Trial Outcomes & Findings for A Study of Oxytocin in Children and Adolescents With Autistic Disorder (NCT NCT01308749)

Last Updated: 2017-07-17

Results Overview

This study will help to determine tolerability of intranasal oxytocin treatment in children with autism by measuring the ability of at least 80% of the sample to tolerate twice daily intranasal administration of oxytocin.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

Week 0 to week 8

Results posted on

2017-07-17

Participant Flow

This study is a 2 sequence (arm) study with 2 periods - double-blind (0-8 weeks) and open label (8-16 weeks). The sequences are 1: oxytocin-oxytocin and 2: placebo-oxytocin. 1 participant from sequence 1 did not enter period 2 due to withdrawal due to adverse events.

Participant milestones

Participant milestones
Measure	Sequence 1: Oxytocin-oxytocin 8 weeks of double blind oxytocin followed by 8 weeks of open label oxytocin	jSequence 2: Placebo-oxytocin 8 weeks of of double blind placebo followed by 8 weeks of open-label oxytocin; this is the control group
Period 1: Double Blind Treatment STARTED	12	13
Period 1: Double Blind Treatment COMPLETED	11	13
Period 1: Double Blind Treatment NOT COMPLETED	1	0
Period 2: Open Label Treatment STARTED	11	13
Period 2: Open Label Treatment COMPLETED	11	11
Period 2: Open Label Treatment NOT COMPLETED	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Sequence 1: Oxytocin-oxytocin 8 weeks of double blind oxytocin followed by 8 weeks of open label oxytocin	jSequence 2: Placebo-oxytocin 8 weeks of of double blind placebo followed by 8 weeks of open-label oxytocin; this is the control group
Period 1: Double Blind Treatment Adverse Event	1	0
Period 2: Open Label Treatment Adverse Event	0	1
Period 2: Open Label Treatment Lost to Follow-up	0	1

Baseline Characteristics

A Study of Oxytocin in Children and Adolescents With Autistic Disorder

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Week 0 to week 8

Population: This is over period 1, the double blind phase (week 0 to week 8) only

Outcome measures

Outcome measures
Measure	Sequence 2: Placebo:Oxytocin n=13 Participants Intervention: Drug: placebo double blind for 8 weeks then oxytocin open label for 8 weeks	Sequence 1: Oxytocin:Oxytocin n=12 Participants Intervention: Drug: oxytocin = Syntocinon® Nasal Spray total of 16 weeks exposure Subjects ages 3-10 years old will be titrated up to a maximum dose of 24IU. Subjects ages 11-17 years old will be titrated up to a maximum dose of 32IU.
Number of Participants Who Could Tolerate Twice Daily Oxytocin	13 Participants	11 Participants

PRIMARY outcome

Timeframe: Week 0 to week 16

Population: all participants who recieved oxytocin at any time

Outcome measures

Outcome measures
Measure	Sequence 2: Placebo:Oxytocin n=13 Participants Intervention: Drug: placebo double blind for 8 weeks then oxytocin open label for 8 weeks	Sequence 1: Oxytocin:Oxytocin n=12 Participants Intervention: Drug: oxytocin = Syntocinon® Nasal Spray total of 16 weeks exposure Subjects ages 3-10 years old will be titrated up to a maximum dose of 24IU. Subjects ages 11-17 years old will be titrated up to a maximum dose of 32IU.
Number of Participants Who Could Tolerate Twice Daily Oxytocin	11 Participants	11 Participants

SECONDARY outcome

Timeframe: Week 0 to week 8

Population: participants with oxytocin plasma levels at baseline and week 8

Blood samples will be collected to obtain proof of concept data regarding changes in afternoon plasma oxytocin levels

Outcome measures

Outcome measures
Measure	Sequence 2: Placebo:Oxytocin n=11 Participants Intervention: Drug: placebo double blind for 8 weeks then oxytocin open label for 8 weeks	Sequence 1: Oxytocin:Oxytocin n=10 Participants Intervention: Drug: oxytocin = Syntocinon® Nasal Spray total of 16 weeks exposure Subjects ages 3-10 years old will be titrated up to a maximum dose of 24IU. Subjects ages 11-17 years old will be titrated up to a maximum dose of 32IU.
Change in Mean Plasma Oxytocin Level During Period 1 - Double Blind Phase	-0.69 picograms/mL (pg/mL) Standard Deviation 1.69	-0.15 picograms/mL (pg/mL) Standard Deviation 1.53

SECONDARY outcome

Timeframe: between weeks 0 and 8

Population: The subject who discontinued after 2 days did not have repeat assessments and is excluded from these analyses

changes during period 1

Outcome measures

Outcome measures
Measure	Sequence 2: Placebo:Oxytocin n=11 Participants Intervention: Drug: placebo double blind for 8 weeks then oxytocin open label for 8 weeks	Sequence 1: Oxytocin:Oxytocin n=13 Participants Intervention: Drug: oxytocin = Syntocinon® Nasal Spray total of 16 weeks exposure Subjects ages 3-10 years old will be titrated up to a maximum dose of 24IU. Subjects ages 11-17 years old will be titrated up to a maximum dose of 32IU.
Change in Mean Weight	1.4 pounds Standard Error 1.3	2.4 pounds Standard Error 0.7

SECONDARY outcome

Timeframe: 0-8 weeks, blinded treatment, period 1

Population: All participants with at least one post baseline assessment, 1 person from sequence 1 discontinued due to no post baseline measures

The 65-item SRS is a standardized measure of the core symptoms of autism. Each item is scored on a 4-point Likert scale. The raw score of each individual item is summed to create a total raw score. The total raw score is then translated into a total T-scores (which are the equivalent of standard scores). Total T-scores results are as follows: 59 and below: within normal limits, 60-65: Mild range of impairment 66-75: Moderate range of impairment 76 or higher: Severe range of impairment.

Outcome measures

Outcome measures
Measure	Sequence 2: Placebo:Oxytocin n=11 Participants Intervention: Drug: placebo double blind for 8 weeks then oxytocin open label for 8 weeks	Sequence 1: Oxytocin:Oxytocin n=13 Participants Intervention: Drug: oxytocin = Syntocinon® Nasal Spray total of 16 weeks exposure Subjects ages 3-10 years old will be titrated up to a maximum dose of 24IU. Subjects ages 11-17 years old will be titrated up to a maximum dose of 32IU.
Change in Mean Total Social Social Responsiveness Scale (SRS) T-score	-5.1 T-scores Standard Error 2.3	-3.9 T-scores Standard Error 3.3

SECONDARY outcome

Timeframe: Baseline to 16 Weeks

Population: 1 patient without post baseline measures is not included

The ADOS is a semi-structured assessment used to assess and diagnose individuals suspected of having autism of varying ages, developmental levels, and language skills (from no speech to verbally fluent). The ADOS includes four modules, each requiring just 35-40 minutes to administer. The individual being evaluated is given just one of 4 modules, depending on his or her expressive language level and chronological age. The rater will observe social and communication behaviors during various activities in the appropriate module. A rater then uses a 0-3 scale to rate each type of behavior. A select number of individual items will be summed for a total score representing communication and reciprocal social interaction. In scoring all 3's are collapsed to a 2. A higher score indicates more severe impairment. Ranges of scores are as follows: Module 1: 0-24, Module 2: 0-24, Module 3: 0-22, Module 4: 0-22.

Outcome measures

Outcome measures
Measure	Sequence 2: Placebo:Oxytocin n=11 Participants Intervention: Drug: placebo double blind for 8 weeks then oxytocin open label for 8 weeks	Sequence 1: Oxytocin:Oxytocin n=13 Participants Intervention: Drug: oxytocin = Syntocinon® Nasal Spray total of 16 weeks exposure Subjects ages 3-10 years old will be titrated up to a maximum dose of 24IU. Subjects ages 11-17 years old will be titrated up to a maximum dose of 32IU.
Change in Mean Autism Diagnostic Observation Schedule (ADOS) Total Score	-0.36 scores on a scale Standard Error 0.39	-0.31 scores on a scale Standard Error 0.29

SECONDARY outcome

Timeframe: Baseline to 16 Weeks

Population: population of participants with all data available for mixed models analysis no data carried forward

Efficacy measures included the Aberrant Behavior Checklist -Social Withdrawal subscale scor. The ABC which focuses on problem behaviors in five subdomains, including irritability, attention, repetitive behaviors, unusual speech, and lethargy. A modified version of the lethargy subscale was used. Typically the Lethargy subscale includes 16 items, however, for our purposes 3 items that were specifically related to lethargy (i.e.: listlessness) were removed so that the focus could primarily be on aberrant social behavior. Differences in only the Social Withdrawal domain were assessed.The is the sum of items, each rated among 0 = Not at all; 1 = Slight in degree; 2 = Moderately serious; and 3 = Severe in degree. The ABC- Social Withdrawal total score ranges from 0 to 39. Higher values represent greater severity of illness.

Outcome measures

Outcome measures
Measure	Sequence 2: Placebo:Oxytocin n=11 Participants Intervention: Drug: placebo double blind for 8 weeks then oxytocin open label for 8 weeks	Sequence 1: Oxytocin:Oxytocin n=11 Participants Intervention: Drug: oxytocin = Syntocinon® Nasal Spray total of 16 weeks exposure Subjects ages 3-10 years old will be titrated up to a maximum dose of 24IU. Subjects ages 11-17 years old will be titrated up to a maximum dose of 32IU.
Change in Mean Aberrant Behavior Checklist (ABC)-Social Withdrawal Subscale Score Over Both Periods	-3.7 scores on a scale Standard Error 1.0	-2.2 scores on a scale Standard Error 1.9

SECONDARY outcome

Timeframe: Baseline to 16 Weeks

Population: used only subjects with all data points no data carried forward

The PDDBI-SV examines both adaptive and maladaptive behaviors related to autism. It has normative scores for children between 2-11 years. For children 12 years and older, the norms (11 years, 11 months) will be used. Each item is scored on a scale from 0-3. For the first 9 items, the total of individual items is summed. For items 10-18, the scores are reversed and then summed (i.e.: 0=3, 1 =2, 2=2, 3 = 0). Then the total of 0-9 and then the reversed scored items 10-18 are summed for a final total score. Higher scores indicate more impairment. The range of total scores is 0-54. ASD/Social deficits unlikely: 0-6, More information needed/borderline: 7-10, autism spectrum disorder (ASD)/social deficits likely (mild):11-14, ASD/social deficits likely (moderate): 15-29, ASD/social deficits likely (severe): 30-37, ASD/social deficits likely (extreme): 38 or higher.

Outcome measures

Outcome measures
Measure	Sequence 2: Placebo:Oxytocin n=11 Participants Intervention: Drug: placebo double blind for 8 weeks then oxytocin open label for 8 weeks	Sequence 1: Oxytocin:Oxytocin n=11 Participants Intervention: Drug: oxytocin = Syntocinon® Nasal Spray total of 16 weeks exposure Subjects ages 3-10 years old will be titrated up to a maximum dose of 24IU. Subjects ages 11-17 years old will be titrated up to a maximum dose of 32IU.
Change in Mean Pervasive Developmental Disorder Behavior Inventory - Screening Version (PDDBI-SV) Total Score Over Both Periods	-3.6 scores on a scale Standard Error 2.4	-3.0 scores on a scale Standard Error 2.2

SECONDARY outcome

Timeframe: Week 0 to 8

Population: The one subject who discontinued at week 1 did not have follow up data to include in the analysis.

Change in mean systolic blood pressure during double blind phase

Outcome measures

Outcome measures
Measure	Sequence 2: Placebo:Oxytocin n=11 Participants Intervention: Drug: placebo double blind for 8 weeks then oxytocin open label for 8 weeks	Sequence 1: Oxytocin:Oxytocin n=13 Participants Intervention: Drug: oxytocin = Syntocinon® Nasal Spray total of 16 weeks exposure Subjects ages 3-10 years old will be titrated up to a maximum dose of 24IU. Subjects ages 11-17 years old will be titrated up to a maximum dose of 32IU.
Change in Mean Systolic Blood Pressure During Period 1	-7.6 millimeters of mercury (mmHg) Standard Error 2.8	1.5 millimeters of mercury (mmHg) Standard Error 3.2

SECONDARY outcome

Timeframe: Week 0 to 8

Serum prolactin levels were collected and analyzed in participants

Outcome measures

Outcome measures
Measure	Sequence 2: Placebo:Oxytocin n=11 Participants Intervention: Drug: placebo double blind for 8 weeks then oxytocin open label for 8 weeks	Sequence 1: Oxytocin:Oxytocin n=13 Participants Intervention: Drug: oxytocin = Syntocinon® Nasal Spray total of 16 weeks exposure Subjects ages 3-10 years old will be titrated up to a maximum dose of 24IU. Subjects ages 11-17 years old will be titrated up to a maximum dose of 32IU.
Mean Change in Prolactin Levels Over Period 1	-3.6 nanograms per milliliter (ng/mL) Standard Error 2.68	1.17 nanograms per milliliter (ng/mL) Standard Error 1.63

SECONDARY outcome

Timeframe: Week 0 to 8

Temperature was collected on each participant via oral or temporal thermometer. The mean change in each group was assessed.

Outcome measures

Outcome measures
Measure	Sequence 2: Placebo:Oxytocin n=11 Participants Intervention: Drug: placebo double blind for 8 weeks then oxytocin open label for 8 weeks	Sequence 1: Oxytocin:Oxytocin n=13 Participants Intervention: Drug: oxytocin = Syntocinon® Nasal Spray total of 16 weeks exposure Subjects ages 3-10 years old will be titrated up to a maximum dose of 24IU. Subjects ages 11-17 years old will be titrated up to a maximum dose of 32IU.
Mean Change in Temperature During Period 1	-0.7 degrees fahrenheit Standard Error 0.2	-0.1 degrees fahrenheit Standard Error 0.2

Adverse Events

Sequence 1: Oxytocin:Oxytocin Period 1weeks 0-8

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Sequence 2: Placebo: Oxytocin Period 1 Weeks 0-8

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Sequence 1: Oxytocin:Oxytocin Period 2, Weeks 8-16

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Sequence 2: Placebo:Oxytocin Period 2

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sequence 1: Oxytocin:Oxytocin Period 1weeks 0-8 n=12 participants at risk Intervention: Drug: Syntocinon® Nasal Spray Oxytocin: Subjects will use the Syntocinon® Nasal Spray (oxytocin) twice daily for 8 weeks if they are randomized to that arm in the Randomized Phase. All subjects will use the Syntocinon® Nasal Spray twice daily for 8 weeks in the Open Label Phase. Subjects ages 3-10 years old will be titrated up to a maximum dose of 24IU. Subjects ages 11-17 years old will be titrated up to a maximum dose of 32IU.	Sequence 2: Placebo: Oxytocin Period 1 Weeks 0-8 n=13 participants at risk Intervention: Drug: placebo Placebo: Placebo Nasal Spray	Sequence 1: Oxytocin:Oxytocin Period 2, Weeks 8-16 n=11 participants at risk；n=24 participants at risk evaluates longer term adverse events with oxytocin	Sequence 2: Placebo:Oxytocin Period 2 n=13 participants at risk evaluates acute exposure to oxytocin in sequence 2 participants
Respiratory, thoracic and mediastinal disorders Croup	8.3% 1/12 • Number of events 1 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	0.00% 0/13 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	0.00% 0/11 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	0.00% 0/13 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2

Other adverse events

Other adverse events
Measure	Sequence 1: Oxytocin:Oxytocin Period 1weeks 0-8 n=12 participants at risk Intervention: Drug: Syntocinon® Nasal Spray Oxytocin: Subjects will use the Syntocinon® Nasal Spray (oxytocin) twice daily for 8 weeks if they are randomized to that arm in the Randomized Phase. All subjects will use the Syntocinon® Nasal Spray twice daily for 8 weeks in the Open Label Phase. Subjects ages 3-10 years old will be titrated up to a maximum dose of 24IU. Subjects ages 11-17 years old will be titrated up to a maximum dose of 32IU.	Sequence 2: Placebo: Oxytocin Period 1 Weeks 0-8 n=13 participants at risk Intervention: Drug: placebo Placebo: Placebo Nasal Spray	Sequence 1: Oxytocin:Oxytocin Period 2, Weeks 8-16 n=11 participants at risk；n=24 participants at risk evaluates longer term adverse events with oxytocin	Sequence 2: Placebo:Oxytocin Period 2 n=13 participants at risk evaluates acute exposure to oxytocin in sequence 2 participants
General disorders # of participants with any adverse event	100.0% 12/12 • Number of events 59 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	76.9% 10/13 • Number of events 53 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	63.6% 7/11 • Number of events 19 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	92.3% 12/13 • Number of events 46 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2
General disorders # with moderate adverse event	41.7% 5/12 • Number of events 16 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	69.2% 9/13 • Number of events 20 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	27.3% 3/11 • Number of events 5 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	46.2% 6/13 • Number of events 16 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2
General disorders # with severe adverse event	41.7% 5/12 • Number of events 12 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	15.4% 2/13 • Number of events 6 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	9.1% 1/11 • Number of events 3 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	7.7% 1/13 • Number of events 5 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2
Nervous system disorders insomnia	33.3% 4/12 • Number of events 4 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	38.5% 5/13 • Number of events 5 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	9.1% 1/11 • Number of events 1 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	15.4% 2/13 • Number of events 2 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2
Psychiatric disorders Anger or irritability	8.3% 1/12 • Number of events 1 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	23.1% 3/13 • Number of events 3 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	9.1% 1/11 • Number of events 1 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	30.8% 4/13 • Number of events 4 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2
Psychiatric disorders oppositional	16.7% 2/12 • Number of events 2 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	23.1% 3/13 • Number of events 3 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	9.1% 1/11 • Number of events 1 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	30.8% 4/13 • Number of events 4 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2
Psychiatric disorders mood lability	8.3% 1/12 • Number of events 1 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	7.7% 1/13 • Number of events 1 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	9.1% 1/11 • Number of events 1 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	23.1% 3/13 • Number of events 3 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2
General disorders # who withdrew due to AE	8.3% 1/12 • Number of events 1 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	0.00% 0/13 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	0.00% 0/11 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	7.7% 1/13 • Number of events 1 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2
Psychiatric disorders Aggression	8.3% 1/12 • Number of events 1 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	30.8% 4/13 • Number of events 4 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	9.1% 1/11 • Number of events 1 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	15.4% 2/13 • Number of events 2 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2
Skin and subcutaneous tissue disorders Rash	25.0% 3/12 • Number of events 3 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	0.00% 0/13 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	0.00% 0/11 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	7.7% 1/13 • Number of events 1 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2
Nervous system disorders Agitation	16.7% 2/12 • Number of events 2 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	15.4% 2/13 • Number of events 2 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	9.1% 1/11 • Number of events 1 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2	30.8% 4/13 • Number of events 4 • Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2

Additional Information

Linmarie Sikich, MD

Duke University Center for Autism and Brain Development

Phone: 9196810026

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Sequence 2:Placebo-oxytocin n=13 Participants Intervention: Drug: placebo Placebo: Placebo Nasal Spray	Sequence 1: Oxytocin-oxytocin n=12 Participants Intervention: Drug: Syntocinon® Nasal Spray Oxytocin: Subjects will use the Syntocinon® Nasal Spray (oxytocin) twice daily for 8 weeks if they are randomized to that arm in the Randomized Phase. All subjects will use the Syntocinon® Nasal Spray twice daily for 8 weeks in the Open Label Phase. Subjects ages 3-10 years old will be titrated up to a maximum dose of 24 international units (IU). Subjects ages 11-17 years old will be titrated up to a maximum dose of 32IU.	Total n=25 Participants Total of all reporting groups
Age, Categorical <=18 years	13 Participants n=5 Participants	12 Participants n=7 Participants	25 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	10.0 years STANDARD_DEVIATION 4.4 • n=5 Participants	10.6 years STANDARD_DEVIATION 4.4 • n=7 Participants	10.3 years STANDARD_DEVIATION 4.4 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants	12 Participants n=7 Participants	25 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	1 Participants n=5 Participants	0 Participants n=7 Participants	1 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	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Non-verbal	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Intelligence Quotient (IQ) <70	10 Participants n=5 Participants	4 Participants n=7 Participants	14 Participants n=5 Participants