To Assess the Safety and Tolerability of an Oral Aripiprazole/Escitalopram Combination Therapy in Participants With Major Depressive Disorder (MDD)

NCT01123707 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: 31-08-2572010-018860-17
• Study Type: interventional
• Target: 173
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a multicenter, 52-week, open-label study designed to assess the safety and tolerability of an oral aripiprazole/escitalopram combination therapy in outpatients with major depressive disorder (MDD). Enrollment into the study will be from eligible participants who have completed participation in Protocol 31-08-255 \[NCT01111539\], 31-08-256 \[NCT01111552\], or 31-08-263 \[NCT01111565\] ("rollover" participants).

Conditions

Major Depressive Disorder (MDD)

Keywords

Major Depressive Disorder; MDD; Depression

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (STEAEs), Severe (Grade 3 or Higher) TEAEs, and Discontinuations From the Trial Due to TEAEs

  An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it did not necessarily have to have a causal relationship with this treatment. An AE was considered serious if it was fatal; life-threatening; persistently or significantly disabling or incapacitating; required in-patient hospitalization or prolonged hospitalization; a congenital anomaly/birth defect; or other medically significant event that, based upon appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention. TEAE is defined as an adverse event that started after start of study drug treatment. The Common Terminology Criteria for Adverse Events v3.0 (CTCAE) was used to determine the severity wherein Grade 1=mild AE, Grade 2=moderate AE, Grade 3=severe AE, Grade 4=life-threatening or disabling AE, Grade 5=death related to AE.

  From first dose up to 30 days post last dose (Up to approximately 40 weeks)

Secondary Outcomes (18)

• Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score

  Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)

• Mean Change From Baseline in Patient Global Impression - Severity of Depression Scale (PGI-S) Score

  Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)

• Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities

  Up to 40 weeks

• Mean Change From Baseline in Body Weight

  Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)

• Mean Change From Baseline in Body Mass Index (BMI)

  Baseline, Week 26 and End of the study visit (Week 43 or before)

Study Arms (4)

Prior Aripiprazole/Escitalopram Combination Therapy

EXPERIMENTAL

Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the maximum tolerated dose (MTD) by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.

Drug: Aripiprazole; Drug: Escitalopram

Prior Escitalopram

EXPERIMENTAL

Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.

Drug: Aripiprazole; Drug: Escitalopram

Prior Aripiprazole

EXPERIMENTAL

Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.

Drug: Aripiprazole; Drug: Escitalopram

Prior Single-blind Escitalopram

EXPERIMENTAL

Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.

Drug: Aripiprazole; Drug: Escitalopram

Interventions

Aripiprazole DRUG

Aripiprazole oral capsules

Also known as: OPC-14597

Prior Aripiprazole; Prior Aripiprazole/Escitalopram Combination Therapy; Prior Escitalopram; Prior Single-blind Escitalopram

Escitalopram DRUG

Escitalopram oral capsules

Prior Aripiprazole; Prior Aripiprazole/Escitalopram Combination Therapy; Prior Escitalopram; Prior Single-blind Escitalopram

Eligibility Criteria

• Age: 18 Years - 66 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants who participated in Protocol 31-08-255, 31-08-256, or 31-08-263.

You may not qualify if:

• Participants with a current need for involuntary commitment or who have been hospitalized ≤ 28 days of the Baseline Visit for the current major depressive episode.
• Participants with a diagnosis of delirium, dementia, amnestic or other cognitive disorder, schizophrenia, schizoaffective disorder, or other psychotic disorder, Bipolar I or II disorder, eating disorder (including anorexia nervosa or bulimia), obsessive compulsive disorder, panic disorder, or posttraumatic stress disorder.
• Participants with a diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder.
• Participants experiencing hallucinations, delusions, or any psychotic symptomatology in the current depressive episode.
• Participants who have met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for substance abuse in the past 6 months (prior to the Baseline Visit) and/or dependence up to and including the past 12 months (prior to the Baseline Visit), including alcohol and benzodiazepines, but excluding caffeine and nicotine. Participants with two positive drug results for cocaine should be excluded from the study.
• Participants with hypothyroidism or hyperthyroidism.
• Participants with a significant risk of committing suicide based on history, investigator's judgment, and/or evaluation based on the Columbia-Suicide Severity Rating Scale (C-SSRS).
• Participants who currently have clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders.
• Participants with insulin-dependent diabetes mellitus (IDDM).
• Participants with epilepsy or significant history of seizure disorders, except for a single childhood febrile seizure, post-traumatic, etc.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Aripiprazole; Escitalopram

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

The study was terminated early due to Sponsor decision; no 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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Group composed of eligible rollover participants who completed one of the previous studies: 31-08-255 \[NCT01111539\], 31-08-256 \[NCT01111552\], or 31-08-263 \[NCT01111565\]

Study Record Dates

• First Submitted: May 12, 2010
• First Posted: May 14, 2010
• Study Start: November 18, 2010
• Primary Completion: September 27, 2011
• Study Completion: September 27, 2011
• Last Updated: December 22, 2021
• Results First Posted: December 22, 2021

Record last verified: 2021-10

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/