Trial Outcomes & Findings for Study of Aripiprazole as an Adjunctive Therapy in Patients With Major Depressive Disorder (NCT NCT00876343)
NCT ID: NCT00876343
Last Updated: 2014-02-10
Results Overview
The change in MADRS total score from the end of the SSRI/SNRI treatment period to Week 6 of the placebo-controlled, double-blind treatment period by covariance analysis, and compared the aripiprazole variable dose group with the placebo group as well as the aripiprazole fixed dose group with the placebo group. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The questionnaire includes questions on the following symptoms 1\. Apparent sadness 2. Reported sadness 3. Inner tension 4. Reduced sleep 5. Reduced appetite 6. Concentration difficulties 7. Lassitude 8. Inability to feel 9. Pessimistic thoughts 10. Suicidal thoughts
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
586 participants
Primary outcome timeframe
Baseline (the end of the SSRI/SNRI treatment period), at completion of administration
Results posted on
2014-02-10
Participant Flow
Participant milestones
| Measure |
Variable Dose Group of Aripiprazole
Aripiprazole 3\~15 mg were administered orally once daily. During the first week, 3 mg was administered once daily. Thereafter, each week, a dose increase of 3 mg per day was carried out
|
Fixed Dose Group of Aripiprazole
Aripiprazole 3 mg were administered orally once daily
|
Placebo Group
Placebo were administered orally once daily
|
|---|---|---|---|
|
Overall Study
STARTED
|
194
|
197
|
195
|
|
Overall Study
COMPLETED
|
177
|
180
|
183
|
|
Overall Study
NOT COMPLETED
|
17
|
17
|
12
|
Reasons for withdrawal
| Measure |
Variable Dose Group of Aripiprazole
Aripiprazole 3\~15 mg were administered orally once daily. During the first week, 3 mg was administered once daily. Thereafter, each week, a dose increase of 3 mg per day was carried out
|
Fixed Dose Group of Aripiprazole
Aripiprazole 3 mg were administered orally once daily
|
Placebo Group
Placebo were administered orally once daily
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
7
|
8
|
2
|
|
Overall Study
Withdrawal by Subject
|
4
|
4
|
3
|
|
Overall Study
Lack of Efficacy
|
0
|
0
|
1
|
|
Overall Study
Protocol Violation
|
4
|
1
|
1
|
|
Overall Study
Physician Decision
|
0
|
1
|
1
|
|
Overall Study
Diabetic glucose level or HbA1C>=6.5%
|
0
|
1
|
1
|
|
Overall Study
Change of residence or other commitments
|
2
|
2
|
3
|
Baseline Characteristics
Study of Aripiprazole as an Adjunctive Therapy in Patients With Major Depressive Disorder
Baseline characteristics by cohort
| Measure |
Variable Dose Group of Aripiprazole
n=194 Participants
Aripiprazole 3\~15 mg were administered orally once daily. During the first week, 3 mg was administered once daily. Thereafter, each week, a dose increase of 3 mg per day was carried out
|
Fixed Dose Group of Aripiprazole
n=197 Participants
Aripiprazole 3 mg were administered orally once daily
|
Placebo Group
n=195 Participants
Placebo were administered orally once daily
|
Total
n=586 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
38.1 years
STANDARD_DEVIATION 9.6 • n=99 Participants
|
39.2 years
STANDARD_DEVIATION 9.1 • n=107 Participants
|
38.7 years
STANDARD_DEVIATION 9.2 • n=206 Participants
|
38.7 years
STANDARD_DEVIATION 9.3 • n=7 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
194 Participants
n=99 Participants
|
197 Participants
n=107 Participants
|
195 Participants
n=206 Participants
|
586 Participants
n=7 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Sex: Female, Male
Female
|
93 Participants
n=99 Participants
|
73 Participants
n=107 Participants
|
80 Participants
n=206 Participants
|
246 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
101 Participants
n=99 Participants
|
124 Participants
n=107 Participants
|
115 Participants
n=206 Participants
|
340 Participants
n=7 Participants
|
|
Region of Enrollment
Japan
|
194 participants
n=99 Participants
|
197 participants
n=107 Participants
|
195 participants
n=206 Participants
|
586 participants
n=7 Participants
|
PRIMARY outcome
Timeframe: Baseline (the end of the SSRI/SNRI treatment period), at completion of administrationThe change in MADRS total score from the end of the SSRI/SNRI treatment period to Week 6 of the placebo-controlled, double-blind treatment period by covariance analysis, and compared the aripiprazole variable dose group with the placebo group as well as the aripiprazole fixed dose group with the placebo group. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The questionnaire includes questions on the following symptoms 1\. Apparent sadness 2. Reported sadness 3. Inner tension 4. Reduced sleep 5. Reduced appetite 6. Concentration difficulties 7. Lassitude 8. Inability to feel 9. Pessimistic thoughts 10. Suicidal thoughts
Outcome measures
| Measure |
Variable Dose Group of Aripiprazole
n=194 Participants
Aripiprazole 3\~15 mg were administered orally once daily. During the first week, 3 mg was administered once daily. Thereafter, each week, a dose increase of 3 mg per day was carried out
|
Fixed Dose Group of Aripiprazole
n=197 Participants
Aripiprazole 3 mg were administered orally once daily
|
Placebo Group
n=195 Participants
Placebo were administered orally once daily
|
|---|---|---|---|
|
Mean Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
|
-9.6 Rating score
Standard Error 0.6
|
-10.5 Rating score
Standard Error 0.6
|
-7.4 Rating score
Standard Error 0.6
|
SECONDARY outcome
Timeframe: Baseline (the end of the SSRI/SNRI treatment period), at completion of administrationThe percentage of subjects with a decrease in MADRS total score of 50% or more, from the end of the SSRI/SNRI treatment period to the end of the placebo-controlled, double-blind treatment period (or withdrawal).
Outcome measures
| Measure |
Variable Dose Group of Aripiprazole
n=194 Participants
Aripiprazole 3\~15 mg were administered orally once daily. During the first week, 3 mg was administered once daily. Thereafter, each week, a dose increase of 3 mg per day was carried out
|
Fixed Dose Group of Aripiprazole
n=197 Participants
Aripiprazole 3 mg were administered orally once daily
|
Placebo Group
n=195 Participants
Placebo were administered orally once daily
|
|---|---|---|---|
|
MADRS Response Rate
|
39.2 percentage of subjects
|
42.1 percentage of subjects
|
28.2 percentage of subjects
|
SECONDARY outcome
Timeframe: Baseline (the end of the SSRI/SNRI treatment period), at completion of administrationThe endpoint evaluated the change in SDISS from the end of the SSRI/SNRI treatment period to Week 6 of the placebo-controlled, double-blind treatment period. The patient rates the extent to which his or her 1) work, 2) social life or leisure activities, and 3) home life or family responsibilities are impaired by his or her symptoms on a 10-point visual analog scale. The three items may be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired).
Outcome measures
| Measure |
Variable Dose Group of Aripiprazole
n=194 Participants
Aripiprazole 3\~15 mg were administered orally once daily. During the first week, 3 mg was administered once daily. Thereafter, each week, a dose increase of 3 mg per day was carried out
|
Fixed Dose Group of Aripiprazole
n=197 Participants
Aripiprazole 3 mg were administered orally once daily
|
Placebo Group
n=195 Participants
Placebo were administered orally once daily
|
|---|---|---|---|
|
Mean Change in Sheehan Disability Scale (SDISS)
|
-1.03 Rating score
Standard Error 0.11
|
-0.96 Rating score
Standard Error 0.11
|
-0.46 Rating score
Standard Error 0.11
|
Adverse Events
Variable Dose Group of Aripiprazole
Serious events: 3 serious events
Other events: 140 other events
Deaths: 0 deaths
Fixed Dose Group of Aripiprazole
Serious events: 2 serious events
Other events: 122 other events
Deaths: 0 deaths
Placebo Group
Serious events: 2 serious events
Other events: 92 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Variable Dose Group of Aripiprazole
n=194 participants at risk
Aripiprazole 3\~15 mg were administered orally once daily. During the first week, 3 mg was administered once daily. Thereafter, each week, a dose increase of 3 mg per day was carried out
|
Fixed Dose Group of Aripiprazole
n=197 participants at risk
Aripiprazole 3 mg were administered orally once daily
|
Placebo Group
n=195 participants at risk
Placebo were administered orally once daily
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/194 • 6 weeks
|
0.00%
0/197 • 6 weeks
|
0.51%
1/195 • Number of events 4 • 6 weeks
|
|
Injury, poisoning and procedural complications
Head Injury
|
0.00%
0/194 • 6 weeks
|
0.00%
0/197 • 6 weeks
|
0.51%
1/195 • Number of events 1 • 6 weeks
|
|
Injury, poisoning and procedural complications
Ligament Sprain
|
0.00%
0/194 • 6 weeks
|
0.00%
0/197 • 6 weeks
|
0.51%
1/195 • Number of events 1 • 6 weeks
|
|
Injury, poisoning and procedural complications
Post-Traumatic Neck Syndrome
|
0.00%
0/194 • 6 weeks
|
0.00%
0/197 • 6 weeks
|
0.51%
1/195 • Number of events 1 • 6 weeks
|
|
Injury, poisoning and procedural complications
Traffic Accident
|
0.00%
0/194 • 6 weeks
|
0.00%
0/197 • 6 weeks
|
0.51%
1/195 • Number of events 1 • 6 weeks
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/194 • 6 weeks
|
0.51%
1/197 • Number of events 1 • 6 weeks
|
0.00%
0/195 • 6 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Melanoma
|
0.52%
1/194 • Number of events 1 • 6 weeks
|
0.00%
0/197 • 6 weeks
|
0.00%
0/195 • 6 weeks
|
|
Psychiatric disorders
Delusion
|
0.00%
0/194 • 6 weeks
|
0.51%
1/197 • Number of events 1 • 6 weeks
|
0.00%
0/195 • 6 weeks
|
|
Psychiatric disorders
Hallucination
|
0.00%
0/194 • 6 weeks
|
0.51%
1/197 • Number of events 1 • 6 weeks
|
0.00%
0/195 • 6 weeks
|
|
Psychiatric disorders
Major Depression
|
0.52%
1/194 • Number of events 1 • 6 weeks
|
0.00%
0/197 • 6 weeks
|
0.00%
0/195 • 6 weeks
|
|
Psychiatric disorders
Suicide Attempt
|
0.52%
1/194 • Number of events 1 • 6 weeks
|
0.51%
1/197 • Number of events 1 • 6 weeks
|
0.51%
1/195 • Number of events 1 • 6 weeks
|
|
Skin and subcutaneous tissue disorders
Haemorrhage Subcutaneous
|
0.00%
0/194 • 6 weeks
|
0.00%
0/197 • 6 weeks
|
0.51%
1/195 • Number of events 1 • 6 weeks
|
Other adverse events
| Measure |
Variable Dose Group of Aripiprazole
n=194 participants at risk
Aripiprazole 3\~15 mg were administered orally once daily. During the first week, 3 mg was administered once daily. Thereafter, each week, a dose increase of 3 mg per day was carried out
|
Fixed Dose Group of Aripiprazole
n=197 participants at risk
Aripiprazole 3 mg were administered orally once daily
|
Placebo Group
n=195 participants at risk
Placebo were administered orally once daily
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Discomfort
|
0.52%
1/194 • Number of events 1 • 6 weeks
|
2.5%
5/197 • Number of events 5 • 6 weeks
|
1.0%
2/195 • Number of events 2 • 6 weeks
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
2.1%
4/194 • Number of events 4 • 6 weeks
|
0.51%
1/197 • Number of events 1 • 6 weeks
|
1.0%
2/195 • Number of events 2 • 6 weeks
|
|
Gastrointestinal disorders
Constipation
|
7.7%
15/194 • Number of events 15 • 6 weeks
|
3.6%
7/197 • Number of events 7 • 6 weeks
|
2.1%
4/195 • Number of events 4 • 6 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
2.6%
5/194 • Number of events 5 • 6 weeks
|
3.0%
6/197 • Number of events 6 • 6 weeks
|
5.1%
10/195 • Number of events 10 • 6 weeks
|
|
Gastrointestinal disorders
Nausea
|
3.1%
6/194 • Number of events 6 • 6 weeks
|
4.6%
9/197 • Number of events 10 • 6 weeks
|
5.1%
10/195 • Number of events 10 • 6 weeks
|
|
Gastrointestinal disorders
Salivary Hypersecretion
|
4.1%
8/194 • Number of events 8 • 6 weeks
|
1.0%
2/197 • Number of events 3 • 6 weeks
|
0.00%
0/195 • 6 weeks
|
|
Gastrointestinal disorders
Vomiting
|
0.52%
1/194 • Number of events 1 • 6 weeks
|
2.5%
5/197 • Number of events 6 • 6 weeks
|
1.5%
3/195 • Number of events 3 • 6 weeks
|
|
General disorders
Malaise
|
5.2%
10/194 • Number of events 10 • 6 weeks
|
1.0%
2/197 • Number of events 2 • 6 weeks
|
4.1%
8/195 • Number of events 8 • 6 weeks
|
|
General disorders
Oedema Peripheral
|
2.1%
4/194 • Number of events 4 • 6 weeks
|
0.51%
1/197 • Number of events 1 • 6 weeks
|
0.00%
0/195 • 6 weeks
|
|
General disorders
Pyrexia
|
2.1%
4/194 • Number of events 5 • 6 weeks
|
0.51%
1/197 • Number of events 1 • 6 weeks
|
0.00%
0/195 • 6 weeks
|
|
General disorders
Thirst
|
6.7%
13/194 • Number of events 13 • 6 weeks
|
5.1%
10/197 • Number of events 10 • 6 weeks
|
1.5%
3/195 • Number of events 3 • 6 weeks
|
|
Infections and infestations
Nasopharyngitis
|
16.0%
31/194 • Number of events 32 • 6 weeks
|
15.2%
30/197 • Number of events 31 • 6 weeks
|
14.4%
28/195 • Number of events 31 • 6 weeks
|
|
Investigations
Alanine Aminotransferase Increased
|
6.7%
13/194 • Number of events 13 • 6 weeks
|
7.1%
14/197 • Number of events 14 • 6 weeks
|
1.5%
3/195 • Number of events 3 • 6 weeks
|
|
Investigations
Aspartate Aminotransferase Increased
|
4.1%
8/194 • Number of events 8 • 6 weeks
|
5.1%
10/197 • Number of events 10 • 6 weeks
|
0.51%
1/195 • Number of events 1 • 6 weeks
|
|
Investigations
Blood Alkaline Phosphatase Increased
|
2.1%
4/194 • Number of events 4 • 6 weeks
|
1.0%
2/197 • Number of events 2 • 6 weeks
|
0.00%
0/195 • 6 weeks
|
|
Investigations
Blood Creatine Phosphokinase Increased
|
3.1%
6/194 • Number of events 6 • 6 weeks
|
5.1%
10/197 • Number of events 10 • 6 weeks
|
0.00%
0/195 • 6 weeks
|
|
Investigations
Blood Pressure Increased
|
1.5%
3/194 • Number of events 3 • 6 weeks
|
2.5%
5/197 • Number of events 5 • 6 weeks
|
1.5%
3/195 • Number of events 3 • 6 weeks
|
|
Investigations
Blood Triglycerides Increased
|
4.1%
8/194 • Number of events 9 • 6 weeks
|
2.0%
4/197 • Number of events 4 • 6 weeks
|
1.0%
2/195 • Number of events 2 • 6 weeks
|
|
Investigations
Gamma-Glutamyltransferase Increased
|
2.6%
5/194 • Number of events 5 • 6 weeks
|
3.0%
6/197 • Number of events 6 • 6 weeks
|
0.51%
1/195 • Number of events 1 • 6 weeks
|
|
Investigations
Weight Increased
|
6.2%
12/194 • Number of events 12 • 6 weeks
|
4.1%
8/197 • Number of events 8 • 6 weeks
|
0.51%
1/195 • Number of events 1 • 6 weeks
|
|
Metabolism and nutrition disorders
Increased Appetite
|
3.1%
6/194 • Number of events 6 • 6 weeks
|
1.0%
2/197 • Number of events 2 • 6 weeks
|
1.5%
3/195 • Number of events 3 • 6 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle Rigidity
|
1.0%
2/194 • Number of events 2 • 6 weeks
|
2.5%
5/197 • Number of events 5 • 6 weeks
|
2.1%
4/195 • Number of events 4 • 6 weeks
|
|
Nervous system disorders
Akathisia
|
36.6%
71/194 • Number of events 73 • 6 weeks
|
14.2%
28/197 • Number of events 30 • 6 weeks
|
4.1%
8/195 • Number of events 8 • 6 weeks
|
|
Nervous system disorders
Dizziness
|
1.0%
2/194 • Number of events 2 • 6 weeks
|
2.5%
5/197 • Number of events 5 • 6 weeks
|
3.1%
6/195 • Number of events 6 • 6 weeks
|
|
Nervous system disorders
Dyskinesia
|
1.0%
2/194 • Number of events 2 • 6 weeks
|
2.5%
5/197 • Number of events 6 • 6 weeks
|
0.51%
1/195 • Number of events 1 • 6 weeks
|
|
Nervous system disorders
Dystonia
|
3.1%
6/194 • Number of events 6 • 6 weeks
|
2.0%
4/197 • Number of events 4 • 6 weeks
|
0.00%
0/195 • 6 weeks
|
|
Nervous system disorders
Headache
|
2.1%
4/194 • Number of events 6 • 6 weeks
|
4.6%
9/197 • Number of events 9 • 6 weeks
|
7.7%
15/195 • Number of events 16 • 6 weeks
|
|
Nervous system disorders
Hypoaesthesia
|
0.52%
1/194 • Number of events 1 • 6 weeks
|
2.0%
4/197 • Number of events 4 • 6 weeks
|
0.00%
0/195 • 6 weeks
|
|
Nervous system disorders
Parkinsonism
|
2.1%
4/194 • Number of events 4 • 6 weeks
|
0.00%
0/197 • 6 weeks
|
0.00%
0/195 • 6 weeks
|
|
Nervous system disorders
Somnolence
|
7.7%
15/194 • Number of events 15 • 6 weeks
|
9.6%
19/197 • Number of events 19 • 6 weeks
|
6.7%
13/195 • Number of events 14 • 6 weeks
|
|
Nervous system disorders
Tremor
|
10.3%
20/194 • Number of events 23 • 6 weeks
|
7.1%
14/197 • Number of events 16 • 6 weeks
|
2.6%
5/195 • Number of events 5 • 6 weeks
|
|
Psychiatric disorders
Insomnia
|
5.2%
10/194 • Number of events 10 • 6 weeks
|
4.1%
8/197 • Number of events 8 • 6 weeks
|
1.5%
3/195 • Number of events 3 • 6 weeks
|
|
Psychiatric disorders
Terminal Insomnia
|
2.6%
5/194 • Number of events 5 • 6 weeks
|
0.00%
0/197 • 6 weeks
|
0.00%
0/195 • 6 weeks
|
Additional Information
Director of Clinical Research and Development
Otsuka Pharmaceutical Co., Ld.
Phone: +81-3-6361-7366
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place