NCT01111552

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.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
237

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Jul 2010

Shorter than P25 for phase_3

Geographic Reach
7 countries

60 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 22, 2010

Completed
5 days until next milestone

First Posted

Study publicly available on registry

April 27, 2010

Completed
3 months until next milestone

Study Start

First participant enrolled

July 29, 2010

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 27, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 27, 2011

Completed
10.1 years until next milestone

Results Posted

Study results publicly available

October 26, 2021

Completed
Last Updated

October 26, 2021

Status Verified

September 1, 2021

Enrollment Period

1.2 years

First QC Date

April 22, 2010

Results QC Date

September 29, 2021

Last Update Submit

September 29, 2021

Conditions

Keywords

Major Depressive DisorderMDDDepression

Outcome Measures

Primary Outcomes (1)

  • 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.

    Week 8 to Week 14

Secondary Outcomes (2)

  • Phase C: Clinical Global Impression - Improvement Scale (CGI-I) Score at The End of Phase C (Week 14)

    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)

    Week 8 to Week 14

Study Arms (5)

Phase B: Single-blind Prospective Treatment Phase

ACTIVE COMPARATOR

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+.

Drug: EscitalopramDrug: Placebo

Phase B+: Single-blind Phase B Responders

ACTIVE COMPARATOR

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+.

Drug: EscitalopramDrug: Placebo

Phase C: Escitalopram Monotherapy

ACTIVE COMPARATOR

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.

Drug: EscitalopramDrug: Placebo

Phase C: Aripiprazole Monotherapy

ACTIVE COMPARATOR

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.

Drug: AripiprazoleDrug: Placebo

Phase C: Aripiprazole/Escitalopram Combination Therapy

ACTIVE COMPARATOR

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.

Drug: EscitalopramDrug: AripiprazoleDrug: Placebo

Interventions

Escitalopram oral capsules.

Phase B+: Single-blind Phase B RespondersPhase B: Single-blind Prospective Treatment PhasePhase C: Aripiprazole/Escitalopram Combination TherapyPhase C: Escitalopram Monotherapy

Aripiprazole oral capsules.

Also known as: OPC-14597
Phase C: Aripiprazole MonotherapyPhase C: Aripiprazole/Escitalopram Combination Therapy

Study drug matching placebo capsule.

Phase B+: Single-blind Phase B RespondersPhase B: Single-blind Prospective Treatment PhasePhase C: Aripiprazole MonotherapyPhase C: Aripiprazole/Escitalopram Combination TherapyPhase C: Escitalopram Monotherapy

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (60)

Unknown Facility

Birmingham, Alabama, 35216, United States

Location

Unknown Facility

Little Rock, Arkansas, 72223, United States

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Unknown Facility

Carson, California, 90746, United States

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Unknown Facility

Garden Grove, California, 95231, United States

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Unknown Facility

Imperial, California, 92251, United States

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Unknown Facility

Mission Viejo, California, 92691, United States

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Unknown Facility

Redlands, California, 92374, United States

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Unknown Facility

San Diego, California, 92128, United States

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Atlanta, Georgia, 30308, United States

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Unknown Facility

Atlanta, Georgia, 30328, United States

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Unknown Facility

Hoffman Estates, Illinois, 60169, United States

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Unknown Facility

Terre Haute, Indiana, 47802, United States

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Unknown Facility

Overland Park, Kansas, 66211, United States

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Unknown Facility

Prairie Village, Kansas, 66206, United States

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Wichita, Kansas, 67207, United States

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Baltimore, Maryland, 21204, United States

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New York, New York, 10021, United States

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Toledo, Ohio, 43623, United States

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Bartlett, Tennessee, 38134, United States

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Wichita Falls, Texas, 76309, United States

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Brisbane, Queensland, 4000, Australia

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Everton Park, Queensland, 4053, Australia

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Malvern, Victoria, 3144, Australia

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Melbourne, Victoria, 3004, Australia

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Fremantle, Western Australia, 6959, Australia

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Unknown Facility

Burgas, 8000, Bulgaria

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Lovech, 5500, Bulgaria

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Novi Iskar, 1282, Bulgaria

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Unknown Facility

Pleven, 5800, Bulgaria

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Plovdiv, 4000, Bulgaria

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Rousse, 7003, Bulgaria

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Sofia, 1113, Bulgaria

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Unknown Facility

Sofia, 1431, Bulgaria

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Unknown Facility

Sofia, 1606, Bulgaria

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Unknown Facility

Tsarev Brod, 9747, Bulgaria

Location

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Tserova Koria, 5047, Bulgaria

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Varna, 9000, Bulgaria

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Unknown Facility

Tirupati, Andhra Pradesh, 517507, India

Location

Unknown Facility

Vijayawada, Andhra Pradesh, 500072, India

Location

Unknown Facility

Manipal, Karnataka, 576104, India

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Unknown Facility

Pune, Maharashtra, 411004, India

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Unknown Facility

Ludhiana, Punjab, 141001, India

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Unknown Facility

Chennai, Tamil Nadu, 600003, India

Location

Unknown Facility

Kanpur, Uttar Pradesh, 208005, India

Location

Unknown Facility

Quezon City, NCR, 1101, Philippines

Location

Unknown Facility

Quezon City, NCR, 1102, Philippines

Location

Unknown Facility

Bucharest, 010825, Romania

Location

Unknown Facility

Bucharest, 030455, Romania

Location

Study Site 1

Bucharest, 041914, Romania

Location

Study Site 2

Bucharest, 041914, Romania

Location

Unknown Facility

Craiova, 200620, Romania

Location

Unknown Facility

Craiova, 540139, Romania

Location

Unknown Facility

Iași, 700282, Romania

Location

Unknown Facility

Târgovişte, 130081, Romania

Location

Unknown Facility

Târgu Mureş, 540139, Romania

Location

Unknown Facility

Michalovce, 07101, Slovakia

Location

Unknown Facility

Rimavská Sobota, 97901, Slovakia

Location

Unknown Facility

Svidník, 8901, Slovakia

Location

Unknown Facility

Trenčín, 91101, Slovakia

Location

Unknown Facility

Zlaté Moravce, 95301, Slovakia

Location

MeSH Terms

Conditions

Depressive Disorder, MajorDepression

Interventions

EscitalopramAripiprazole

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental DisordersBehavioral SymptomsBehavior

Intervention Hierarchy (Ancestors)

PropylaminesAminesOrganic ChemicalsNitrilesBenzofuransHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsPiperazinesHeterocyclic Compounds, 1-RingQuinolonesQuinolines

Limitations and Caveats

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.

Results Point of Contact

Title
Global Clinical Development
Organization
Otsuka Pharmaceutical Development & Commercialization, Inc.

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 22, 2010

First Posted

April 27, 2010

Study Start

July 29, 2010

Primary Completion

September 27, 2011

Study Completion

September 27, 2011

Last Updated

October 26, 2021

Results First Posted

October 26, 2021

Record last verified: 2021-09

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP, CSR
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.
Access Criteria
Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
More information

Locations