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A Study to Investigate the Efficacy and Safety of Balovaptan (RO5285119) in Participants With Autism Spectrum Disorder (ASD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02901431
Recruitment Status : Terminated (The 24-week analysis indicated no clinical or statistical benefit for the primary endpoint for the overall study population. No new safety concerns identified.)
First Posted : September 15, 2016
Results First Posted : February 8, 2021
Last Update Posted : February 8, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Autism Spectrum Disorder
Interventions Drug: Placebo
Drug: RO5285119
Enrollment 339
Recruitment Details A total of 339 participants were enrolled from 44 sites in the United States.
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.
Arm/Group Title PK Part - Placebo PK Part - Balovaptan (RO5285119) 4 mg/d Equivalent PK Part - Balovaptan (RO5285119) 10 mg/d Equivalent Main Study Part - Placebo Main Study Part - Low Exposure Tertile Main Study Part - Medium Exposure Tertile Main Study Part - High Exposure Tertile Main Study Part - Dose Adjusters Open Label Extension Part - Placebo Open Label Extension Part - Low Exposure Tertile Open Label Extension Part - Medium Exposure Tertile Open Label Extension Part - High Exposure Tertile Open Label Extension Part - Dose-Adjusters
Hide Arm/Group Description Participants received a matching placebo orally. Approximate treatment duration was up to 8 weeks. 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. 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. Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks in Main Study Part. 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. 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. 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. 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. 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. 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. 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. 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. 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.
Period Title: PK Part
Started 12 11 15 0 0 0 0 0 0 0 0 0 0
Completed 5 5 6 0 0 0 0 0 0 0 0 0 0
Not Completed 7 6 9 0 0 0 0 0 0 0 0 0 0
Reason Not Completed
Adverse Event             0             1             0             0             0             0             0             0             0             0             0             0             0
Lost to Follow-up             0             0             1             0             0             0             0             0             0             0             0             0             0
Pending IMC/SOC Dose Confirmation             2             0             0             0             0             0             0             0             0             0             0             0             0
Pending dose confirmation             0             1             0             0             0             0             0             0             0             0             0             0             0
8 weeks of treatment ran out             2             0             0             0             0             0             0             0             0             0             0             0             0
Stopped treatment after 8 weeks             1             0             1             0             0             0             0             0             0             0             0             0             0
Stopped on Sponsor instruction pending dose confirmation             1             0             4             0             0             0             0             0             0             0             0             0             0
Discontinued per Sponsor             0             3             0             0             0             0             0             0             0             0             0             0             0
Withdrawal by Subject             1             1             3             0             0             0             0             0             0             0             0             0             0
Period Title: Main Treatment Part
Started 0 0 0 112 57 66 66 7 0 0 0 0 0
Completed 0 0 0 86 50 54 55 7 0 0 0 0 0
Not Completed 0 0 0 26 7 12 11 0 0 0 0 0 0
Reason Not Completed
Adverse Event             0             0             0             3             3             4             1             0             0             0             0             0             0
Lack of Efficacy             0             0             0             1             0             0             0             0             0             0             0             0             0
Lost to Follow-up             0             0             0             3             1             2             3             0             0             0             0             0             0
Withdrawal by Caregiver             0             0             0             0             0             1             0             0             0             0             0             0             0
Physician Decision             0             0             0             1             0             0             1             0             0             0             0             0             0
Withdrawal by Subject             0             0             0             18             3             5             6             0             0             0             0             0             0
Period Title: Open Label Part
Started 0 0 0 0 0 0 0 0 68 35 40 46 5
Completed 0 0 0 0 0 0 0 0 20 11 11 7 2
Not Completed 0 0 0 0 0 0 0 0 48 24 29 39 3
Reason Not Completed
Adverse Event             0             0             0             0             0             0             0             0             4             4             0             4             1
Lost to Follow-up             0             0             0             0             0             0             0             0             2             2             1             1             1
Physician Decision             0             0             0             0             0             0             0             0             1             1             0             0             0
Study Terminated By Sponsor             0             0             0             0             0             0             0             0             35             12             21             31             0
Withdrawal by Subject             0             0             0             0             0             0             0             0             6             5             7             3             1
Arm/Group Title PK Part (Study Part 1) - Placebo PK Part (Study Part 1) - Balovaptan (RO5285119) 4 mg/d Equivalent PK Part (Study Part 1) - Balovaptan (RO5285119) 10 mg/d Equivalent Main Study Part (Study Part 2) - Placebo Main Study Part (Study Part 2) - Low Exposure Tertile Main Study Part (Study Part 2) - Medium Exposure Tertile Main Study Part (Study Part 2) - High Exposure Tertile Main Study Part (Study Part 2) - Dose-Adjusters Total
Hide Arm/Group Description Participants received a matching placebo orally. Approximate treatment duration was up to 8 weeks. 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. 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. Participants in the Main Study Part received a matching placebo orally. Approximate treatment duration was up to 24 weeks. 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. 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. 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 12 11 15 112 57 66 66 7 346
Hide Baseline Analysis Population Description
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.
Age, Continuous   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 11 participants 15 participants 0 participants 0 participants 0 participants 0 participants 0 participants 38 participants
8.9  (3.8) 9.9  (3.3) 10.4  (3.5) 9.8  (3.5)
[1]
Measure Description: Participants in the PK part of the study.
[2]
Measure Analysis Population Description: Participants in the PK part of the study.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 0 participants 0 participants 0 participants 112 participants 57 participants 66 participants 66 participants 7 participants 308 participants
12.5  (3.0) 13.3  (2.3) 12.6  (3.0) 11.8  (3.3) 12.6  (2.1) 12.5  (3.0)
[1]
Measure Analysis Population Description: Participants in the Main part of the study.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 11 participants 15 participants 0 participants 0 participants 0 participants 0 participants 0 participants 38 participants
Female
3
  25.0%
1
   9.1%
4
  26.7%
 0 0 0 0 0
8
  21.1%
Male
9
  75.0%
10
  90.9%
11
  73.3%
 0 0 0 0 0
30
  78.9%
[1]
Measure Analysis Population Description: Participants in the PK part of the study.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants 112 participants 57 participants 66 participants 66 participants 7 participants 308 participants
Female 0 0 0
17
  15.2%
9
  15.8%
8
  12.1%
11
  16.7%
0
   0.0%
45
  14.6%
Male 0 0 0
95
  84.8%
48
  84.2%
58
  87.9%
55
  83.3%
7
 100.0%
263
  85.4%
[1]
Measure Analysis Population Description: Participants in Main Part of study.
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 11 participants 15 participants 0 participants 0 participants 0 participants 0 participants 0 participants 38 participants
Hispanic or Latino
2
  16.7%
1
   9.1%
3
  20.0%
 0 0 0 0 0
6
  15.8%
Not Hispanic or Latino
10
  83.3%
10
  90.9%
11
  73.3%
 0 0 0 0 0
31
  81.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
1
   6.7%
 0 0 0 0 0
1
   2.6%
[1]
Measure Analysis Population Description: Participants in the PK part of the study.
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants 112 participants 57 participants 66 participants 66 participants 7 participants 308 participants
Hispanic or Latino 0 0 0
17
  15.2%
7
  12.3%
8
  12.1%
6
   9.1%
0
   0.0%
38
  12.3%
Not Hispanic or Latino 0 0 0
93
  83.0%
49
  86.0%
58
  87.9%
59
  89.4%
7
 100.0%
266
  86.4%
Unknown or Not Reported 0 0 0
2
   1.8%
1
   1.8%
0
   0.0%
1
   1.5%
0
   0.0%
4
   1.3%
[1]
Measure Analysis Population Description: Participants in the main part of the study.
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 11 participants 15 participants 0 participants 0 participants 0 participants 0 participants 0 participants 38 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
 0 0 0 0 0
0
   0.0%
Asian
0
   0.0%
1
   9.1%
0
   0.0%
 0 0 0 0 0
1
   2.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
 0 0 0 0 0
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
3
  20.0%
 0 0 0 0 0
3
   7.9%
White
11
  91.7%
9
  81.8%
10
  66.7%
 0 0 0 0 0
30
  78.9%
More than one race
0
   0.0%
0
   0.0%
1
   6.7%
 0 0 0 0 0
1
   2.6%
Unknown or Not Reported
1
   8.3%
1
   9.1%
1
   6.7%
 0 0 0 0 0
3
   7.9%
[1]
Measure Analysis Population Description: Participants in PK part of the study.
Race (NIH/OMB)   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants 112 participants 57 participants 66 participants 66 participants 7 participants 308 participants
American Indian or Alaska Native 0 0 0
0
   0.0%
1
   1.8%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.3%
Asian 0 0 0
5
   4.5%
3
   5.3%
7
  10.6%
3
   4.5%
0
   0.0%
18
   5.8%
Native Hawaiian or Other Pacific Islander 0 0 0
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.5%
0
   0.0%
1
   0.3%
Black or African American 0 0 0
4
   3.6%
1
   1.8%
4
   6.1%
5
   7.6%
0
   0.0%
14
   4.5%
White 0 0 0
93
  83.0%
46
  80.7%
54
  81.8%
51
  77.3%
6
  85.7%
250
  81.2%
More than one race 0 0 0
9
   8.0%
5
   8.8%
1
   1.5%
5
   7.6%
1
  14.3%
21
   6.8%
Unknown or Not Reported 0 0 0
1
   0.9%
1
   1.8%
0
   0.0%
1
   1.5%
0
   0.0%
3
   1.0%
[1]
Measure Description: Participants in Main Part of study
[2]
Measure Analysis Population Description: Participants in Main Part of study.
1.Primary Outcome
Title 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
Hide Description 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.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Balovaptan (RO5285119) 10 mg/d Equivalent
Hide Arm/Group Description:
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
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.
Overall Number of Participants Analyzed 81 86
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
2.34  (1.15) 2.17  (1.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Balovaptan (RO5285119) 10 mg/d Equivalent
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.911
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted LSMeans
Estimated Value -0.16
Confidence Interval (2-Sided) 90%
-2.56 to 2.23
Estimation Comments [Not Specified]
2.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Balovaptan (RO5285119) 10 mg/d Equivalent
Hide Arm/Group Description:
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
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.
Overall Number of Participants Analyzed 81 86
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
Week 12 1.45  (1.07) 1.74  (1.04)
Week 24 2.20  (1.19) 1.97  (1.15)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Balovaptan (RO5285119) 10 mg/d Equivalent
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in adjused LSMean
Estimated Value 0.29
Confidence Interval (2-Sided) 90%
-1.85 to 2.43
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Balovaptan (RO5285119) 10 mg/d Equivalent
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in adjusted LSMean
Estimated Value -0.23
Confidence Interval (2-Sided) 90%
-2.67 to 2.22
Estimation Comments [Not Specified]
3.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Balovaptan (RO5285119) 10 mg/d Equivalent
Hide Arm/Group Description:
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
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.
Overall Number of Participants Analyzed 81 86
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
Communication Domain Standard Score, Week 12 1.86  (1.06) 1.64  (1.03)
Communication Domain Standard Score, Week 24 1.51  (1.13) 2.21  (1.09)
Socialization Domain Standard Score, Week 12 1.69  (1.31) 2.20  (1.26)
Socialization Domain Standard Score, Week 24 2.87  (1.50) 2.26  (1.45)
Daily Living Skills Domain Standard Score, Week 12 -0.01  (1.38) 2.13  (1.35)
Daily Living Skills Domain Standard Score, Week 24 1.44  (1.49) 1.61  (1.45)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Balovaptan (RO5285119) 10 mg/d Equivalent
Comments Communication Domain Standard Score, Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in adjusted LSMean
Estimated Value -0.22
Confidence Interval (2-Sided) 90%
-2.36 to 1.92
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Balovaptan (RO5285119) 10 mg/d Equivalent
Comments Communication Domain Standard Score, Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in adjusted LSMean
Estimated Value 0.71
Confidence Interval (2-Sided) 90%
-1.60 to 3.02
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Balovaptan (RO5285119) 10 mg/d Equivalent
Comments Socialization Domain Standard Score, Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in adjusted LSMean
Estimated Value 0.51
Confidence Interval (2-Sided) 90%
-2.10 to 3.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Balovaptan (RO5285119) 10 mg/d Equivalent
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Socialization Domain Standard Score, Week 24
Method of Estimation Estimation Parameter Difference in adjusted LSMean
Estimated Value -0.61
Confidence Interval (2-Sided) 90%
-3.74 to 2.51
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Balovaptan (RO5285119) 10 mg/d Equivalent
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Daily Living Skills Domain Standard Score, Week 12
Method of Estimation Estimation Parameter Difference in adjusted LSMean
Estimated Value 2.14
Confidence Interval (2-Sided) 90%
-0.63 to 4.90
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Balovaptan (RO5285119) 10 mg/d Equivalent
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Daily Living Skills Domain Standard Score, Week 24
Method of Estimation Estimation Parameter Differences in adjusted LSMean
Estimated Value 0.18
Confidence Interval (2-Sided) 90%
-2.87 to 3.22
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Proportion of Subjects With >=6 Points Improvement in the Vineland-II 2DC Score for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
Hide Description 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.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Balovaptan (RO5285119) 10 mg/d Equivalent
Hide Arm/Group Description:
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
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.
Overall Number of Participants Analyzed 66 70
Measure Type: Number
Unit of Measure: Percentage of participants
Week 12 Number Analyzed 66 participants 70 participants
30.3 27.1
Week 24 Number Analyzed 61 participants 67 participants
34.4 32.8
5.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Balovaptan (RO5285119) 10 mg/d Equivalent
Hide Arm/Group Description:
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
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.
Overall Number of Participants Analyzed 67 74
Measure Type: Number
Unit of Measure: Percentage of participants
-3 (Very much improved), Week 12 Number Analyzed 67 participants 74 participants
1.5 0
-2 (Much improved), Week 12 Number Analyzed 67 participants 74 participants
1.5 2.7
-1 (Minimally improved), Week 12 Number Analyzed 67 participants 74 participants
31.3 31.1
0 (No change), Week 12 Number Analyzed 67 participants 74 participants
65.7 63.5
+1 (Minimally worse), Week 12 Number Analyzed 67 participants 74 participants
0 2.7
+2 (Much worse), Week 12 Number Analyzed 67 participants 74 participants
0 0
+3 (Very Much worse), Week 12 Number Analyzed 67 participants 74 participants
0 0
-3 (Very much improved), Week 24 Number Analyzed 62 participants 69 participants
1.6 0
-2 (Much improved), Week 24 Number Analyzed 62 participants 69 participants
6.5 4.3
-1 (Minimally improved), Week 24 Number Analyzed 62 participants 69 participants
32.3 31.9
0 (No change), Week 24 Number Analyzed 62 participants 69 participants
59.7 63.8
+1 (Minimally worse), Week 24 Number Analyzed 62 participants 69 participants
0 0
+2 (Much worse), Week 24 Number Analyzed 62 participants 69 participants
0 0
+3 (Very much worse), Week 24 Number Analyzed 62 participants 69 participants
0 0
6.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Balovaptan (RO5285119) 10 mg/d Equivalent
Hide Arm/Group Description:
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
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.
Overall Number of Participants Analyzed 67 73
Measure Type: Number
Unit of Measure: Percentage of participants
-3 (Very much improved), Week 12 Number Analyzed 67 participants 73 participants
3.0 0
-2 (Much improved), Week 12 Number Analyzed 67 participants 73 participants
6.0 6.8
-1 (Minimally improved), Week 12 Number Analyzed 67 participants 73 participants
28.4 34.2
0 (No change), Week 12 Number Analyzed 67 participants 73 participants
59.7 57.5
+1 (Minimally worse), Week 12 Number Analyzed 67 participants 73 participants
3.0 1.4
+2 (Much worse), Week 12 Number Analyzed 67 participants 73 participants
0 0
+3 (Very much worse), Week 12 Number Analyzed 67 participants 73 participants
0 0
-3 (Very much improved), Week 24 Number Analyzed 62 participants 67 participants
6.5 0
-2 (Much improved), Week 24 Number Analyzed 62 participants 67 participants
8.1 7.5
-1 (Minimally improved), Week 24 Number Analyzed 62 participants 67 participants
33.9 28.4
0 (No change), Week 24 Number Analyzed 62 participants 67 participants
48.4 61.2
+1 (Minimally worse), Week 24 Number Analyzed 62 participants 67 participants
3.2 3.0
+2 (Much worse), Week 24 Number Analyzed 62 participants 67 participants
0 0
+3 (Very much worse), Week 24 Number Analyzed 62 participants 67 participants
0 0
7.Secondary Outcome
Title Clinical Global Impressions- Improvement (CGI-I) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
Hide Description 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.
Time Frame Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Balovaptan (RO5285119) 10 mg/d Equivalent
Hide Arm/Group Description:
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
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.
Overall Number of Participants Analyzed 67 74
Measure Type: Number
Unit of Measure: Percentage of participants
1 - Very much improved, Week 12 Number Analyzed 67 participants 74 participants
0 0
2 - Much improved, Week 12 Number Analyzed 67 participants 74 participants
22.4 21.6
3 - Minimally improved, Week 12 Number Analyzed 67 participants 74 participants
49.3 35.1
4 - No change, Week 12 Number Analyzed 67 participants 74 participants
22.4 43.2
5 - Minimally worse, Week 12 Number Analyzed 67 participants 74 participants
6.0 0
6 - Much worse, Week 12 Number Analyzed 67 participants 74 participants
0 0
7 - Very much worse, Week 12 Number Analyzed 67 participants 74 participants
0 0
1 - Very much improved, Week 24 Number Analyzed 62 participants 68 participants
0 4.4
2 - Much improved, Week 24 Number Analyzed 62 participants 68 participants
30.6 26.5
3 - Minimally improved, Week 24 Number Analyzed 62 participants 68 participants
48.4 30.9
4 - No change, Week 24 Number Analyzed 62 participants 68 participants
19.4 36.8
5 - Minimally worse, Week 24 Number Analyzed 62 participants 68 participants
1.6 1.5
6 - Much worse, Week 24 Number Analyzed 62 participants 68 participants
0 0
7 - Very much worse, Week 24 Number Analyzed 62 participants 68 participants
0 0
8.Secondary Outcome
Title Ohio Autism Clinical Impressions Scale- Improvement (OACIS-I) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
Hide Description 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).
Time Frame Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Balovaptan (RO5285119) 10 mg/d Equivalent
Hide Arm/Group Description:
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
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.
Overall Number of Participants Analyzed 67 74
Measure Type: Number
Unit of Measure: Percentage of participants
1 - Very much improved, Week 12 Number Analyzed 67 participants 74 participants
1.5 0
2 - Much improved, Week 12 Number Analyzed 67 participants 74 participants
16.4 20.3
3 - Minimally improved, Week 12 Number Analyzed 67 participants 74 participants
38.8 25.7
4 - No change, Week 12 Number Analyzed 67 participants 74 participants
40.3 54.1
5 - Minimally worse, Week 12 Number Analyzed 67 participants 74 participants
3.0 0
6 - Much worse, Week 12 Number Analyzed 67 participants 74 participants
0 0
7 - Very much worse, Week 12 Number Analyzed 67 participants 74 participants
0 0
1 - Very much improved, Week 24 Number Analyzed 62 participants 68 participants
0 2.9
2 - Much improved, Week 24 Number Analyzed 62 participants 68 participants
25.8 22.1
3 - Minimally improved, Week 24 Number Analyzed 62 participants 68 participants
46.8 25.0
4 - No change, Week 24 Number Analyzed 62 participants 68 participants
25.8 50.0
5 - Minimally worse, Week 24 Number Analyzed 62 participants 68 participants
1.6 0
6 - Much worse, Week 24 Number Analyzed 62 participants 68 participants
0 0
7 - Very much worse, Week 24 Number Analyzed 62 participants 68 participants
0 0
9.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Balovaptan (RO5285119) 10 mg/d Equivalent
Hide Arm/Group Description:
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
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.
Overall Number of Participants Analyzed 62 72
Least Squares Mean (Standard Error)
Unit of Measure: Score on scale
Change from Baseline at Week 12 Number Analyzed 62 participants 72 participants
2.42  (1.49) 6.16  (1.41)
Change from Baseline at Week 24 Number Analyzed 59 participants 65 participants
3.70  (1.50) 5.98  (1.44)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Balovaptan (RO5285119) 10 mg/d Equivalent
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Adjusted LS Means
Estimated Value 3.74
Confidence Interval (2-Sided) 90%
0.78 to 6.70
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Balovaptan (RO5285119) 10 mg/d Equivalent
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Adjusted LS means
Estimated Value 2.28
Confidence Interval (2-Sided) 90%
-0.73 to 5.29
Estimation Comments [Not Specified]
10.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Balovaptan (RO5285119) 10 mg/d Equivalent
Hide Arm/Group Description:
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
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.
Overall Number of Participants Analyzed 44 48
Mean (Standard Deviation)
Unit of Measure: Score on scale
5-12 Years Age Group, Absolute Value at Baseline Number Analyzed 44 participants 48 participants
73.9  (9.7) 77.3  (10.9)
5-12 Years Age Group, Change From Baseline at Week 12 Number Analyzed 37 participants 38 participants
3.6  (8.4) 1.2  (7.8)
5-12 Years Age Group, Change From Baseline at Week 24 Number Analyzed 34 participants 37 participants
4.8  (9.1) 1.0  (8.4)
13-17 Years Age Group, Absolute Baseline Value Number Analyzed 35 participants 36 participants
71.0  (10.3) 73.5  (8.9)
13-17 Years Age Group, Change From Baseline at Week 12 Number Analyzed 29 participants 32 participants
1.8  (4.8) 3.7  (9.4)
13-17 Years Age Group, Change From Baseline at Week 24 Number Analyzed 27 participants 30 participants
2.7  (8.6) 3.3  (8.7)
11.Secondary Outcome
Title Change From Baseline in Vineland-II Adaptive Behavior Scale 2DC Score at Week 12 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
Hide Description 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.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Balovaptan (RO5285119) 10 mg/d Equivalent
Hide Arm/Group Description:
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
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.
Overall Number of Participants Analyzed 81 86
Least Squares Mean (Standard Error)
Unit of Measure: Score on scale
1.87  (1.00) 1.88  (0.97)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Balovaptan (RO5285119) 10 mg/d Equivalent
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.992
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Adjusted LS Means
Estimated Value 0.01
Confidence Interval (2-Sided) 90%
-1.99 to 2.01
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Percentage of Participants With Adverse Events for Treatment With Balovaptan
Hide 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.
Time Frame Baseline to Week 24 and up to Week 76
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population consisted of all participants who received a least one dose of study medication; Used for safety analyses and divided by exposure tertiles.
Arm/Group Title Main Study Part, Low Exposure Tertile Main Study Part, Medium Exposure Tertile Main Study Part, High Exposure Tertile Main Study Part (Study Part 2) - All Treated Open Label Extension Part, Low Exposure Tertile Open Label Extension Part, Medium Exposure Tertile Open Label Extension Part, High Exposure Tertile Open Label Extension Part, All Treated
Hide Arm/Group Description:
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.
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.
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.
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 57 66 66 196 35 40 46 126
Measure Type: Number
Unit of Measure: Percentage of Participants
77.2 71.2 66.7 71.4 68.6 70.0 78.3 72.2
Time Frame From the first study drug to the data cutoff date: 30 June 2020 (up to 43 months)
Adverse Event Reporting 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.
 
Arm/Group Title PK Part (Study Part 1) - Placebo PK Part (Study Part 1) - Balovaptan (RO5285119) 4 mg/d Equivalent PK Part (Study Part 1) - Balovaptan (RO5285119) 10 mg/d Equivalent Main Study Part (Study Part 2) - Placebo Main Study Part (Study Part 2) - Low Exposure Tertile Main Study Part (Study Part 2) - Medium Exposure Tertile Main Study Part (Study Part 2) - High Exposure Tertile Main Study Part (Study Part 2) - Dose-Adjusters Open Label Extension Part (Study Part 3) - Placebo Open Label Extension Part (Study Part 3) - Low Exposure Tertile Open Label Extension Part (Study Part 3) - Medium Exposure Tertile Open Label Extension Part (Study Part 3) - High Exposure Tertile Open Label Extension Part (Study Part 3) - Dose-Adjusters
Hide Arm/Group Description Participants in the PK Part of the study who received a matching placebo orally. Approximate treatment duration was up to 8 weeks. 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. 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. Participants in the Main Study Part received a matching placebo orally. Approximate treatment duration was up to 24 weeks. 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. 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. 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. 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. 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. 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. 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. 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. 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.
All-Cause Mortality
PK Part (Study Part 1) - Placebo PK Part (Study Part 1) - Balovaptan (RO5285119) 4 mg/d Equivalent PK Part (Study Part 1) - Balovaptan (RO5285119) 10 mg/d Equivalent Main Study Part (Study Part 2) - Placebo Main Study Part (Study Part 2) - Low Exposure Tertile Main Study Part (Study Part 2) - Medium Exposure Tertile Main Study Part (Study Part 2) - High Exposure Tertile Main Study Part (Study Part 2) - Dose-Adjusters Open Label Extension Part (Study Part 3) - Placebo Open Label Extension Part (Study Part 3) - Low Exposure Tertile Open Label Extension Part (Study Part 3) - Medium Exposure Tertile Open Label Extension Part (Study Part 3) - High Exposure Tertile Open Label Extension Part (Study Part 3) - Dose-Adjusters
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/12 (0.00%)      0/11 (0.00%)      0/15 (0.00%)      0/112 (0.00%)      0/57 (0.00%)      0/66 (0.00%)      0/66 (0.00%)      0/7 (0.00%)      0/68 (0.00%)      0/35 (0.00%)      0/40 (0.00%)      0/46 (0.00%)      0/5 (0.00%)    
Hide Serious Adverse Events
PK Part (Study Part 1) - Placebo PK Part (Study Part 1) - Balovaptan (RO5285119) 4 mg/d Equivalent PK Part (Study Part 1) - Balovaptan (RO5285119) 10 mg/d Equivalent Main Study Part (Study Part 2) - Placebo Main Study Part (Study Part 2) - Low Exposure Tertile Main Study Part (Study Part 2) - Medium Exposure Tertile Main Study Part (Study Part 2) - High Exposure Tertile Main Study Part (Study Part 2) - Dose-Adjusters Open Label Extension Part (Study Part 3) - Placebo Open Label Extension Part (Study Part 3) - Low Exposure Tertile Open Label Extension Part (Study Part 3) - Medium Exposure Tertile Open Label Extension Part (Study Part 3) - High Exposure Tertile Open Label Extension Part (Study Part 3) - Dose-Adjusters
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/12 (0.00%)      1/11 (9.09%)      0/15 (0.00%)      4/112 (3.57%)      1/57 (1.75%)      0/66 (0.00%)      1/66 (1.52%)      0/7 (0.00%)      2/68 (2.94%)      0/35 (0.00%)      0/40 (0.00%)      2/46 (4.35%)      0/5 (0.00%)    
Infections and infestations                           
Pneumonia † 1  0/12 (0.00%)  0 1/11 (9.09%)  1 0/15 (0.00%)  0 0/112 (0.00%)  0 0/57 (0.00%)  0 0/66 (0.00%)  0 0/66 (0.00%)  0 0/7 (0.00%)  0 0/68 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/46 (0.00%)  0 0/5 (0.00%)  0
Gastroenteritis viral † 1  0/12 (0.00%)  0 0/11 (0.00%)  0 0/15 (0.00%)  0 1/112 (0.89%)  1 0/57 (0.00%)  0 0/66 (0.00%)  0 0/66 (0.00%)  0 0/7 (0.00%)  0 0/68 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/46 (0.00%)  0 0/5 (0.00%)  0
Metabolism and nutrition disorders                           
Dehydration † 1  0/12 (0.00%)  0 0/11 (0.00%)  0 0/15 (0.00%)  0 0/112 (0.00%)  0 0/57 (0.00%)  0 0/66 (0.00%)  0 0/66 (0.00%)  0 0/7 (0.00%)  0 0/68 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 1/46 (2.17%)  1 0/5 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                           
Acute lymphocytic leukaemia † 1  0/12 (0.00%)  0 0/11 (0.00%)  0 0/15 (0.00%)  0 0/112 (0.00%)  0 0/57 (0.00%)  0 0/66 (0.00%)  0 0/66 (0.00%)  0 0/7 (0.00%)  0 0/68 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 1/46 (2.17%)  1 0/5 (0.00%)  0
Psychiatric disorders                           
Aggression † 1  0/12 (0.00%)  0 0/11 (0.00%)  0 0/15 (0.00%)  0 1/112 (0.89%)  1 0/57 (0.00%)  0 0/66 (0.00%)  0 0/66 (0.00%)  0 0/7 (0.00%)  0 0/68 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/46 (0.00%)  0 0/5 (0.00%)  0
Agitation † 1  0/12 (0.00%)  0 0/11 (0.00%)  0 0/15 (0.00%)  0 0/112 (0.00%)  0 0/57 (0.00%)  0 0/66 (0.00%)  0 0/66 (0.00%)  0 0/7 (0.00%)  0 1/68 (1.47%)  1 0/35 (0.00%)  0 0/40 (0.00%)  0 0/46 (0.00%)  0 0/5 (0.00%)  0
Anxiety † 1  0/12 (0.00%)  0 0/11 (0.00%)  0 0/15 (0.00%)  0 0/112 (0.00%)  0 0/57 (0.00%)  0 0/66 (0.00%)  0 0/66 (0.00%)  0 0/7 (0.00%)  0 0/68 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 1/46 (2.17%)  1 0/5 (0.00%)  0
Depression † 1  0/12 (0.00%)  0 0/11 (0.00%)  0 0/15 (0.00%)  0 1/112 (0.89%)  2 0/57 (0.00%)  0 0/66 (0.00%)  0 0/66 (0.00%)  0 0/7 (0.00%)  0 0/68 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/46 (0.00%)  0 0/5 (0.00%)  0
Intentional self-injury † 1  0/12 (0.00%)  0 0/11 (0.00%)  0 0/15 (0.00%)  0 1/112 (0.89%)  1 0/57 (0.00%)  0 0/66 (0.00%)  0 0/66 (0.00%)  0 0/7 (0.00%)  0 0/68 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/46 (0.00%)  0 0/5 (0.00%)  0
Suicidal ideation † 1  0/12 (0.00%)  0 0/11 (0.00%)  0 0/15 (0.00%)  0 0/112 (0.00%)  0 1/57 (1.75%)  1 0/66 (0.00%)  0 1/66 (1.52%)  1 0/7 (0.00%)  0 1/68 (1.47%)  1 0/35 (0.00%)  0 0/40 (0.00%)  0 0/46 (0.00%)  0 0/5 (0.00%)  0
Respiratory, thoracic and mediastinal disorders                           
Laryngospasm † 1  0/12 (0.00%)  0 0/11 (0.00%)  0 0/15 (0.00%)  0 0/112 (0.00%)  0 0/57 (0.00%)  0 0/66 (0.00%)  0 0/66 (0.00%)  0 0/7 (0.00%)  0 1/68 (1.47%)  1 0/35 (0.00%)  0 0/40 (0.00%)  0 0/46 (0.00%)  0 0/5 (0.00%)  0
1
Term from vocabulary, MedDRA version 23.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
PK Part (Study Part 1) - Placebo PK Part (Study Part 1) - Balovaptan (RO5285119) 4 mg/d Equivalent PK Part (Study Part 1) - Balovaptan (RO5285119) 10 mg/d Equivalent Main Study Part (Study Part 2) - Placebo Main Study Part (Study Part 2) - Low Exposure Tertile Main Study Part (Study Part 2) - Medium Exposure Tertile Main Study Part (Study Part 2) - High Exposure Tertile Main Study Part (Study Part 2) - Dose-Adjusters Open Label Extension Part (Study Part 3) - Placebo Open Label Extension Part (Study Part 3) - Low Exposure Tertile Open Label Extension Part (Study Part 3) - Medium Exposure Tertile Open Label Extension Part (Study Part 3) - High Exposure Tertile Open Label Extension Part (Study Part 3) - Dose-Adjusters
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/12 (58.33%)      7/11 (63.64%)      7/15 (46.67%)      58/112 (51.79%)      34/57 (59.65%)      31/66 (46.97%)      34/66 (51.52%)      5/7 (71.43%)      35/68 (51.47%)      21/35 (60.00%)      25/40 (62.50%)      27/46 (58.70%)      3/5 (60.00%)    
Blood and lymphatic system disorders                           
Anaemia † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  2/35 (5.71%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Neutropenia † 1  1/12 (8.33%)  0/11 (0.00%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Cardiac disorders                           
Tachycardia † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  1/112 (0.89%)  3/57 (5.26%)  1/66 (1.52%)  0/66 (0.00%)  1/7 (14.29%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Eye disorders                           
Vision blurred † 1  0/12 (0.00%)  1/11 (9.09%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Gastrointestinal disorders                           
Abdominal discomfort † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  5/112 (4.46%)  1/57 (1.75%)  0/66 (0.00%)  6/66 (9.09%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Abdominal pain upper † 1  0/12 (0.00%)  1/11 (9.09%)  2/15 (13.33%)  6/112 (5.36%)  1/57 (1.75%)  2/66 (3.03%)  4/66 (6.06%)  0/7 (0.00%)  3/68 (4.41%)  2/35 (5.71%)  0/40 (0.00%)  2/46 (4.35%)  0/5 (0.00%) 
Constipation † 1  0/12 (0.00%)  1/11 (9.09%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Diarrhoea † 1  2/12 (16.67%)  0/11 (0.00%)  0/15 (0.00%)  4/112 (3.57%)  5/57 (8.77%)  4/66 (6.06%)  7/66 (10.61%)  0/7 (0.00%)  3/68 (4.41%)  2/35 (5.71%)  1/40 (2.50%)  2/46 (4.35%)  0/5 (0.00%) 
Mouth ulceration † 1  0/12 (0.00%)  0/11 (0.00%)  1/15 (6.67%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Nausea † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  7/112 (6.25%)  3/57 (5.26%)  2/66 (3.03%)  4/66 (6.06%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Vomiting † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  6/112 (5.36%)  5/57 (8.77%)  4/66 (6.06%)  4/66 (6.06%)  0/7 (0.00%)  2/68 (2.94%)  2/35 (5.71%)  1/40 (2.50%)  3/46 (6.52%)  0/5 (0.00%) 
General disorders                           
Fatigue † 1  1/12 (8.33%)  1/11 (9.09%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Pyrexia † 1  0/12 (0.00%)  0/11 (0.00%)  1/15 (6.67%)  4/112 (3.57%)  4/57 (7.02%)  4/66 (6.06%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  3/35 (8.57%)  2/40 (5.00%)  3/46 (6.52%)  0/5 (0.00%) 
Immune system disorders                           
Seasonal allergy † 1  0/12 (0.00%)  1/11 (9.09%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Infections and infestations                           
Bronchitis † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  2/40 (5.00%)  0/46 (0.00%)  0/5 (0.00%) 
Ear infection † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  4/68 (5.88%)  0/35 (0.00%)  0/40 (0.00%)  3/46 (6.52%)  0/5 (0.00%) 
Gastroenteritis † 1  0/12 (0.00%)  1/11 (9.09%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Influenza † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  5/112 (4.46%)  1/57 (1.75%)  3/66 (4.55%)  3/66 (4.55%)  1/7 (14.29%)  4/68 (5.88%)  3/35 (8.57%)  0/40 (0.00%)  2/46 (4.35%)  0/5 (0.00%) 
Nasopharyngitis † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  15/112 (13.39%)  8/57 (14.04%)  12/66 (18.18%)  11/66 (16.67%)  2/7 (28.57%)  9/68 (13.24%)  5/35 (14.29%)  10/40 (25.00%)  6/46 (13.04%)  0/5 (0.00%) 
Otitis media † 1  1/12 (8.33%)  0/11 (0.00%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Pharyngitis streptococcal † 1  0/12 (0.00%)  0/11 (0.00%)  1/15 (6.67%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  2/68 (2.94%)  0/35 (0.00%)  1/40 (2.50%)  1/46 (2.17%)  1/5 (20.00%) 
Rhinitis † 1  0/12 (0.00%)  0/11 (0.00%)  1/15 (6.67%)  1/112 (0.89%)  1/57 (1.75%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Sinusitis † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  3/68 (4.41%)  0/35 (0.00%)  3/40 (7.50%)  0/46 (0.00%)  0/5 (0.00%) 
Upper respiratory tract infection † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  4/112 (3.57%)  2/57 (3.51%)  3/66 (4.55%)  5/66 (7.58%)  0/7 (0.00%)  3/68 (4.41%)  4/35 (11.43%)  3/40 (7.50%)  3/46 (6.52%)  0/5 (0.00%) 
Viral infection † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  0/112 (0.00%)  3/57 (5.26%)  2/66 (3.03%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Injury, poisoning and procedural complications                           
Accidental overdose † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  2/68 (2.94%)  2/35 (5.71%)  2/40 (5.00%)  2/46 (4.35%)  0/5 (0.00%) 
Arthropod bite † 1  0/12 (0.00%)  1/11 (9.09%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Contusion † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  1/112 (0.89%)  2/57 (3.51%)  1/66 (1.52%)  0/66 (0.00%)  1/7 (14.29%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Facial bones fracture † 1  0/12 (0.00%)  0/11 (0.00%)  1/15 (6.67%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Investigations                           
Weight increased † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  1/68 (1.47%)  2/35 (5.71%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Metabolism and nutrition disorders                           
Increased appetite † 1  0/12 (0.00%)  1/11 (9.09%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Musculoskeletal and connective tissue disorders                           
Myalgia † 1  0/12 (0.00%)  1/11 (9.09%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  1/68 (1.47%)  0/35 (0.00%)  2/40 (5.00%)  0/46 (0.00%)  0/5 (0.00%) 
Nervous system disorders                           
Headache † 1  0/12 (0.00%)  0/11 (0.00%)  2/15 (13.33%)  16/112 (14.29%)  6/57 (10.53%)  7/66 (10.61%)  8/66 (12.12%)  0/7 (0.00%)  4/68 (5.88%)  3/35 (8.57%)  2/40 (5.00%)  5/46 (10.87%)  0/5 (0.00%) 
Poor quality sleep † 1  0/12 (0.00%)  1/11 (9.09%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Psychomotor hyperactivity † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  1/35 (2.86%)  0/40 (0.00%)  1/46 (2.17%)  1/5 (20.00%) 
Seizure † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  2/40 (5.00%)  0/46 (0.00%)  0/5 (0.00%) 
Somnolence † 1  0/12 (0.00%)  1/11 (9.09%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Syncope † 1  1/12 (8.33%)  0/11 (0.00%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Tremor † 1  0/12 (0.00%)  1/11 (9.09%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Psychiatric disorders                           
Aggression † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  2/68 (2.94%)  1/35 (2.86%)  2/40 (5.00%)  1/46 (2.17%)  0/5 (0.00%) 
Anxiety † 1  1/12 (8.33%)  0/11 (0.00%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  5/68 (7.35%)  2/35 (5.71%)  4/40 (10.00%)  1/46 (2.17%)  0/5 (0.00%) 
Impulsive behaviour † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  1/5 (20.00%) 
Insomnia † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  2/68 (2.94%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  2/5 (40.00%) 
Irritability † 1  0/12 (0.00%)  2/11 (18.18%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Mood swings † 1  1/12 (8.33%)  0/11 (0.00%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Nightmare † 1  0/12 (0.00%)  1/11 (9.09%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Stereotypy † 1  0/12 (0.00%)  0/11 (0.00%)  1/15 (6.67%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Suicidal ideation † 1  1/12 (8.33%)  0/11 (0.00%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Middle insomnia † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  1/112 (0.89%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Renal and urinary disorders                           
Pollakiuria † 1  2/12 (16.67%)  0/11 (0.00%)  0/15 (0.00%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Reproductive system and breast disorders                           
Gynaecomastia † 1  0/12 (0.00%)  0/11 (0.00%)  1/15 (6.67%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
Respiratory, thoracic and mediastinal disorders                           
Cough † 1  1/12 (8.33%)  0/11 (0.00%)  1/15 (6.67%)  5/112 (4.46%)  3/57 (5.26%)  1/66 (1.52%)  2/66 (3.03%)  0/7 (0.00%)  5/68 (7.35%)  0/35 (0.00%)  1/40 (2.50%)  4/46 (8.70%)  0/5 (0.00%) 
Nasal congestion † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  5/112 (4.46%)  3/57 (5.26%)  0/66 (0.00%)  6/66 (9.09%)  1/7 (14.29%)  2/68 (2.94%)  2/35 (5.71%)  3/40 (7.50%)  1/46 (2.17%)  0/5 (0.00%) 
Oropharyngeal pain † 1  0/12 (0.00%)  0/11 (0.00%)  0/15 (0.00%)  7/112 (6.25%)  2/57 (3.51%)  3/66 (4.55%)  4/66 (6.06%)  0/7 (0.00%)  3/68 (4.41%)  1/35 (2.86%)  2/40 (5.00%)  4/46 (8.70%)  0/5 (0.00%) 
Rhinorrhoea † 1  1/12 (8.33%)  0/11 (0.00%)  0/15 (0.00%)  1/112 (0.89%)  5/57 (8.77%)  2/66 (3.03%)  3/66 (4.55%)  0/7 (0.00%)  1/68 (1.47%)  3/35 (8.57%)  1/40 (2.50%)  3/46 (6.52%)  0/5 (0.00%) 
Skin and subcutaneous tissue disorders                           
Acne † 1  0/12 (0.00%)  0/11 (0.00%)  1/15 (6.67%)  0/112 (0.00%)  0/57 (0.00%)  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/68 (0.00%)  0/35 (0.00%)  0/40 (0.00%)  0/46 (0.00%)  0/5 (0.00%) 
1
Term from vocabulary, MedDRA version 23.0
†
Indicates events were collected by systematic assessment
Study was terminated early, therefore, there was limited data collected in Open Label Extension part of the study.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
EMail: genentech@druginfo.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02901431    
Other Study ID Numbers: BP30153
First Submitted: September 12, 2016
First Posted: September 15, 2016
Results First Submitted: December 7, 2020
Results First Posted: February 8, 2021
Last Update Posted: February 8, 2021