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

Otsuka

Status and phase: Terminated; Phase 3

Conditions: Major Depressive Disorder (MDD)

Treatments: Drug: Escitalopram; Drug: Aripiprazole; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01111552

2010-018858-12 (EudraCT Number)

31-08-256

Details and patient eligibility

About

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.

Full 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

Enrollment: 237 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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 17-item 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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237 participants in 5 patient groups

Phase B: Single-blind Prospective Treatment Phase

Active Comparator group

Description:

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+.

Treatment:

Drug: Placebo

Drug: Escitalopram

Phase B+: Single-blind Phase B Responders

Active Comparator group

Description:

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+.

Treatment:

Drug: Placebo

Drug: Escitalopram

Phase C: Escitalopram Monotherapy

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: Escitalopram

Phase C: Aripiprazole Monotherapy

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: Aripiprazole

Phase C: Aripiprazole/Escitalopram Combination Therapy

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: Aripiprazole

Drug: Escitalopram