Trial Outcomes & Findings for Biomarkers in Autism of Aripiprazole and Risperidone Treatment (BAART) (NCT NCT01333072)

Results Overview

Multi-center, blinded clinical trial to evaluate biomarkers as predictors of efficacy and safety in children with autistic disorder to risperidone, an atypical antipsychotic drug and aripiprazole, an antipsychotic having a unique clinical and receptor-binding profile. The major outcome measure was the score on the Irritability subscale of the Aberrant Behavior Checklist (ABC-I) . The ABC has 58 items describing some aspect of behavior and the Irritability sub-scale has 15 items, each completed by a parent or caregiver under the supervision of an investigator. Scores on each item range from 0 = no problem and 3 = severe problem (range of total scores 0 to 45). A fall in scores indicates behavioral improvement.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

80 participants

Primary outcome timeframe

baseline to 10 weeks

Results posted on

2018-09-26

Participant Flow

80 participants were enrolled but 19 dropped from the study due to placebo response (16), parent withdrew child (2) and physician withdrew 1 subject. This left 61 subjects for randomization, as specified

Participant milestones

Participant milestones
Measure	Risperidone Atypical antipsychotic Risperidone: Children weighing 20-45 kg will receive an initial dose of 0.5 mg daily that will be increased to twice daily on day 4 (morning and bedtime). The dosage will be gradually increased in 0.5 mg increments to a maximum dose of 2.5 mg per day (1.0 mg in the morning and 1.5 mg at bedtime) by the fourth treatment week. A slightly accelerated dosage will be allowed for children who weigh more than 45 kg for a maximum dosage of 3.5 mg /day.	Aripiprazole Atypical antipsychotic Aripiprazole: The starting dosage will be 2.0 mg/day. The dosage will be allowed to increase to 5.0 mg/day on day 4 and can be increased thereafter as judged clinically appropriate until the maximum dosage of 15 mg/day. The dosage will only be increased in 5.0 mg intervals. No dosage adjustments will be allowed for either drug after 4 weeks.
Overall Study STARTED	30	31
Overall Study COMPLETED	24	27
Overall Study NOT COMPLETED	6	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Risperidone Atypical antipsychotic Risperidone: Children weighing 20-45 kg will receive an initial dose of 0.5 mg daily that will be increased to twice daily on day 4 (morning and bedtime). The dosage will be gradually increased in 0.5 mg increments to a maximum dose of 2.5 mg per day (1.0 mg in the morning and 1.5 mg at bedtime) by the fourth treatment week. A slightly accelerated dosage will be allowed for children who weigh more than 45 kg for a maximum dosage of 3.5 mg /day.	Aripiprazole Atypical antipsychotic Aripiprazole: The starting dosage will be 2.0 mg/day. The dosage will be allowed to increase to 5.0 mg/day on day 4 and can be increased thereafter as judged clinically appropriate until the maximum dosage of 15 mg/day. The dosage will only be increased in 5.0 mg intervals. No dosage adjustments will be allowed for either drug after 4 weeks.
Overall Study Lost to Follow-up	3	0
Overall Study Adverse Event	2	4
Overall Study Physician Decision	1	0

Baseline Characteristics

Biomarkers in Autism of Aripiprazole and Risperidone Treatment (BAART)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Risperidone n=30 Participants Atypical antipsychotic Risperidone: Children weighing 20-45 kg will receive an initial dose of 0.5 mg daily that will be increased to twice daily on day 4 (morning and bedtime). The dosage will be gradually increased in 0.5 mg increments to a maximum dose of 2.5 mg per day (1.0 mg in the morning and 1.5 mg at bedtime) by the fourth treatment week. A slightly accelerated dosage will be allowed for children who weigh more than 45 kg for a maximum dosage of 3.5 mg /day (McCracken et al 2002).	Aripiprazole n=31 Participants Atypical antipsychotic Aripiprazole: The starting dosage will be 2.0 mg/day. The dosage will be allowed to increase to 5.0 mg/day on day 4 and can be increased thereafter as judged clinically appropriate until the maximum dosage of 15 mg/day. The dosage will only be increased in 5.0 mg intervals. No dosage adjustments will be allowed for either drug after 4 weeks.	Total n=61 Participants Total of all reporting groups
Age, Continuous	8.3 years n=5 Participants	8.5 years n=7 Participants	8.4 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	25 Participants n=7 Participants	48 Participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants	31 participants n=7 Participants	61 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline to 10 weeks

Population: Score on Aberrant Behavior Checklist (ABC) scale for Irritability

Multi-center, blinded clinical trial to evaluate biomarkers as predictors of efficacy and safety in children with autistic disorder to risperidone, an atypical antipsychotic drug and aripiprazole, an antipsychotic having a unique clinical and receptor-binding profile. The major outcome measure was the score on the Irritability subscale of the Aberrant Behavior Checklist (ABC-I) . The ABC has 58 items describing some aspect of behavior and the Irritability sub-scale has 15 items, each completed by a parent or caregiver under the supervision of an investigator. Scores on each item range from 0 = no problem and 3 = severe problem (range of total scores 0 to 45). A fall in scores indicates behavioral improvement.

Outcome measures

Outcome measures
Measure	Risperidone n=24 Participants Atypical antipsychotic Risperidone: Children weighing 20-45 kg will receive an initial dose of 0.5 mg daily that will be increased to twice daily on day 4 (morning and bedtime). The dosage will be gradually increased in 0.5 mg increments to a maximum dose of 2.5 mg per day (1.0 mg in the morning and 1.5 mg at bedtime) by the fourth treatment week. A slightly accelerated dosage will be allowed for children who weigh more than 45 kg for a maximum dosage of 3.5 mg /day (McCracken et al 2002).	Aripiprazole n=27 Participants Atypical antipsychotic Aripiprazole: The starting dosage will be 2.0 mg/day. The dosage will be allowed to increase to 5.0 mg/day on day 4 and can be increased thereafter as judged clinically appropriate until the maximum dosage of 15 mg/day. The dosage will only be increased in 5.0 mg intervals. No dosage adjustments will be allowed for either drug after 4 weeks.
Changes in the Irritability Subscale of the Larger ABC (Abberent Behavior Checklist) That Occur From Baseline to 10 Weeks	12.7 units on a scale Standard Deviation 3.0	14.1 units on a scale Standard Deviation 3.5

Adverse Events

Risperidone

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Aripiprazole

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Risperidone n=30 participants at risk Atypical antipsychotic Risperidone: Children weighing 20-45 kg will receive an initial dose of 0.5 mg daily that will be increased to twice daily on day 4 (morning and bedtime). The dosage will be gradually increased in 0.5 mg increments to a maximum dose of 2.5 mg per day (1.0 mg in the morning and 1.5 mg at bedtime) by the fourth treatment week. A slightly accelerated dosage will be allowed for children who weigh more than 45 kg for a maximum dosage of 3.5 mg /day (McCracken et al 2002).	Aripiprazole n=31 participants at risk Atypical antipsychotic Aripiprazole: The starting dosage will be 2.0 mg/day. The dosage will be allowed to increase to 5.0 mg/day on day 4 and can be increased thereafter as judged clinically appropriate until the maximum dosage of 15 mg/day. The dosage will only be increased in 5.0 mg intervals. No dosage adjustments will be allowed for either drug after 4 weeks.
Psychiatric disorders sedation	6.7% 2/30	22.6% 7/31
Metabolism and nutrition disorders weight gain	70.0% 21/30	25.8% 8/31
Psychiatric disorders enuresis	0.00% 0/30	12.9% 4/31

Additional Information

C. Lindsay DeVane, Pharm.D.

MUSouthCarolina

Phone: 8432701818

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place