Study to Evaluate the Efficacy, Safety and Tolerability of an Oral Aripiprazole/Escitalopram Combination Therapy in Participants With Major Depressive Disorder (MDD)

September 28, 2021 updated by: Otsuka Pharmaceutical Development & Commercialization, Inc.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
211

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Estonia
      • Jamejala, Estonia, 71024
      • Tallinn, Estonia, 10617
      • Tartu, Estonia, 50406
      • Tartu, Estonia, 50407
  • Finland
      • Helsinki, Finland, 00250
      • Helsinki, Finland, 00260
      • Kuopio, Finland, 70100
      • Oulu, Finland, 90100
  • Germany
      • Berlin, Germany, 10117
      • Berlin, Germany, 10969
      • Hamburg, Germany, 20246
      • Munich, Germany, 80336
      • Ostfildern, Germany, 73760
  • India
    • Gujarat
      • Ahmedabad, Gujarat, India, 380006
        • Study Site 1
      • Ahmedabad, Gujarat, India, 380006
        • Study Site 2
    • Karnataka
      • Mangalore, Karnataka, India, 575001
    • Maharashtra
      • Mumbai, Maharashtra, India, 400026
      • Pune, Maharashtra, India, 411030
    • Uttar Pradesh
      • Varanasi, Uttar Pradesh, India, 221005
  • Italy
      • Catania, Italy, 95123
      • Siena, Italy, 53100
  • Korea, Republic of
      • Gwangju, Korea, Republic of, 501-75
      • Seoul, Korea, Republic of, 150-713
      • Seoul, Korea, Republic of, 138-736
      • Seoul, Korea, Republic of, 139-872
      • Seoul, Korea, Republic of, 156-755
  • Mexico
      • Durango, Mexico, 34000
      • San Luis Potosi, Mexico, 78218
    • DF
      • Mexico, DF, Mexico, 06700
    • Estado Do Mexico
      • Tlalnepantla de Baz, Estado Do Mexico, Mexico, 54050
    • Jalisco
      • Zapopan, Jalisco, Mexico, 45200
    • Nuevo Leon
      • Monterrey, Nuevo Leon, Mexico, 64040
    • Sinaloa
      • Culiacan, Sinaloa, Mexico, 80020
    • Tabasco
      • Villahermosa, Tabasco, Mexico, 86035
  • Taiwan
      • Changhua, Taiwan, 500
      • Kaohsiung, Taiwan, 802
      • Keelung, Taiwan, 204
      • Taoyuan, Taiwan, 333
  • United States
    • California
      • Cerritos, California, United States, 90703
      • Costa Mesa, California, United States, 92626
      • Irvine, California, United States, 92618
      • San Diego, California, United States, 92102
      • Santa Ana, California, United States, 92705
    • Colorado
      • Denver, Colorado, United States, 80204
    • Connecticut
      • Cromwell, Connecticut, United States, 06416
      • Hartford, Connecticut, United States, 06106
    • Florida
      • Fort Walton Beach, Florida, United States, 32547
      • Gainesville, Florida, United States, 32607
    • Illinois
      • Chicago, Illinois, United States, 60612
      • Libertyville, Illinois, United States, 60048
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
      • Fall River, Massachusetts, United States, 02721
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
    • New York
      • Bronx, New York, United States, 10467
      • Fresh Meadows, New York, United States, 11366
      • Staten Island, New York, United States, 10305
    • North Carolina
      • Cary, North Carolina, United States, 27518
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
    • Tennessee
      • Memphis, Tennessee, United States, 38119
    • Texas
      • DeSoto, Texas, United States, 75115
    • Virginia
      • Richmond, Virginia, United States, 23230
    • Wisconsin
      • Brown Deer, Wisconsin, United States, 53223

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Phase B: Single-blind Prospective Treatment Phase
Participants received initial dose of escitalopram 10 milligram (mg) blinded capsule (over-encapsulated tablet), orally, once daily, increased to 20 mg/day at the end of Week 1 based upon tolerability profile, for up to maximum of Week 8. 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+.
Drug: Escitalopram
Escitalopram capsule administered orally, once daily without regard to meals.
Drug: Blinded capsule
Blinded capsule administered orally, once daily.
Experimental: Phase B+: Single-blind Phase B Responders
Participants with response (≥50% reduction in depressive symptom severity in Hamilton Depression Rating Scale {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 blinded capsules) taken during the final week of Phase B, for up to maximum of Week 14, in Phase B+.
Drug: Escitalopram
Escitalopram capsule administered orally, once daily without regard to meals.
Drug: Blinded capsule
Blinded capsule administered orally, once daily.
Experimental: Phase C: Aripiprazole/Escitalopram Combination
Participants with incomplete response (less than 50% reduction in depressive symptom severity between Baseline and Week 8 measured by the HAM-D17 Total Score and HAM-D17 Total Score of ≥14 at Week 8 and CGI-I Score of ≥3 at Week 6 and 8) at Week 8 received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily at Week 9. Participants were up titrated to aripiprazole target dose of 12 mg/day at Week 10 (if initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on initial 6 mg/day dose), and thereafter received same dose up to maximum of Week 14. No dose increases were allowed for aripiprazole after end of Week 12, however, doses might be decreased at any visit based upon tolerability. In combination with aripiprazole, participants received escitalopram (10 or 20 mg/day blinded capsules) taken during final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments allowed for escitalopram during Phase C.
Drug: Escitalopram
Escitalopram capsule administered orally, once daily without regard to meals.
Drug: Blinded capsule
Blinded capsule administered orally, once daily.
Drug: Aripiprazole
Aripiprazole capsule administered orally, once daily without regard to meals.
Experimental: Phase C: Escitalopram Monotherapy
Participants with incomplete response (less than a 50% reduction in depressive symptom severity between the Baseline and Week 8 as measured by the HAM-D17 Total Score and a HAM-D17 Total Score of ≥14 at Week 8 and a CGI-I Score of ≥3 at Week 6 and 8) at Week 8, received escitalopram dose (10 or 20 mg/day blinded capsules) taken during the final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C.
Drug: Escitalopram
Escitalopram capsule administered orally, once daily without regard to meals.
Drug: Blinded capsule
Blinded capsule administered orally, once daily.
Experimental: Phase C: Aripiprazole Monotherapy
Participants with incomplete response (less than a 50% reduction in depressive symptom severity between the Baseline and Week 8 as measured by the HAM-D17 Total Score and a HAM-D17 Total Score of ≥14 at Week 8 and a CGI-I Score of ≥3 at Week 6 and 8) at Week 8, received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily for Week 9. Participants were up titrated to the aripiprazole target dose of 12 mg/day at Week 10 (if the initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on the initial 6 mg/day dose), and thereafter received the same dose for up to maximum of Week 14. No dose increases were allowed for aripiprazole after the end of Week 12, however, doses might be decreased at any visit based upon tolerability.
Drug: Blinded capsule
Blinded capsule administered orally, once daily.
Drug: Aripiprazole
Aripiprazole capsule administered orally, once daily without regard to meals.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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 from Week 8 indicates improvement.
Week 8 to Week 14

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Phase C: Mean Clinical Global Impression - Improvement (CGI-I) Scale Score at the End of Phase C (Week 14)
Time Frame: Week 14
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.
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
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). 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 from Week 8 indicates improvement.
Week 8 to Week 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 13, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 20, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 20, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 22, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 26, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 27, 2010

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 20, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 28, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 31-08-255
  • 2010-018796-21 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD 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 Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Clinical Study Report (CSR)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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