000
Placebo
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
Secondary
Change From Baseline in Vineland-II Adaptive Behavior Scale 2DC Score at Week 12 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
The Vineland-II is an instrument that measures communication, daily living skills, socialization, motor skills (only in children up to 6 years) and maladaptive (not assessed in this study) behavior of individuals with developmental disabilities. The Survey Interview Form (i.e., semi -structured interview) will be administered to a subject's reliable caregiver in this study, during which the rater or clinician will ask to the caregiver open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, Daily Living Skills, and motor skills (up to 6 years only) and used to calculate the Vineland-II Adaptive Behavior Composite score. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning. Mixed model with repeated measures (MMRM) was used for analysis.
Efficacy Inferential Population included participants that were divided by randomized treatment and included participants taking balovaptan 10 mg equivalent dose and participants from the concurrently randomized placebo group in the corresponding randomization stage. Participants with dose adjustments or interruptions, or who were on a different dose than the final dose for their age group, were excluded.
Posted
Least Squares Mean
Standard Error
Score on scale
Baseline, Week 12
ID
Title
Description
OG000
Placebo
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
Secondary
Percentage of Participants With Adverse Events for Treatment With Balovaptan
PK review revealed that age-adjusted doses of 4 and 10 mg in 5-17 year olds were not equivalent to target exposure. For the Main Study Part, data was summarised by exposure ranges (tertiles) based on individual participants PK exposure at Week 12, estimated as the average plasma concentration since treatment start. To allow clear analysis by exposure tertiles, participants with dose adjustment were excluded from analysis by tertiles.
Safety Population consisted of all participants who received a least one dose of study medication; Used for safety analyses and divided by exposure tertiles.
Posted
Number
Percentage of Participants
Baseline to Week 24 and up to Week 76
ID
Title
Description
OG000
Main Study Part, Low Exposure Tertile
Participants in the Main Study Part in the Low Exposure Tertile received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 or 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
OG001
Main Study Part, Medium Exposure Tertile
Participants in the Main Study Part in the Medium Exposure Tertile received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 or 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
Time Frame
From the first study drug to the data cutoff date: 30 June 2020 (up to 43 months)
Description
PK review revealed that age-adjusted doses of 4 and 10 mg in 5-17 year olds were not equivalent to target exposure. For the Main Study Part, data was summarised by exposure ranges (tertiles) based on individual participants PK exposure at Week 12, estimated as the average plasma concentration since treatment start. To allow clear analysis by exposure tertiles, participants with dose adjustment were excluded from analysis by tertiles.
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
PK Part (Study Part 1) - Placebo
Participants in the PK Part of the study who received a matching placebo orally. Approximate treatment duration was up to 8 weeks.
0
12
0
12
7
12
EG001
PK Part (Study Part 1) - Balovaptan (RO5285119) 4 mg/d Equivalent
Participants in the PK Part of the study who received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 8 weeks.
0
11
1
11
7
11
EG002
PK Part (Study Part 1) - Balovaptan (RO5285119) 10 mg/d Equivalent
Participants in the PK Part of the study who received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 8 weeks.
0
15
0
15
7
15
EG003
Main Study Part (Study Part 2) - Placebo
Participants in the Main Study Part received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
0
112
4
112
58
112
EG004
Main Study Part (Study Part 2) - Low Exposure Tertile
Participants in the Main Study Part in the Low Exposure Tertile received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 or 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
0
57
1
57
34
57
EG005
Main Study Part (Study Part 2) - Medium Exposure Tertile
Participants in the Main Study Part in the Medium Exposure Tertile received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 or 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
0
66
0
66
31
66
EG006
Main Study Part (Study Part 2) - High Exposure Tertile
Participants in the Main Study Part in the High Exposure Tertile received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 or 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
0
66
1
66
34
66
EG007
Main Study Part (Study Part 2) - Dose-Adjusters
Participants with dose adjustment who were excluded from the analysis by tertiles. Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 or 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks in Main Study Part.
0
7
0
7
5
7
EG008
Open Label Extension Part (Study Part 3) - Placebo
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 52 weeks in Open Label Extension Part.
0
68
2
68
35
68
EG009
Open Label Extension Part (Study Part 3) - Low Exposure Tertile
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 52 weeks in Open Label Extension Part.
0
35
0
35
21
35
EG010
Open Label Extension Part (Study Part 3) - Medium Exposure Tertile
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 52 weeks in Open Label Extension Part.
0
40
0
40
25
40
EG011
Open Label Extension Part (Study Part 3) - High Exposure Tertile
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 52 weeks in Open Label Extension Part.
0
46
2
46
27
46
EG012
Open Label Extension Part (Study Part 3) - Dose-Adjusters
Participants with dose adjustment who were excluded from the analysis by tertiles. Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 52 weeks in Open Label Extension Part.
0
5
0
5
3
5
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Pneumonia
Infections and infestations
MedDRA version 23.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0011 events1 affected11 at risk
EG0020 events0 affected15 at risk
EG0030 events0 affected112 at risk
EG0040 events0 affected57 at risk
EG0050 events0 affected66 at risk
EG0060 events0 affected66 at risk
EG0070 events0 affected7 at risk
EG0080 events0 affected68 at risk
EG0090 events0 affected35 at risk
EG0100 events0 affected40 at risk
EG0110 events0 affected46 at risk
EG0120 events0 affected5 at risk
Gastroenteritis viral
Infections and infestations
MedDRA version 23.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected11 at risk
EG0020 events0 affected15 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA version 23.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected11 at risk
EG0020 events0 affected15 at risk
EG003
Acute lymphocytic leukaemia
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version 23.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected11 at risk
EG0020 events0 affected15 at risk
EG003
Aggression
Psychiatric disorders
MedDRA version 23.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected11 at risk
EG0020 events0 affected15 at risk
EG003
Agitation
Psychiatric disorders
MedDRA version 23.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected11 at risk
EG0020 events0 affected15 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA version 23.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected11 at risk
EG0020 events0 affected15 at risk
EG003
Depression
Psychiatric disorders
MedDRA version 23.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected11 at risk
EG0020 events0 affected15 at risk
EG003
Intentional self-injury
Psychiatric disorders
MedDRA version 23.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected11 at risk
EG0020 events0 affected15 at risk
EG003
Suicidal ideation
Psychiatric disorders
MedDRA version 23.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected11 at risk
EG0020 events0 affected15 at risk
EG003
Laryngospasm
Respiratory, thoracic and mediastinal disorders
MedDRA version 23.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected11 at risk
EG0020 events0 affected15 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG0030 affected112 at risk
EG0040 affected57 at risk
EG0050 affected66 at risk
EG0060 affected66 at risk
EG0070 affected7 at risk
EG0080 affected68 at risk
EG0092 affected35 at risk
EG0100 affected40 at risk
EG0110 affected46 at risk
EG0120 affected5 at risk
Neutropenia
Blood and lymphatic system disorders
MedDRA version 23.0
Systematic Assessment
EG0001 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Vision blurred
Eye disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0011 affected11 at risk
EG0020 affected15 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0011 affected11 at risk
EG0022 affected15 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0011 affected11 at risk
EG0020 affected15 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA version 23.0
Systematic Assessment
EG0002 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Mouth ulceration
Gastrointestinal disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0021 affected15 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Fatigue
General disorders
MedDRA version 23.0
Systematic Assessment
EG0001 affected12 at risk
EG0011 affected11 at risk
EG0020 affected15 at risk
EG003
Pyrexia
General disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0021 affected15 at risk
EG003
Seasonal allergy
Immune system disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0011 affected11 at risk
EG0020 affected15 at risk
EG003
Bronchitis
Infections and infestations
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Ear infection
Infections and infestations
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0011 affected11 at risk
EG0020 affected15 at risk
EG003
Influenza
Infections and infestations
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Otitis media
Infections and infestations
MedDRA version 23.0
Systematic Assessment
EG0001 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Pharyngitis streptococcal
Infections and infestations
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0021 affected15 at risk
EG003
Rhinitis
Infections and infestations
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0021 affected15 at risk
EG003
Sinusitis
Infections and infestations
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Viral infection
Infections and infestations
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Accidental overdose
Injury, poisoning and procedural complications
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Arthropod bite
Injury, poisoning and procedural complications
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0011 affected11 at risk
EG0020 affected15 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Facial bones fracture
Injury, poisoning and procedural complications
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0021 affected15 at risk
EG003
Weight increased
Investigations
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Increased appetite
Metabolism and nutrition disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0011 affected11 at risk
EG0020 affected15 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0011 affected11 at risk
EG0020 affected15 at risk
EG003
Headache
Nervous system disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0022 affected15 at risk
EG003
Poor quality sleep
Nervous system disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0011 affected11 at risk
EG0020 affected15 at risk
EG003
Psychomotor hyperactivity
Nervous system disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Seizure
Nervous system disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Somnolence
Nervous system disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0011 affected11 at risk
EG0020 affected15 at risk
EG003
Syncope
Nervous system disorders
MedDRA version 23.0
Systematic Assessment
EG0001 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Tremor
Nervous system disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0011 affected11 at risk
EG0020 affected15 at risk
EG003
Aggression
Psychiatric disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA version 23.0
Systematic Assessment
EG0001 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Impulsive behaviour
Psychiatric disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Irritability
Psychiatric disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0012 affected11 at risk
EG0020 affected15 at risk
EG003
Mood swings
Psychiatric disorders
MedDRA version 23.0
Systematic Assessment
EG0001 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Nightmare
Psychiatric disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0011 affected11 at risk
EG0020 affected15 at risk
EG003
Stereotypy
Psychiatric disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0021 affected15 at risk
EG003
Suicidal ideation
Psychiatric disorders
MedDRA version 23.0
Systematic Assessment
EG0001 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Pollakiuria
Renal and urinary disorders
MedDRA version 23.0
Systematic Assessment
EG0002 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Gynaecomastia
Reproductive system and breast disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0021 affected15 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA version 23.0
Systematic Assessment
EG0001 affected12 at risk
EG0010 affected11 at risk
EG0021 affected15 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA version 23.0
Systematic Assessment
EG0001 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Acne
Skin and subcutaneous tissue disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0021 affected15 at risk
EG003
Middle insomnia
Psychiatric disorders
MedDRA version 23.0
Systematic Assessment
EG0000 affected12 at risk
EG0010 affected11 at risk
EG0020 affected15 at risk
EG003
Study was terminated early, therefore, there was limited data collected in Open Label Extension part of the study.
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 received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
Units
Counts
Participants
OG00081
OG00186
Title
Denominators
Categories
Week 12
Title
Measurements
OG0001.45± 1.07
OG0011.74± 1.04
Week 24
Title
Measurements
OG0002.20± 1.19
OG0011.97± 1.15
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Week 12
Difference in adjused LSMean
0.29
2-Sided
90
-1.85
2.43
Superiority
OG000
OG001
Week 24
Difference in adjusted LSMean
-0.23
2-Sided
90
-2.67
2.22
Superiority
OG001
Balovaptan (RO5285119) 10 mg/d Equivalent
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
Units
Counts
Participants
OG00081
OG00186
Title
Denominators
Categories
Communication Domain Standard Score, Week 12
Title
Measurements
OG0001.86± 1.06
OG0011.64± 1.03
Communication Domain Standard Score, Week 24
Title
Measurements
OG0001.51± 1.13
OG0012.21± 1.09
Socialization Domain Standard Score, Week 12
Title
Measurements
OG0001.69± 1.31
OG0012.20± 1.26
Socialization Domain Standard Score, Week 24
Title
Measurements
OG0002.87± 1.50
OG0012.26± 1.45
Daily Living Skills Domain Standard Score, Week 12
Title
Measurements
OG000-0.01± 1.38
OG0012.13± 1.35
Daily Living Skills Domain Standard Score, Week 24
Title
Measurements
OG0001.44± 1.49
OG0011.61± 1.45
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Communication Domain Standard Score, Week 12
Difference in adjusted LSMean
-0.22
2-Sided
90
-2.36
1.92
Superiority
OG000
OG001
Communication Domain Standard Score, Week 24
Difference in adjusted LSMean
0.71
2-Sided
90
-1.60
3.02
Superiority
OG000
OG001
Socialization Domain Standard Score, Week 12
Difference in adjusted LSMean
0.51
2-Sided
90
-2.10
3.12
Superiority
OG000
OG001
Difference in adjusted LSMean
-0.61
2-Sided
90
-3.74
2.51
Superiority
Socialization Domain Standard Score, Week 24
OG000
OG001
Difference in adjusted LSMean
2.14
2-Sided
90
-0.63
4.90
Superiority
Daily Living Skills Domain Standard Score, Week 12
OG000
OG001
Differences in adjusted LSMean
0.18
2-Sided
90
-2.87
3.22
Superiority
Daily Living Skills Domain Standard Score, Week 24
OG001
Balovaptan (RO5285119) 10 mg/d Equivalent
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
Units
Counts
Participants
OG00066
OG00170
Title
Denominators
Categories
Week 12
ParticipantsOG00066
ParticipantsOG00170
Title
Measurements
OG00030.3
OG00127.1
Week 24
ParticipantsOG00061
ParticipantsOG00167
Title
Measurements
OG00034.4
OG001
Units
Counts
Participants
OG00067
OG00174
Title
Denominators
Categories
-3 (Very much improved), Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG0001.5
OG0010
-2 (Much improved), Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG0001.5
OG001
-1 (Minimally improved), Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG00031.3
OG001
0 (No change), Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG00065.7
OG001
+1 (Minimally worse), Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG0000
OG001
+2 (Much worse), Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG0000
OG001
+3 (Very Much worse), Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG0000
OG001
-3 (Very much improved), Week 24
ParticipantsOG00062
ParticipantsOG00169
Title
Measurements
OG0001.6
OG001
-2 (Much improved), Week 24
ParticipantsOG00062
ParticipantsOG00169
Title
Measurements
OG0006.5
OG001
-1 (Minimally improved), Week 24
ParticipantsOG00062
ParticipantsOG00169
Title
Measurements
OG00032.3
OG001
0 (No change), Week 24
ParticipantsOG00062
ParticipantsOG00169
Title
Measurements
OG00059.7
OG001
+1 (Minimally worse), Week 24
ParticipantsOG00062
ParticipantsOG00169
Title
Measurements
OG0000
OG001
+2 (Much worse), Week 24
ParticipantsOG00062
ParticipantsOG00169
Title
Measurements
OG0000
OG001
+3 (Very much worse), Week 24
ParticipantsOG00062
ParticipantsOG00169
Title
Measurements
OG0000
OG001
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
Units
Counts
Participants
OG00067
OG00173
Title
Denominators
Categories
-3 (Very much improved), Week 12
ParticipantsOG00067
ParticipantsOG00173
Title
Measurements
OG0003.0
OG0010
-2 (Much improved), Week 12
ParticipantsOG00067
ParticipantsOG00173
Title
Measurements
OG0006.0
OG001
-1 (Minimally improved), Week 12
ParticipantsOG00067
ParticipantsOG00173
Title
Measurements
OG00028.4
OG001
0 (No change), Week 12
ParticipantsOG00067
ParticipantsOG00173
Title
Measurements
OG00059.7
OG001
+1 (Minimally worse), Week 12
ParticipantsOG00067
ParticipantsOG00173
Title
Measurements
OG0003.0
OG001
+2 (Much worse), Week 12
ParticipantsOG00067
ParticipantsOG00173
Title
Measurements
OG0000
OG001
+3 (Very much worse), Week 12
ParticipantsOG00067
ParticipantsOG00173
Title
Measurements
OG0000
OG001
-3 (Very much improved), Week 24
ParticipantsOG00062
ParticipantsOG00167
Title
Measurements
OG0006.5
OG001
-2 (Much improved), Week 24
ParticipantsOG00062
ParticipantsOG00167
Title
Measurements
OG0008.1
OG001
-1 (Minimally improved), Week 24
ParticipantsOG00062
ParticipantsOG00167
Title
Measurements
OG00033.9
OG001
0 (No change), Week 24
ParticipantsOG00062
ParticipantsOG00167
Title
Measurements
OG00048.4
OG001
+1 (Minimally worse), Week 24
ParticipantsOG00062
ParticipantsOG00167
Title
Measurements
OG0003.2
OG001
+2 (Much worse), Week 24
ParticipantsOG00062
ParticipantsOG00167
Title
Measurements
OG0000
OG001
+3 (Very much worse), Week 24
ParticipantsOG00062
ParticipantsOG00167
Title
Measurements
OG0000
OG001
Units
Counts
Participants
OG00067
OG00174
Title
Denominators
Categories
1 - Very much improved, Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG0000
OG0010
2 - Much improved, Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG00022.4
OG001
3 - Minimally improved, Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG00049.3
OG001
4 - No change, Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG00022.4
OG001
5 - Minimally worse, Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG0006.0
OG001
6 - Much worse, Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG0000
OG001
7 - Very much worse, Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG0000
OG001
1 - Very much improved, Week 24
ParticipantsOG00062
ParticipantsOG00168
Title
Measurements
OG0000
OG001
2 - Much improved, Week 24
ParticipantsOG00062
ParticipantsOG00168
Title
Measurements
OG00030.6
OG001
3 - Minimally improved, Week 24
ParticipantsOG00062
ParticipantsOG00168
Title
Measurements
OG00048.4
OG001
4 - No change, Week 24
ParticipantsOG00062
ParticipantsOG00168
Title
Measurements
OG00019.4
OG001
5 - Minimally worse, Week 24
ParticipantsOG00062
ParticipantsOG00168
Title
Measurements
OG0001.6
OG001
6 - Much worse, Week 24
ParticipantsOG00062
ParticipantsOG00168
Title
Measurements
OG0000
OG001
7 - Very much worse, Week 24
ParticipantsOG00062
ParticipantsOG00168
Title
Measurements
OG0000
OG001
Units
Counts
Participants
OG00067
OG00174
Title
Denominators
Categories
1 - Very much improved, Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG0001.5
OG0010
2 - Much improved, Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG00016.4
OG001
3 - Minimally improved, Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG00038.8
OG001
4 - No change, Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG00040.3
OG001
5 - Minimally worse, Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG0003.0
OG001
6 - Much worse, Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG0000
OG001
7 - Very much worse, Week 12
ParticipantsOG00067
ParticipantsOG00174
Title
Measurements
OG0000
OG001
1 - Very much improved, Week 24
ParticipantsOG00062
ParticipantsOG00168
Title
Measurements
OG0000
OG001
2 - Much improved, Week 24
ParticipantsOG00062
ParticipantsOG00168
Title
Measurements
OG00025.8
OG001
3 - Minimally improved, Week 24
ParticipantsOG00062
ParticipantsOG00168
Title
Measurements
OG00046.8
OG001
4 - No change, Week 24
ParticipantsOG00062
ParticipantsOG00168
Title
Measurements
OG00025.8
OG001
5 - Minimally worse, Week 24
ParticipantsOG00062
ParticipantsOG00168
Title
Measurements
OG0001.6
OG001
6 - Much worse, Week 24
ParticipantsOG00062
ParticipantsOG00168
Title
Measurements
OG0000
OG001
7 - Very much worse, Week 24
ParticipantsOG00062
ParticipantsOG00168
Title
Measurements
OG0000
OG001
OG001
Balovaptan (RO5285119) 10 mg/d Equivalent
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
Units
Counts
Participants
OG00062
OG00172
Title
Denominators
Categories
Change from Baseline at Week 12
ParticipantsOG00062
ParticipantsOG00172
Title
Measurements
OG0002.42± 1.49
OG0016.16± 1.41
Change from Baseline at Week 24
ParticipantsOG00059
ParticipantsOG00165
Title
Measurements
OG0003.70± 1.50
OG001
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Week 12
Mixed Models Analysis
Difference of Adjusted LS Means
3.74
2-Sided
90
0.78
6.70
Superiority
OG000
OG001
Week 24
Difference of Adjusted LS means
2.28
2-Sided
90
-0.73
5.29
Superiority
OG001
Balovaptan (RO5285119) 10 mg/d Equivalent
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
Units
Counts
Participants
OG00044
OG00148
Title
Denominators
Categories
5-12 Years Age Group, Absolute Value at Baseline
ParticipantsOG00044
ParticipantsOG00148
Title
Measurements
OG00073.9± 9.7
OG00177.3± 10.9
5-12 Years Age Group, Change From Baseline at Week 12
ParticipantsOG00037
ParticipantsOG00138
Title
Measurements
OG0003.6± 8.4
OG001
5-12 Years Age Group, Change From Baseline at Week 24
ParticipantsOG00034
ParticipantsOG00137
Title
Measurements
OG0004.8± 9.1
OG001
13-17 Years Age Group, Absolute Baseline Value
ParticipantsOG00035
ParticipantsOG00136
Title
Measurements
OG00071.0± 10.3
OG001
13-17 Years Age Group, Change From Baseline at Week 12
ParticipantsOG00029
ParticipantsOG00132
Title
Measurements
OG0001.8± 4.8
OG001
13-17 Years Age Group, Change From Baseline at Week 24
ParticipantsOG00027
ParticipantsOG00130
Title
Measurements
OG0002.7± 8.6
OG001
OG001
Balovaptan (RO5285119) 10 mg/d Equivalent
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
Units
Counts
Participants
OG00081
OG00186
Title
Denominators
Categories
Title
Measurements
OG0001.87± 1.00
OG0011.88± 0.97
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Mixed Models Analysis
0.992
Difference in Adjusted LS Means
0.01
2-Sided
90
-1.99
2.01
Superiority
OG002
Main Study Part, High Exposure Tertile
Participants in the Main Study Part in the High Exposure Tertile received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 or 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks.
OG003
Main Study Part (Study Part 2) - All Treated
All participants in the Main Study Part received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 or 10 milligrams per day (mg/d) of balovaptan (RO5285119). This group includes participants from the low, medium, and high exposure tertiles, as well as the Dose-Adjusters. Approximate treatment duration was up to 24 weeks.
OG004
Open Label Extension Part, Low Exposure Tertile
Participants in the Open Label Extension Part of the study in the Low Exposure Tertile received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 52 weeks.
OG005
Open Label Extension Part, Medium Exposure Tertile
Participants in the Open Label Extension Part of the study in the Medium Exposure Tertile received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 52 weeks in Open Label Extension Part.
OG006
Open Label Extension Part, High Exposure Tertile
Participants in the Open Label Extension Part of the study in the High Exposure Tertile received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up 52 weeks.
OG007
Open Label Extension Part, All Treated
All participants in the Open Label Extension Part of the study received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). This group includes participants from the low, medium, and high exposure tertiles, as well as the Dose-Adjusters. Approximate treatment duration was up to 52 weeks.