Major Depressive Disorder (MDD)Phase 3NCT01111565
Study to Evaluate the Efficacy, Safety and Tolerability of an Oral Aripiprazole/Escitalopram Combination Therapy in Participants With Major Depressive Disorder (MDD)
A Phase 3 study testing Escitalopram and Aripiprazole in people with Major Depressive Disorder (MDD), run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 53 sites in 11 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder (MDD)
- What is being tested?
- Escitalopram and Aripiprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 137 participants
- Where
- 53 sitesin 11 countries
- Study dates
- 4 Oct 2010to 1 Sep 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
53 sites in 11 countries.
53 sites in 11 countries
United States15 sites
Study site
Belmont, Massachusetts, 02478
Study site
Brooklyn, New York, 11235
Study site
Chino, California, 91710
Study site
East Providence, Rhode Island, 02914
Study site
Garfield Heights, Ohio, 44125
Study site
Hamden, Connecticut, 06518
Study site
Kirkland, Washington, 98033
Study site
Marietta, Georgia, 30060
Study site
Philadelphia, Pennsylvania, 19107
Study site
Riverside, California, 92506
Study site
Saint Charles, Missouri, 63301
Study site
St Louis, Missouri, 63141
Study site
Torrance, California, 90502
Study site
Tucson, Arizona, 85710
Study site
Weymouth, Massachusetts, 02190
Poland7 sites
Study site
Bełchatów, 97-400
Study site
Bialystok, 15-464
Study site
Bialystok, 15-879
Study Site 1
Choroszcz, 16-070
Study Site 2
Choroszcz, 16-070
Study site
Sosnowiec, 41-200
Study site
Tuszyn, 95-080
South Africa6 sites
Study Site 1
Cape Town, 7530
Study Site 2
Cape Town, 7530
Study site
Durban, 3630
Study site
Pretoria, 0001
Study site
Pretoria, 0145
Study site
Pretoria, 0181
Hungary5 sites
Study site
Baja, 6500
Study site
Balassagyarmat, 2660
Study site
Budapest, 1053
Study site
Budapest, 1137
Study site
Gyula, 5700
Croatia4 sites
Study site
Osijek, 31000
Study site
Rijeka, 51000
Study site
Zagreb, 10000
Study site
Zagreb, 10090
Malaysia4 sites
Study site
Kajang, Selangor, 43000
Study site
Kuala Lumpur, 50603
Study site
Tampoi, Johor Bahru, 80100
Study site
Tampoi, Johor Bahru, 81200
Canada3 sites
Study site
Burlington, Ontario, L7R 4E2
Study site
Penticton, British Columbia, V2A 4M4
Study site
Vancouver, British Columbia, V6Z 2L4
India3 sites
Study site
Hyderabad, Andhra Pradesh, 500034
Study site
Mumbai, Maharashtra, 400605
Study site
Visakhapatnam, Andhra Pradesh, 530002
About this study
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
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.
Read the 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
- Conditions
- Major Depressive Disorder (MDD)
- Being tested
- Escitalopram, Aripiprazole
- Keywords
- Major Depressive Disorder, MDD, Depression
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EscitalopramDrug
Escitalopram capsule administered orally, once daily without regard to meals.
AripiprazoleDrug
Aripiprazole capsule administered orally, once daily without regard to meals.
| Study group | Role | What they receive |
|---|---|---|
| Phase B: Single-blind Prospective Treatment Phase | Experimental | 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+. Receives: Drug: Escitalopram |
| Phase B+: Single-blind Phase B Responders | Experimental | 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+. Receives: Drug: Escitalopram |
| Phase C: Aripiprazole/Escitalopram Combination | Experimental | 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. Receives: Drug: Escitalopram; Drug: Aripiprazole |
| Phase C: Escitalopram Monotherapy | Experimental | 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. Receives: Drug: Escitalopram |
| Phase C: Aripiprazole Monotherapy | Experimental | 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. Receives: Drug: Aripiprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 8 to Week 14
Secondary outcomes (2)
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.
Measured: Week 14
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.
Measured: Week 8 to Week 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2010 (estimated)
- Study start4 Oct 2010
- Primary completion1 Sep 2011
- Study completion1 Sep 2011
Why it 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Major Depressive Disorder (MDD)Studies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 137 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01111565
- Sponsor's protocol ID
- 31-08-263
- Other IDs
- 2010-018859-97
- Status last verified
- Dec 2021
- First submitted
- 22 Apr 2010
- Last updated
- 21 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01111565
- Acronym / sponsor ID
- 31-08-263
- Conditions
- Major Depressive Disorder (MDD)
- Keywords
- Major Depressive Disorder, MDD, Depression
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason 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.
- Enrolment
- 137 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Study start
- 4 Oct 2010 (actual)
- Primary completion
- 1 Sep 2011 (actual)
- Study completion
- 1 Sep 2011 (actual)
- First posted
- 27 Apr 2010 (estimated)
- Results
- Posted 21 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Phase B: Single-blind Prospective Treatment Phase | Experimental | Drug: EscitalopramEscitalopram 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+. |
| Phase B+: Single-blind Phase B Responders | Experimental | Drug: EscitalopramParticipants 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+. |
| Phase C: Aripiprazole/Escitalopram Combination | Experimental | Drug: Escitalopram, Drug: AripiprazoleParticipants 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. |
| Phase C: Escitalopram Monotherapy | Experimental | Drug: EscitalopramParticipants 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. |
| Phase C: Aripiprazole Monotherapy | Experimental | Drug: AripiprazoleParticipants 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EscitalopramEscitalopram capsule administered orally, once daily without regard to meals. | Drug | Phase B+: Single-blind Phase B Responders, Phase B: Single-blind Prospective Treatment Phase, Phase C: Aripiprazole/Escitalopram Combination, Phase C: Escitalopram Monotherapy |
| AripiprazoleAripiprazole capsule administered orally, once daily without regard to meals. | Drug | Phase C: Aripiprazole Monotherapy, Phase C: Aripiprazole/Escitalopram Combination |
Primary outcome
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)
Time frame: Week 8 to 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.
2 secondary outcomes
Phase C: Clinical Global Impression - Improvement Scale (CGI-I) Score at the End of Phase C
Time frame: Week 14
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)
Time frame: Week 8 to Week 14
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
53 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Escitalopram and Aripiprazole in people with Major Depressive Disorder (MDD), run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 53 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 53 sites in United States, Poland, South Africa, Hungary, Croatia and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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) (time frame: Week 8 to Week 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2021; AzTrials last refreshed its copy on 26 Oct 2026.