Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors (SOARS-B)

• ClinicalTrials.gov Identifier: NCT01944046
• Recruitment Status: Completed
• First Posted: September 17, 2013
• Results First Posted: January 5, 2021
• Last Update Posted: January 5, 2021
• Sponsor: Linmarie Sikich
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Linmarie Sikich, Duke University

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Autism Spectrum Disorders
• Interventions: Drug: Double blind phase Placebo Nasal Spray; Drug: double Blind Oxytocin Nasal Spray; Drug: Open Label intranasal oxytocin
• Enrollment: 290

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Oxytocin Nasal Spray	Placebo Nasal Spray
Arm/Group Description	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 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.
Period Title: Randomized to DB
Started	146	144
Completed	125	125
Not Completed	21	19
Reason Not Completed
Adverse Event	5	2
Clinical Worsening	3	2
Lost to Follow-up	3	3
Withdrawal by Subject	2	4
Physician Decision	1	2
Did not have baseline ABC-SW	2	0
Did not have a postbaseline ABC SW	5	6
Period Title: Open Label Eligible and Consented
Started [1]	124	124
Completed	110	116
Not Completed	14	8
Reason Not Completed
Lost to Follow-up	3	5
Adverse Event	6	1
Clinical Worsening	4	2
Withdrawal by Subject	1	0
[1] 1 from each treatment group declined to consent for openlabel

Baseline Characteristics

Arm/Group Title		Oxytocin Nasal Spray	Placebo Nasal Spray	Total
Arm/Group Description		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 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 of all reporting groups
Overall Number of Baseline Participants		139	138	277
Baseline Analysis Population Description		Double-Blind Full Analysis Set (FAS). The DB FAS was defined as having both baseline and at least one post-baseline ABC-SW assessment. The DB-FAS excludes 7 participants randomized to oxytocin (2 with no baseline ABC-SW and 5 with no post-baseline ABC-SW) and 6 participants assigned to placebo who had no post-baseline ABC-SW.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	139 participants	138 participants	277 participants
		10.4 (4.06)	10.4 (3.99)	10.4 (4.04)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	139 participants	138 participants	277 participants
	Female	17 12.2%	18 13.0%	35 12.6%
	Male	122 87.8%	120 87.0%	242 87.4%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	139 participants	138 participants	277 participants
	Hispanic or Latino	13 9.4%	15 10.9%	28 10.1%
	Not Hispanic or Latino	126 90.6%	123 89.1%	249 89.9%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	139 participants	138 participants	277 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	11 7.9%	12 8.7%	23 8.3%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	9 6.5%	14 10.1%	23 8.3%
	White	104 74.8%	100 72.5%	204 73.6%
	More than one race	14 10.1%	9 6.5%	23 8.3%
	Unknown or Not Reported	1 0.7%	3 2.2%	4 1.4%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	139 participants	138 participants	277 participants
		139 100.0%	138 100.0%	277 100.0%
Aberrant Behavior Checklist Social Withdrawal Subscale Score (ABC-SW) abc-SW (mean [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	139 participants	138 participants	277 participants
		11.0 (6.9)	11.6 (7.8)	11.3 (7.4)
		[1] Measure Description: the Aberrant Behavior Scale Social withdrawal score assesses reciprocal social behaviors. It is composed of 13 questions from the Aberrant Behavior Scale Lethargy subscale that consists of 16 questions. The ABC-SW does not include the 3 questions (i.e. 3,32,53) of the Lethargy subscale that refer to sedentary behaviors. Score for each item ranges from 0 (not at all a problem) to 3 (a serious problem). Items are summed to give a minimal score of 0 and a maximal score of 39. Lower Scores are better

Outcome Measures

1. Primary Outcome

Title	Change in Aberrant Behavior Checklist-Social Withdrawal Subscale ABC-SW, a Measure of Reciprocal Social Behavior
Description	The primary outcome is Change in Aberrant Behavior Checklist-Social Withdrawal subscale- a measure ofreciprocal social behaviors. ABC-SW is a modification of the ABC-Lethargy subscale. The ABC-SW 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 higher level of social withdrawal.
Time Frame	Double-blind phase: baseline, weeks 4, 8, 12, 16, 20, 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Oxytocin Nasal Spray	Placebo Nasal Spray
Arm/Group Description:	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 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.
Overall Number of Participants Analyzed	139	138
Mean (Standard Error); Unit of Measure: score on a scale
Double-blind baseline to w4	8.81 (0.39)	8.68 (0.39)
Double-blind baseline to w8	8.97 (0.45)	8.68 (0.45)
Double-blind baseline-w12	7.48 (0.43)	8.13 (0.43)
DB w0- w16	7.99 (0.46)	8.04 (0.46)
DB w0- w20	7.81 (0.05)	7.75 (0.45)
DB w0-w24	7.75 (0.46)	8.05 (0.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oxytocin Nasal Spray, Placebo Nasal Spray
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.503
	Comments	not adjusted primary outcome
	Method	Mixed Models Analysis
	Comments	adjusted for baseline, age category, functionality category

2. Primary Outcome

Title	ABC-SW (Aberrant Behavior Checklist-Social Withdrawal) Subscale - Reciprocal Social Behavior
Description	The ABC-SW 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.
Time Frame	Least mean squares for Open Label: weeks 24 -48

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oxytocin Nasal Spray	Placebo Nasal Spray
Arm/Group Description:	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 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.
Overall Number of Participants Analyzed	125	122
Least Squares Mean (95% Confidence Interval); Unit of Measure: score on a scale
Open Label week 24	7.83; (7.11 to 8.55)	7.81; (7.09 to 8.52)
Open Label week 48	6.99; (6.10 to 7.89)	6.78; (5.89 to 7.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oxytocin Nasal Spray, Placebo Nasal Spray
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.61
	Comments	not adjusted primary outcome, p threshold 0.05
	Method	Mixed Models Analysis
	Comments	adjustment for value at week 24,

3. Primary Outcome

Title	Change in Sociability Factor (SF)
Description	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. NOTE THIS MEASURE WAS ELIMINATED FROM FINAL SAP'S
Time Frame	Double-blind phase: change in least means squares between week 0 & 24.

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Oxytocin Nasal Spray	Placebo Nasal Spray
Arm/Group Description:	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 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.
Overall Number of Participants Analyzed	139	138
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
DB w0	35.8 (1.24)	36.1 (1.28)
DB w0-w4	-5.57 (0.69)	-5.81 (0.69)
DB w0-w8	-5.99 (0.66)	-6.30 (0.66)
DB w0-w12	-6.40 (0.66)	-6.79 (0.66)
DB w0-w16	-6.82 (0.70)	-7.28 (0.71)
DB w0-w20	-7.24 (0.88)	-7.77 (0.88)
DB w0-w24	-7.66 (0.78)	-8.27 (0.88)

4. Secondary Outcome

Title	Change in Social Reciprocity Scale-2 (SRS-2) Social Motivation Subscale Score
Description	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.
Time Frame	Double-blind phase: baseline, weeks 12, 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Oxytocin Nasal Spray	Placebo Nasal Spray
Arm/Group Description:	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 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.
Overall Number of Participants Analyzed	139	138
Mean (Standard Deviation); Unit of Measure: T-score
Double-blind baseline to week 12	-4.58 (0.68)	-5.72 (0.69)
Double-blind baseline to week 24	-4.49 (0.70)	-5.42 (0.70)

5. Secondary Outcome

Title	Social Reciprocity Scale-2 (SRS-2) Social Motivation Subscale Score
Description	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.
Time Frame	Open Label: weeks 24, 48

Outcome Measure Data

Analysis Population Description

Open Label phase participants

Arm/Group Title	Oxytocin Nasal Spray	Placebo Nasal Spray
Arm/Group Description:	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 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.
Overall Number of Participants Analyzed	127	122
Mean (Standard Error); Unit of Measure: T-score
Open Label week 24	88.5 (1.37)	86.6 (1.37)
Open Label week 48	87.9 (1.83)	83.0 (1.81)

6. Secondary Outcome

Title	Change in Stanford Binet-5th Edition (SB-5) IQ Score
Description	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.
Time Frame	Double-blind phase: baseline to week 24

Outcome Measure Data

Analysis Population Description

Participants with scores collected at baseline and week 24.

Arm/Group Title	Oxytocin Nasal Spray	Placebo Nasal Spray
Arm/Group Description:	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 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.
Overall Number of Participants Analyzed	94	98
Mean (Standard Deviation); Unit of Measure: score on a scale
	0.40 (11.64)	1.0 (10.84)

7. Secondary Outcome

Title	Change in Vineland II Adaptive Behavior Scales (VABS-II) Composite Score
Description	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.
Time Frame	Double-blind phase: baseline, week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Oxytocin Nasal Spray	Placebo Nasal Spray
Arm/Group Description:	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 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.
Overall Number of Participants Analyzed	139	138
Mean (Standard Deviation); Unit of Measure: score on a scale
	2.61 (1.26)	1.50 (1.27)

8. Secondary Outcome

Title	Change in Vineland II Adaptive Behavior Scales (VABS-II) Socialization Domain Score
Description	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.
Time Frame	Double-blind phase: baseline, week 24; Open Label: week 48

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title		Oxytocin Nasal Spray	Placebo Nasal Spray
Arm/Group Description:		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 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.
Overall Number of Participants Analyzed		139	138
Mean (Standard Error); Unit of Measure: score on a scale
Double-blind baseline to week 24	Number Analyzed	139 participants	138 participants
		4.45 (1.27)	4.87 (1.25)
Open Label week 24 to week 48	Number Analyzed	127 participants	122 participants
		1.59 (1.11)	0.54 (1.10)

9. Secondary Outcome

Title	Change in Vineland II Adaptive Behavior Scales (VABS-II) Daily Living Domain Score
Description	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.
Time Frame	Double-blind phase: baseline, week 24; Open Label: week 48

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title		Oxytocin Nasal Spray	Placebo Nasal Spray
Arm/Group Description:		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 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.
Overall Number of Participants Analyzed		139	138
Mean (Standard Error); Unit of Measure: score on a scale
Double-blind baseline to week 24	Number Analyzed	139 participants	138 participants
		2.50 (1.10)	1.24 (1.14)
Open Label week 24 to week 48	Number Analyzed	127 participants	122 participants
		1.76 (1.19)	0.62 (0.11)

10. Secondary Outcome

Title	Change in Vineland II Adaptive Behavior Scales (VABS-II) Communication Domain Score
Description	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.
Time Frame	Double-blind phase: baseline, week 24; Open Label: week 48

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title		Oxytocin Nasal Spray	Placebo Nasal Spray
Arm/Group Description:		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 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.
Overall Number of Participants Analyzed		139	138
Mean (Standard Error); Unit of Measure: score on a scale
Double-blind baseline to week 24	Number Analyzed	139 participants	138 participants
		3.88 (0.89)	2.27 (0.90)
Open Label week 24 to week 48	Number Analyzed	127 participants	122 participants
		4.06 (1.35)	5.98 (1.41)

11. Secondary Outcome

Title	Change in Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Score
Description	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.
Time Frame	Double-blind phase: baseline, week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Oxytocin Nasal Spray	Placebo Nasal Spray
Arm/Group Description:	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 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.
Overall Number of Participants Analyzed	139	138
Mean (Standard Error); Unit of Measure: score on a scale
	-0.16 (0.07)	-0.29 (0.07)

12. Secondary Outcome

Title	Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Mean Score
Description	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.
Time Frame	Open Label: weeks 24, 48

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oxytocin Nasal Spray	Placebo Nasal Spray
Arm/Group Description:	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 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.
Overall Number of Participants Analyzed	110	119
Mean (Standard Deviation); Unit of Measure: mean score on a scale
Open Label week 24	2.96 (0.99)	2.85 (1.00)
Open Label week 48	2.97 (0.99)	2.85 (0.97)

13. Secondary Outcome

Title	Change in Caregiver Strain Questionnaire (CSQ) Subjective Externalizing Subscale Score
Description	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.
Time Frame	Double-blind phase: baseline, week 24; Open Label: week 48

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title		Oxytocin Nasal Spray	Placebo Nasal Spray
Arm/Group Description:		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 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.
Overall Number of Participants Analyzed		139	138
Mean (Standard Error); Unit of Measure: score on a scale
Double-blind baseline to week 24	Number Analyzed	139 participants	138 participants
		-0.08 (0.04)	-0.04 (0.04)
Open Label week 24 to week 48	Number Analyzed	110 participants	119 participants
		0.01 (0.07)	0 (0.08)

14. Secondary Outcome

Title	Change in Caregiver Strain Questionnaire (CSQ) Objective Subscale Score
Description	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.
Time Frame	Double-blind phase: baseline, week 24; Open Label: week 48

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title		Oxytocin Nasal Spray	Placebo Nasal Spray
Arm/Group Description:		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 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.
Overall Number of Participants Analyzed		139	138
Mean (Standard Error); Unit of Measure: score on a scale
Double-blind baseline to week 24	Number Analyzed	139 participants	138 participants
		-0.16 (0.06)	-0.22 (0.06)
Open Label week 24 to week 48	Number Analyzed	110 participants	119 participants
		0.13 (0.06)	0.44 (0.08)

15. Other Pre-specified Outcome

Title	Changes in Biologic Outcome Measures
Description	Investigators will obtain blood, urine and vital signs from participants at regular intervals in order to assess the safety of oxytocin. In addition,the blood samples will also be used to assess oxytocin levels, OTXR differential methylation status and to assess mRNA expression. Investigators will obtain saliva at the same time points to perform salivary oxytocin levels.
Time Frame	Double blind phase: change from Baseline to week 8, and week 24. Open label phase change from week 24 to week 36.

Outcome Measure Data Not Reported

16. Other Pre-specified Outcome

Title	Change in Clinical Global Impressions -Improvement Score (CGI-I)
Description	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
Time Frame	Double blind phase: change from Baseline to week 12, and week 24. Open label phase change from week 24 to week 48

Outcome Measure Data

Analysis Population Description

full analysis set

Arm/Group Title	Placebo Nasal Spray	Oxytocin Nasal Spray
Arm/Group Description:	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 oxytocin will NOT be 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 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.
Overall Number of Participants Analyzed	138	139
Measure Type: Number; Unit of Measure: percentage of participants in arm
	64	53

17. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

only subjects who could define feelings from fluently verbal subgroup

Arm/Group Title	Oxytocin Nasal Spray	Placebo Nasal Spray
Arm/Group Description:	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 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.
Overall Number of Participants Analyzed	69	64
Mean (Standard Deviation); Unit of Measure: percentage of correct responses
DB w0	51.1 (18.76)	48.2 (18.61)
DB w24	54.9 (14.02)	49.92 (13.84)

Adverse Events

Time Frame	Through post-treatment follow-up, approximately 55 weeks.
Adverse Event Reporting Description	Adverse events collected on Safety Population (subjects who started each phase).
Arm/Group Title	Oxytocin Nasal Spray: Double-blind Phase	Placebo Nasal Spray: Double-blind Phase	Oxytocin Nasal Spray: Open Label Phase	Placebo Nasal Spray: Open Label Phase
Arm/Group Description	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 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 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 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.
All-Cause Mortality
	Oxytocin Nasal Spray: Double-blind Phase	Placebo Nasal Spray: Double-blind Phase	Oxytocin Nasal Spray: Open Label Phase	Placebo Nasal Spray: Open Label Phase
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/146 (0.00%)	0/144 (0.00%)	1/127 (0.79%)	0/122 (0.00%)
Serious Adverse Events
	Oxytocin Nasal Spray: Double-blind Phase	Placebo Nasal Spray: Double-blind Phase	Oxytocin Nasal Spray: Open Label Phase	Placebo Nasal Spray: Open Label Phase
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	2/146 (1.37%)	1/144 (0.69%)	4/127 (3.15%)	0/122 (0.00%)
Gastrointestinal disorders
Constipation * 1	0/146 (0.00%)	0/144 (0.00%)	1/127 (0.79%)	0/122 (0.00%)
General disorders
Appendicitis * 1	1/146 (0.68%)	0/144 (0.00%)	0/127 (0.00%)	0/122 (0.00%)
Nervous system disorders
Seizures * 1	0/146 (0.00%)	0/144 (0.00%)	1/127 (0.79%)	0/122 (0.00%)
Sedation * 1	1/146 (0.68%)	0/144 (0.00%)	0/127 (0.00%)	0/122 (0.00%)
Psychiatric disorders
Dysphoria * 1	0/146 (0.00%)	1/144 (0.69%)	0/127 (0.00%)	0/122 (0.00%)
Irritability * 1	0/146 (0.00%)	1/144 (0.69%)	0/127 (0.00%)	0/122 (0.00%)
Aggression * 1	0/146 (0.00%)	0/144 (0.00%)	1/127 (0.79%)	0/122 (0.00%)
Anxiety * 1	0/146 (0.00%)	0/144 (0.00%)	1/127 (0.79%)	0/122 (0.00%)
1 Term from vocabulary, MedDRA; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Oxytocin Nasal Spray: Double-blind Phase	Placebo Nasal Spray: Double-blind Phase	Oxytocin Nasal Spray: Open Label Phase	Placebo Nasal Spray: Open Label Phase
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	120/146 (82.19%)	120/144 (83.33%)	91/127 (71.65%)	92/122 (75.41%)
Blood and lymphatic system disorders
Increased Tendency To Bruise * 1	0/146 (0.00%)	3/144 (2.08%)	0/127 (0.00%)	0/122 (0.00%)
Lymphadenopathy * 1	3/146 (2.05%)	0/144 (0.00%)	0/127 (0.00%)	0/122 (0.00%)
Cardiac disorders
Dizziness * 1	1/146 (0.68%)	2/144 (1.39%)	1/127 (0.79%)	2/122 (1.64%)
Cardiac Rhythm Abnormality * 1	0/146 (0.00%)	1/144 (0.69%)	0/127 (0.00%)	0/122 (0.00%)
Palpitations * 1	1/146 (0.68%)	0/144 (0.00%)	2/127 (1.57%)	0/122 (0.00%)
Ear and labyrinth disorders
Ear Ache * 1	7/146 (4.79%)	9/144 (6.25%)	2/127 (1.57%)	2/122 (1.64%)
Ear Congestion * 1	4/146 (2.74%)	4/144 (2.78%)	0/127 (0.00%)	3/122 (2.46%)
Tinnitus * 1	1/146 (0.68%)	1/144 (0.69%)	2/127 (1.57%)	0/122 (0.00%)
Hypoacusis * 1	0/146 (0.00%)	0/144 (0.00%)	0/127 (0.00%)	1/122 (0.82%)
Endocrine disorders
Precocious Puberty * 1	1/146 (0.68%)	0/144 (0.00%)	0/127 (0.00%)	0/122 (0.00%)
Eye disorders
Blepharospasm * 1	2/146 (1.37%)	3/144 (2.08%)	0/127 (0.00%)	1/122 (0.82%)
Dry Eye * 1	3/146 (2.05%)	1/144 (0.69%)	2/127 (1.57%)	1/122 (0.82%)
Eye Discomfort * 1	1/146 (0.68%)	1/144 (0.69%)	1/127 (0.79%)	0/122 (0.00%)
Visual Acuity Reduced * 1	1/146 (0.68%)	1/144 (0.69%)	2/127 (1.57%)	1/122 (0.82%)
Gastrointestinal disorders
Diarrhea * 1	13/146 (8.90%)	15/144 (10.42%)	6/127 (4.72%)	3/122 (2.46%)
Abdominal Pain Or Discomfort * 1	6/146 (4.11%)	14/144 (9.72%)	6/127 (4.72%)	7/122 (5.74%)
Vomiting Or Nausea * 1	6/146 (4.11%)	12/144 (8.33%)	7/127 (5.51%)	8/122 (6.56%)
Constipation * 1	7/146 (4.79%)	9/144 (6.25%)	4/127 (3.15%)	6/122 (4.92%)
Stomatitis * 1	3/146 (2.05%)	7/144 (4.86%)	0/127 (0.00%)	0/122 (0.00%)
Tooth Disorder * 1	3/146 (2.05%)	5/144 (3.47%)	3/127 (2.36%)	3/122 (2.46%)
Encopresis * 1	3/146 (2.05%)	4/144 (2.78%)	2/127 (1.57%)	1/122 (0.82%)
Dry Mouth * 1	1/146 (0.68%)	2/144 (1.39%)	1/127 (0.79%)	0/122 (0.00%)
Salivary Hypersecretion * 1	0/146 (0.00%)	1/144 (0.69%)	1/127 (0.79%)	0/122 (0.00%)
Anorectal Discomfort * 1	0/146 (0.00%)	0/144 (0.00%)	0/127 (0.00%)	1/122 (0.82%)
Flatulence * 1	0/146 (0.00%)	0/144 (0.00%)	0/127 (0.00%)	1/122 (0.82%)
Dysphagia * 1	0/146 (0.00%)	0/144 (0.00%)	0/127 (0.00%)	1/122 (0.82%)
General disorders
Energy Increased * 1	14/146 (9.59%)	5/144 (3.47%)	4/127 (3.15%)	4/122 (3.28%)
Fatigue * 1	8/146 (5.48%)	8/144 (5.56%)	1/127 (0.79%)	6/122 (4.92%)
Pyrexia * 1	9/146 (6.16%)	7/144 (4.86%)	2/127 (1.57%)	6/122 (4.92%)
Swelling * 1	3/146 (2.05%)	2/144 (1.39%)	0/127 (0.00%)	1/122 (0.82%)
Asthenia * 1	2/146 (1.37%)	2/144 (1.39%)	0/127 (0.00%)	0/122 (0.00%)
Chest Pain Or Discomfort * 1	2/146 (1.37%)	1/144 (0.69%)	3/127 (2.36%)	0/122 (0.00%)
Night Sweats * 1	0/146 (0.00%)	0/144 (0.00%)	1/127 (0.79%)	0/122 (0.00%)
Enamel Discoloration * 1	0/146 (0.00%)	1/144 (0.69%)	0/127 (0.00%)	0/122 (0.00%)
Immune system disorders
Allergic Hypersensitivity * 1	14/146 (9.59%)	15/144 (10.42%)	10/127 (7.87%)	2/122 (1.64%)
Infections and infestations
Infection * 1	53/146 (36.30%)	67/144 (46.53%)	33/127 (25.98%)	33/122 (27.05%)
Injury, poisoning and procedural complications
Injury * 1	8/146 (5.48%)	6/144 (4.17%)	13/127 (10.24%)	7/122 (5.74%)
Intentional Self-Injury * 1	5/146 (3.42%)	6/144 (4.17%)	1/127 (0.79%)	1/122 (0.82%)
Fracture * 1	0/146 (0.00%)	1/144 (0.69%)	0/127 (0.00%)	0/122 (0.00%)
Sunburn * 1	1/146 (0.68%)	0/144 (0.00%)	0/127 (0.00%)	0/122 (0.00%)
Investigations
Pituitary Analyses Anterior * 1	0/146 (0.00%)	1/144 (0.69%)	0/127 (0.00%)	0/122 (0.00%)
Abnormal Urinalysis * 1	0/146 (0.00%)	0/144 (0.00%)	1/127 (0.79%)	0/122 (0.00%)
Thrombocytopenia * 1	0/146 (0.00%)	0/144 (0.00%)	1/127 (0.79%)	0/122 (0.00%)
Metabolism and nutrition disorders
Increased Appetite * 1	23/146 (15.75%)	14/144 (9.72%)	9/127 (7.09%)	10/122 (8.20%)
Decreased Appetite * 1	9/146 (6.16%)	13/144 (9.03%)	7/127 (5.51%)	5/122 (4.10%)
Abnormal Weight Gain * 1	11/146 (7.53%)	9/144 (6.25%)	8/127 (6.30%)	8/122 (6.56%)
Abnormal Weight Loss * 1	10/146 (6.85%)	5/144 (3.47%)	2/127 (1.57%)	4/122 (3.28%)
Thirst * 1	8/146 (5.48%)	4/144 (2.78%)	10/127 (7.87%)	3/122 (2.46%)
Musculoskeletal and connective tissue disorders
Myalgia * 1	5/146 (3.42%)	1/144 (0.69%)	1/127 (0.79%)	1/122 (0.82%)
Arthralgia * 1	2/146 (1.37%)	1/144 (0.69%)	2/127 (1.57%)	0/122 (0.00%)
Growing Pains * 1	1/146 (0.68%)	0/144 (0.00%)	0/127 (0.00%)	0/122 (0.00%)
Specific Muscle Pain * 1	0/146 (0.00%)	0/144 (0.00%)	1/127 (0.79%)	0/122 (0.00%)
Skeletal Pain * 1	0/146 (0.00%)	1/144 (0.69%)	0/127 (0.00%)	0/122 (0.00%)
Nervous system disorders
Agitation * 1	19/146 (13.01%)	16/144 (11.11%)	11/127 (8.66%)	11/122 (9.02%)
Headache * 1	11/146 (7.53%)	22/144 (15.28%)	6/127 (4.72%)	8/122 (6.56%)
Initial Insomnia * 1	14/146 (9.59%)	19/144 (13.19%)	5/127 (3.94%)	12/122 (9.84%)
Sedation * 1	19/146 (13.01%)	12/144 (8.33%)	5/127 (3.94%)	8/122 (6.56%)
Stereotypy * 1	13/146 (8.90%)	8/144 (5.56%)	3/127 (2.36%)	5/122 (4.10%)
Terminal Insomnia * 1	10/146 (6.85%)	11/144 (7.64%)	1/127 (0.79%)	4/122 (3.28%)
Middle Insomnia * 1	6/146 (4.11%)	12/144 (8.33%)	1/127 (0.79%)	4/122 (3.28%)
Restlessness * 1	11/146 (7.53%)	3/144 (2.08%)	4/127 (3.15%)	3/122 (2.46%)
Hypersomnia * 1	3/146 (2.05%)	3/144 (2.08%)	1/127 (0.79%)	1/122 (0.82%)
Confusional State * 1	1/146 (0.68%)	2/144 (1.39%)	2/127 (1.57%)	0/122 (0.00%)
Speech Disorder * 1	2/146 (1.37%)	1/144 (0.69%)	1/127 (0.79%)	1/122 (0.82%)
Dyskinesia * 1	1/146 (0.68%)	1/144 (0.69%)	0/127 (0.00%)	0/122 (0.00%)
Dystonia * 1	1/146 (0.68%)	1/144 (0.69%)	0/127 (0.00%)	0/122 (0.00%)
Paresthesia * 1	2/146 (1.37%)	0/144 (0.00%)	0/127 (0.00%)	0/122 (0.00%)
Ganglion Cyst * 1	1/146 (0.68%)	0/144 (0.00%)	0/127 (0.00%)	0/122 (0.00%)
Photophobia * 1	1/146 (0.68%)	0/144 (0.00%)	0/127 (0.00%)	1/122 (0.82%)
Tremor * 1	1/146 (0.68%)	0/144 (0.00%)	1/127 (0.79%)	0/122 (0.00%)
Seizure Or Convulsion * 1	0/146 (0.00%)	0/144 (0.00%)	2/127 (1.57%)	0/122 (0.00%)
Coordination Abnormal * 1	0/146 (0.00%)	0/144 (0.00%)	0/127 (0.00%)	1/122 (0.82%)
Sleep Walking * 1	0/146 (0.00%)	0/144 (0.00%)	1/127 (0.79%)	0/122 (0.00%)
Psychiatric disorders
Negativism * 1	24/146 (16.44%)	23/144 (15.97%)	10/127 (7.87%)	10/122 (8.20%)
Aggression Or Hostility * 1	23/146 (15.75%)	20/144 (13.89%)	10/127 (7.87%)	6/122 (4.92%)
Anger Or Irritability * 1	20/146 (13.70%)	20/144 (13.89%)	14/127 (11.02%)	6/122 (4.92%)
Frustration * 1	15/146 (10.27%)	18/144 (12.50%)	7/127 (5.51%)	9/122 (7.38%)
Crying * 1	13/146 (8.90%)	17/144 (11.81%)	10/127 (7.87%)	10/122 (8.20%)
Inappropriate Affect * 1	13/146 (8.90%)	13/144 (9.03%)	5/127 (3.94%)	4/122 (3.28%)
Psychomotor Hyperactivity * 1	11/146 (7.53%)	10/144 (6.94%)	3/127 (2.36%)	7/122 (5.74%)
Impulse-Control Disorder * 1	9/146 (6.16%)	9/144 (6.25%)	8/127 (6.30%)	5/122 (4.10%)
Anxiety * 1	6/146 (4.11%)	8/144 (5.56%)	2/127 (1.57%)	5/122 (4.10%)
Disturbance In Attention * 1	9/146 (6.16%)	4/144 (2.78%)	3/127 (2.36%)	4/122 (3.28%)
Mood Swings * 1	3/146 (2.05%)	10/144 (6.94%)	4/127 (3.15%)	3/122 (2.46%)
Obsessive Rumination * 1	4/146 (2.74%)	6/144 (4.17%)	3/127 (2.36%)	3/122 (2.46%)
Apathy Or Boredom * 1	4/146 (2.74%)	5/144 (3.47%)	5/127 (3.94%)	4/122 (3.28%)
Depressed Mood * 1	3/146 (2.05%)	5/144 (3.47%)	3/127 (2.36%)	3/122 (2.46%)
Perseveration * 1	2/146 (1.37%)	6/144 (4.17%)	1/127 (0.79%)	3/122 (2.46%)
Tic * 1	3/146 (2.05%)	4/144 (2.78%)	5/127 (3.94%)	4/122 (3.28%)
Nightmares * 1	3/146 (2.05%)	3/144 (2.08%)	2/127 (1.57%)	2/122 (1.64%)
Insomnia * 1	1/146 (0.68%)	2/144 (1.39%)	0/127 (0.00%)	1/122 (0.82%)
Suicidal Ideation * 1	1/146 (0.68%)	2/144 (1.39%)	2/127 (1.57%)	1/122 (0.82%)
Delusion * 1	0/146 (0.00%)	1/144 (0.69%)	0/127 (0.00%)	0/122 (0.00%)
Hallucination * 1	0/146 (0.00%)	1/144 (0.69%)	0/127 (0.00%)	0/122 (0.00%)
Mania Or Hypomania * 1	1/146 (0.68%)	0/144 (0.00%)	0/127 (0.00%)	0/122 (0.00%)
Pressure Of Speech * 1	1/146 (0.68%)	0/144 (0.00%)	2/127 (1.57%)	1/122 (0.82%)
Renal and urinary disorders
Enuresis * 1	3/146 (2.05%)	16/144 (11.11%)	7/127 (5.51%)	8/122 (6.56%)
Pollakiuria * 1	5/146 (3.42%)	6/144 (4.17%)	0/127 (0.00%)	1/122 (0.82%)
Dysuria * 1	1/146 (0.68%)	0/144 (0.00%)	0/127 (0.00%)	0/122 (0.00%)
Hematuria * 1	0/146 (0.00%)	0/144 (0.00%)	0/127 (0.00%)	1/122 (0.82%)
Micturition Frequency Decreased * 1	0/146 (0.00%)	0/144 (0.00%)	0/127 (0.00%)	1/122 (0.82%)
Reproductive system and breast disorders
Libido Increased * 1	7/146 (4.79%)	6/144 (4.17%)	6/127 (4.72%)	5/122 (4.10%)
Breast Pain * 1	2/146 (1.37%)	0/144 (0.00%)	0/127 (0.00%)	1/122 (0.82%)
Menstrual Disorder * 1	0/146 (0.00%)	2/144 (1.39%)	0/127 (0.00%)	1/122 (0.82%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	26/146 (17.81%)	18/144 (12.50%)	9/127 (7.09%)	13/122 (10.66%)
Asthma * 1	2/146 (1.37%)	7/144 (4.86%)	0/127 (0.00%)	1/122 (0.82%)
Dyspnea * 1	1/146 (0.68%)	4/144 (2.78%)	0/127 (0.00%)	1/122 (0.82%)
Nasal Discomfort * 1	3/146 (2.05%)	2/144 (1.39%)	0/127 (0.00%)	0/122 (0.00%)
Nasal Congestion * 1	1/146 (0.68%)	0/144 (0.00%)	0/127 (0.00%)	2/122 (1.64%)
Rhinitis Nos * 1	1/146 (0.68%)	0/144 (0.00%)	1/127 (0.79%)	0/122 (0.00%)
Sore Throat * 1	1/146 (0.68%)	0/144 (0.00%)	2/127 (1.57%)	0/122 (0.00%)
Skin and subcutaneous tissue disorders
Rash * 1	16/146 (10.96%)	14/144 (9.72%)	15/127 (11.81%)	9/122 (7.38%)
Acne * 1	5/146 (3.42%)	12/144 (8.33%)	4/127 (3.15%)	6/122 (4.92%)
Eczema * 1	7/146 (4.79%)	4/144 (2.78%)	7/127 (5.51%)	7/122 (5.74%)
Wart * 1	0/146 (0.00%)	0/144 (0.00%)	1/127 (0.79%)	0/122 (0.00%)
Vascular disorders
Epistaxis * 1	11/146 (7.53%)	10/144 (6.94%)	6/127 (4.72%)	4/122 (3.28%)
Hypertension * 1	0/146 (0.00%)	0/144 (0.00%)	1/127 (0.79%)	0/122 (0.00%)
1 Term from vocabulary, MedDRA; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Linmarie Sikich, M.D.
• Organization: Duke University
• Phone: 919-681-0026
• EMail: linmarie.sikich@duke.edu

Publications:

Spanos M, Chandrasekhar T, Kim SJ, Hamer RM, King BH, McDougle CJ, Sanders KB, Gregory SG, Kolevzon A, Veenstra-VanderWeele J, Sikich L. Rationale, design, and methods of the Autism Centers of Excellence (ACE) network Study of Oxytocin in Autism to improve Reciprocal Social Behaviors (SOARS-B). Contemp Clin Trials. 2020 Nov;98:106103. doi: 10.1016/j.cct.2020.106103. Epub 2020 Aug 8.

• Responsible Party: Linmarie Sikich, Duke University
• ClinicalTrials.gov Identifier: NCT01944046
• Other Study ID Numbers: Pro00063950; 1U01HD073984 ( U.S. NIH Grant/Contract ); 13-0593 ( Other Identifier: UNC )
• First Submitted: June 13, 2013
• First Posted: September 17, 2013
• Results First Submitted: July 31, 2020
• Results First Posted: January 5, 2021
• Last Update Posted: January 5, 2021