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Assess the Efficacy and Safety of ASC-01 in Patients With Major Depressive Disorder

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ClinicalTrials.gov Identifier: NCT02046564
Recruitment Status : Completed
First Posted : January 28, 2014
Results First Posted : May 21, 2018
Last Update Posted : May 21, 2018
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Co., Ltd.

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: ASC-01
Drug: Placebo
Enrollment 412
Recruitment Details  
Pre-assignment Details  
Arm/Group Title ASC-01 Placebo
Hide Arm/Group Description
  • Formulation A: ASC-01 (aripiprazole/sertraline combination) 3 mg/100 mg tablet
  • Formulation B: ASC-01 (aripiprazole/sertraline combination) 6 mg/100 mg tablet
  • Formulation C: ASC-01 (aripiprazole/sertraline combination) 9 mg/100 mg tablet
  • Formulation D: ASC-01 (aripiprazole/sertraline combination) 12 mg/100 mg tablet Formulation A or, B, C, or D was orally administered once daily. For Week 1, Formulation A was administered after which administration was conducted according to the dose-increase criteria. The formulation was fixed from Week 5 to Week 6.
The dose of 0mg/100mg (Placebo/Sertraline Combination )will be orally administered once daily.
Period Title: Overall Study
Started 209 203
Completed 194 183
Not Completed 15 20
Reason Not Completed
Adverse Event             6             3
Physician Decision             0             1
Protocol Violation             3             1
Withdrawal by Subject             4             10
Subject met withdrawal criteria             2             5
Arm/Group Title ASC-01 Placebo Total
Hide Arm/Group Description
  • Formulation A: ASC-01 (aripiprazole/sertraline combination) 3 mg/100 mg tablet
  • Formulation B: ASC-01 (aripiprazole/sertraline combination) 6 mg/100 mg tablet
  • Formulation C: ASC-01 (aripiprazole/sertraline combination) 9 mg/100 mg tablet
  • Formulation D: ASC-01 (aripiprazole/sertraline combination) 12 mg/100 mg tablet Formulation A or, B, C, or D was orally administered once daily. For Week 1, Formulation A was administered after which administration was conducted according to the dose-increase criteria. The formulation was fixed from Week 5 to Week 6.
The dose of 0mg/100mg (Placebo/Sertraline Combination )will be orally administered once daily. Total of all reporting groups
Overall Number of Baseline Participants 208 203 411
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 208 participants 203 participants 411 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
208
 100.0%
203
 100.0%
411
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 208 participants 203 participants 411 participants
38.3  (11.8) 39.5  (11.8) 38.9  (11.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 208 participants 203 participants 411 participants
Female
79
  38.0%
72
  35.5%
151
  36.7%
Male
129
  62.0%
131
  64.5%
260
  63.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 208 participants 203 participants 411 participants
South Korea 36 42 78
Japan 157 142 299
Taiwan 7 10 17
Malaysia 6 5 11
Australia 2 4 6
1.Primary Outcome
Title The Mean Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
Hide Description The MADRS is a clinician-rated scale which evaluates the level of depression. The MADRS consists of 10 items assessing apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thought. Each item is scored from 0 to 6, with higher scores indicating worse condition.Summed subscales are combined to compute a total score. Total score ranges from 0 to 60, with higher score indicating worse condition.
Time Frame 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF])
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ASC-01 Placebo
Hide Arm/Group Description:
  • Formulation A: ASC-01 (aripiprazole/sertraline combination) 3 mg/100 mg tablet
  • Formulation B: ASC-01 (aripiprazole/sertraline combination) 6 mg/100 mg tablet
  • Formulation C: ASC-01 (aripiprazole/sertraline combination) 9 mg/100 mg tablet
  • Formulation D: ASC-01 (aripiprazole/sertraline combination) 12 mg/100 mg tablet Formulation A or, B, C, or D was orally administered once daily. For Week 1, Formulation A was administered after which administration was conducted according to the dose-increase criteria. The formulation was fixed from Week 5 to Week 6.
The dose of 0mg/100mg (Placebo/Sertraline Combination )will be orally administered once daily.
Overall Number of Participants Analyzed 208 203
Mean (Standard Error)
Unit of Measure: units on a scale
-9.2  (0.5) -7.2  (0.5)
2.Secondary Outcome
Title The Montgomery-Åsberg Depression Rating Scale (MADRS) Response Rate
Time Frame 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF])
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ASC-01 Placebo
Hide Arm/Group Description:
  • Formulation A: ASC-01 (aripiprazole/sertraline combination) 3 mg/100 mg tablet
  • Formulation B: ASC-01 (aripiprazole/sertraline combination) 6 mg/100 mg tablet
  • Formulation C: ASC-01 (aripiprazole/sertraline combination) 9 mg/100 mg tablet
  • Formulation D: ASC-01 (aripiprazole/sertraline combination) 12 mg/100 mg tablet Formulation A or, B, C, or D was orally administered once daily. For Week 1, Formulation A was administered after which administration was conducted according to the dose-increase criteria. The formulation was fixed from Week 5 to Week 6.
The dose of 0mg/100mg (Placebo/Sertraline Combination )will be orally administered once daily.
Overall Number of Participants Analyzed 208 203
Measure Type: Number
Unit of Measure: percentage of participants
37.5 25.6
3.Secondary Outcome
Title The Montgomery-Åsberg Depression Rating Scale (MADRS) Remission Rate
Time Frame 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF])
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ASC-01 Placebo
Hide Arm/Group Description:
  • Formulation A: ASC-01 (aripiprazole/sertraline combination) 3 mg/100 mg tablet
  • Formulation B: ASC-01 (aripiprazole/sertraline combination) 6 mg/100 mg tablet
  • Formulation C: ASC-01 (aripiprazole/sertraline combination) 9 mg/100 mg tablet
  • Formulation D: ASC-01 (aripiprazole/sertraline combination) 12 mg/100 mg tablet Formulation A or, B, C, or D was orally administered once daily. For Week 1, Formulation A was administered after which administration was conducted according to the dose-increase criteria. The formulation was fixed from Week 5 to Week 6.
The dose of 0mg/100mg (Placebo/Sertraline Combination )will be orally administered once daily.
Overall Number of Participants Analyzed 208 203
Measure Type: Number
Unit of Measure: percentage of participants
29.3 20.2
4.Secondary Outcome
Title The Clinical Global Impression - Improvement (CGI-I) Improvement Rate
Hide Description The CGI-I Scale is a clinician-rated scale which assesses the total improvement of the patient’s condition compared to that at baseline. Scores range from 0 to 7: 0 = Not assessed, 1= Very much improved, 2 = Much improved, 3= Minimally improved, 4= No change, 5= Minimally worse, 6= Much worse, 7= Very much worse. Higher scores indicate worse condition. CGI-I Improvement Rate is the percentage of subjects whose CGI-I score is 1 or 2.
Time Frame 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF])
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ASC-01 Placebo
Hide Arm/Group Description:
  • Formulation A: ASC-01 (aripiprazole/sertraline combination) 3 mg/100 mg tablet
  • Formulation B: ASC-01 (aripiprazole/sertraline combination) 6 mg/100 mg tablet
  • Formulation C: ASC-01 (aripiprazole/sertraline combination) 9 mg/100 mg tablet
  • Formulation D: ASC-01 (aripiprazole/sertraline combination) 12 mg/100 mg tablet Formulation A or, B, C, or D was orally administered once daily. For Week 1, Formulation A was administered after which administration was conducted according to the dose-increase criteria. The formulation was fixed from Week 5 to Week 6.
The dose of 0mg/100mg (Placebo/Sertraline Combination )will be orally administered once daily.
Overall Number of Participants Analyzed 208 203
Measure Type: Number
Unit of Measure: percentage of participants
46.2 34.5
5.Secondary Outcome
Title The Mean Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S)
Hide Description The CGI-S Scale is a clinician-rated scale which assesses how mentally ill the patient is at the time. Scores range from 0 to 7: 0 = Not assessed, 1= Normal, not at all ill, 2 =Borderline mentally ill, 3= Mildly ill, 4= Moderately ill, 5= Markedly ill, 6= Severely ill, 7= Among the most extremely ill patients. Higher scores indicate worse condition.
Time Frame 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF])
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ASC-01 Placebo
Hide Arm/Group Description:
  • Formulation A: ASC-01 (aripiprazole/sertraline combination) 3 mg/100 mg tablet
  • Formulation B: ASC-01 (aripiprazole/sertraline combination) 6 mg/100 mg tablet
  • Formulation C: ASC-01 (aripiprazole/sertraline combination) 9 mg/100 mg tablet
  • Formulation D: ASC-01 (aripiprazole/sertraline combination) 12 mg/100 mg tablet Formulation A or, B, C, or D was orally administered once daily. For Week 1, Formulation A was administered after which administration was conducted according to the dose-increase criteria. The formulation was fixed from Week 5 to Week 6.
The dose of 0mg/100mg (Placebo/Sertraline Combination )will be orally administered once daily.
Overall Number of Participants Analyzed 208 203
Mean (Standard Error)
Unit of Measure: units on a scale
-1.0  (0.1) -0.8  (0.1)
6.Secondary Outcome
Title The Mean Change From Baseline in the Hamilton Depression Rating Scale 17 (HAM-D17) Total Score
Hide Description

The HAM-D is a clinician-rated scale which evaluates the level of depression. The HAM-D consists of 17 items such as depression mood, feeling of guilt, suicide, insomnia, work and activities, retardation, and so on.

Each item is scored from 0 to 2, 3 or 4, with higher scores indicating worse condition. Summed subscales are combined to compute a total score. Total score ranges from 0 to 52, with higher score indicating worse condition.

Time Frame 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF])
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ASC-01 Placebo
Hide Arm/Group Description:
  • Formulation A: ASC-01 (aripiprazole/sertraline combination) 3 mg/100 mg tablet
  • Formulation B: ASC-01 (aripiprazole/sertraline combination) 6 mg/100 mg tablet
  • Formulation C: ASC-01 (aripiprazole/sertraline combination) 9 mg/100 mg tablet
  • Formulation D: ASC-01 (aripiprazole/sertraline combination) 12 mg/100 mg tablet Formulation A or, B, C, or D was orally administered once daily. For Week 1, Formulation A was administered after which administration was conducted according to the dose-increase criteria. The formulation was fixed from Week 5 to Week 6.
The dose of 0mg/100mg (Placebo/Sertraline Combination )will be orally administered once daily.
Overall Number of Participants Analyzed 208 203
Mean (Standard Error)
Unit of Measure: units on a scale
-6.8  (0.4) -5.6  (0.4)
7.Secondary Outcome
Title The Mean Change From Baseline in the Social Adaptation Self-evaluation Scale (SASS) Total Score
Hide Description The SASS is a self-rating scale which assesses the social motivation and behavior in participants with depression. The SASS consists of 21 items covering the different aspects of social interactions, global social attitude, and self-perception. Each item is scored from 0 to 3, with higher scores indicating better condition.
Time Frame 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF])
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ASC-01 Placebo
Hide Arm/Group Description:
  • Formulation A: ASC-01 (aripiprazole/sertraline combination) 3 mg/100 mg tablet
  • Formulation B: ASC-01 (aripiprazole/sertraline combination) 6 mg/100 mg tablet
  • Formulation C: ASC-01 (aripiprazole/sertraline combination) 9 mg/100 mg tablet
  • Formulation D: ASC-01 (aripiprazole/sertraline combination) 12 mg/100 mg tablet Formulation A or, B, C, or D was orally administered once daily. For Week 1, Formulation A was administered after which administration was conducted according to the dose-increase criteria. The formulation was fixed from Week 5 to Week 6.
The dose of 0mg/100mg (Placebo/Sertraline Combination )will be orally administered once daily.
Overall Number of Participants Analyzed 164 149
Mean (Standard Error)
Unit of Measure: units on a scale
3.7  (0.3) 1.5  (0.3)
8.Secondary Outcome
Title The Mean Change From Baseline in the Apathy Scale (AS) Total Score
Hide Description The AS consists of 14 items. Items 1-8 are scored as follows: 3= Not at all, 2= Slightly, 1= Some, 0= A lot. Items 9-14 are scored as follows: 0= Not at all, 1= Slightly, 2= Some, 3= A lot. Total score ranges from 0-42, with higher score indicating worse condition.
Time Frame 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF])
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ASC-01 Placebo
Hide Arm/Group Description:
  • Formulation A: ASC-01 (aripiprazole/sertraline combination) 3 mg/100 mg tablet
  • Formulation B: ASC-01 (aripiprazole/sertraline combination) 6 mg/100 mg tablet
  • Formulation C: ASC-01 (aripiprazole/sertraline combination) 9 mg/100 mg tablet
  • Formulation D: ASC-01 (aripiprazole/sertraline combination) 12 mg/100 mg tablet Formulation A or, B, C, or D was orally administered once daily. For Week 1, Formulation A was administered after which administration was conducted according to the dose-increase criteria. The formulation was fixed from Week 5 to Week 6.
The dose of 0mg/100mg (Placebo/Sertraline Combination )will be orally administered once daily.
Overall Number of Participants Analyzed 164 149
Mean (Standard Error)
Unit of Measure: units on a scale
-3.3  (0.4) -1.1  (0.4)
9.Secondary Outcome
Title The Mean Change From Baseline in the Self-rating Version of Montgomery-Åsberg Depression Rating Scale (MADRS-S) Total Score
Hide Description The MADRS-S is a patient-reported scale based on MADRS, administered to evaluate the level of depression. This scale consists of 9 items assessing patients' mood, feelings of unease, sleep, appetite, ability to concentrate, initiative, emotional involvement, pessimism and zest for life. Each item is scored from 0 to 3, with higher scores indicating worse condition. Summed subscales are combined to compute a total score. Total score ranges from 0 to 27, with higher score indicating worse condition.
Time Frame 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF])
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ASC-01 Placebo
Hide Arm/Group Description:
  • Formulation A: ASC-01 (aripiprazole/sertraline combination) 3 mg/100 mg tablet
  • Formulation B: ASC-01 (aripiprazole/sertraline combination) 6 mg/100 mg tablet
  • Formulation C: ASC-01 (aripiprazole/sertraline combination) 9 mg/100 mg tablet
  • Formulation D: ASC-01 (aripiprazole/sertraline combination) 12 mg/100 mg tablet Formulation A or, B, C, or D was orally administered once daily. For Week 1, Formulation A was administered after which administration was conducted according to the dose-increase criteria. The formulation was fixed from Week 5 to Week 6.
The dose of 0mg/100mg (Placebo/Sertraline Combination )will be orally administered once daily.
Overall Number of Participants Analyzed 208 203
Mean (Standard Error)
Unit of Measure: units on a scale
-2.85  (0.22) -1.86  (0.23)
Time Frame Double-blind period (6 weeks)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title ASC-01 Placebo
Hide Arm/Group Description
  • Formulation A: ASC-01 (aripiprazole/sertraline combination) 3 mg/100 mg tablet
  • Formulation B: ASC-01 (aripiprazole/sertraline combination) 6 mg/100 mg tablet
  • Formulation C: ASC-01 (aripiprazole/sertraline combination) 9 mg/100 mg tablet
  • Formulation D: ASC-01 (aripiprazole/sertraline combination) 12 mg/100 mg tablet Formulation A or, B, C, or D was orally administered once daily. For Week 1, Formulation A was administered after which administration was conducted according to the dose-increase criteria. The formulation was fixed from Week 5 to Week 6.
The dose of 0mg/100mg (Placebo/Sertraline Combination )will be orally administered once daily.
All-Cause Mortality
ASC-01 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/209 (0.00%)      0/203 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
ASC-01 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/209 (0.00%)      2/203 (0.99%)    
Gastrointestinal disorders     
Gastric ulcer  1  0/209 (0.00%)  0 1/203 (0.49%)  1
Injury, poisoning and procedural complications     
Clavicle fracture  1  0/209 (0.00%)  0 1/203 (0.49%)  1
1
Term from vocabulary, MedDRA Ver. 19.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
ASC-01 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   128/209 (61.24%)      107/203 (52.71%)    
Gastrointestinal disorders     
Constipation  1  5/209 (2.39%)  4/203 (1.97%) 
Diarrhoea  1  2/209 (0.96%)  4/203 (1.97%) 
Nausea  1  9/209 (4.31%)  10/203 (4.93%) 
Stomatitis  1  1/209 (0.48%)  4/203 (1.97%) 
Vomiting  1  5/209 (2.39%)  3/203 (1.48%) 
General disorders     
Drug withdrawal syndrome  1  5/209 (2.39%)  3/203 (1.48%) 
Infections and infestations     
Nasopharyngitis  1  28/209 (13.40%)  23/203 (11.33%) 
Investigations     
Alanine aminotransferase increased  1  6/209 (2.87%)  2/203 (0.99%) 
Aspartate aminotransferase increased  1  5/209 (2.39%)  1/203 (0.49%) 
Weight increased  1  9/209 (4.31%)  1/203 (0.49%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/209 (0.48%)  4/203 (1.97%) 
Muscle rigidity  1  0/209 (0.00%)  5/203 (2.46%) 
Nervous system disorders     
Akathisia  1  27/209 (12.92%)  7/203 (3.45%) 
Dizziness  1  10/209 (4.78%)  10/203 (4.93%) 
Headache  1  8/209 (3.83%)  13/203 (6.40%) 
Somnolence  1  5/209 (2.39%)  5/203 (2.46%) 
Tremor  1  12/209 (5.74%)  11/203 (5.42%) 
Psychiatric disorders     
Insomnia  1  9/209 (4.31%)  5/203 (2.46%) 
1
Term from vocabulary, MedDRA Ver. 19.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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: Director of Clinical Trials
Organization: Otsuka Pharmaceutical Co. Ltd.
Phone: +81-3-6361-7366
Responsible Party: Otsuka Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier: NCT02046564     History of Changes
Other Study ID Numbers: 031-12-005
JapicCTI-142413 ( Other Identifier: Japic )
First Submitted: January 23, 2014
First Posted: January 28, 2014
Results First Submitted: August 16, 2017
Results First Posted: May 21, 2018
Last Update Posted: May 21, 2018