Trial Outcomes & Findings for Impact of Combined Medication and Behavioral Treatment for ASD & ADHD (NCT NCT03242772)

Last Updated: 2022-03-22

Results Overview

Child engagement states measured by the Joint Engagement Rating Inventory (JERI); our outcome contains four items (rated on a 7-point Likert scale) that characterize various aspects of engagement. Higher scores mean greater/higher quality engagement and lower scores represent less/poorer engagement. Total range of score is 4-28.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

18 participants

Primary outcome timeframe

Baseline (Week -1), Endpoint (Week 10)

Results posted on

2022-03-22

Participant Flow

Recruitment occurred through our autism research registry, community events and Duke clinics

Confirmation of dual diagnosis was required prior to randomization

Participant milestones

Participant milestones
Measure	ESDM Informed Parent Coaching + Amphetamine Amphetamine regimen (11 weeks total duration) will begin 2 weeks prior to initiation of ESDM informed parent coaching (8 weekly sessions) and continue through the week 11 endpoint assessment. The drug is an orally dissolvable, extended-release form of d- and l-amphetamine. Amphetamine: Study drug will be administered in the morning. Treatment will be initiated at 1 tablet = 3.1 mg or 0 mg of mixed amphetamine. Doses will be flexibly titrated upward and may be decreased or stopped at any time. ESDM informed parent coaching: All participants will receive 8 weekly parent child therapy sessions will be delivered by a therapist trained in parent coaching and ESDM principles and strategies and utilizing a therapy manual,(includes coaching for behavior management and handouts).	ESDM Informed Parent Coaching + Placebo Oral Tablet Placebo regimen (11 weeks total duration) will begin 2 weeks prior to initiation of ESDM informed parent coaching (8 weekly sessions) and continue through the week 11 endpoint assessment. The placebo contains no active drug and appears identical to the amphetamine (active drug). ESDM informed parent coaching: All participants will receive 8 weekly parent child therapy sessions will be delivered by a therapist trained in parent coaching and ESDM principles and strategies and utilizing a therapy manual,(includes coaching for behavior management and handouts). Placebo Oral Tablet: Matched placebo tablets will be administered in the morning and provided for 11 weeks . The tablets will be titrated in the same way as the active drug and may be stopped at any time.
Overall Study STARTED	9	9
Overall Study COMPLETED	6	8
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	ESDM Informed Parent Coaching + Amphetamine Amphetamine regimen (11 weeks total duration) will begin 2 weeks prior to initiation of ESDM informed parent coaching (8 weekly sessions) and continue through the week 11 endpoint assessment. The drug is an orally dissolvable, extended-release form of d- and l-amphetamine. Amphetamine: Study drug will be administered in the morning. Treatment will be initiated at 1 tablet = 3.1 mg or 0 mg of mixed amphetamine. Doses will be flexibly titrated upward and may be decreased or stopped at any time. ESDM informed parent coaching: All participants will receive 8 weekly parent child therapy sessions will be delivered by a therapist trained in parent coaching and ESDM principles and strategies and utilizing a therapy manual,(includes coaching for behavior management and handouts).	ESDM Informed Parent Coaching + Placebo Oral Tablet Placebo regimen (11 weeks total duration) will begin 2 weeks prior to initiation of ESDM informed parent coaching (8 weekly sessions) and continue through the week 11 endpoint assessment. The placebo contains no active drug and appears identical to the amphetamine (active drug). ESDM informed parent coaching: All participants will receive 8 weekly parent child therapy sessions will be delivered by a therapist trained in parent coaching and ESDM principles and strategies and utilizing a therapy manual,(includes coaching for behavior management and handouts). Placebo Oral Tablet: Matched placebo tablets will be administered in the morning and provided for 11 weeks . The tablets will be titrated in the same way as the active drug and may be stopped at any time.
Overall Study Lost to Follow-up	2	0
Overall Study Physician Decision	0	1
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Impact of Combined Medication and Behavioral Treatment for ASD & ADHD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ESDM Informed Parent Coaching + Amphetamine n=9 Participants Amphetamine regimen (11 weeks total duration) will begin 2 weeks prior to initiation of ESDM informed parent coaching (8 weekly sessions) and continue through the week 11 endpoint assessment. The drug is an orally dissolvable, extended-release form of d- and l-amphetamine. Amphetamine: Study drug will be administered in the morning. Treatment will be initiated at 1 tablet = 3.1 mg or 0 mg of mixed amphetamine. Doses will be flexibly titrated upward and may be decreased or stopped at any time. ESDM informed parent coaching: All participants will receive 8 weekly parent child therapy sessions will be delivered by a therapist trained in parent coaching and ESDM principles and strategies and utilizing a therapy manual,(includes coaching for behavior management and handouts).	ESDM Informed Parent Coaching + Placebo Oral Tablet n=9 Participants Placebo regimen (11 weeks total duration) will begin 2 weeks prior to initiation of ESDM informed parent coaching (8 weekly sessions) and continue through the week 11 endpoint assessment. The placebo contains no active drug and appears identical to the amphetamine (active drug). ESDM informed parent coaching: All participants will receive 8 weekly parent child therapy sessions will be delivered by a therapist trained in parent coaching and ESDM principles and strategies and utilizing a therapy manual,(includes coaching for behavior management and handouts). Placebo Oral Tablet: Matched placebo tablets will be administered in the morning and provided for 11 weeks . The tablets will be titrated in the same way as the active drug and may be stopped at any time.	Total n=18 Participants Total of all reporting groups
Age, Continuous	86.83 months STANDARD_DEVIATION 20.80 • n=5 Participants	103.00 months STANDARD_DEVIATION 18.88 • n=7 Participants	94.92 months STANDARD_DEVIATION 19.84 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	7 Participants n=7 Participants	16 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	4 Participants n=7 Participants	5 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
Region of Enrollment United States	9 participants n=5 Participants	9 participants n=7 Participants	18 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Week -1), Endpoint (Week 10)

Population: This variable required behavioral coding of videotaped caregiver-child interactions collected at two time points. This coding were not conducted due to the fact that the study was terminated and time 2 data were not collected for participants due to safety concerns related to Covid-19.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (Week -1), Endpoint (Week 10)

Population: Not all participants completed all surveys.

Mean of standard scores for VABS-3 (socialization subscale and communication subscales) assess how the participant actually has been functioning over the preceding month with regard to communication and social behaviors. The VABS-3 comprehensive form will be administered as a semi-structured interview by a trained and research reliable staff member. The standard score is based on the participant's age and is normed from a large sample of typically developing children. The standard score has a mean of 100 and a standard deviation of 15. The composite score range is 20-140; higher scores represent more adaptive functioning and lower scores represent less adaptive functioning.

Outcome measures

Outcome measures
Measure	ESDM Informed Parent Coaching + Amphetamine n=6 Participants Amphetamine regimen (11 weeks total duration) will begin 2 weeks prior to initiation of ESDM informed parent coaching (8 weekly sessions) and continue through the week 11 endpoint assessment. The drug is an orally dissolvable, extended-release form of d- and l-amphetamine. Amphetamine: Study drug will be administered in the morning. Treatment will be initiated at 1 tablet = 3.1 mg or 0 mg of mixed amphetamine. Doses will be flexibly titrated upward and may be decreased or stopped at any time. ESDM informed parent coaching: All participants will receive 8 weekly parent child therapy sessions will be delivered by a therapist trained in parent coaching and ESDM principles and strategies and utilizing a therapy manual,(includes coaching for behavior management and handouts).	ESDM Informed Parent Coaching + Placebo Oral Tablet n=7 Participants Placebo regimen (11 weeks total duration) will begin 2 weeks prior to initiation of ESDM informed parent coaching (8 weekly sessions) and continue through the week 11 endpoint assessment. The placebo contains no active drug and appears identical to the amphetamine (active drug). ESDM informed parent coaching: All participants will receive 8 weekly parent child therapy sessions will be delivered by a therapist trained in parent coaching and ESDM principles and strategies and utilizing a therapy manual,(includes coaching for behavior management and handouts). Placebo Oral Tablet: Matched placebo tablets will be administered in the morning and provided for 11 weeks . The tablets will be titrated in the same way as the active drug and may be stopped at any time.
Change in Mean Composite Score (Socialization and Communication Subscales Standard Scores) of the Vineland Adaptive Behavior Scale - 3rd Edition, Interview Version (VABS-3)	5.92 score on a scale Standard Deviation 5.34	1.86 score on a scale Standard Deviation 6.89

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 10

Population: Not all participants completed all surveys.

ADHD Rating Scale (ADHD-RS) will assess symptom frequency using data from clinician completed ADHD-RS and parent completed ADHD-RS. The ADHD-RS includes 18 items, each rated on a 4 point scale (0-3);Total Score is the sum of all responses (0-54). An Inattention subscale and Hyperactivity/Impulsivity subscale (each range 0-27) are calculated based on individual items assessing those symptoms. Higher values represent worse outcomes for the subscales and the total scale. Clinically significant scores in boys are 14 for inattention and 17 for hyperactivity/impulsivity items; thresholds in girls are 12 and 14 respectively. If subscales are used, they would be summed to compute the total score. \*Baseline measures occur on visits weeks -1 and week 0 in the study.

Outcome measures

Outcome measures
Measure	ESDM Informed Parent Coaching + Amphetamine n=4 Participants Amphetamine regimen (11 weeks total duration) will begin 2 weeks prior to initiation of ESDM informed parent coaching (8 weekly sessions) and continue through the week 11 endpoint assessment. The drug is an orally dissolvable, extended-release form of d- and l-amphetamine. Amphetamine: Study drug will be administered in the morning. Treatment will be initiated at 1 tablet = 3.1 mg or 0 mg of mixed amphetamine. Doses will be flexibly titrated upward and may be decreased or stopped at any time. ESDM informed parent coaching: All participants will receive 8 weekly parent child therapy sessions will be delivered by a therapist trained in parent coaching and ESDM principles and strategies and utilizing a therapy manual,(includes coaching for behavior management and handouts).	ESDM Informed Parent Coaching + Placebo Oral Tablet n=8 Participants Placebo regimen (11 weeks total duration) will begin 2 weeks prior to initiation of ESDM informed parent coaching (8 weekly sessions) and continue through the week 11 endpoint assessment. The placebo contains no active drug and appears identical to the amphetamine (active drug). ESDM informed parent coaching: All participants will receive 8 weekly parent child therapy sessions will be delivered by a therapist trained in parent coaching and ESDM principles and strategies and utilizing a therapy manual,(includes coaching for behavior management and handouts). Placebo Oral Tablet: Matched placebo tablets will be administered in the morning and provided for 11 weeks . The tablets will be titrated in the same way as the active drug and may be stopped at any time.
Change in ADHD Symptoms Using Preschool or School Age ADHD Rating Scale (ADHD-RS) Total Score	-10.00 score on a scale Standard Deviation 6.81	-4.75 score on a scale Standard Deviation 10.02

SECONDARY outcome

Timeframe: Baseline (Week -1), Week 10

Population: This variable required processing of eye tracking data collected at two time points. We chose not to process the eye tracking data due to the fact that the study was terminated and time 2 data were not collected for participants because of safety concerns related to Covid-19.

Eye Gaze Tracking (EGT) during presentation of social and nonsocial stimuli. Key measure used is Proportion Looking Time, which is a number between 0 and 1, with a higher number indicating improved attention.

Outcome measures

Outcome data not reported

Adverse Events

ESDM Informed Parent Coaching + Amphetamine

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

ESDM Informed Parent Coaching + Placebo Oral Tablet

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Geraldine Dawson, PhD, PI of Duke Autism Center of Excellence

Duke Center for Autism and Brain Development

Phone: 919-668-0070

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	ESDM Informed Parent Coaching + Amphetamine n=9 participants at risk Amphetamine regimen (11 weeks total duration) will begin 2 weeks prior to initiation of ESDM informed parent coaching (8 weekly sessions) and continue through the week 11 endpoint assessment. The drug is an orally dissolvable, extended-release form of d- and l-amphetamine. Amphetamine: Study drug will be administered in the morning. Treatment will be initiated at 1 tablet = 3.1 mg or 0 mg of mixed amphetamine. Doses will be flexibly titrated upward and may be decreased or stopped at any time. ESDM informed parent coaching: All participants will receive 8 weekly parent child therapy sessions will be delivered by a therapist trained in parent coaching and ESDM principles and strategies and utilizing a therapy manual,(includes coaching for behavior management and handouts).	ESDM Informed Parent Coaching + Placebo Oral Tablet n=9 participants at risk Placebo regimen (11 weeks total duration) will begin 2 weeks prior to initiation of ESDM informed parent coaching (8 weekly sessions) and continue through the week 11 endpoint assessment. The placebo contains no active drug and appears identical to the amphetamine (active drug). ESDM informed parent coaching: All participants will receive 8 weekly parent child therapy sessions will be delivered by a therapist trained in parent coaching and ESDM principles and strategies and utilizing a therapy manual,(includes coaching for behavior management and handouts). Placebo Oral Tablet: Matched placebo tablets will be administered in the morning and provided for 11 weeks . The tablets will be titrated in the same way as the active drug and may be stopped at any time.
Psychiatric disorders Mood Dysregulation	55.6% 5/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	44.4% 4/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
Psychiatric disorders Insomnia	55.6% 5/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	11.1% 1/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
Psychiatric disorders Aggression	22.2% 2/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	11.1% 1/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
Psychiatric disorders Compulsions	22.2% 2/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	0.00% 0/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
Psychiatric disorders Hyperfocused	11.1% 1/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	0.00% 0/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
Psychiatric disorders Stereotypies, worsened	11.1% 1/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	0.00% 0/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
Psychiatric disorders Hyperactivity, worsened	11.1% 1/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	0.00% 0/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
Psychiatric disorders Flat affect, worsened	11.1% 1/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	0.00% 0/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
Psychiatric disorders Oppositionality, worsened	11.1% 1/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	0.00% 0/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
Nervous system disorders Headache	11.1% 1/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	0.00% 0/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
Nervous system disorders Subjective Temperature Dysregulation	11.1% 1/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	0.00% 0/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
General disorders Decreased Appetite	22.2% 2/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	11.1% 1/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
Infections and infestations Viral Infections	44.4% 4/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	77.8% 7/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
Injury, poisoning and procedural complications Accidental Injury	11.1% 1/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	0.00% 0/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
Immune system disorders Environmental Allergies, worsened	33.3% 3/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	0.00% 0/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
Musculoskeletal and connective tissue disorders Inflamed Toe	11.1% 1/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	0.00% 0/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
Musculoskeletal and connective tissue disorders Myalgia	11.1% 1/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	0.00% 0/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
Gastrointestinal disorders Constipation, increased	11.1% 1/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	11.1% 1/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
Ear and labyrinth disorders Motion Sickness	0.00% 0/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	11.1% 1/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	11.1% 1/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).
Skin and subcutaneous tissue disorders Pruitis	11.1% 1/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).	0.00% 0/9 • First three participants had a time frame of 52-64 weeks, and the remaining 15 had a timeframe 24 weeks, per protocol. First three participants were systematic using the SLAES, next 15 subjects were spontaneous (non-systematic).