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A Double-Blind, Placebo-Controlled Study of Aripiprazole Adjunctive to Antidepressant Therapy

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ClinicalTrials.gov Identifier: NCT00683852
Recruitment Status : Completed
First Posted : May 26, 2008
Results First Posted : July 19, 2017
Last Update Posted : July 19, 2017
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Maurizio Fava, MD, Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: Aripiprazole 5mg
Drug: Aripiprazole 2mg
Drug: Placebo
Enrollment 225

Recruitment Details 23 U.S. sites enrolled 225 patients over 10 months. 221 patients are included in the analysis. Enrollment began in September, 2008 and completed in July, 2009.
Pre-assignment Details Patients completed a SAFER interview before randomization. No other significant events occurred prior to randomization.
Arm/Group Title ADAPT Drug/Drug Group ADAPT Placebo/Placebo Group ADAPT Placebo/Drug Group
Hide Arm/Group Description Patients randomly assigned to the drug/drug sequence: the dose of aripiprazole will be 2 mg/day during the first phase of the study, and 5 mg/day in the second phase. Patients randomly assigned to the placebo/placebo sequence: the patients will receive a placebo treatment during the first phase of the study, and a placebo treatment in the second phase. Patients will be randomly assigned to placebo during the first phase of the study. In the second phase of the study, they will receive the aripiprazole drug at a dose of 2 mg/day.
Period Title: 30-Day Phase 1 Period
Started 56 84 85
Completed 54 83 84
Not Completed 2 1 1
Period Title: 30-Day Phase 2 Period
Started 54 83 84
Completed 48 78 75
Not Completed 6 5 9
Arm/Group Title ADAPT Drug/Drug Group ADAPT Placebo Group (Placebo/Placebo & Placebo/Drug Groups) Total
Hide Arm/Group Description patients randomly assigned to the drug/drug sequence, the dose of aripiprazole will be 2 mg/day during the first phase of the study, and 5 mg/day in the second phase. This data was analyzed for the study by comparing placebo vs. drug. Therefore the two groups (placebo/placebo and placebo/drug) that started with placebo during the first phase of the study are combined as one group. Patients in the placebo/placebo sequence received a placebo treatment during the first phase of the study, and a placebo treatment in the second phase. Patients in the placebo/drug sequence received a placebo treatment during the first phase of the study and they received the aripiprazole drug at a dose of 2 mg/day in the second phase of the study. Total of all reporting groups
Overall Number of Baseline Participants 56 169 225
Hide Baseline Analysis Population Description
This data was analyzed for the study by comparing placebo vs. drug. Therefore the two groups (placebo/placebo and placebo/drug) that started with placebo during the first phase of the study are combined as one group called Placebo. The patients who were took the study drug in both phases are in the Drug/Drug group.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 56 participants 169 participants 225 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
56
 100.0%
169
 100.0%
225
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 56 participants 169 participants 225 participants
45.36  (10.35) 45.06  (11.34) 45.16  (10.85)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 56 participants 169 participants 225 participants
Female
37
  66.1%
108
  63.9%
145
  64.4%
Male
19
  33.9%
61
  36.1%
80
  35.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 56 participants 169 participants 225 participants
56 169 225
1.Primary Outcome
Title MADRS (Montgomery-Asberg Depression Rating Scale) Response Rate
Time Frame 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase 1 Drug Phase 1 Placebo Non-Responders on Drug in Phase 2 Phase I Placebo Phase 1 Placebo Non-Responders on Placebo in Phase 2
Hide Arm/Group Description:
Patients who received drug in phase 1 (aripiprazole 2 mg/day)
Patients who received (and had no response) to a Placebo in Phase 1 and then received drug (aripiprazole 2mg/day) in Phase 2
Patients who received Placebo in Phase 1
Patients who received (and had no response) to a Placebo in Phase 1 and then received a placebo treatment in Phase 2
Overall Number of Participants Analyzed 54 61 167 63
Measure Type: Count of Participants
Unit of Measure: Participants
10
  18.5%
11
  18.0%
29
  17.4%
5
   7.9%
2.Secondary Outcome
Title MADRS (Montgomery-Asberg Depression Rating Scale) Readmission Rate
Hide Description MADRS readmission rate is defined as MADRS score<11. The 10-item Montgomery-Asberg Depression Rating Scale (MADRS), which measures depression severity over the past week, was completed by clinicians using an MGH structured interview. Each item is measured on a scale from 0 to 6, and the items are summed to find the total score. The total minimum score is 0 units on a scale and the total maximum score is 60 units on a scale, where higher scores indicate more severe depression.
Time Frame 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase 1 Drug Phase 1 Placebo Non-Responders on Drug in Phase 2 Phase I Placebo Phase 1 Placebo Non-Responders on Placebo in Phase 2
Hide Arm/Group Description:
Patients who received drug in phase 1 (aripiprazole 2 mg/day)
Patients who received (and had no response) to a Placebo in Phase 1 and then received drug (aripiprazole 2mg/day) in Phase 2
Patients who received Placebo in Phase 1
Patients who received (and had no response) to a Placebo in Phase 1 and then received a placebo treatment in Phase 2
Overall Number of Participants Analyzed 54 61 167 63
Measure Type: Count of Participants
Unit of Measure: Participants
4
   7.4%
8
  13.1%
16
   9.6%
4
   6.3%
3.Secondary Outcome
Title Mean Change in MADRS (Montgomery-Asberg Depression Rating Scale) Score From Baseline to the End of Follow-up
Hide Description The 10-item Montgomery-Asberg Depression Rating Scale (MADRS), which measures depression severity over the past week, was completed by clinicians using an MGH structured interview. Each item is measured on a scale from 0 to 6, and the items are summed to find the total score. The total minimum score is 0 units on a scale and the total maximum score is 60 units on a scale, where higher scores indicate more severe depression.
Time Frame Baseline and 12 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase 1 Drug Phase 1 Placebo Non-Responders on Drug in Phase 2 Phase I Placebo Phase 1 Placebo Non-Responders on Placebo in Phase 2
Hide Arm/Group Description:
Patients who received drug in phase 1 (aripiprazole 2 mg/day)
Patients who received (and had no response) to a Placebo in Phase 1 and then received drug (aripiprazole 2mg/day) in Phase 2
Patients who received Placebo in Phase 1
Patients who received (and had no response) to a Placebo in Phase 1 and then received a placebo treatment in Phase 2
Overall Number of Participants Analyzed 54 61 167 63
Mean (Standard Deviation)
Unit of Measure: units on a scale
-8.54  (7.21) -5.80  (7.08) -8.09  (8.13) -3.32  (5.97)
4.Secondary Outcome
Title Mean Change in Clinical Global Impression of Severity (CGI-S)
Hide Description The CGI-S scale was administered by clinicians based on assessment of the patient’s clinical status. They measured, based on history and scores on other instruments, depressive severity. It consists of one question scored on a seven-point scale (1 = normal to 7 = among the most severe), so a higher total score indicates greater depressive severity. The minimum score is 1, and the maximum score is 7.
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This analysis used observed cases rather than LOCF (last observation carried forward), so some participants were missing follow-up data.
Arm/Group Title Phase 1 Drug Phase 1 Placebo Non-Responders on Drug in Phase 2 Phase I Placebo Phase 1 Placebo Non-Responders on Placebo in Phase 2
Hide Arm/Group Description:
Patients who received drug in phase 1 (aripiprazole 2 mg/day)
Patients who received (and had no response) to a Placebo in Phase 1 and then received drug (aripiprazole 2mg/day) in Phase 2
Patients who received Placebo in Phase 1
Patients who received (and had no response) to a Placebo in Phase 1 and then received a placebo treatment in Phase 2
Overall Number of Participants Analyzed 52 58 162 61
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.81  (1.03) -0.64  (0.95) -0.84  (1.15) -0.43  (0.78)
5.Secondary Outcome
Title Mean Change in Symptom Questionnaire (SQ)
Hide Description The SQ, a 92-item (yes/no) self-rating questionnaire, includes 4 distress and 4 well-being subscales. There are 68 items for the distress subscales and 24 items for the well-being subscales. Each item has either a Yes/No or True/False answer. For the distress symptom score, add together the following items and score 1 when the answer is Yes/True: 1, 2, 3, 5, 6, 8, 11, 12, 15, 18, 20, 22, 24, 25, 26, 27, 28, 29, 30, 32, 33, 34, 36, 37, 39, 41, 42, 44, 45, 47, 48, 49, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 72, 73, 74, 75, 76, 77, 79, 80, 81, 82, 84, 85, 86, 87, 88, 90, 91, 92. Minimum score is 0 and maximum score is 68. A higher score indicates more distress symptoms. For the well-being subscale score, add together the following items and score 1 when the answer is No/False: 4, 7, 9, 10, 13, 14, 16, 17, 19, 21, 23, 29, 31, 35, 38, 40, 43, 46, 50, 51, 71, 78, 83, 89. Minimum score is 0 and maximum score is 24. A higher score indicates more well-being.
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This analysis used observed cases rather than LOCF (last observation carried forward), so some participants were missing follow-up data.
Arm/Group Title Phase 1 Drug Phase 1 Placebo Non-Responders on Drug in Phase 2 Phase I Placebo Phase 1 Placebo Non-Responders on Placebo in Phase 2
Hide Arm/Group Description:
Patients who received drug in phase 1 (aripiprazole 2 mg/day)
Patients who received (and had no response) to a Placebo in Phase 1 and then received drug (aripiprazole 2mg/day) in Phase 2
Patients who received Placebo in Phase 1
Patients who received (and had no response) to a Placebo in Phase 1 and then received a placebo treatment in Phase 2
Overall Number of Participants Analyzed 52 59 162 61
Mean (Standard Deviation)
Unit of Measure: units on a scale
Sum of 4 subscaled distress scores -9.44  (11.19) -6.78  (13.78) -9.70  (12.51) -4.52  (9.52)
Sum of 4 subscaled well-being scores 3.71  (5.12) 3.34  (5.79) 2.75  (5.88) 1.98  (4.97)
6.Other Pre-specified Outcome
Title Treatment Emergent AEs in Two Treatment Groups - Safety Sample
Hide Description Differences in the incidence of treatment emergent AEs between the treatment groups were examined and evaluated using descriptive statistics. In this analysis, AEs were summarized according to person-phase of occurrence. Each AE was attributed to the person and then to phase 1 or phase 2, depending on the initial date of onset.
Time Frame 12 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
AEs were summarized according to person-phase of occurrence. Each AE will be attributed to the person and then to phase 1 or phase 2, depending on the initial date of onset. If the severity or other characteristic of the AE changes between phases, it can be counted in both phases. Also see Table 5 in Reference.
Arm/Group Title ADAPT Drug Group ADAPT Placebo Group
Hide Arm/Group Description:
Aripiprazole patient-phases from the Drug/Drug and Placebo/Drug Groups
Placebo patient-phases from Placebo/Placebo and Placebo/Drug groups.
Overall Number of Participants Analyzed 115 167
Overall Number of Units Analyzed
Type of Units Analyzed: Participant-phases
115 231
Measure Type: Number
Unit of Measure: adverse events
58 110
7.Other Pre-specified Outcome
Title Number of Patients With Treatment Emergent AEs in Two Treatment Groups - Placebo Non-Responders
Hide Description Differences in the incidence of treatment emergent AEs between the treatment groups were examined and evaluated using descriptive statistics. This analysis focused on placebo non-responders in phase 1 and presented them by their treatment assignment in phase 2.
Time Frame 12 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of the 138 phase 1 placebo non-responders, 14 dropped out in phase 2: 9 in the drug arm and 5 in the placebo arm. Therefore, 124 total placebo non-responders from phase 1 were included in the analysis.
Arm/Group Title Phase 1 Placebo Non-Responders on Drug in Phase 2 Phase 1 Placebo Non-Responders on Placebo in Phase 2
Hide Arm/Group Description:
Patients who received (and had no response) to a Placebo in Phase 1 and then received drug (aripiprazole 2mg/day) in Phase 2
Patients who received (and had no response) to a Placebo in Phase 1 and then received a placebo treatment in Phase 2
Overall Number of Participants Analyzed 61 63
Measure Type: Number
Unit of Measure: Patients
40 44
8.Other Pre-specified Outcome
Title Number of Patients With Treatment Emergent AEs in Two Treatment Groups - People Exclusively on Drug or Placebo Throughout the Study
Hide Description Differences in the incidence of treatment emergent AEs between the treatment groups were examined and evaluated using descriptive statistics. This analysis compared AEs between the arms that received exclusively drug throughout the study or placebo throughout the study.
Time Frame 12 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ADAPT Drug/Drug Group ADAPT Placebo/Placebo Group
Hide Arm/Group Description:
patients randomly assigned to the drug/drug sequence, the dose of aripiprazole will be 2 mg/day during the first phase of the study, and 5 mg/day in the second phase
Patients in the placebo/placebo sequence received a placebo treatment during the first phase of the study, and a placebo treatment in the second phase.
Overall Number of Participants Analyzed 54 83
Measure Type: Number
Unit of Measure: Patients
39 60
Time Frame Adverse events were collected for the 12 week study period.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Drug/Drug Group Placebo/Placebo Group Placebo/Drug Group
Hide Arm/Group Description Aripiprazole will be 2 mg/day during the first phase of the study, and 5 mg/day in the second phase for drug/drug group. Patients on placebo in phases 1 and 2 Patients on placebo in Phase 1 who are on drug in phase 2 (Aripiprazole 2 mg/day)
All-Cause Mortality
Drug/Drug Group Placebo/Placebo Group Placebo/Drug Group
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Drug/Drug Group Placebo/Placebo Group Placebo/Drug Group
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/54 (0.00%)   0/83 (0.00%)   0/85 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Drug/Drug Group Placebo/Placebo Group Placebo/Drug Group
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   39/54 (72.22%)   60/83 (72.29%)   58/85 (68.24%) 
Gastrointestinal disorders       
Constipation  1  6/54 (11.11%)  2/83 (2.41%)  3/85 (3.53%) 
Diarrhoea  1  7/54 (12.96%)  7/83 (8.43%)  9/85 (10.59%) 
Nausea  1  5/54 (9.26%)  9/83 (10.84%)  4/85 (4.71%) 
Dry mouth  1  4/54 (7.41%)  3/83 (3.61%)  2/85 (2.35%) 
General disorders       
Fatigue  1  3/54 (5.56%)  1/83 (1.20%)  5/85 (5.88%) 
Oedema peripheral  1  14/54 (25.93%)  11/83 (13.25%)  1/85 (1.18%) 
Infections and infestations       
Nasopharyngitis  1  7/54 (12.96%)  1/83 (1.20%)  4/85 (4.71%) 
Investigations       
Weight increased  1  13/54 (24.07%)  23/83 (27.71%)  6/85 (7.06%) 
Nervous system disorders       
Somnolence  1  4/54 (7.41%)  3/83 (3.61%)  1/85 (1.18%) 
Headache  1  4/54 (7.41%)  9/83 (10.84%)  13/85 (15.29%) 
Psychiatric disorders       
Insomnia  1  5/54 (9.26%)  7/83 (8.43%)  7/85 (8.24%) 
Respiratory, thoracic and mediastinal disorders       
Upper respiratory tract infection  1  4/54 (7.41%)  7/83 (8.43%)  4/85 (4.71%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
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.
Results Point of Contact
Name/Title: Martina Flynn, Director, Clinical Trial Operations
Organization: Massachusetts General Hospital, CTNI
Phone: 617-643-6028
Responsible Party: Maurizio Fava, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00683852     History of Changes
Other Study ID Numbers: BMS - 2008A053242
First Submitted: May 22, 2008
First Posted: May 26, 2008
Results First Submitted: November 12, 2012
Results First Posted: July 19, 2017
Last Update Posted: July 19, 2017