Post-Marketing Surveillance Study of Aripiprazole in Patients With Autism

• Sponsor: Otsuka Pharmaceutical Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03179787
• Collaborator: (none)
• Enrollment: 528
• Location: 1
• Actual Duration (Months): 39.2
• Patients Per Site Per Month: 13.5

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and effectiveness of aripiprazole in patients with autism in the real world clinical setting in Japan.

Condition or Disease	Intervention/Treatment	Phase
Autism	Drug: Aripiprazole oral product

Study Design

• Study Type: Observational
• Actual Enrollment: 528 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Post-Marketing Surveillance Study of Aripiprazole in Patients With Autism
• Actual Study Start Date: Apr 1, 2017
• Actual Primary Completion Date: Mar 17, 2020
• Actual Study Completion Date: Jul 6, 2020

Outcome Measures

Primary Outcome Measures

1. Mean Changes of Aberrant Behavior Checklist-Japanese Version (ABC-J) Irritability Subscale Scores From Baseline. [Baseline, Week 4, 8, 16, 24, 52]

   Using caregiver-rated ABC-J, the degree of aberrant behaviors was scored on four levels ranging from 0 'not at all a problem', 1 'slight problem', 2 'moderately serious problem' to 3 'the problem is severe in degree' in irritability subscale (including 15 items describing symptoms of irritability, such as temper tantrums, aggression, mood changes, and self-injury). The irritability subscale score ranging from 0 to 45 was derived from the sum of the 15 items and higher values represent a worse outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• diagnosed as autism with irritability

Exclusion Criteria:

• patients who has ever been treated with aripiprazole

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Otsuka Pharmaceutical Co., Ltd.	Tokyo		Japan

Sponsors and Collaborators

• Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Director: Pharmacovigilance, Otsuka Pharmaceutical Co., Ltd.

Study Documents (Full-Text)

• Study Protocol - Dec 6, 2016
• Statistical Analysis Plan - Feb 26, 2020

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03179787
• Other Study ID Numbers: 031-101-00116
• First Posted: Jun 7, 2017
• Last Update Posted: Sep 16, 2021
• Last Verified: Aug 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Autistic Disorder; Aripiprazole

Study Results

Participant Flow

Recruitment Details	This surveillance was conducted in 528 participants from 100 trial sites in Japan.
Pre-assignment Detail	Patients newly treated with aripiprazole for irritability associated with autism spectrum disorder (ASD) in children and adolescents (≥6 years and <18 years) were included.

Arm/Group Title	Safety Analysis Group
Arm/Group Description	Five hundred and twenty-eight patients were enrolled at 100 sites across Japan, and 526 case reports were collected during the period of April 2017 to September 2019. The safety analysis population consisted of 510 patients. Among excluded patients, 15 patients were lost to follow-up, and one patient was not treated with aripiprazole.
Period Title: Overall Study
STARTED	528
COMPLETED	510
NOT COMPLETED	18

Baseline Characteristics

Arm/Group Title	Safety Analysis Group
Arm/Group Description	Five hundred and twenty-eight patients were enrolled at 100 sites across Japan, and 526 case reports were collected during the period of April 2017 to September 2019. The safety analysis population consisted of 510 patients. Among excluded patients, 15 patients were lost to follow-up, and one patient was not treated with aripiprazole.
Overall Participants	510
Age (Count of Participants)
<=18 years	510 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.4 (3.1)
Sex: Female, Male (Count of Participants)
Female	134 26.3%
Male	376 73.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	510 100%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
Japan	510 100%

Outcome Measures

1. Primary Outcome

Title	Mean Changes of Aberrant Behavior Checklist-Japanese Version (ABC-J) Irritability Subscale Scores From Baseline.
Description	Using caregiver-rated ABC-J, the degree of aberrant behaviors was scored on four levels ranging from 0 'not at all a problem', 1 'slight problem', 2 'moderately serious problem' to 3 'the problem is severe in degree' in irritability subscale (including 15 items describing symptoms of irritability, such as temper tantrums, aggression, mood changes, and self-injury). The irritability subscale score ranging from 0 to 45 was derived from the sum of the 15 items and higher values represent a worse outcome.
Time Frame	Baseline, Week 4, 8, 16, 24, 52

Outcome Measure Data

Analysis Population Description

Twenty-one patients with the protocol deviations (including all effectiveness measures were not assessed after treatment: n = 11, all effectiveness measures were assessed over 7 days after last dose: n = 7, the daily dose was > 15 mg: n = 2, all effectiveness were assessed after day 393: n = 1) were excluded, and then efficacy sample consisted of all participants who have Baseline and at least one Post-Baseline effectiveness evaluation.

Arm/Group Title	Safety Analysis Group
Arm/Group Description	Five hundred and twenty-eight patients were enrolled at 100 sites across Japan, and 526 case reports were collected during the period of April 2017 to September 2019. The safety analysis population consisted of 510 patients. Among excluded patients, 15 patients were lost to follow-up, and one patient was not treated with aripiprazole.
Measure Participants	396
Baseline	19.8 (9.5)
Week 4	14.7 (8.8)
Week 8	12.9 (8.1)
Week 16	12.7 (8.3)
Week 24	13.4 (8.9)
Week 52	13.1 (9.1)
End-point (LOCF)	13.0 (9.0)

Adverse Events

Time Frame	Adverse events were observed from first dose until follow-up for 52 weeks.
Adverse Event Reporting Description	The adverse events (if any occurred), onset date, seriousness, outcome, date of outcome, causality to aripiprazole, other possible causal factors, and treatment for adverse events during the observation period were recorded. Seriousness was determined by the physicians.
Arm/Group Title	Safety Analysis Group
Arm/Group Description	Five hundred and twenty-eight patients were enrolled at 100 sites across Japan, and 526 case reports were collected during the period of April 2017 to September 2019. The safety analysis population consisted of 510 patients. Among excluded patients, 15 patients were lost to follow-up, and one patient was not treated with aripiprazole.
All Cause Mortality
	Safety Analysis Group
	Affected / at Risk (%)	# Events
Total	0/510 (0%)
Serious Adverse Events
	Safety Analysis Group
	Affected / at Risk (%)	# Events
Total	3/510 (0.6%)
Nervous system disorders
Epilepsy	1/510 (0.2%)	1
Partial seizures	1/510 (0.2%)	1
Psychiatric disorders
Insomnia	1/510 (0.2%)	1
Impulsive behaviour	1/510 (0.2%)	1
Renal and urinary disorders
Renal impairment	1/510 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Safety Analysis Group
	Affected / at Risk (%)	# Events
Total	82/510 (16.1%)
Gastrointestinal disorders
Nausea	7/510 (1.4%)	7
Investigations
Weight increased	18/510 (3.5%)	18
Metabolism and nutrition disorders
Increased appetite	6/510 (1.2%)	6
Obesity	5/510 (1%)	5
Nervous system disorders
Somnolence	48/510 (9.4%)	48
Headache	8/510 (1.6%)	8

Limitations/Caveats

It was an observational study in daily clinical practice without a comparison group. In addition, there were deficiencies in the assessments and variations in the reports and evaluation based on the reporting made by the physicians and caregivers.

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.