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

NCT ID: NCT01111539

Last Updated: 2021-10-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 211 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-13
• Study Completion Date: 2011-09-20

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

Conditions

Major Depressive Disorder (MDD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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+.

Group Type: EXPERIMENTAL

Escitalopram

Intervention Type: DRUG

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

Blinded capsule

Intervention Type: DRUG

Blinded capsule administered orally, once daily.

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+.

Group Type: EXPERIMENTAL

Escitalopram

Intervention Type: DRUG

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

Blinded capsule

Intervention Type: DRUG

Blinded capsule administered orally, once daily.

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.

Group Type: EXPERIMENTAL

Escitalopram

Intervention Type: DRUG

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

Aripiprazole

Intervention Type: DRUG

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

Blinded capsule

Intervention Type: DRUG

Blinded capsule administered orally, once daily.

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.

Group Type: EXPERIMENTAL

Escitalopram

Intervention Type: DRUG

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

Blinded capsule

Intervention Type: DRUG

Blinded capsule administered orally, once daily.

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.

Group Type: EXPERIMENTAL

Aripiprazole

Intervention Type: DRUG

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

Blinded capsule

Intervention Type: DRUG

Blinded capsule administered orally, once daily.

Interventions

Escitalopram

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

Intervention Type: DRUG

Aripiprazole

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

Intervention Type: DRUG

Blinded capsule

Blinded capsule administered orally, once daily.

Intervention Type: DRUG

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 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Cerritos, California, United States

Costa Mesa, California, United States

Irvine, California, United States

San Diego, California, United States

Santa Ana, California, United States

Denver, Colorado, United States

Cromwell, Connecticut, United States

Hartford, Connecticut, United States

Fort Walton Beach, Florida, United States

Gainesville, Florida, United States

Chicago, Illinois, United States

Libertyville, Illinois, United States

Boston, Massachusetts, United States

Fall River, Massachusetts, United States

Albuquerque, New Mexico, United States

Fresh Meadows, New York, United States

Staten Island, New York, United States

The Bronx, New York, United States

Cary, North Carolina, United States

Oklahoma City, Oklahoma, United States

Memphis, Tennessee, United States

DeSoto, Texas, United States

Richmond, Virginia, United States

Brown Deer, Wisconsin, United States

Jämejala, , Estonia

Tallinn, , Estonia

Tartu, , Estonia

Tartu, , Estonia

Helsinki, , Finland

Helsinki, , Finland

Kuopio, , Finland

Oulu, , Finland

Berlin, , Germany

Berlin, , Germany

Hamburg, , Germany

Munich, , Germany

Ostfildern, , Germany

Study Site 1

Ahmedabad, Gujarat, India

Study Site 2

Ahmedabad, Gujarat, India

Mangalore, Karnataka, India

Mumbai, Maharashtra, India

Pune, Maharashtra, India

Varanasi, Uttar Pradesh, India

Catania, , Italy

Siena, , Italy

Tlalnepantla, Estado Do Mexico, Mexico

Zapopan, Jalisco, Mexico

Mexico City, Mexico City, Mexico

Monterrey, Nuevo León, Mexico

Culiacán, Sinaloa, Mexico

Villahermosa, Tabasco, Mexico

Durango, , Mexico

San Luis Potosí City, , Mexico

Gwangju, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Changhua, , Taiwan

Kaohsiung City, , Taiwan

Keelung, , Taiwan

Taoyuan District, , Taiwan

Countries

United States; Estonia; Finland; Germany; India; Italy; Mexico; South Korea; Taiwan

Other Identifiers

2010-018796-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

31-08-255

Identifier Type: -

Identifier Source: org_study_id