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
Placebo
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 Visit 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
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Arm Label
Phase B: Single-blind Prospective Treatment Phase
Phase B+: Single-blind Phase B Responders
Phase C: Escitalopram Monotherapy
Phase C: Aripiprazole Monotherapy
Phase C: Aripiprazole/Escitalopram Combination Therapy
Arm Description
Escitalopram 10 mg capsule, orally, once daily increased to 20 mg/day at the end of Week 1 based upon tolerability profile, plus one matching placebo capsule, 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 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 plus one matching placebo capsule, for an additional 6 weeks, in Phase B+.
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 plus one matching placebo capsule for 6 weeks, 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 plus one matching placebo capsule for 6 weeks, 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 week, based upon tolerability.
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, once daily plus one matching placebo capsule for 6 weeks, 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.
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 from Week 8 indicates improvement. 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 (Week 14)
The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. Last observation carried forward (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)
The 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. All items are rated on an 11-point continuum (0= no impairment to 10= most severe) with the total SDS score ranging from 0 (no impairment) to 30 (most severe). A negative change from Week 8 indicates improvement. Last observation carried forward (LOCF) method was used for analyses.
Full Information
NCT ID
NCT01111552
First Posted
April 22, 2010
Last Updated
September 29, 2021
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01111552
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
September 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
July 29, 2010 (Actual)
Primary Completion Date
September 27, 2011 (Actual)
Study Completion Date
September 27, 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
237 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase B: Single-blind Prospective Treatment Phase
Arm Type
Active Comparator
Arm Description
Escitalopram 10 mg capsule, orally, once daily increased to 20 mg/day at the end of Week 1 based upon tolerability profile, plus one matching placebo capsule, 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
Active Comparator
Arm Description
Participants with response 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 plus one matching placebo capsule, for an additional 6 weeks, in Phase B+.
Arm Title
Phase C: Escitalopram Monotherapy
Arm Type
Active Comparator
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 plus one matching placebo capsule for 6 weeks, in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C.
Arm Title
Phase C: Aripiprazole Monotherapy
Arm Type
Active Comparator
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 plus one matching placebo capsule for 6 weeks, 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 week, based upon tolerability.
Arm Title
Phase C: Aripiprazole/Escitalopram Combination Therapy
Arm Type
Active Comparator
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, once daily plus one matching placebo capsule for 6 weeks, 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.
Intervention Type
Drug
Intervention Name(s)
Escitalopram
Intervention Description
Escitalopram oral capsules.
Intervention Type
Drug
Intervention Name(s)
Aripiprazole
Other Intervention Name(s)
OPC-14597
Intervention Description
Aripiprazole oral capsules.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Study drug matching placebo capsule.
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 from Week 8 indicates improvement. 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 (Week 14)
Description
The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. Last observation carried forward (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
The 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. All items are rated on an 11-point continuum (0= no impairment to 10= most severe) with the total SDS score ranging from 0 (no impairment) to 30 (most severe). A negative change from Week 8 indicates improvement. Last observation carried forward (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 Visit 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
Birmingham
State/Province
Alabama
ZIP/Postal Code
35216
Country
United States
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72223
Country
United States
City
Carson
State/Province
California
ZIP/Postal Code
90746
Country
United States
City
Garden Grove
State/Province
California
ZIP/Postal Code
95231
Country
United States
City
Imperial
State/Province
California
ZIP/Postal Code
92251
Country
United States
City
Mission Viejo
State/Province
California
ZIP/Postal Code
92691
Country
United States
City
Redlands
State/Province
California
ZIP/Postal Code
92374
Country
United States
City
San Diego
State/Province
California
ZIP/Postal Code
92128
Country
United States
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30328
Country
United States
City
Hoffman Estates
State/Province
Illinois
ZIP/Postal Code
60169
Country
United States
City
Terre Haute
State/Province
Indiana
ZIP/Postal Code
47802
Country
United States
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66211
Country
United States
City
Prairie Village
State/Province
Kansas
ZIP/Postal Code
66206
Country
United States
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67207
Country
United States
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21204
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43623
Country
United States
City
Bartlett
State/Province
Tennessee
ZIP/Postal Code
38134
Country
United States
City
Wichita Falls
State/Province
Texas
ZIP/Postal Code
76309
Country
United States
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4000
Country
Australia
City
Everton Park
State/Province
Queensland
ZIP/Postal Code
4053
Country
Australia
City
Malvern
State/Province
Victoria
ZIP/Postal Code
3144
Country
Australia
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
City
Fremantle
State/Province
Western Australia
ZIP/Postal Code
6959
Country
Australia
City
Bourgas
ZIP/Postal Code
8000
Country
Bulgaria
City
Lovech
ZIP/Postal Code
5500
Country
Bulgaria
City
Novi Iskar
ZIP/Postal Code
1282
Country
Bulgaria
City
Pleven
ZIP/Postal Code
5800
Country
Bulgaria
City
Plovdiv
ZIP/Postal Code
4000
Country
Bulgaria
City
Rousse
ZIP/Postal Code
7003
Country
Bulgaria
City
Sofia
ZIP/Postal Code
1113
Country
Bulgaria
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
City
Sofia
ZIP/Postal Code
1606
Country
Bulgaria
City
Tsarev Brod
ZIP/Postal Code
9747
Country
Bulgaria
City
Tserova Koria
ZIP/Postal Code
5047
Country
Bulgaria
City
Varna
ZIP/Postal Code
9000
Country
Bulgaria
City
Tirupati
State/Province
Andhra Pradesh
ZIP/Postal Code
517507
Country
India
City
Vijayawada
State/Province
Andhra Pradesh
ZIP/Postal Code
500072
Country
India
City
Manipala
State/Province
Karnataka
ZIP/Postal Code
576104
Country
India
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411004
Country
India
City
Ludhiana
State/Province
Punjab
ZIP/Postal Code
141001
Country
India
City
Chennai
State/Province
Tamil Nadu
ZIP/Postal Code
600003
Country
India
City
Kanpur
State/Province
Uttar Pradesh
ZIP/Postal Code
208005
Country
India
City
Quezon City
State/Province
NCR
ZIP/Postal Code
1101
Country
Philippines
City
Quezon City
State/Province
NCR
ZIP/Postal Code
1102
Country
Philippines
City
Bucuresti
ZIP/Postal Code
010825
Country
Romania
City
Bucuresti
ZIP/Postal Code
030455
Country
Romania
Facility Name
Study Site 1
City
Bucuresti
ZIP/Postal Code
041914
Country
Romania
Facility Name
Study Site 2
City
Bucuresti
ZIP/Postal Code
041914
Country
Romania
City
Craiova
ZIP/Postal Code
200620
Country
Romania
City
Craiova
ZIP/Postal Code
540139
Country
Romania
City
Iasi
ZIP/Postal Code
700282
Country
Romania
City
Targoviste
ZIP/Postal Code
130081
Country
Romania
City
Targu Mures
ZIP/Postal Code
540139
Country
Romania
City
Michalovce
ZIP/Postal Code
07101
Country
Slovakia
City
Rimavska Sobota
ZIP/Postal Code
97901
Country
Slovakia
City
Svidnik
ZIP/Postal Code
8901
Country
Slovakia
City
Trencin
ZIP/Postal Code
91101
Country
Slovakia
City
Zlate Moravce
ZIP/Postal Code
95301
Country
Slovakia
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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