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

NCT01111539 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: 31-08-2552010-018796-21
• Study Type: interventional
• Target: 211
• Locations: 9 countries
• Sites: 62

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.

Conditions

Major Depressive Disorder (MDD)

Keywords

Major Depressive Disorder; MDD; Depression

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.

  Week 8 to Week 14

Secondary Outcomes (2)

• Phase C: Mean Clinical Global Impression - Improvement (CGI-I) Scale 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

EXPERIMENTAL

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; Drug: Blinded capsule

Phase B+: Single-blind Phase B Responders

EXPERIMENTAL

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; Drug: Blinded capsule

Phase C: Aripiprazole/Escitalopram Combination

EXPERIMENTAL

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; Drug: Aripiprazole; Drug: Blinded capsule

Phase C: Escitalopram Monotherapy

EXPERIMENTAL

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; Drug: Blinded capsule

Phase C: Aripiprazole Monotherapy

EXPERIMENTAL

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: Aripiprazole; Drug: Blinded capsule

Interventions

Escitalopram DRUG

Escitalopram capsule administered orally, once daily without regard to meals.

Phase B+: Single-blind Phase B Responders; Phase B: Single-blind Prospective Treatment Phase; Phase C: Aripiprazole/Escitalopram Combination; Phase C: Escitalopram Monotherapy

Aripiprazole DRUG

Aripiprazole capsule administered orally, once daily without regard to meals.

Phase C: Aripiprazole Monotherapy; Phase C: Aripiprazole/Escitalopram Combination

Blinded capsule DRUG

Blinded capsule administered orally, once daily.

Phase B+: Single-blind Phase B Responders; Phase B: Single-blind Prospective Treatment Phase; Phase C: Aripiprazole Monotherapy; Phase C: Aripiprazole/Escitalopram Combination; Phase C: Escitalopram Monotherapy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (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 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

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (62)

Unknown Facility

Cerritos, California, 90703, United States

Location

Unknown Facility

Costa Mesa, California, 92626, United States

Location

Unknown Facility

Irvine, California, 92618, United States

Location

Unknown Facility

San Diego, California, 92102, United States

Location

Unknown Facility

Santa Ana, California, 92705, United States

Location

Unknown Facility

Denver, Colorado, 80204, United States

Location

Unknown Facility

Cromwell, Connecticut, 06416, United States

Location

Unknown Facility

Hartford, Connecticut, 06106, United States

Location

Unknown Facility

Fort Walton Beach, Florida, 32547, United States

Location

Unknown Facility

Gainesville, Florida, 32607, United States

Location

Unknown Facility

Chicago, Illinois, 60612, United States

Location

Unknown Facility

Libertyville, Illinois, 60048, United States

Location

Unknown Facility

Boston, Massachusetts, 02114, United States

Location

Unknown Facility

Fall River, Massachusetts, 02721, United States

Location

Unknown Facility

Albuquerque, New Mexico, 87109, United States

Location

Unknown Facility

Fresh Meadows, New York, 11366, United States

Location

Unknown Facility

Staten Island, New York, 10305, United States

Location

Unknown Facility

The Bronx, New York, 10467, United States

Location

Unknown Facility

Cary, North Carolina, 27518, United States

Location

Unknown Facility

Oklahoma City, Oklahoma, 73112, United States

Location

Unknown Facility

Memphis, Tennessee, 38119, United States

Location

Unknown Facility

DeSoto, Texas, 75115, United States

Location

Unknown Facility

Richmond, Virginia, 23230, United States

Location

Unknown Facility

Brown Deer, Wisconsin, 53223, United States

Location

Unknown Facility

Jämejala, 71024, Estonia

Location

Unknown Facility

Tallinn, 10617, Estonia

Location

Unknown Facility

Tartu, 50406, Estonia

Location

Unknown Facility

Tartu, 50407, Estonia

Location

Unknown Facility

Helsinki, 00250, Finland

Location

Unknown Facility

Helsinki, 00260, Finland

Location

Unknown Facility

Kuopio, 70100, Finland

Location

Unknown Facility

Oulu, 90100, Finland

Location

Unknown Facility

Berlin, 10117, Germany

Location

Unknown Facility

Berlin, 10969, Germany

Location

Unknown Facility

Hamburg, 20246, Germany

Location

Unknown Facility

Munich, 80336, Germany

Location

Unknown Facility

Ostfildern, 73760, Germany

Location

Study Site 1

Ahmedabad, Gujarat, 380006, India

Location

Study Site 2

Ahmedabad, Gujarat, 380006, India

Location

Unknown Facility

Mangalore, Karnataka, 575001, India

Location

Unknown Facility

Mumbai, Maharashtra, 400026, India

Location

Unknown Facility

Pune, Maharashtra, 411030, India

Location

Unknown Facility

Varanasi, Uttar Pradesh, 221005, India

Location

Unknown Facility

Catania, 95123, Italy

Location

Unknown Facility

Siena, 53100, Italy

Location

Unknown Facility

Tlalnepantla, Estado Do Mexico, 54050, Mexico

Location

Unknown Facility

Zapopan, Jalisco, 45200, Mexico

Location

Unknown Facility

Mexico City, Mexico City, 06700, Mexico

Location

Unknown Facility

Monterrey, Nuevo León, 64040, Mexico

Location

Unknown Facility

Culiacán, Sinaloa, 80020, Mexico

Location

Unknown Facility

Villahermosa, Tabasco, 86035, Mexico

Location

Unknown Facility

Durango, 34000, Mexico

Location

Unknown Facility

San Luis Potosí City, 78218, Mexico

Location

Unknown Facility

Gwangju, 501-75, South Korea

Location

Unknown Facility

Seoul, 138-736, South Korea

Location

Unknown Facility

Seoul, 139-872, South Korea

Location

Unknown Facility

Seoul, 150-713, South Korea

Location

Unknown Facility

Seoul, 156-755, South Korea

Location

Unknown Facility

Changhua, 500, Taiwan

Location

Unknown Facility

Kaohsiung City, 802, Taiwan

Location

Unknown Facility

Keelung, 204, Taiwan

Location

Unknown Facility

Taoyuan District, 333, Taiwan

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Escitalopram; Aripiprazole

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Quinolones; Quinolines

Limitations and Caveats

The trial was terminated to allow support of additional programs in the central nervous system (CNS) therapeutic area where limited therapies are available and, thus, there exists heightened unmet medical need and is unrelated to any safety issues.

Results Point of Contact

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

clinicaltransparency@otsuka-us.com

1-609-524-6788

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 13, 2010
• Primary Completion: September 20, 2011
• Study Completion: September 20, 2011
• Last Updated: October 20, 2021
• Results First Posted: October 20, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• 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/

Locations

ES (4); TW (4); FI (4); IN (6); US (24); IT (2); KR (5); ME (8); DE (5)