Trial Outcomes & Findings for Trial of Aripiprazole in the Treatment of CD in Adolescents (NCT NCT00250705)

Last Updated: 2017-07-11

Results Overview

Rating of Aggression Against People and/or Property Scale (RAAPP) (Kemph et al 1993) is a global rating scale of aggression completed by clinicians. Score given based on following severity scale with subject assigned 1 number: Intolerable behavior-frequently physically attacks others and destroys property (5); Severe-occasionally physically attacks people and destroys property (4); Moderately 21); and No aggressiveness reported (1). A minimum score of 1 is best and a maximum score of 5 is worst. There are no subscale scores.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

12 participants

Primary outcome timeframe

6 weeks

Results posted on

2017-07-11

Participant Flow

Subjects were recruited through the child psychiatric clinic after being identified as diagnosed with DSM 4 conduct disorder. Subjects and their parents were approached about participation in the study. Recruitment time was November 2004 through March 2009

The study was an open label study with no separate treatment groups, i.e., different doses or placebo. All subjects that were enrolled into participation were entered into active treatment.

Participant milestones

Participant milestones
Measure	Aripiprazole Treatment of Conduct Disorde The study was a 6-week open label study evaluating aripiprazole in the treatment of 12 male post-pubertal adolescents (13-17 years, Tanner Stage 4) diagnosed with conduct disorder (American Psychiatric Association 2000). The initial aripiprazole dose depending on the weight of the patient was: \< 25 kg = 1 mg/d; 25-50 kg = 2 mg/d; 50-70 kg = 5 mg/d; \> 70 kg = 10 mg/d (Data on File, 2003, Bristol-Myers Squibb). Thereafter the dose was individualized based on the response and tolerance to the drug with a maximum aripiprazole dose of 20 mg/d. Current psychotropic medications were not washed out of the patients at the beginning of the study due to the exploratory stage of use of the drug for the conduct disorder indication.
Overall Study STARTED	12
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Aripiprazole Treatment of Conduct Disorde The study was a 6-week open label study evaluating aripiprazole in the treatment of 12 male post-pubertal adolescents (13-17 years, Tanner Stage 4) diagnosed with conduct disorder (American Psychiatric Association 2000). The initial aripiprazole dose depending on the weight of the patient was: \< 25 kg = 1 mg/d; 25-50 kg = 2 mg/d; 50-70 kg = 5 mg/d; \> 70 kg = 10 mg/d (Data on File, 2003, Bristol-Myers Squibb). Thereafter the dose was individualized based on the response and tolerance to the drug with a maximum aripiprazole dose of 20 mg/d. Current psychotropic medications were not washed out of the patients at the beginning of the study due to the exploratory stage of use of the drug for the conduct disorder indication.
Overall Study Lack of Efficacy	2

Baseline Characteristics

10 subjects who completed the study with last visit carried forward for two.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aripiprazole Treatment of Conduct Disorder n=10 Participants The study was a 6-week open label study evaluating aripiprazole in the treatment of 12 male post-pubertal adolescents (13-17 years, Tanner Stage 4) diagnosed with conduct disorder (American Psychiatric Association 2000).
Age, Categorical <=18 years	10 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	14.6 years STANDARD_DEVIATION 1.1 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Rating of Aggression Against People and/or Property Scale	3.0 scores on a scale STANDARD_DEVIATION 0.9 • n=5 Participants • 10 subjects who completed the study with last visit carried forward for two.
Overt Aggression Scale-Modified (OAS-M) (Kay et al 1988) OAS-M, verbal aggression	2.2 weighted scores on a scale STANDARD_DEVIATION 1.2 • n=5 Participants
Overt Aggression Scale-Modified (OAS-M) (Kay et al 1988) OAS-M, aggression against property	4.2 weighted scores on a scale STANDARD_DEVIATION 3.0 • n=5 Participants
Overt Aggression Scale-Modified (OAS-M) (Kay et al 1988) OAS-M, autoaggression	0.6 weighted scores on a scale STANDARD_DEVIATION 1.9 • n=5 Participants
Overt Aggression Scale-Modified (OAS-M) (Kay et al 1988) OAS-M, physical aggression	4.5 weighted scores on a scale STANDARD_DEVIATION 3.9 • n=5 Participants
Children's Aggression Scale-Parent Version Verbal Aggression	12.9 units on a scale STANDARD_DEVIATION 4.3 • n=5 Participants
Children's Aggression Scale-Parent Version Agression Against Objects and Animals	3.8 units on a scale STANDARD_DEVIATION 2.2 • n=5 Participants
Children's Aggression Scale-Parent Version Provoked Aggression	2.1 units on a scale STANDARD_DEVIATION 2.2 • n=5 Participants
Children's Aggression Scale-Parent Version Initiated Aggression	1.6 units on a scale STANDARD_DEVIATION 2.0 • n=5 Participants
Children's Aggression Scale-Parent Version Use of Weapons	0.4 units on a scale STANDARD_DEVIATION 1.0 • n=5 Participants

PRIMARY outcome

Timeframe: 6 weeks

Population: ITT

Outcome measures

Outcome measures
Measure	Aripiprazole Treatment of Conduct Disorder n=10 Participants The study was a 6-week open label study evaluating aripiprazole in the treatment of 10 male post-pubertal adolescents (13-17 years, Tanner Stage 4) diagnosed with conduct disorder (American Psychiatric Association 2000). The initial aripiprazole dose depending on the weight of the patient was: \< 25 kg = 1 mg/d; 25-50 kg = 2 mg/d; 50-70 kg = 5 mg/d; \> 70 kg = 10 mg/d (Data on File, 2003, Bristol-Myers Squibb). Thereafter the dose was individualized based on the response and tolerance to the drug with a maximum aripiprazole dose of 20 mg/d. Current psychotropic medications were not washed out of the patients at the beginning of the study due to the exploratory stage of use of the drug for the conduct disorder indication.
The Primary Outcome Efficacy Measure: Rating of Aggression Against People and/or Property Scale (RAAPP) (Kemph et al 1993)	1.7 units on a scale Standard Deviation 0.8

PRIMARY outcome

Timeframe: 6 weeks

Population: ITT

OAS-M divides aggressions into 4 subtypes: 1) verbal aggression, 2) property aggression, 3) self aggression (autoaggression), and 4) physical aggression. Each subtype has an initial score ranging from 0 (least aggressive) to 4 (most aggressive). The score for each subscale is further weighed (multiplied) by a constant: verbal scale's constant is 1 (max adjusted score of 4); property scale's constant is 2 (max adjusted score 8); self scale's constant is 3 (max adjusted score 12); and physical scale's constant is 4 (max adjusted score of 16). Within a given scale, "0" is the best score and maximum adjusted scale score is worst.

Outcome measures

Outcome measures
Measure	Aripiprazole Treatment of Conduct Disorder n=10 Participants The study was a 6-week open label study evaluating aripiprazole in the treatment of 10 male post-pubertal adolescents (13-17 years, Tanner Stage 4) diagnosed with conduct disorder (American Psychiatric Association 2000). The initial aripiprazole dose depending on the weight of the patient was: \< 25 kg = 1 mg/d; 25-50 kg = 2 mg/d; 50-70 kg = 5 mg/d; \> 70 kg = 10 mg/d (Data on File, 2003, Bristol-Myers Squibb). Thereafter the dose was individualized based on the response and tolerance to the drug with a maximum aripiprazole dose of 20 mg/d. Current psychotropic medications were not washed out of the patients at the beginning of the study due to the exploratory stage of use of the drug for the conduct disorder indication.
Overt Aggression Scale-Modified (OAS-M) verbal aggression	1.0 units on a scale Standard Deviation 1.2
Overt Aggression Scale-Modified (OAS-M) property aggression	0.6 units on a scale Standard Deviation 1.9
Overt Aggression Scale-Modified (OAS-M) self aggression	0.6 units on a scale Standard Deviation 1.9
Overt Aggression Scale-Modified (OAS-M) physical aggression	1.6 units on a scale Standard Deviation 3.9

PRIMARY outcome

Timeframe: 6 weeks

Population: ITT

CAS-P is a 33 item scale representing 5 domains of aggression: Items in a domain were computed based on two reference points. The first was based on a 5 point frequency range with "0" being best (never) and "4" (\> 10 times being) worst. These same items were then adjusted such that more severe acts would be weighted more heavily compared to less severe aggressive behaviors. Within a domain, 0 was the best score. Worst score for the various aggression domains were: Verbal 26.16, Against Objects and Animals 11.8, Provoked 15.84, Initiated 17.84, and Use of Weapons 13.16.

Outcome measures

Outcome measures
Measure	Aripiprazole Treatment of Conduct Disorder n=10 Participants The study was a 6-week open label study evaluating aripiprazole in the treatment of 10 male post-pubertal adolescents (13-17 years, Tanner Stage 4) diagnosed with conduct disorder (American Psychiatric Association 2000). The initial aripiprazole dose depending on the weight of the patient was: \< 25 kg = 1 mg/d; 25-50 kg = 2 mg/d; 50-70 kg = 5 mg/d; \> 70 kg = 10 mg/d (Data on File, 2003, Bristol-Myers Squibb). Thereafter the dose was individualized based on the response and tolerance to the drug with a maximum aripiprazole dose of 20 mg/d. Current psychotropic medications were not washed out of the patients at the beginning of the study due to the exploratory stage of use of the drug for the conduct disorder indication.
Children's Aggression Scale-Parent Version Provoked Aggression	1.6 units on a scale Standard Deviation 0.5
Children's Aggression Scale-Parent Version Initiated Aggression	0.6 units on a scale Standard Deviation 1.2
Children's Aggression Scale-Parent Version Verbal Aggression	2.7 units on a scale Standard Deviation 2.8
Children's Aggression Scale-Parent Version Aggression Against Objects and Animals	0.4 units on a scale Standard Deviation 0.8
Children's Aggression Scale-Parent Version Aggression with Use of Weapons	0.1 units on a scale Standard Deviation 0.3

SECONDARY outcome

Timeframe: 6 weeks

The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Possible ratings are: 1. Normal, not at all ill; 2. Borderline mentally ill, 3. Mildly ill; 4. Moderately ill; 5. Markedly ill; 6. Severely ill; or 7. Among the most extremely ill patients.

Outcome measures

Outcome measures
Measure	Aripiprazole Treatment of Conduct Disorder n=10 Participants The study was a 6-week open label study evaluating aripiprazole in the treatment of 10 male post-pubertal adolescents (13-17 years, Tanner Stage 4) diagnosed with conduct disorder (American Psychiatric Association 2000). The initial aripiprazole dose depending on the weight of the patient was: \< 25 kg = 1 mg/d; 25-50 kg = 2 mg/d; 50-70 kg = 5 mg/d; \> 70 kg = 10 mg/d (Data on File, 2003, Bristol-Myers Squibb). Thereafter the dose was individualized based on the response and tolerance to the drug with a maximum aripiprazole dose of 20 mg/d. Current psychotropic medications were not washed out of the patients at the beginning of the study due to the exploratory stage of use of the drug for the conduct disorder indication.
Secondary Outcome Measures Were the Clinical Global Impression-Severity (CGI-S) Scale (NIMH, 1985a).	3.0 units on a scale Standard Deviation 1.5

SECONDARY outcome

Timeframe: 6 weeks

The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: 1. Very much improved; 2. Much improved; 3. Minimally improved; 4. No change; 5. Minimally worse; 6. Much worse; or 7. Much worse)

Outcome measures

Outcome measures
Measure	Aripiprazole Treatment of Conduct Disorder n=10 Participants The study was a 6-week open label study evaluating aripiprazole in the treatment of 10 male post-pubertal adolescents (13-17 years, Tanner Stage 4) diagnosed with conduct disorder (American Psychiatric Association 2000). The initial aripiprazole dose depending on the weight of the patient was: \< 25 kg = 1 mg/d; 25-50 kg = 2 mg/d; 50-70 kg = 5 mg/d; \> 70 kg = 10 mg/d (Data on File, 2003, Bristol-Myers Squibb). Thereafter the dose was individualized based on the response and tolerance to the drug with a maximum aripiprazole dose of 20 mg/d. Current psychotropic medications were not washed out of the patients at the beginning of the study due to the exploratory stage of use of the drug for the conduct disorder indication.
Secondary Outcome Measures Were the Clinical Global Impression--Improvement (CGI-I) Scales (NIMH, 1985a).	2.1 units on a scale Standard Deviation 1.4

Adverse Events

Aripiprazole in the Treatment of Conduct Disorder

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Aripiprazole in the Treatment of Conduct Disorder n=10 participants at risk The study was a 6-week open label study evaluating aripiprazole in the treatment of 12 male post-pubertal adolescents (13-17 years, Tanner Stage 4) diagnosed with conduct disorder (American Psychiatric Association 2000).
General disorders fatigue	100.0% 10/10 • Number of events 29 • Subjects were enrolled for a 6 week study. Safety measures for extrapyramidal ADRs included the AIMS (NIMH, 1985b) for tardive dyskinesia Barnes Akathisia Scale (Barnes 1989) (BAS) and the Simpson-Angus Scale (SAS) for parkinsonian movements (Simpson and Angus 1970). The UKU (Lingjaerde et al 1987) was used for monitoring non-motor ADRs.
Nervous system disorders muscle rigidity	40.0% 4/10 • Subjects were enrolled for a 6 week study. Safety measures for extrapyramidal ADRs included the AIMS (NIMH, 1985b) for tardive dyskinesia Barnes Akathisia Scale (Barnes 1989) (BAS) and the Simpson-Angus Scale (SAS) for parkinsonian movements (Simpson and Angus 1970). The UKU (Lingjaerde et al 1987) was used for monitoring non-motor ADRs.
Nervous system disorders tremor	30.0% 3/10 • Subjects were enrolled for a 6 week study. Safety measures for extrapyramidal ADRs included the AIMS (NIMH, 1985b) for tardive dyskinesia Barnes Akathisia Scale (Barnes 1989) (BAS) and the Simpson-Angus Scale (SAS) for parkinsonian movements (Simpson and Angus 1970). The UKU (Lingjaerde et al 1987) was used for monitoring non-motor ADRs.
Nervous system disorders akathisia	50.0% 5/10 • Subjects were enrolled for a 6 week study. Safety measures for extrapyramidal ADRs included the AIMS (NIMH, 1985b) for tardive dyskinesia Barnes Akathisia Scale (Barnes 1989) (BAS) and the Simpson-Angus Scale (SAS) for parkinsonian movements (Simpson and Angus 1970). The UKU (Lingjaerde et al 1987) was used for monitoring non-motor ADRs.
Gastrointestinal disorders Nausea/Vomiting	50.0% 5/10 • Subjects were enrolled for a 6 week study. Safety measures for extrapyramidal ADRs included the AIMS (NIMH, 1985b) for tardive dyskinesia Barnes Akathisia Scale (Barnes 1989) (BAS) and the Simpson-Angus Scale (SAS) for parkinsonian movements (Simpson and Angus 1970). The UKU (Lingjaerde et al 1987) was used for monitoring non-motor ADRs.
Skin and subcutaneous tissue disorders Increase perspiraton	60.0% 6/10 • Subjects were enrolled for a 6 week study. Safety measures for extrapyramidal ADRs included the AIMS (NIMH, 1985b) for tardive dyskinesia Barnes Akathisia Scale (Barnes 1989) (BAS) and the Simpson-Angus Scale (SAS) for parkinsonian movements (Simpson and Angus 1970). The UKU (Lingjaerde et al 1987) was used for monitoring non-motor ADRs.
Nervous system disorders Head Aches	90.0% 9/10 • Subjects were enrolled for a 6 week study. Safety measures for extrapyramidal ADRs included the AIMS (NIMH, 1985b) for tardive dyskinesia Barnes Akathisia Scale (Barnes 1989) (BAS) and the Simpson-Angus Scale (SAS) for parkinsonian movements (Simpson and Angus 1970). The UKU (Lingjaerde et al 1987) was used for monitoring non-motor ADRs.
Metabolism and nutrition disorders Weight Gain	40.0% 4/10 • Subjects were enrolled for a 6 week study. Safety measures for extrapyramidal ADRs included the AIMS (NIMH, 1985b) for tardive dyskinesia Barnes Akathisia Scale (Barnes 1989) (BAS) and the Simpson-Angus Scale (SAS) for parkinsonian movements (Simpson and Angus 1970). The UKU (Lingjaerde et al 1987) was used for monitoring non-motor ADRs.

Additional Information

An Open Label Trial of Aripiprazole in the Treatment of Conduct Disorder in Adolescents.

The University of Iowa

Phone: 319-356-1482

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place