Efficacy and Safety of Brexpiprazole as Adjunctive Treatment in Elderly Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment

Interventional, Randomised, Double-blind, Parallel-group, Placebo-controlled, Fixed-dose Study to Evaluate the Efficacy and Safety of Brexpiprazole (1 and 3 mg/Day) as Adjunctive Treatment in Elderly Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment

To evaluate the efficacy and safety of brexpiprazole as adjunctive treatment in elderly patients with Major Depressive Disorder (MDD)

Study Overview

• Status: Terminated
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Brexpiprazole 1 mg; Drug: Brexpiprazole 3 mg

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • National City, California, United States, 91950
      • US001
  • Florida
    • Orlando, Florida, United States, 32806
      • US008

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The patient is an outpatient consulting a psychiatrist.
• The patient has a recurrent Major Depressive Disorder diagnosed according to DSM-IV-TR™. The current Major Depressive Episode (MDE) should be confirmed using the Mini International Neuropsychiatric Interview (MINI).
• The patient had at least one previous MDE before the age of 60 years.
• The patient has a moderate to severe depression and an insufficient response to at least one and no more than three adequate antidepressants treatments.
• The patient, if a woman, must have had her last natural menstruation ≥24 months prior to the Screening Visit.
• The patient, if a man, agrees to protocol-defined use of effective contraception if his female partner is of childbearing potential.

Exclusion Criteria:

• The patient has any current psychiatric disorder or Axis I disorder (DSM-IV-TR™ criteria), established as the primary diagnosis, other than MDD.
• The patient has a current Axis II (DSM-IV-TR™) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypical or histrionic personality disorder.
• The patient has experienced/experiences hallucinations, delusions or any psychotic symptomatology in the current MDE.
• The patient suffers from mental retardation, organic mental disorders, or mental disorders due to a general medical condition (DSM-IV-TR™ criteria).
• The patient, in the opinion of the investigator, or according to Columbia Suicide Severity Rating Scale (C-SSRS), is at significant risk of suicide.
• The patient has had neuroleptic malignant syndrome.
• The patient has any relevant medical history or current presence of systemic disease.
• The patient has a neurodegenerative disorder.
• The patient has, at the Screening Visit an abnormal ECG that is, in the investigator's opinion, clinically significant.
• The patient has a history of cancer, other than basal cell or Stage 1 squamous cell carcinoma of the skin, that has not been in remission for >5 years prior to the first dose of IMP.
• The patient is, in the investigator's opinion, unlikely to comply with the protocol or is unsuitable for any reason.

Other inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo adjunct to open-label treatment with a commercially available antidepressant (ADT)	Drug: Placebo; Once daily, tablets, orally
Experimental: Brexpiprazole 1 mg; Brexpiprazole adjunct to open-label treatment with a commercially available ADT. Brexpiprazole dosing was 0.5 mg/day in the first 1 week followed by 1 mg/day.	Drug: Brexpiprazole 1 mg; once daily dose, tablets, orally
Experimental: Brexpiprazole 3 mg; Brexpiprazole adjunct to open-label treatment with a commercially available ADT. Brexpiprazole dosing was 0.5 mg/day in the first 1 week, 1 mg/day in the second week, followed by 3 mg/day.	Drug: Brexpiprazole 3 mg; once daily dose, tablets, orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Randomisation in Depressive Symptoms During the Randomised Treatment	Montgomery and Aasberg Depression Rating Scale (MADRS) total score	From randomisation to end of treatment (week 20)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events	15 patients were enrolled to Period 2; only 3 patients completed due to study termination	From randomisation to follow-up (week 24)
Change From Randomisation in Clinical Global Impression During the Randomised Treatment	Clinical Global Impression - Severity of illness (CGI-S) score	From randomisation to end of treatment (week 20)
Change From Randomisation in Functionality Assessed by SDS During the Randomised Treatment	Sheehan Disability Scale (SDS) total score	From randomisation to end of treatment (week 20)
Change From Randomisation in Social Adaptation During the Randomised Treatment	Social Adaptation Self-evaluation Scale (SASS) total score	From randomisation to end of treatment (week 20)
Response During the Randomised Treatment	Based on a pre-specified decrease in MADRS total score	From randomisation to end of treatment (week 20)
Sustained Response During the Randomised Treatment	Based on a pre-specified decrease in MADRS total score	From randomisation to end of treatment (week 20)
Remission During the Randomised Treatment	Based on a pre-specified MADRS total score	From randomisation to end of treatment (week 20)
Sustained Remission During the Randomised Treatment	Based on a pre-specified MADRS total score	From randomisation to end of treatment (week 20)
Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS)	The Columbia Suicide Severity Rating Scale (eC-SSRS) is a semi-structured interview developed to systematically assess suicidal ideation and behaviour of patients participating in a clinical study. The C-SSRS has 5 questions addressing suicidal ideation, 5 sub-questions assessing the intensity of ideation, and 4 questions addressing suicidal behaviour.	From randomisation to end of treatment (week 20)

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S
• Collaborators: Otsuka Pharmaceutical Co., Ltd.

Publications and helpful links

Helpful Links

• EMA EudraCT Result Posting

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: April 4, 2013
• First Submitted That Met QC Criteria: April 18, 2013
• First Posted (Estimate): April 23, 2013

Study Record Updates

• Last Update Posted (Actual): October 17, 2018
• Last Update Submitted That Met QC Criteria: September 18, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Agents; Dopamine Agonists; Dopamine Agents; Brexpiprazole
• Other Study ID Numbers: 14571A; 2012-001361-32 (EudraCT Number)