Back to resultsStudy to Evaluate the Efficacy, Safety and Tolerability of an Oral Aripiprazole/Escitalopram Combination Therapy in Participants With Major Depressive Disorder (MDD)
Primary Purpose
Major Depressive Disorder (MDD)
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Escitalopram
Aripiprazole
Sponsored by
About this trial
This is an interventional treatment trial for Major Depressive Disorder (MDD) focused on measuring Major Depressive Disorder, MDD, Depression
Eligibility Criteria
Inclusion Criteria:
- Participants with a current diagnosis of a major depressive episode. The current depressive episode must be ≥8 weeks in duration
- Participants willing to discontinue all prohibited psychotropic medication starting from the time of signing the informed consent and during the study period
- Participants with a 17-item Hamilton Depression Rating Scale (HAM-D17) Total Score ≥18 at the Baseline for the Prospective Treatment Phase
Exclusion Criteria:
- Lack of prior treatment with an antidepressant during the current depressive episode
- Participants who report treatment with adjunctive or monotherapy antipsychotic treatment during the current depressive episode.
- Participants experiencing hallucinations, delusions or any psychotic symptomatology in the current depressive episode
- Participants with epilepsy or significant history of seizure disorders
- Participants with a clinically significant current diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder
- Participants who have received electroconvulsive therapy (ECT) in the last 10 years
Sites / Locations
- Study Site 1
- Study Site 2
- Study Site 1
- Study Site 2
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Phase B: Single-blind Prospective Treatment Phase
Phase B+: Single-blind Phase B Responders
Phase C: Aripiprazole/Escitalopram Combination
Phase C: Escitalopram Monotherapy
Phase C: Aripiprazole Monotherapy
Arm Description
Escitalopram 10 mg capsule, orally, once daily increased to 20 mg/day at the Week 1 (end of Week 1) based upon tolerability profile, for 8 weeks. No dose reductions were allowed after Week 4 and no dose increments were allowed after Week 3. Participants with incomplete response at the end of the Phase B (Week 8) entered Phase C and the rest of the participants continued to Phase B+.
Participants with response (≥50% reduction in depressive symptom severity in HAM-D17 Total Score; or a HAM-D17 Total Score of <14 at Week 8 or a Clinical Global Impression of Improvement (CGI-I) Score of <3 at the Week 6 or 8) at the end of the Phase B (Week 8) continued treatment with the single-blind escitalopram monotherapy at the dose (10 or 20 mg/day) taken during the final week of Phase B, for an additional 6 weeks (Up to Week 14), in Phase B+.
Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily in combination with the escitalopram 10 or 20 mg orally for 6 weeks (Up to Week 14), in Phase C. No dose adjustments were allowed for escitalopram during Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated.
Participants with incomplete response at Week 8 who were randomized to this arm group received escitalopram monotherapy 10 or 20 mg capsule, orally, once daily, whichever dose was taken during the final week of Phase B for 6 weeks (Up to Week 14), in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C.
Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily for 6 weeks (Up to Week 14), in Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated. No dose increments were allowed after Week 12; however, doses may have been decreased at any visit, based upon tolerability.
Outcomes
Primary Outcome Measures
Phase C: Mean Change From End of Phase B (Week 8) in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to End of Phase C (Week 14)
The MADRS assessed severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms). Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). A negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms. Last observation carried forward (LOCF) method was used for analyses.
Secondary Outcome Measures
Phase C: Clinical Global Impression - Improvement Scale (CGI-I) Score at the End of Phase C
CGI-I is a 7-point clinician-rated scale ranging from 1 to 7, rated as 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. A higher score indicates greater impairment. LOCF method was used for analyses.
Phase C: Mean Change From End of Phase B (Week 8) in the Sheehan Disability Scale (SDS) Mean Score to End of Phase C (Week 14)
SDS is a 3-item clinician-rated questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. The participant is asked to rate the degree to which their functioning is impaired on an 11-point scale, ranging from 0 (not at all) to 10 (extremely). Scores of 0 to 3 indicate mild functional impairment, 4 to 6 indicate moderate functional impairment, and 7 to 9 indicate marked functional impairment. The scores for the 3 domains are summed into a total score that ranges from 0 (unimpaired) to 30 (highly impaired). A higher score indicates greater impairment. A negative change score indicates improvement. LOCF method was used for analyses.
Full Information
NCT ID
NCT01111565
First Posted
April 22, 2010
Last Updated
December 20, 2021
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01111565
Brief Title
Study to Evaluate the Efficacy, Safety and Tolerability of an Oral Aripiprazole/Escitalopram Combination Therapy in Participants With Major Depressive Disorder (MDD)
Official Title
A Multicenter, Randomized, Double-blind Study to Evaluate the Efficacy, Safety and Tolerability of an Oral Aripiprazole/Escitalopram Combination Therapy in Patients With Major Depressive Disorder
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated early due to Sponsor decision, closure of this combination therapy program is unrelated to any safety issues, no signals of concern.
Study Start Date
October 4, 2010 (Actual)
Primary Completion Date
September 1, 2011 (Actual)
Study Completion Date
September 1, 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This will be a multicenter, randomized, double-blind study designed to assess the efficacy, safety and tolerability of an oral Aripiprazole/Escitalopram combination therapy in participants with MDD who have demonstrated an incomplete response to a prospective trial of Escitalopram, and report a treatment history for the current MDD episode of an inadequate response to at least one and no more than three adequate trials of an approved antidepressant other than Escitalopram. An inadequate response is defined as less than a 50% reduction in depressive symptom severity as assessed by the participant's self-report on the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (ATRQ) and evaluated by the investigator as part of the participant's medical and psychiatric history. An adequate trial is defined as an antidepressant treatment for at least 6 weeks duration (or at least 3 weeks for combination treatments) at an approved dose as specified in the ATRQ.
Detailed Description
The study will be organized as follows:
Screening Phase
Single-blind Prospective Treatment Phase
Single-blind Continuation Phase (Responder)or Double-blind Randomization Phase (non-Responder)
30 day Post Treatment Follow-up
Assigned Interventions:
Escitalopram monotherapy
Aripiprazole/Escitalopram combination therapy
Aripiprazole monotherapy
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder (MDD)
Keywords
Major Depressive Disorder, MDD, Depression
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
137 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase B: Single-blind Prospective Treatment Phase
Arm Type
Experimental
Arm Description
Escitalopram 10 mg capsule, orally, once daily increased to 20 mg/day at the Week 1 (end of Week 1) based upon tolerability profile, for 8 weeks. No dose reductions were allowed after Week 4 and no dose increments were allowed after Week 3. Participants with incomplete response at the end of the Phase B (Week 8) entered Phase C and the rest of the participants continued to Phase B+.
Arm Title
Phase B+: Single-blind Phase B Responders
Arm Type
Experimental
Arm Description
Participants with response (≥50% reduction in depressive symptom severity in HAM-D17 Total Score; or a HAM-D17 Total Score of <14 at Week 8 or a Clinical Global Impression of Improvement (CGI-I) Score of <3 at the Week 6 or 8) at the end of the Phase B (Week 8) continued treatment with the single-blind escitalopram monotherapy at the dose (10 or 20 mg/day) taken during the final week of Phase B, for an additional 6 weeks (Up to Week 14), in Phase B+.
Arm Title
Phase C: Aripiprazole/Escitalopram Combination
Arm Type
Experimental
Arm Description
Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily in combination with the escitalopram 10 or 20 mg orally for 6 weeks (Up to Week 14), in Phase C. No dose adjustments were allowed for escitalopram during Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated.
Arm Title
Phase C: Escitalopram Monotherapy
Arm Type
Experimental
Arm Description
Participants with incomplete response at Week 8 who were randomized to this arm group received escitalopram monotherapy 10 or 20 mg capsule, orally, once daily, whichever dose was taken during the final week of Phase B for 6 weeks (Up to Week 14), in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C.
Arm Title
Phase C: Aripiprazole Monotherapy
Arm Type
Experimental
Arm Description
Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily for 6 weeks (Up to Week 14), in Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated. No dose increments were allowed after Week 12; however, doses may have been decreased at any visit, based upon tolerability.
Intervention Type
Drug
Intervention Name(s)
Escitalopram
Intervention Description
Escitalopram capsule administered orally, once daily without regard to meals.
Intervention Type
Drug
Intervention Name(s)
Aripiprazole
Intervention Description
Aripiprazole capsule administered orally, once daily without regard to meals.
Primary Outcome Measure Information:
Title
Phase C: Mean Change From End of Phase B (Week 8) in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to End of Phase C (Week 14)
Description
The MADRS assessed severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms). Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). A negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms. Last observation carried forward (LOCF) method was used for analyses.
Time Frame
Week 8 to Week 14
Secondary Outcome Measure Information:
Title
Phase C: Clinical Global Impression - Improvement Scale (CGI-I) Score at the End of Phase C
Description
CGI-I is a 7-point clinician-rated scale ranging from 1 to 7, rated as 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. A higher score indicates greater impairment. LOCF method was used for analyses.
Time Frame
Week 14
Title
Phase C: Mean Change From End of Phase B (Week 8) in the Sheehan Disability Scale (SDS) Mean Score to End of Phase C (Week 14)
Description
SDS is a 3-item clinician-rated questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. The participant is asked to rate the degree to which their functioning is impaired on an 11-point scale, ranging from 0 (not at all) to 10 (extremely). Scores of 0 to 3 indicate mild functional impairment, 4 to 6 indicate moderate functional impairment, and 7 to 9 indicate marked functional impairment. The scores for the 3 domains are summed into a total score that ranges from 0 (unimpaired) to 30 (highly impaired). A higher score indicates greater impairment. A negative change score indicates improvement. LOCF method was used for analyses.
Time Frame
Week 8 to Week 14
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants with a current diagnosis of a major depressive episode. The current depressive episode must be ≥8 weeks in duration
Participants willing to discontinue all prohibited psychotropic medication starting from the time of signing the informed consent and during the study period
Participants with a 17-item Hamilton Depression Rating Scale (HAM-D17) Total Score ≥18 at the Baseline for the Prospective Treatment Phase
Exclusion Criteria:
Lack of prior treatment with an antidepressant during the current depressive episode
Participants who report treatment with adjunctive or monotherapy antipsychotic treatment during the current depressive episode.
Participants experiencing hallucinations, delusions or any psychotic symptomatology in the current depressive episode
Participants with epilepsy or significant history of seizure disorders
Participants with a clinically significant current diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder
Participants who have received electroconvulsive therapy (ECT) in the last 10 years
Facility Information:
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85710
Country
United States
City
Chino
State/Province
California
ZIP/Postal Code
91710
Country
United States
City
Riverside
State/Province
California
ZIP/Postal Code
92506
Country
United States
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
City
Hamden
State/Province
Connecticut
ZIP/Postal Code
06518
Country
United States
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30060
Country
United States
City
Belmont
State/Province
Massachusetts
ZIP/Postal Code
02478
Country
United States
City
Weymouth
State/Province
Massachusetts
ZIP/Postal Code
02190
Country
United States
City
Saint Charles
State/Province
Missouri
ZIP/Postal Code
63301
Country
United States
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11235
Country
United States
City
Garfield Heights
State/Province
Ohio
ZIP/Postal Code
44125
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
City
East Providence
State/Province
Rhode Island
ZIP/Postal Code
02914
Country
United States
City
Kirkland
State/Province
Washington
ZIP/Postal Code
98033
Country
United States
City
Penticton
State/Province
British Columbia
ZIP/Postal Code
V2A 4M4
Country
Canada
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 2L4
Country
Canada
City
Burlington
State/Province
Ontario
ZIP/Postal Code
L7R 4E2
Country
Canada
City
Osijek
ZIP/Postal Code
31000
Country
Croatia
City
Rijeka
ZIP/Postal Code
51000
Country
Croatia
City
Zagreb
ZIP/Postal Code
10000
Country
Croatia
City
Zagreb
ZIP/Postal Code
10090
Country
Croatia
City
Douai
ZIP/Postal Code
59500
Country
France
City
Elancourt
ZIP/Postal Code
78990
Country
France
City
Baja
ZIP/Postal Code
6500
Country
Hungary
City
Balassagyarmat
ZIP/Postal Code
2660
Country
Hungary
City
Budapest
ZIP/Postal Code
1053
Country
Hungary
City
Budapest
ZIP/Postal Code
1137
Country
Hungary
City
Gyula
ZIP/Postal Code
5700
Country
Hungary
City
Hyderabad
State/Province
Andhra Pradesh
ZIP/Postal Code
500034
Country
India
City
Visakhapatnam
State/Province
Andhra Pradesh
ZIP/Postal Code
530002
Country
India
City
Mumbai
State/Province
Maharashtra
ZIP/Postal Code
400605
Country
India
City
Tampoi
State/Province
Johor Bahru
ZIP/Postal Code
80100
Country
Malaysia
City
Tampoi
State/Province
Johor Bahru
ZIP/Postal Code
81200
Country
Malaysia
City
Kajang
State/Province
Selangor
ZIP/Postal Code
43000
Country
Malaysia
City
Kuala Lumpur
ZIP/Postal Code
50603
Country
Malaysia
City
Belchatow
ZIP/Postal Code
97-400
Country
Poland
City
Bialystok
ZIP/Postal Code
15-464
Country
Poland
City
Bialystok
ZIP/Postal Code
15-879
Country
Poland
Facility Name
Study Site 1
City
Choroszcz
ZIP/Postal Code
16-070
Country
Poland
Facility Name
Study Site 2
City
Choroszcz
ZIP/Postal Code
16-070
Country
Poland
City
Sosnowiec
ZIP/Postal Code
41-200
Country
Poland
City
Tuszyn
ZIP/Postal Code
95-080
Country
Poland
Facility Name
Study Site 1
City
Cape Town
ZIP/Postal Code
7530
Country
South Africa
Facility Name
Study Site 2
City
Cape Town
ZIP/Postal Code
7530
Country
South Africa
City
Durban
ZIP/Postal Code
3630
Country
South Africa
City
Pretoria
ZIP/Postal Code
0001
Country
South Africa
City
Pretoria
ZIP/Postal Code
0145
Country
South Africa
City
Pretoria
ZIP/Postal Code
0181
Country
South Africa
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
City
Salamanca
ZIP/Postal Code
37002
Country
Spain
City
Göteborg
ZIP/Postal Code
41685
Country
Sweden
City
Malmö
ZIP/Postal Code
21135
Country
Sweden
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
IPD Sharing Time Frame
Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
IPD Sharing Access Criteria
Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
IPD Sharing URL
https://clinical-trials.otsuka.com
Learn more about this trial
Study to Evaluate the Efficacy, Safety and Tolerability of an Oral Aripiprazole/Escitalopram Combination Therapy in Participants With Major Depressive Disorder (MDD)
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