Trial Outcomes & Findings for Quetiapine and Concerta in the Treatment for ADHD and Aggressive Behavior. (NCT NCT00550147)

NCT ID: NCT00550147

Last Updated: 2015-05-13

Results Overview

The RAAPP is a global rating scale of aggression that is completed by a clinician based on interview and observation data. It is scored from 1 (no aggression reported) to 5 (intolerable behavior).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 30 participants
• Primary outcome timeframe: See Arm/Group - Repeated Measures
• Results posted on: 2015-05-13

Participant Flow

Subjects were recruited during the time period 2004-2005, using flyers and letters sent to local schools, clinics, and community agencies, as well as from referrals to the site at which the study was conducted.

All eligible subjects were assigned to the first phase of treatment (Oros MPH alone).

Participant milestones

Measure	OROS Methylphenidate and Quetiapine This is the Baseline Visit, immediately after enrollment and prior to taking any medication. All enrolled subjects start taking OROS methylphenidate until Visit 5. At visit 5, if there is significant improvement (decrease in aggressive symptoms), then subject is discontinued from the study. If there is not significant improvement, then subject continues in study and begins taking OROS methylphenidate plus quetiapine. 24 of 30 subjects entered the OROS methylphenidate and quetiapine arm. 4 subjects made significant improvement at visit 5 and were discontinued from the study; 2 subjects were withdrawn from the study prior to visit 5. Therefore, 6 of 30 subjects did not enter the OROS methylphenidate and quetiapine arm. Only 24 of 30 subjects entered this arm. Visit 10 is measured at the end of OROS MPH+Quetiapine treatment
OROS Methylphenidate Monotherapy STARTED	30
OROS Methylphenidate Monotherapy COMPLETED	24
OROS Methylphenidate Monotherapy NOT COMPLETED	6
Quetiapine Addition Treatment Period STARTED	24
Quetiapine Addition Treatment Period COMPLETED	18
Quetiapine Addition Treatment Period NOT COMPLETED	6

Reasons for withdrawal

Measure	OROS Methylphenidate and Quetiapine This is the Baseline Visit, immediately after enrollment and prior to taking any medication. All enrolled subjects start taking OROS methylphenidate until Visit 5. At visit 5, if there is significant improvement (decrease in aggressive symptoms), then subject is discontinued from the study. If there is not significant improvement, then subject continues in study and begins taking OROS methylphenidate plus quetiapine. 24 of 30 subjects entered the OROS methylphenidate and quetiapine arm. 4 subjects made significant improvement at visit 5 and were discontinued from the study; 2 subjects were withdrawn from the study prior to visit 5. Therefore, 6 of 30 subjects did not enter the OROS methylphenidate and quetiapine arm. Only 24 of 30 subjects entered this arm. Visit 10 is measured at the end of OROS MPH+Quetiapine treatment
OROS Methylphenidate Monotherapy significant improvement at visit 5	4
OROS Methylphenidate Monotherapy Withdrawal by Subject	2
Quetiapine Addition Treatment Period Adverse Event	3
Quetiapine Addition Treatment Period Noncompliance	2
Quetiapine Addition Treatment Period Moved out of state	1

Baseline Characteristics

Quetiapine and Concerta in the Treatment for ADHD and Aggressive Behavior.

Baseline characteristics by cohort

Measure	OROS Methylphenidate and Quetiapine n=30 Participants All enrolled subjects start taking OROS methylphenidate. At visit 5, if there is significant improvement (decrease in aggressive symptoms), then subject is discontinued from the study. If there is not significant improvement, then subject continues in study and begins taking OROS methylphenidate plus quetiapine. Therefore enters the OROS methylphenidate and quetiapine arm. 24 of 30 subjects entered the OROS methylphenidate and quetiapine arm. 4 subjects made significant improvement at visit 5 and were discontinued from the study, and, therefore, did not enter the OROS methylphenidate and quetiapine arm. 2 subjects were withdrawn from the study prior to visit 5, and, therefore, did not enter the OROS methylphenidate and quetiapine arm. Therefore, 6 of 30 subjects did not enter the OROS methylphenidate and quetiapine arm. Only 24 of 30 subjects entered this arm.
Age, Categorical <=18 years	30 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	13.2 years STANDARD_DEVIATION 1.2 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants

PRIMARY outcome

Timeframe: See Arm/Group - Repeated Measures

Population: Participants were those who qualified for the augmentation portion of the study (inadequate response to Oros MPH alone). Analysis was per protocol (intent-to-treat, LOCF).

The RAAPP is a global rating scale of aggression that is completed by a clinician based on interview and observation data. It is scored from 1 (no aggression reported) to 5 (intolerable behavior).

Outcome measures

Measure	Baseline n=24 Participants Baseline score at study entry	Visit 5 - MPH Monotherapy - Week 4 n=24 Participants Score following treatment with MPH monotherapy after Week 4	Visit 10 - MPH+Quetiapine - Week 13 n=24 Participants Score following treatment with combined MPH and quetiapine after Week 13
RAAPP: Rating of Aggression Against People and/or Property Scale	4.3 units on a scale Standard Deviation 0.4	3.2 units on a scale Standard Deviation 0.6	2.0 units on a scale Standard Deviation 0.8

SECONDARY outcome

Timeframe: See Arm/Group - Repeated Measures

Population: Participants were those who qualified for the augmentation portion of the study (inadequate response to Oros MPH alone). Analysis was per protocol (intent-to-treat, LOCF).

The CGI-S is a 1-7 investigator rating of overall severity of target behavioral symptoms, which will be completed at each visit as a secondary efficacy measure of global behavioral functioning. A score of 1 indicates "normal, not ill at all" and a score of 7 indicates "among the most extremely ill patients".

Outcome measures

Measure	Baseline n=24 Participants Baseline score at study entry	Visit 5 - MPH Monotherapy - Week 4 n=24 Participants Score following treatment with MPH monotherapy after Week 4	Visit 10 - MPH+Quetiapine - Week 13 n=24 Participants Score following treatment with combined MPH and quetiapine after Week 13
CGI-S: Clinical Global Improvement Scale	5.3 units on a scale Standard Deviation 0.6	4.1 units on a scale Standard Deviation 0.8	2.8 units on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: See arm/group - repeated measures

Population: Participants were those who qualified for the augmentation portion of the study (inadequate response to Oros MPH alone). Analysis was per protocol (intent-to-treat, LOCF).

The Modified Overt Aggression Scale (MOAS) is a clinician-rated scale of aggressive outbursts experienced in the past week. Weightings are assigned for severity and frequency of aggression. MOAS total severity score will be completed as a secondary efficacy measure of aggressive behavior. The range for the MOAS is 0-235. A score of 0 indicates "no aggression" and a score of 235 indicates "the most severe and frequent aggressive outbursts".

Outcome measures

Measure	Baseline n=24 Participants Baseline score at study entry	Visit 5 - MPH Monotherapy - Week 4 n=24 Participants Score following treatment with MPH monotherapy after Week 4	Visit 10 - MPH+Quetiapine - Week 13 n=24 Participants Score following treatment with combined MPH and quetiapine after Week 13
Modified Overt Aggression Scale (MOAS)	229.0 units on a scale Standard Deviation 194.3	73.7 units on a scale Standard Deviation 57.9	26.3 units on a scale Standard Deviation 33.0

SECONDARY outcome

Timeframe: See arm/group - repeated measures analysis

Population: Participants were those who qualified for the augmentation portion of the study (inadequate response to Oros MPH alone). Analysis was per protocol (intent-to-treat, LOCF).

The Swanson, Nolan and Pelham (SNAP-IV) is a 90-item, parent-completed questionnaire consisting of symptoms of ADHD, aggression, depression, and mania. Parents rate each item from 0(not at all) to 3 (very much) based on their child's behavior during the past week. The scores from the Oppositional-Defiant Disorder section of this questionnaire will be used as secondary efficacy measures of parent-reported aggressive behavior. These scores range from 0-24.

Outcome measures

Measure	Baseline n=24 Participants Baseline score at study entry	Visit 5 - MPH Monotherapy - Week 4 n=24 Participants Score following treatment with MPH monotherapy after Week 4	Visit 10 - MPH+Quetiapine - Week 13 n=24 Participants Score following treatment with combined MPH and quetiapine after Week 13
Swanson, Nolan and Pelham IV (SNAP-IV) Oppositional-Defiant Disorder Subscale	19.0 units on a scale Standard Deviation 4.1	14.5 units on a scale Standard Deviation 6.2	10.3 units on a scale Standard Deviation 6.5

SECONDARY outcome

Timeframe: See Arm/Group - repeated measures

Population: Participants were those who qualified for the augmentation portion of the study (inadequate response to Oros MPH alone). Analysis was per protocol (intent-to-treat, LOCF).

The Attention Deficit/Hyperactivity Disorder Rating Scale -IV- Parent Version (ADHDRS-IV-Parent:Inv) (Faries, Yalcin, Harder, & Heiligenstein, 2001) is an interviewer-administered semi structured interview with the parent, focusing on the 18 DSM-IV symptoms. Ratings are made on a 0 (never or rarely) to 3 (very often) scale. The range of the ADHDRS-IV is 0-54. A zero (0) scores indicates no ADHD symptoms and 54 indicates most severe ADHD symptoms. The ADHDRS-IV-Parent:Inv provides an overall severity score, symptom count, and ADHD diagnosis for the child.

Outcome measures

Measure	Baseline n=24 Participants Baseline score at study entry	Visit 5 - MPH Monotherapy - Week 4 n=24 Participants Score following treatment with MPH monotherapy after Week 4	Visit 10 - MPH+Quetiapine - Week 13 n=24 Participants Score following treatment with combined MPH and quetiapine after Week 13
Attention Deficit/Hyperactivity Disorder Rating Scale -IV- Parent Version (ADHDRS-IV-Parent Version)	45.7 units on a scale Standard Deviation 5.8	32.7 units on a scale Standard Deviation 10.8	19.4 units on a scale Standard Deviation 9.6

Adverse Events

OROS Methylphenidate and Quetiapine

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	OROS Methylphenidate and Quetiapine n=24 participants at risk All enrolled subjects start taking OROS methylphenidate. At visit 5, if there is significant improvement (decrease in aggressive symptoms), then subject is discontinued from the study. If there is not significant improvement, then subject continues in study and begins taking OROS methylphenidate plus quetiapine. Therefore enters the OROS methylphenidate and quetiapine arm. 24 of 30 subjects entered the OROS methylphenidate and quetiapine arm. 4 subjects made significant improvement at visit 5 and were discontinued from the study, and, therefore, did not enter the OROS methylphenidate and quetiapine arm. 2 subjects were withdrawn from the study prior to visit 5, and, therefore, did not enter the OROS methylphenidate and quetiapine arm. Therefore, 6 of 30 subjects did not enter the OROS methylphenidate and quetiapine arm. Only 24 of 30 subjects entered this arm.
Respiratory, thoracic and mediastinal disorders repiratory illness	37.5% 9/24 • Number of events 9
General disorders headache	16.7% 4/24 • Number of events 4
General disorders fatigue/sedation	50.0% 12/24 • Number of events 12
Metabolism and nutrition disorders reduced appetite	16.7% 4/24 • Number of events 4
General disorders difficulty sleeping	29.2% 7/24 • Number of events 7
Gastrointestinal disorders stomachache/nausea	29.2% 7/24 • Number of events 7
Gastrointestinal disorders vomiting	16.7% 4/24 • Number of events 4
General disorders flu-like syndrome	20.8% 5/24 • Number of events 5
General disorders lability/irritability	16.7% 4/24 • Number of events 4
Skin and subcutaneous tissue disorders bruises/cuts/bumps	12.5% 3/24 • Number of events 3
General disorders dizziness	12.5% 3/24 • Number of events 3

Additional Information

David W. Dunn, MD

Indiana University School of Medicine

Phone: 317-944-8162

Email: ddunn@iupui.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place