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Trial record 12 of 31 for:    Developmental Disabilities | ( Map: Alabama, United States )

Phase IV Long-term Maintenance Study of Aripiprazole in the Treatment of Irritability Associated With Autistic Disorder

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ClinicalTrials.gov Identifier: NCT01227668
Recruitment Status : Completed
First Posted : October 25, 2010
Results First Posted : May 2, 2014
Last Update Posted : May 2, 2014
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Irritability Associated With Autistic Disorder
Interventions Drug: Aripiprazole
Drug: Placebo
Enrollment 215
Recruitment Details  
Pre-assignment Details Of 215 participants enrolled, 58 discontinued during screening and before entry into Phase 1. Of the 58 who discontinued, 1 withdrew for an adverse event, 12 withdrew consent, 8 were lost to follow-up, 36 no longer met study criteria, and 1 withdrew for other reason.
Arm/Group Title Aripiprazole, 2-15 mg Once Daily (Titered to Optimum Dose) Placebo
Hide Arm/Group Description

Phase 1: Participants received an initial dose of aripiprazole 2 mg daily, titered up to 5, 10, or 15 mg once daily to optimize clinical benefit, for a maximum of 26 weeks.

Phase 2: Aripiprazole was continued at the dose prescribed at the end of Phase 1, once daily for 16 weeks. The dose (within the range of 2-15 mg/day) could have been adjusted based on efficacy and tolerability.

Phase 2 only: Participants received placebo for 16 weeks.
Period Title: Phase 1 (Stabilization Phase)
Started 157 [1] 0
Received Treatment 155 0
Completed 85 0
Not Completed 72 0
Reason Not Completed
Adverse Event             12             0
Withdrawal by Subject             7             0
Lost to Follow-up             8             0
Sponsor's administrative reason             11             0
No longer meets study criteria             7             0
Lack of Efficacy             25             0
Poor compliance/noncompliance             2             0
[1]
Randomized
Period Title: Phase 2 (Randomization Phase)
Started 41 [1] 44 [1]
Received Treatment 39 43
Completed 22 19
Not Completed 19 25
Reason Not Completed
Adverse Event             0             1
Withdrawal by Subject             5             0
Lost to Follow-up             1             0
Lack of Efficacy             13             23
Poor compliance/noncompliance             0             1
[1]
Randomized
Arm/Group Title Aripiprazole, 2-15 mg Once Daily (Titered to Optimum Dose) Placebo Total
Hide Arm/Group Description Phase 2: Aripiprazole was continued at the dose prescribed at the end of Phase 1, once daily for 16 weeks. The dose (within the range of 2-15 mg/day) could have been adjusted based on efficacy and tolerability. Phase 2: Participants received placebo for 16 weeks. Total of all reporting groups
Overall Number of Baseline Participants 41 44 85
Hide Baseline Analysis Population Description
All participants who were randomized to receive treatment in Phase 2
Age, Customized  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 41 participants 44 participants 85 participants
10.1  (2.80) 10.8  (2.77) 10.4  (2.79)
Age, Customized  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 41 participants 44 participants 85 participants
10.0
(6 to 16)
11.0
(6 to 17)
10.0
(6 to 17)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 44 participants 85 participants
Female
11
  26.8%
6
  13.6%
17
  20.0%
Male
30
  73.2%
38
  86.4%
68
  80.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 41 participants 44 participants 85 participants
American Indian or Alaska Native 0 1 1
Asian 0 3 3
Native Hawaiian or Other Pacific Islander 0 0 0
Black or African American 8 11 19
White 31 28 59
Other 2 1 3
1.Primary Outcome
Title Percentage of Patients Relapsing by Week 16
Hide Description Time of relapse=date when patient meets relapse criteria. There are 4 definitions for relapse: 1. Patient meets the following criteria for 2 consecutive visits: (a) Aberrant Behavior Checklist Irritability score ≥25% than score at end of Phase 1 AND (b) Clinical Global Impression Improvement scale rating of ‘Much Worse’ or ‘Very Much Worse’ relative to rating at end of Phase 1. If relapse criteria met at 1 visit, 2nd visit should occur in about 1 week to reevaluate whether relapse criteria are still met. 2. Patient discontinues for "Lost to Follow-up" after a visit in which he or she met Definition 1 criteria (a&b). 3. Patient begins a prohibited drug (whether a study investigator or outside source prescribed) to treat worsening symptoms of irritability of autistic disorder after a visit where patient met Definition 1 criteria (a&b). 4. Patient discontinues due to hospitalization for worsening symptoms of irritability or due to lack of efficacy based on investigator’s assessment.
Time Frame From end of Phase 1 (Date of randomization) to Week 16 of Phase 2 and end of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized in Phase 2
Arm/Group Title Aripiprazole, 2-15 mg Once Daily (Titered to Optimum Dose) Placebo
Hide Arm/Group Description:
Phase 2: Participants continued aripiprazole at the dose prescribed at the end of Phase 1, once daily for 16 weeks. The dose (within the range of 2-15 mg/day) could have been adjusted based on efficacy and tolerability.
Phase 2 only: Participants received placebo for 16 weeks.
Overall Number of Participants Analyzed 41 44
Measure Type: Number
Unit of Measure: Percentage of participants
32 50
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aripiprazole, 2-15 mg Once Daily (Titered to Optimum Dose), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.097
Comments [Not Specified]
Method Stratified log rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
0.28 to 1.12
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Adjusted Mean Change From Baseline to Week 16 on the Aberrant Behavior Checklist Irritability (ABC-I) Subscale Score (Last Observation Carried Forward [LOCF])
Hide Description ABC is an informant-based checklist used to assess and classify problem behaviors of children and adolescents with mental retardation. The 58 items are rated on a 4-point scale (0=not at all a problem to 3=the problem is severe in degree), and resolve into 5 subscales: 1) irritability, agitation; 2) lethargy, social withdrawal; 3) stereotypic behavior; 4) hyperactivity, noncompliance; and 5) inappropriate speech. The ABC can be completed by parents, special educators, psychologists, direct caregivers, nurses, and others knowing the participant. Psychometric assessment of the ABC indicates that its subscales have high internal consistency, adequate reliability, and established validity. The ABC-I Subscale Score ranges from 0 to 45, with a negative change in score signifying improvement. LOCF data set includes data recorded at a given visit or, if no observation was recorded at that visit, data carried forward from the prior visit. chg=change; BL=baseline; APR=aripiprazole; vs=versus.
Time Frame From Baseline (end of Phase 1) to Week 16 of Phase 2
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized and took at least 1 dose of double-blind medication in Phase 2 and who had at least 1 efficacy evaluation after the start of Phase 2 study drug.
Arm/Group Title Aripiprazole, 2-15 mg Once Daily (Titered to Optimum Dose) Placebo
Hide Arm/Group Description:
Phase 2: Participants continued aripiprazole at the dose prescribed at the end of Phase 1, once daily for 16 weeks. The dose (within the range of 2-15 mg/day) could have been adjusted based on efficacy and tolerability.
Phase 2 only: Participants received placebo for 16 weeks.
Overall Number of Participants Analyzed 39 43
Mean (Standard Error)
Unit of Measure: Units on a scale
5.2  (1.61) 9.6  (1.56)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aripiprazole, 2-15 mg Once Daily (Titered to Optimum Dose), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.051
Comments For secondary endpoints, hierarchical testing aimed to keep the overall experiment-wise type I error rate to <=0.05. Difference in chg from BL was tested at 0.05 significance only if APR arm significantly differed vs placebo from primary analysis.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.40
Confidence Interval (2-Sided) 95%
-8.82 to 0.02
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Mean Clinical Global Impression Improvement (CGI-I) Scale Score at Week 16 (Last Observation Carried Forward [LOCF])
Hide Description CG-I rating scale permits global evaluation of patient’s improvement over time. At baseline (BL), CGI Severity of Illness assessment is performed, in which the clinician rates severity of patient’s condition on a 7-point scale ranging from 1=no symptoms to 7=very severe symptoms. Higher total score=worse symptoms. At subsequent visits, clinician assesses patient’s improvement relative to symptoms at baseline on CGI-I 7-point scale ranging from 1=very much improved to 7=very much worse. Since the drug targets irritability symptoms, the CGI focuses on severity of irritability secondary to autistic disorder. Lower score=more improved symptoms. LOCF data set includes data recorded at a given visit or, if nothing recorded, data areccarried forward from the prior visit. For secondary endpoints (endpt), hierarchical testing was used to keep overall experiment-wise type I error rate to <=0.05. diff=difference; IS=irritability scale; PA=primary analysis; signif=significance/significantly.
Time Frame From Baseline (end of Phase 1) to Week 16 of Phase 2
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized and took at least 1 dose of double-blind medication in Phase 2 and who had at least 1 efficacy evaluation after the start of Phase 2 study drug.
Arm/Group Title Aripiprazole, 2-15 mg Once Daily (Titered to Optimum Dose) Placebo
Hide Arm/Group Description:
Phase 2: Participants continued aripiprazole (ARP) at the dose prescribed at the end of Phase 1, once daily for 16 weeks. The dose (within the range of 2-15 mg/day) could have been adjusted based on efficacy and tolerability.
Phase 2 only: Participants received placebo (pb)for 16 weeks.
Overall Number of Participants Analyzed 39 43
Mean (Standard Error)
Unit of Measure: Units on a scale
4.2  (0.26) 4.8  (0.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aripiprazole, 2-15 mg Once Daily (Titered to Optimum Dose), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.090
Comments Treatment diff in chg from BL to endpnt in IS score was tested at 0.05 signif only if ARP arm signif differed vs pb from PA. Thus, if ARP arm signif differed vs pb in IS score, treatment diff in mean CGI-I score at endpnt was tested at 0.05 signfnce.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.3 to 0.1
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation During Phase 1
Hide Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Time Frame Weekly from Week 1 to Week 26 and continuously to end of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who took at least 1 dose of single-blind aripiprazole in Phase 1
Arm/Group Title Aripiprazole, 2-15 mg Once Daily (Titered to Optimum Dose)
Hide Arm/Group Description:
Phase 1: Participants received an initial dose of aripiprazole 2 mg daily, titered up to 5, 10, or 15 mg once daily to optimize clinical benefit, for a maximum of 26 weeks.
Overall Number of Participants Analyzed 155
Measure Type: Number
Unit of Measure: Participants
Death 0
SAEs 1
AEs leading to discontinuation 13
5.Other Pre-specified Outcome
Title Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Treatment-related AEs During Phase 2
Hide Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug.
Time Frame Weekly from Weeks 1 through 16 (end of treatment) of Phase 2
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized and took at least 1 dose of double-blind medication in Phase 2
Arm/Group Title Aripiprazole, 2-15 mg Once Daily (Titered to Optimum Dose) Placebo
Hide Arm/Group Description:
Phase 2: Participants continued aripiprazole at the dose prescribed at the end of Phase 1, once daily for 16 weeks. The dose (within the range of 2-15 mg/day) could have been adjusted based on efficacy and tolerability.
Phase 2 only: Participants received placebo for 16 weeks.
Overall Number of Participants Analyzed 39 43
Measure Type: Number
Unit of Measure: Participants
Death 0 0
SAEs 0 0
AEs leading to discontinuation 0 0
Treatment-related AEs 9 6
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Aripiprazole, 2-15 mg (Phase 1) Aripiprazole, 2-15 mg (Phase 2) Placebo (Phase 2 Only)
Hide Arm/Group Description Phase 1: Participants received an initial dose of aripiprazole 2 mg daily, titered up to 5, 10, or 15 mg once daily to optimize clinical benefit, for a maximum of 26 weeks. Phase 2: Participants continued aripiprazole at the dose prescribed at the end of Phase 1, once daily for 16 weeks. The dose (within the range of 2-15 mg/day) could have been adjusted based on efficacy and tolerability. Phase 2 only: Participants received placebo for 16 weeks.
All-Cause Mortality
Aripiprazole, 2-15 mg (Phase 1) Aripiprazole, 2-15 mg (Phase 2) Placebo (Phase 2 Only)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Aripiprazole, 2-15 mg (Phase 1) Aripiprazole, 2-15 mg (Phase 2) Placebo (Phase 2 Only)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/155 (0.65%)   0/39 (0.00%)   0/43 (0.00%) 
Psychiatric disorders       
Aggression  1  1/155 (0.65%)  0/39 (0.00%)  0/43 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Aripiprazole, 2-15 mg (Phase 1) Aripiprazole, 2-15 mg (Phase 2) Placebo (Phase 2 Only)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   112/155 (72.26%)   11/39 (28.21%)   5/43 (11.63%) 
Gastrointestinal disorders       
Constipation  1  4/155 (2.58%)  2/39 (5.13%)  0/43 (0.00%) 
Vomiting  1  22/155 (14.19%)  2/39 (5.13%)  2/43 (4.65%) 
Diarrhoea  1  11/155 (7.10%)  1/39 (2.56%)  0/43 (0.00%) 
General disorders       
Fatigue  1  13/155 (8.39%)  1/39 (2.56%)  0/43 (0.00%) 
Pyrexia  1  8/155 (5.16%)  1/39 (2.56%)  0/43 (0.00%) 
Infections and infestations       
Nasopharyngitis  1  9/155 (5.81%)  1/39 (2.56%)  1/43 (2.33%) 
Upper respiratory tract infection  1  16/155 (10.32%)  4/39 (10.26%)  1/43 (2.33%) 
Investigations       
Weight increased  1  39/155 (25.16%)  0/39 (0.00%)  0/43 (0.00%) 
Metabolism and nutrition disorders       
Increased appetite  1  20/155 (12.90%)  1/39 (2.56%)  2/43 (4.65%) 
Nervous system disorders       
Tremor  1  10/155 (6.45%)  1/39 (2.56%)  1/43 (2.33%) 
Movement disorder  1  3/155 (1.94%)  2/39 (5.13%)  0/43 (0.00%) 
Somnolence  1  23/155 (14.84%)  0/39 (0.00%)  0/43 (0.00%) 
Lethargy  1  8/155 (5.16%)  0/39 (0.00%)  0/43 (0.00%) 
Headache  1  8/155 (5.16%)  0/39 (0.00%)  0/43 (0.00%) 
Psychiatric disorders       
Insomnia  1  13/155 (8.39%)  1/39 (2.56%)  1/43 (2.33%) 
Aggression  1  8/155 (5.16%)  0/39 (0.00%)  1/43 (2.33%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01227668     History of Changes
Other Study ID Numbers: CN138-603
First Submitted: October 22, 2010
First Posted: October 25, 2010
Results First Submitted: November 7, 2013
Results First Posted: May 2, 2014
Last Update Posted: May 2, 2014