Trial Outcomes & Findings for Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors (NCT NCT01944046)

NCT ID: NCT01944046

Last Updated: 2021-06-18

Results Overview

The primary outcome is Change in Aberrant Behavior Checklist-Modified Social Withdrawal subscale- a measure of reciprocal social behaviors. ABC-mSW is a modification of the ABC-Lethargy subscale. The ABC-mSW consists of the sum of questions 5,12,16, 20, 23, 26, 30, 37, 40, 42, 43, 55, and 58. In contrast to the ABC-Lethargy subscale it eliminates question 3 (listless, sluggish, inactive), question 32 (sits or stands in one position for a long time), and question 53 (inactive, never moves spontaneously). Thirteen individual items are scored 0-3, therefore the range is 0-39. Higher score indicates lower social reciprocity. Repeated measures were obtained at baseline, weeks 4, 8, 12, 16, 20, 24.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

290 participants

Primary outcome timeframe

Least Mean Squares Double-blind phase: change from baseline to week 24

Results posted on

2021-06-18

Participant Flow

Participant milestones

Participant milestones
Measure	Oxytocin Nasal Spray Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
Randomized to DB STARTED	146	144
Randomized to DB COMPLETED	125	125
Randomized to DB NOT COMPLETED	21	19
Open Label Eligible and Consented STARTED	124	124
Open Label Eligible and Consented COMPLETED	110	116
Open Label Eligible and Consented NOT COMPLETED	14	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Oxytocin Nasal Spray Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
Randomized to DB Adverse Event	5	2
Randomized to DB Clinical Worsening	3	2
Randomized to DB Lost to Follow-up	3	3
Randomized to DB Withdrawal by Subject	2	4
Randomized to DB Physician Decision	1	2
Randomized to DB Did not have baseline ABC-SW	2	0
Randomized to DB Did not have a postbaseline ABC SW	5	6
Open Label Eligible and Consented Lost to Follow-up	3	5
Open Label Eligible and Consented Adverse Event	6	1
Open Label Eligible and Consented Clinical Worsening	4	2
Open Label Eligible and Consented Withdrawal by Subject	1	0

Baseline Characteristics

Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Oxytocin Nasal Spray n=139 Participants Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray n=138 Participants Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.	Total n=277 Participants Total of all reporting groups
Age, Continuous	10.4 years STANDARD_DEVIATION 4.06 • n=5 Participants	10.4 years STANDARD_DEVIATION 3.99 • n=7 Participants	10.4 years STANDARD_DEVIATION 4.04 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	18 Participants n=7 Participants	35 Participants n=5 Participants
Sex: Female, Male Male	122 Participants n=5 Participants	120 Participants n=7 Participants	242 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=5 Participants	15 Participants n=7 Participants	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	126 Participants n=5 Participants	123 Participants n=7 Participants	249 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	14 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) White	104 Participants n=5 Participants	100 Participants n=7 Participants	204 Participants n=5 Participants
Race (NIH/OMB) More than one race	14 Participants n=5 Participants	9 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment United States	139 Participants n=5 Participants	138 Participants n=7 Participants	277 Participants n=5 Participants
Aberrant Behavior Checklist Social Withdrawal Subscale Score (ABC-SW) abc-SW (mean	11.0 units on a scale STANDARD_DEVIATION 6.9 • n=5 Participants	11.6 units on a scale STANDARD_DEVIATION 7.8 • n=7 Participants	11.3 units on a scale STANDARD_DEVIATION 7.4 • n=5 Participants

PRIMARY outcome

Timeframe: Least Mean Squares Double-blind phase: change from baseline to week 24

Population: Full Analysis Set

Outcome measures

Outcome measures
Measure	Oxytocin Nasal Spray n=139 Participants Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray n=138 Participants Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity DB w0- w16	7.99 score on a scale Standard Error 0.46	8.04 score on a scale Standard Error 0.46
Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity Double-blind baseline-w12	7.48 score on a scale Standard Error 0.43	8.13 score on a scale Standard Error 0.43
Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity Double-blind baseline to w4	8.81 score on a scale Standard Error 0.39	8.68 score on a scale Standard Error 0.39
Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity Double-blind baseline to w8	8.97 score on a scale Standard Error 0.45	8.68 score on a scale Standard Error 0.45
Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity DB w0- w20	7.81 score on a scale Standard Error 0.05	7.75 score on a scale Standard Error 0.45
Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity DB w0-w24	7.75 score on a scale Standard Error 0.46	8.05 score on a scale Standard Error 0.46

PRIMARY outcome

Timeframe: Least mean squares for Open Label: Change between weeks 24-48

Population: Open Label phase participants in OLE FAS excluding 2 participants without usable ABC-sws (either w24 or at least one pw24 ABC-sw.

The ABC-mSW is described above and involves 13 items reflecting lack of reciprocal interaction. Each item is scored from 0 (never shows behavior) to 3 (behavior is a major problem). The range is 0-39. Higher scores indicate worse reciprocal social functioning.

Outcome measures

Outcome measures
Measure	Oxytocin Nasal Spray n=125 Participants Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray n=122 Participants Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity Open Label week 48	6.99 score on a scale Interval 6.1 to 7.89	6.78 score on a scale Interval 5.89 to 7.67
Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity Open Label week 24	7.83 score on a scale Interval 7.11 to 8.55	7.81 score on a scale Interval 7.09 to 8.52

SECONDARY outcome

Timeframe: Double-blind phase: change in least means squares between week 0 & 24.

Population: Full Analysis Set

The Sociability Factor (SF) is a summed measure of the13 items of the ABC-SW and the 18 items of the Pervasive Development Disorders Behavior Inventory-Screening Version (PDDBI-SV).The PDDBI-SV assesses both adaptive social behaviors and social problems typical of ASD. The adaptive behaviors are reverse scored so that all the analyzed scores range from 0-performing in a neurotypical fashion to 3 typically performs in a way associated with ASD. the total # of items on this summed measure is 31 with a range from 0 to 93. More impaired social functioning indicated by higher scores. This measure was changed to a secondary outcome in the final statistical analysis plan.

Outcome measures

Outcome measures
Measure	Oxytocin Nasal Spray n=139 Participants Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray n=138 Participants Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
Change in Sociability Factor (SF) DB w0	35.8 score on a scale Standard Error 1.24	36.1 score on a scale Standard Error 1.28
Change in Sociability Factor (SF) DB w0-w4	-5.57 score on a scale Standard Error 0.69	-5.81 score on a scale Standard Error 0.69
Change in Sociability Factor (SF) DB w0-w8	-5.99 score on a scale Standard Error 0.66	-6.30 score on a scale Standard Error 0.66
Change in Sociability Factor (SF) DB w0-w12	-6.40 score on a scale Standard Error 0.66	-6.79 score on a scale Standard Error 0.66
Change in Sociability Factor (SF) DB w0-w16	-6.82 score on a scale Standard Error 0.70	-7.28 score on a scale Standard Error 0.71
Change in Sociability Factor (SF) DB w0-w20	-7.24 score on a scale Standard Error 0.88	-7.77 score on a scale Standard Error 0.88
Change in Sociability Factor (SF) DB w0-w24	-7.66 score on a scale Standard Error 0.78	-8.27 score on a scale Standard Error 0.88

SECONDARY outcome

Timeframe: Double-blind phase: baseline, weeks 12, 24

Population: Full Analysis Set

The SRS-Social Motivation subscale was developed to provide a quantitative measure of social impairments typically observed in ASD in children 3-18 years. Reported as T-score with a range of 38-90 for both boys and girls. Higher score indicates more severe clinical condition. Lower value in change indicates more improvement.

Outcome measures

Outcome measures
Measure	Oxytocin Nasal Spray n=139 Participants Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray n=138 Participants Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
Change in Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score Double-blind baseline to week 12	-4.58 T-score Standard Deviation 0.68	-5.72 T-score Standard Deviation 0.69
Change in Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score Double-blind baseline to week 24	-4.49 T-score Standard Deviation 0.70	-5.42 T-score Standard Deviation 0.70

SECONDARY outcome

Timeframe: Double-blind phase: baseline to week 24

Population: Participants with scores collected at baseline and week 24.

Cognitive skills will be assessed using the Stanford Binet-5th Edition (SB-5) (Roid). Acceptable IQ range is 47-153, with higher score being better. Higher change scores indicate more improvement.

Outcome measures

Outcome measures
Measure	Oxytocin Nasal Spray n=94 Participants Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray n=98 Participants Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
Change in Stanford Binet-5th Edition (SB-5) IQ Score	0.40 score on a scale Standard Deviation 11.64	1.0 score on a scale Standard Deviation 10.84

OTHER_PRE_SPECIFIED outcome

Timeframe: Open Label: weeks 24, 48

Population: Open Label phase participants

Outcome measures

Outcome measures
Measure	Oxytocin Nasal Spray n=127 Participants Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray n=122 Participants Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score Open Label week 24	88.5 T-score Standard Error 1.37	86.6 T-score Standard Error 1.37
Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score Open Label week 48	87.9 T-score Standard Error 1.83	83.0 T-score Standard Error 1.81

OTHER_PRE_SPECIFIED outcome

Timeframe: Double-blind phase: baseline, week 24; Open Label: week 48

Population: Full Analysis Set

Functional skills will be assessed using the VABS-II Daily Living Domain Score. Uses standard score with a mean of 100 and SD of 15 with a range of 20-160. Higher score is better. Higher value in change indicates more improvement.

Outcome measures

Outcome measures
Measure	Oxytocin Nasal Spray n=139 Participants Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray n=138 Participants Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
Change in Vineland II Adaptive Behavior Scales (VABS-II) Daily Living Domain Score Double-blind baseline to week 24	2.50 score on a scale Standard Error 1.10	1.24 score on a scale Standard Error 1.14
Change in Vineland II Adaptive Behavior Scales (VABS-II) Daily Living Domain Score Open Label week 24 to week 48	1.76 score on a scale Standard Error 1.19	0.62 score on a scale Standard Error 0.11

OTHER_PRE_SPECIFIED outcome

Timeframe: Open Label: weeks 24, 48

Population: Full Analysis Set participants who entered double blind and have values at week 24 AND 48

Caregiver questionnaire that assesses the impact of caring for the proband on caregiver and family. Each item on the subjective internalizing CSQ subscale is rated from 1 to 5. Then all items within the subscale are summed and the mean is determined based on the number of items in the subscale. Higher score indicates more caregiver strain. Lower value in change indicates more improvement.

Outcome measures

Outcome measures
Measure	Oxytocin Nasal Spray n=110 Participants Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray n=119 Participants Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Mean Score Open Label week 24	2.96 mean score on a scale Standard Deviation 0.99	2.85 mean score on a scale Standard Deviation 1.00
Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Mean Score Open Label week 48	2.97 mean score on a scale Standard Deviation 0.99	2.85 mean score on a scale Standard Deviation 0.97

OTHER_PRE_SPECIFIED outcome

Timeframe: Double-blind phase: baseline, week 24; Open Label: week 48

Population: Full Analysis Set

Functional skills will be assessed using the VABS-II Communication Domain Score. Uses standard score with a mean of 100 and SD of 15 with a range of 20-160. Higher score is better. Higher value in change indicates more improvement.

Outcome measures

Outcome measures
Measure	Oxytocin Nasal Spray n=139 Participants Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray n=138 Participants Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
Change in Vineland II Adaptive Behavior Scales (VABS-II) Communication Domain Score Double-blind baseline to week 24	3.88 score on a scale Standard Error 0.89	2.27 score on a scale Standard Error 0.90
Change in Vineland II Adaptive Behavior Scales (VABS-II) Communication Domain Score Open Label week 24 to week 48	4.06 score on a scale Standard Error 1.35	5.98 score on a scale Standard Error 1.41

OTHER_PRE_SPECIFIED outcome

Timeframe: Double-blind phase: baseline, week 24

Population: Full Analysis Set

Caregiver questionnaire that assesses the impact of caring for the proband on caregiver and family. CSQ subscale scores are ranged from 1 to 5. with each item of the subscale having the same range, the sum of the items within the subscale are summed, and the mean score is determined (I.e. a single # between 1 and 5) and reported. Higher scores indicate more caregiver strain. Lower value in change indicates more improvement.

Outcome measures

Outcome measures
Measure	Oxytocin Nasal Spray n=139 Participants Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray n=138 Participants Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
Change in Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Score	-0.16 score on a scale Standard Error 0.07	-0.29 score on a scale Standard Error 0.07

OTHER_PRE_SPECIFIED outcome

Timeframe: Double-blind phase: baseline, week 24; Open Label: week 48

Population: Full Analysis Set

Functional skills will be assessed using the VABS-II Socialization Domain Score. Uses standard score with a mean of 100 and SD of 15 with a range of 20-160. Higher score is better. Higher value in change indicates more improvement.

Outcome measures

Outcome measures
Measure	Oxytocin Nasal Spray n=139 Participants Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray n=138 Participants Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
Change in Vineland II Adaptive Behavior Scales (VABS-II) Socialization Domain Score Double-blind baseline to week 24	4.45 score on a scale Standard Error 1.27	4.87 score on a scale Standard Error 1.25
Change in Vineland II Adaptive Behavior Scales (VABS-II) Socialization Domain Score Open Label week 24 to week 48	1.59 score on a scale Standard Error 1.11	0.54 score on a scale Standard Error 1.10

OTHER_PRE_SPECIFIED outcome

Timeframe: Double-blind phase: baseline, week 24; Open Label: week 48

Population: Full Analysis Set

Caregiver questionnaire that assesses the impact of caring for the proband on caregiver and family. CSQ subscale scores are ranged from 1 to 5. Higher score indicates more caregiver strain. Lower value in change indicates more improvement. The analysis directions for the instrument that are used in these analyses are the mean of all the responses in the scale or subscale.

Outcome measures

Outcome measures
Measure	Oxytocin Nasal Spray n=139 Participants Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray n=138 Participants Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
Change in Caregiver Strain Questionnaire (CSQ) Objective Subscale Score Double-blind baseline to week 24	-0.16 score on a scale Standard Error 0.06	-0.22 score on a scale Standard Error 0.06
Change in Caregiver Strain Questionnaire (CSQ) Objective Subscale Score Open Label week 24 to week 48	0.13 score on a scale Standard Error 0.06	0.44 score on a scale Standard Error 0.08

OTHER_PRE_SPECIFIED outcome

Timeframe: Double-blind phase: baseline, week 24; Open Label: week 48

Population: Full Analysis Set

Outcome measures

Outcome measures
Measure	Oxytocin Nasal Spray n=139 Participants Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray n=138 Participants Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
Change in Caregiver Strain Questionnaire (CSQ) Subjective Externalizing Subscale Score Double-blind baseline to week 24	-0.08 score on a scale Standard Error 0.04	-0.04 score on a scale Standard Error 0.04
Change in Caregiver Strain Questionnaire (CSQ) Subjective Externalizing Subscale Score Open Label week 24 to week 48	0.01 score on a scale Standard Error 0.07	0 score on a scale Standard Error 0.08

OTHER_PRE_SPECIFIED outcome

Timeframe: Double-blind phase: baseline, week 24

Population: Full Analysis Set

Functional skills including communication will be assessed using the VABS-II Adaptive Behavior Composite Score. Uses standard score with a mean of 100 and SD of 15 with a range of 20-160. Higher score is better. Higher value in change indicates more improvement.

Outcome measures

Outcome measures
Measure	Oxytocin Nasal Spray n=139 Participants Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray n=138 Participants Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
Change in Vineland II Adaptive Behavior Scales (VABS-II) Composite Score	2.61 score on a scale Standard Deviation 1.26	1.50 score on a scale Standard Deviation 1.27

OTHER_PRE_SPECIFIED outcome

Timeframe: Double blind phase: change from Baseline to week 12, and week 24. Open label phase change from week 24 to week 48

Population: full analysis set

The Clinical Global Impressions - Improvement score and Severity score, which is routinely used in pharmacologic clinical trials, will capture the study physician's global impression of response. scores of 1 and 2 are considered as a percentage of total subjects in arm

Outcome measures

Outcome measures
Measure	Oxytocin Nasal Spray n=138 Participants Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray n=139 Participants Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
Change in Clinical Global Impressions -Improvement Score (CGI-I)	64 percentage of participants in arm	53 percentage of participants in arm

OTHER_PRE_SPECIFIED outcome

Timeframe: Double blind phase: change from Baseline and week 24. Note: only those who demonstrated understanding of these concepts were included in sample.

Population: only subjects who could define feelings from fluently verbal subgroup

This computerized task consists of a series of pictures of eyes in which the participant needs to determine which emotion the eyes are expressing from 4 emotions listed along with the picture. The outcome is the % of pictures with correct emotion identified. The range is 0 to 100%. The larger percent identified correctly indicates better ability to perceive emotions. An increase or positive change indicates better ability to identify emotions since baseline.

Outcome measures

Outcome measures
Measure	Oxytocin Nasal Spray n=69 Participants Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray n=64 Participants Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
Reading Mind in the Eyes Test is an Objective Measures of the Extent to Which Verbal Participants With Rudimentary Knowledge of Emotion Names Are Able to Correctly Identify the Emotion Shown in a Black and White Picture of the Eyes and Nose of an Actor. DB w0	51.1 percentage of correct responses Standard Deviation 18.76	48.2 percentage of correct responses Standard Deviation 18.61
Reading Mind in the Eyes Test is an Objective Measures of the Extent to Which Verbal Participants With Rudimentary Knowledge of Emotion Names Are Able to Correctly Identify the Emotion Shown in a Black and White Picture of the Eyes and Nose of an Actor. DB w24	54.9 percentage of correct responses Standard Deviation 14.02	49.92 percentage of correct responses Standard Deviation 13.84

Adverse Events

Oxytocin Nasal Spray: Double-blind Phase

Serious events: 2 serious events

Other events: 120 other events

Deaths: 0 deaths

Placebo Nasal Spray: Double-blind Phase

Serious events: 1 serious events

Other events: 120 other events

Deaths: 0 deaths

Oxytocin Nasal Spray: Open Label Phase

Serious events: 4 serious events

Other events: 91 other events

Deaths: 1 deaths

Placebo Nasal Spray: Open Label Phase

Serious events: 0 serious events

Other events: 92 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Oxytocin Nasal Spray: Double-blind Phase n=146 participants at risk Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray: Double-blind Phase n=144 participants at risk Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.	Oxytocin Nasal Spray: Open Label Phase n=127 participants at risk Oxytocin Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.	Placebo Nasal Spray: Open Label Phase n=122 participants at risk Placebo Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
Nervous system disorders Seizures	0.00% 0/146 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.00% 0/144 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.79% 1/127 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.00% 0/122 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).
Gastrointestinal disorders Constipation	0.00% 0/146 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.00% 0/144 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.79% 1/127 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.00% 0/122 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).
Psychiatric disorders Dysphoria	0.00% 0/146 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.69% 1/144 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.00% 0/127 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.00% 0/122 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).
Psychiatric disorders Irritability	0.00% 0/146 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.69% 1/144 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.00% 0/127 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.00% 0/122 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).
Nervous system disorders Sedation	0.68% 1/146 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.00% 0/144 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.00% 0/127 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.00% 0/122 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).
General disorders Appendicitis	0.68% 1/146 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.00% 0/144 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.00% 0/127 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.00% 0/122 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).
Psychiatric disorders Aggression	0.00% 0/146 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.00% 0/144 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.79% 1/127 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.00% 0/122 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).
Psychiatric disorders Anxiety	0.00% 0/146 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.00% 0/144 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.79% 1/127 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).	0.00% 0/122 • Through post-treatment follow-up, approximately 55 weeks. Adverse events collected on Safety Population (subjects who started each phase).

Other adverse events

Additional Information

Linmarie Sikich, M.D.

Duke University

Phone: 919-681-0026

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place