Trial Outcomes & Findings for A Double-Blind, Placebo-Controlled Study of Aripiprazole Adjunctive to Antidepressant Therapy (NCT NCT00683852)

NCT ID: NCT00683852

Last Updated: 2017-07-19

Results Overview

The primary outcome was the difference in response rate (decrease in MADRS total score of at least 50%) using the SPCD (sequential parallel comparison design). 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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 225 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2017-07-19

Participant Flow

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.

Patients completed a SAFER interview before randomization. No other significant events occurred prior to randomization.

Participant milestones

Measure	ADAPT Drug/Drug Group 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.	ADAPT Placebo/Placebo Group 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.	ADAPT Placebo/Drug Group 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.
30-Day Phase 1 Period STARTED	56	84	85
30-Day Phase 1 Period COMPLETED	54	83	84
30-Day Phase 1 Period NOT COMPLETED	2	1	1
30-Day Phase 2 Period STARTED	54	83	84
30-Day Phase 2 Period COMPLETED	48	78	75
30-Day Phase 2 Period NOT COMPLETED	6	5	9

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	ADAPT Drug/Drug Group n=56 Participants 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.	ADAPT Placebo Group (Placebo/Placebo & Placebo/Drug Groups) n=169 Participants 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 n=225 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	56 Participants n=5 Participants	169 Participants n=7 Participants	225 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	45.36 years STANDARD_DEVIATION 10.35 • n=5 Participants	45.06 years STANDARD_DEVIATION 11.34 • n=7 Participants	45.16 years STANDARD_DEVIATION 10.85 • n=5 Participants
Sex: Female, Male Female	37 Participants n=5 Participants	108 Participants n=7 Participants	145 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	61 Participants n=7 Participants	80 Participants n=5 Participants
Region of Enrollment United States	56 participants n=5 Participants	169 participants n=7 Participants	225 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

The primary outcome was the difference in response rate (decrease in MADRS total score of at least 50%) using the SPCD (sequential parallel comparison design). 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.

Outcome measures

Measure	Phase 1 Drug n=54 Participants Patients who received drug in phase 1 (aripiprazole 2 mg/day)	Phase 1 Placebo Non-Responders on Drug in Phase 2 n=61 Participants Patients who received (and had no response) to a Placebo in Phase 1 and then received drug (aripiprazole 2mg/day) in Phase 2	Phase I Placebo n=167 Participants Patients who received Placebo in Phase 1	Phase 1 Placebo Non-Responders on Placebo in Phase 2 n=63 Participants Patients who received (and had no response) to a Placebo in Phase 1 and then received a placebo treatment in Phase 2
MADRS (Montgomery-Asberg Depression Rating Scale) Response Rate	10 Participants	11 Participants	29 Participants	5 Participants

SECONDARY outcome

Timeframe: 12 weeks

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.

Outcome measures

Measure	Phase 1 Drug n=54 Participants Patients who received drug in phase 1 (aripiprazole 2 mg/day)	Phase 1 Placebo Non-Responders on Drug in Phase 2 n=61 Participants Patients who received (and had no response) to a Placebo in Phase 1 and then received drug (aripiprazole 2mg/day) in Phase 2	Phase I Placebo n=167 Participants Patients who received Placebo in Phase 1	Phase 1 Placebo Non-Responders on Placebo in Phase 2 n=63 Participants Patients who received (and had no response) to a Placebo in Phase 1 and then received a placebo treatment in Phase 2
MADRS (Montgomery-Asberg Depression Rating Scale) Readmission Rate	4 Participants	8 Participants	16 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline and 12 Weeks

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.

Outcome measures

Measure	Phase 1 Drug n=54 Participants Patients who received drug in phase 1 (aripiprazole 2 mg/day)	Phase 1 Placebo Non-Responders on Drug in Phase 2 n=61 Participants Patients who received (and had no response) to a Placebo in Phase 1 and then received drug (aripiprazole 2mg/day) in Phase 2	Phase I Placebo n=167 Participants Patients who received Placebo in Phase 1	Phase 1 Placebo Non-Responders on Placebo in Phase 2 n=63 Participants Patients who received (and had no response) to a Placebo in Phase 1 and then received a placebo treatment in Phase 2
Mean Change in MADRS (Montgomery-Asberg Depression Rating Scale) Score From Baseline to the End of Follow-up	-8.54 units on a scale Standard Deviation 7.21	-5.80 units on a scale Standard Deviation 7.08	-8.09 units on a scale Standard Deviation 8.13	-3.32 units on a scale Standard Deviation 5.97

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: This analysis used observed cases rather than LOCF (last observation carried forward), so some participants were missing follow-up data.

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.

Outcome measures

Measure	Phase 1 Drug n=52 Participants Patients who received drug in phase 1 (aripiprazole 2 mg/day)	Phase 1 Placebo Non-Responders on Drug in Phase 2 n=58 Participants Patients who received (and had no response) to a Placebo in Phase 1 and then received drug (aripiprazole 2mg/day) in Phase 2	Phase I Placebo n=162 Participants Patients who received Placebo in Phase 1	Phase 1 Placebo Non-Responders on Placebo in Phase 2 n=61 Participants Patients who received (and had no response) to a Placebo in Phase 1 and then received a placebo treatment in Phase 2
Mean Change in Clinical Global Impression of Severity (CGI-S)	-0.81 units on a scale Standard Deviation 1.03	-0.64 units on a scale Standard Deviation 0.95	-0.84 units on a scale Standard Deviation 1.15	-0.43 units on a scale Standard Deviation 0.78

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: This analysis used observed cases rather than LOCF (last observation carried forward), so some participants were missing follow-up data.

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.

Outcome measures

Measure	Phase 1 Drug n=52 Participants Patients who received drug in phase 1 (aripiprazole 2 mg/day)	Phase 1 Placebo Non-Responders on Drug in Phase 2 n=59 Participants Patients who received (and had no response) to a Placebo in Phase 1 and then received drug (aripiprazole 2mg/day) in Phase 2	Phase I Placebo n=162 Participants Patients who received Placebo in Phase 1	Phase 1 Placebo Non-Responders on Placebo in Phase 2 n=61 Participants Patients who received (and had no response) to a Placebo in Phase 1 and then received a placebo treatment in Phase 2
Mean Change in Symptom Questionnaire (SQ) Sum of 4 subscaled distress scores	-9.44 units on a scale Standard Deviation 11.19	-6.78 units on a scale Standard Deviation 13.78	-9.70 units on a scale Standard Deviation 12.51	-4.52 units on a scale Standard Deviation 9.52
Mean Change in Symptom Questionnaire (SQ) Sum of 4 subscaled well-being scores	3.71 units on a scale Standard Deviation 5.12	3.34 units on a scale Standard Deviation 5.79	2.75 units on a scale Standard Deviation 5.88	1.98 units on a scale Standard Deviation 4.97

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 Weeks

Population: 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.

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.

Outcome measures

Measure	Phase 1 Drug n=115 participant-phases Patients who received drug in phase 1 (aripiprazole 2 mg/day)	Phase 1 Placebo Non-Responders on Drug in Phase 2 n=231 participant-phases Patients who received (and had no response) to a Placebo in Phase 1 and then received drug (aripiprazole 2mg/day) in Phase 2	Phase I Placebo Patients who received Placebo in Phase 1	Phase 1 Placebo Non-Responders on Placebo 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
Treatment Emergent AEs in Two Treatment Groups - Safety Sample	58 adverse events	110 adverse events	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 Weeks

Population: 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.

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.

Outcome measures

Measure	Phase 1 Drug n=61 Participants Patients who received drug in phase 1 (aripiprazole 2 mg/day)	Phase 1 Placebo Non-Responders on Drug in Phase 2 n=63 Participants Patients who received (and had no response) to a Placebo in Phase 1 and then received drug (aripiprazole 2mg/day) in Phase 2	Phase I Placebo Patients who received Placebo in Phase 1	Phase 1 Placebo Non-Responders on Placebo 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
Number of Patients With Treatment Emergent AEs in Two Treatment Groups - Placebo Non-Responders	40 Patients	44 Patients	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 Weeks

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.

Outcome measures

Measure	Phase 1 Drug n=54 Participants Patients who received drug in phase 1 (aripiprazole 2 mg/day)	Phase 1 Placebo Non-Responders on Drug in Phase 2 n=83 Participants Patients who received (and had no response) to a Placebo in Phase 1 and then received drug (aripiprazole 2mg/day) in Phase 2	Phase I Placebo Patients who received Placebo in Phase 1	Phase 1 Placebo Non-Responders on Placebo 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
Number of Patients With Treatment Emergent AEs in Two Treatment Groups - People Exclusively on Drug or Placebo Throughout the Study	39 Patients	60 Patients	—	—

Adverse Events

Drug/Drug Group

Serious events: 0 serious events

Other events: 39 other events

Deaths: 0 deaths

Placebo/Placebo Group

Serious events: 0 serious events

Other events: 60 other events

Deaths: 0 deaths

Placebo/Drug Group

Serious events: 0 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Drug/Drug Group n=54 participants at risk 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.	Placebo/Placebo Group n=83 participants at risk Patients on placebo in phases 1 and 2	Placebo/Drug Group n=85 participants at risk Patients on placebo in Phase 1 who are on drug in phase 2 (Aripiprazole 2 mg/day)
Gastrointestinal disorders Constipation	11.1% 6/54 • Adverse events were collected for the 12 week study period.	2.4% 2/83 • Adverse events were collected for the 12 week study period.	3.5% 3/85 • Adverse events were collected for the 12 week study period.
Gastrointestinal disorders Diarrhoea	13.0% 7/54 • Adverse events were collected for the 12 week study period.	8.4% 7/83 • Adverse events were collected for the 12 week study period.	10.6% 9/85 • Adverse events were collected for the 12 week study period.
Gastrointestinal disorders Nausea	9.3% 5/54 • Adverse events were collected for the 12 week study period.	10.8% 9/83 • Adverse events were collected for the 12 week study period.	4.7% 4/85 • Adverse events were collected for the 12 week study period.
Psychiatric disorders Insomnia	9.3% 5/54 • Adverse events were collected for the 12 week study period.	8.4% 7/83 • Adverse events were collected for the 12 week study period.	8.2% 7/85 • Adverse events were collected for the 12 week study period.
Nervous system disorders Somnolence	7.4% 4/54 • Adverse events were collected for the 12 week study period.	3.6% 3/83 • Adverse events were collected for the 12 week study period.	1.2% 1/85 • Adverse events were collected for the 12 week study period.
General disorders Fatigue	5.6% 3/54 • Adverse events were collected for the 12 week study period.	1.2% 1/83 • Adverse events were collected for the 12 week study period.	5.9% 5/85 • Adverse events were collected for the 12 week study period.
Investigations Weight increased	24.1% 13/54 • Adverse events were collected for the 12 week study period.	27.7% 23/83 • Adverse events were collected for the 12 week study period.	7.1% 6/85 • Adverse events were collected for the 12 week study period.
Nervous system disorders Headache	7.4% 4/54 • Adverse events were collected for the 12 week study period.	10.8% 9/83 • Adverse events were collected for the 12 week study period.	15.3% 13/85 • Adverse events were collected for the 12 week study period.
Gastrointestinal disorders Dry mouth	7.4% 4/54 • Adverse events were collected for the 12 week study period.	3.6% 3/83 • Adverse events were collected for the 12 week study period.	2.4% 2/85 • Adverse events were collected for the 12 week study period.
General disorders Oedema peripheral	25.9% 14/54 • Adverse events were collected for the 12 week study period.	13.3% 11/83 • Adverse events were collected for the 12 week study period.	1.2% 1/85 • Adverse events were collected for the 12 week study period.
Infections and infestations Nasopharyngitis	13.0% 7/54 • Adverse events were collected for the 12 week study period.	1.2% 1/83 • Adverse events were collected for the 12 week study period.	4.7% 4/85 • Adverse events were collected for the 12 week study period.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	7.4% 4/54 • Adverse events were collected for the 12 week study period.	8.4% 7/83 • Adverse events were collected for the 12 week study period.	4.7% 4/85 • Adverse events were collected for the 12 week study period.

Additional Information

Martina Flynn, Director, Clinical Trial Operations

Massachusetts General Hospital, CTNI

Phone: 617-643-6028

Email: mflynn2@partners.org

Results disclosure agreements

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

Restriction type: LTE60