NCT01111552

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

Terminated Phase 3 Results posted Last updated 26 October 2021

What this trial tests

Phase 3 trial testing Escitalopram in Major Depressive Disorder (MDD) in 237 participants. Terminated before completion.

Timeline

29 July 2010

Primary endpoint
27 September 2011

27 September 2011

Quick facts

Lead sponsor	Otsuka Pharmaceutical Development & Commercialization, Inc.
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	237
Start date	29 July 2010
Primary completion	27 September 2011
Estimated completion	27 September 2011
Sites	60 locations across Slovakia, Philippines, Romania, Bulgaria, Australia, United States, India

Drugs / interventions tested

• Escitalopram (escitalopram) — full drug profile →
• Aripiprazole (aripiprazole) — full drug profile →
• Placebo

Conditions studied

• Major Depressive Disorder (MDD) — all drugs for Major Depressive Disorder (MDD) →

Sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc. — full company profile →

Who can join

Adults 18 to 65, any sex, with Major Depressive Disorder (MDD). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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) Primary · 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. Last observation carried forward (LOCF) method was used for analyses.

Group	Value	95% CI
Phase C: Escitalopram Monotherapy	-8.0	± 1.7
Phase C: Aripiprazole Monotherapy	-9.6	± 1.7
Phase C: Aripiprazole/Escitalopram Combination Therapy	-9.2	± 1.6

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

The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. Last observation carried forward (LOCF) method was used for analyses.

Group	Value	95% CI
Phase C: Escitalopram Monotherapy	2.4	± 0.3
Phase C: Aripiprazole Monotherapy	2.3	± 0.2
Phase C: Aripiprazole/Escitalopram Combination Therapy	2.3	± 0.2

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) Secondary · Week 8 to Week 14

The 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. All items are rated on an 11-point continuum (0= no impairment to 10= most severe) with the total SDS score ranging from 0 (no impairment) to 30 (most severe). A negative change from Week 8 indicates improvement. Last observation carried forward (LOCF) method was used for analyses.

Group	Value	95% CI
Phase C: Escitalopram Monotherapy	-0.9	± 0.5
Phase C: Aripiprazole Monotherapy	-1.4	± 0.5
Phase C: Aripiprazole/Escitalopram Combination Therapy	-1.2	± 0.5

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug through end of study (up to 22 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase B: Single-blind Prospective Treatment Phase

Serious: 2/237 (1%)

Deaths: 0/237

Phase B+: Single-blind Phase B Responders

Serious: 1/54 (2%)

Deaths: 0/54

Phase C: Escitalopram Monotherapy

Serious: 1/22 (5%)

Deaths: 0/22

Phase C: Aripiprazole Monotherapy

Serious: 0/21 (0%)

Deaths: 0/21

Phase C: Aripiprazole/Escitalopram Combination Therapy

Serious: 0/23 (0%)

Deaths: 0/23

Serious adverse events (4 terms)

Reaction	System	Phase B: Single-blind Pros…	Phase B+: Single-blind Pha…	Phase C: Escitalopram Mono…	Phase C: Aripiprazole Mono…	Phase C: Aripiprazole/Esci…
Alanine aminotransferase increased	Investigations	—	—	—	—	—
Asthma	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Depression	Psychiatric disorders	—	—	—	—	—
Physical assault	Social circumstances	—	—	—	—	—

Other adverse events (10 terms — click to expand)

Reaction	System	Phase B: Single-blind Pros…	Phase B+: Single-blind Pha…	Phase C: Escitalopram Mono…	Phase C: Aripiprazole Mono…	Phase C: Aripiprazole/Esci…
Headache	Nervous system disorders	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—
Upper Respiratory Tract Infection	Infections and infestations	—	—	—	—	—
Akathisia	Nervous system disorders	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—
Weight increased	Investigations	—	—	—	—	—
Restlessness	Psychiatric disorders	—	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—

Most-reported serious reactions: Alanine aminotransferase increased, Asthma, Depression, Physical assault.

Data from ClinicalTrials.gov NCT01111552 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Comparative efficacy and safety of 4 atypical antipsychotics augmentation treatment for major depressive disorder in adults: A systematic review and network meta-analysis.
   Wang J, Li W, Li M, Wu H, et al · · 2023 · cited 1× · PMID 37746943 · DOI 10.1097/md.0000000000034670