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

• ClinicalTrials.gov Identifier: NCT01837797
• Recruitment Status: Terminated
• First Posted: April 23, 2013
• Results First Posted: March 3, 2016
• Last Update Posted: October 17, 2018
• Sponsor: H. Lundbeck A/S
• Collaborator: Otsuka Pharmaceutical Co., Ltd.
• Information provided by (Responsible Party): H. Lundbeck A/S

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder	Drug: Placebo; Drug: Brexpiprazole 1 mg; Drug: Brexpiprazole 3 mg	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 129 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: April 2013
• Actual Primary Completion Date: May 2014
• Actual Study Completion Date: May 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change From Randomisation in Depressive Symptoms During the Randomised Treatment [ Time Frame: From randomisation to end of treatment (week 20) ]
   Montgomery and Aasberg Depression Rating Scale (MADRS) total score

Secondary Outcome Measures :

1. Number of Adverse Events [ Time Frame: From randomisation to follow-up (week 24) ]
   15 patients were enrolled to Period 2; only 3 patients completed due to study termination
2. Change From Randomisation in Clinical Global Impression During the Randomised Treatment [ Time Frame: From randomisation to end of treatment (week 20) ]
   Clinical Global Impression - Severity of illness (CGI-S) score
3. Change From Randomisation in Functionality Assessed by SDS During the Randomised Treatment [ Time Frame: From randomisation to end of treatment (week 20) ]
   Sheehan Disability Scale (SDS) total score
4. Change From Randomisation in Social Adaptation During the Randomised Treatment [ Time Frame: From randomisation to end of treatment (week 20) ]
   Social Adaptation Self-evaluation Scale (SASS) total score
5. Response During the Randomised Treatment [ Time Frame: From randomisation to end of treatment (week 20) ]
   Based on a pre-specified decrease in MADRS total score
6. Sustained Response During the Randomised Treatment [ Time Frame: From randomisation to end of treatment (week 20) ]
   Based on a pre-specified decrease in MADRS total score
7. Remission During the Randomised Treatment [ Time Frame: From randomisation to end of treatment (week 20) ]
   Based on a pre-specified MADRS total score
8. Sustained Remission During the Randomised Treatment [ Time Frame: From randomisation to end of treatment (week 20) ]
   Based on a pre-specified MADRS total score
9. Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) [ Time Frame: From randomisation to end of treatment (week 20) ]
   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, California

US001

National City, California, United States, 91950

United States, Florida

US008

Orlando, Florida, United States, 32806

Sponsors and Collaborators

H. Lundbeck A/S

Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Director: Email contact via H. Lundbeck A/S; LundbeckClinicalTrials@lundbeck.com

More Information

Additional Information:

EMA EudraCT Result Posting 

• Responsible Party: H. Lundbeck A/S
• ClinicalTrials.gov Identifier: NCT01837797
• Other Study ID Numbers: 14571A; 2012-001361-32 ( EudraCT Number )
• First Posted: April 23, 2013
• Results First Posted: March 3, 2016
• Last Update Posted: October 17, 2018
• Last Verified: September 2018

Additional relevant MeSH terms:

Depressive Disorder; Depression; Depressive Disorder, Major; Mood Disorders; Mental Disorders; Behavioral Symptoms; Brexpiprazole; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Dopamine Agonists; Dopamine Agents