Evaluation of the Safety of Adjunct Brexpiprazole in Elderly Patients With Major Depressive Disorder and an Inadequate Response to Antidepressant Treatment

• Sponsor: H. Lundbeck A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02400346
• Collaborator: (none)
• Enrollment: 132
• Locations: 34
• Arm: 1
• Duration (Months): 15
• Patients Per Site: 3.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of brexpiprazole as adjunctive treatment in an elderly population with major depressive disorder and an inadequate response to antidepressant treatment

Condition or Disease	Intervention/Treatment	Phase
Major Depression Disorder	Drug: Adjunct brexpiprazole; Drug: ADT	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 132 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Interventional, Open-label, Flexible-dose, Long-term Study to Evaluate the Safety and Tolerability of Brexpiprazole as Adjunctive Treatment in Elderly Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment
• Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Adjunct brexpiprazole All patients continue their current antidepressant treatment (ADT) and receive brexpiprazole in addition

Drug: Adjunct brexpiprazole; Weeks 1-4 titration from 0.5 up to 2 mg once daily, in weekly steps. For the rest of the 26 treatment weeks, maintenance with 1-3 mg once daily. Tablets for oral use once daily during 26 weeks. Tablet strengths: 0.5 mg, 1 mg, 2 mg and 3 mg.; Drug: ADT; Citalopram, ecitalopram, fluoxetine, sertraline, paroxetine IR, paroxetine CR, venlafaxine IR, venlafaxine XR (extended release), desvenlafaxine, duloxetine, mirtazapine, agomelatine, bupropion; dosing according to label

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Treatment-Emergent Adverse Events [Baseline to 30 weeks]

   Treatment-emergent adverse event is an adverse event that started or increased in intensity at or after baseline visit

Eligibility Criteria

Criteria

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

Main Inclusion Criteria:

• • The patient is a man or woman aged ≥65 yrs

• The patient has Major Depressive Disorder according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR™).

• The patient has an inadequate response to at least one adequate antidepressant treatment in the current Major Depressive Episode (MDE).

• The patient has had the current MDE for ≥8 weeks

• The patient is currently treated with a protocol specified ADT for at least 6 weeks

• The patient is judged to benefit from adjunctive treatment with brexpiprazole according to the clinical opinion of the investigator.

• Montgomery and Åsberg Depression Rating Scale (MADRS) total score > 18 at screening and baseline

• Clinical Global Impression - Severity (CGI-S) total score ≥3 at screening and baseline

Main Exclusion Criteria:

• • The patient has a clinically significant unstable illness

• The patient has newly diagnosed or unstable diabetes

• The patient has a Mini Mental State Exam (MMSE) score <24

• The patient has received Transcranial Magnetic Stimulation (TMS) and/or electroconvulsive therapy (ECT) less than 6 months prior to the Screening.

• The patient, in the opinion of the investigator or based on Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation and behaviour rating, is at significant risk of suicide

Other protocol defined inclusion and exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	US012	Arcadia	California	United States
2	US004	Miami	Florida	United States
3	US007	Orlando	Florida	United States
4	US006	Smyrna	Georgia	United States
5	US002	O'Fallon	Missouri	United States
6	US010	Toms River	New Jersey	United States
7	US005	New York	New York	United States
8	US008	New York	New York	United States
9	US003	Staten Island	New York	United States
10	US014	Oklahoma City	Oklahoma	United States
11	US009	Allentown	Pennsylvania	United States
12	US001	Memphis	Tennessee	United States
13	US011	San Antonio	Texas	United States
14	EE002	Tallinn		Estonia
15	EE001	Tartu		Estonia
16	EE004	Tartu		Estonia
17	EE003	Voru		Estonia
18	FI001	Helsinki		Finland
19	FI002	Kuopio		Finland
20	FI003	Oulu		Finland
21	FI004	Tampere		Finland
22	DE002	Berlin		Germany
23	DE008	Berlin		Germany
24	DE003	Frankfurt		Germany
25	DE007	Hannover		Germany
26	DE006	Mittweida		Germany
27	DE001	Schwerin		Germany
28	DE005	Wiesbaden		Germany
29	PL006	Bialystok		Poland
30	PL003	Bydgoszcz		Poland
31	PL001	Chelmno		Poland
32	PL005	Gdansk		Poland
33	PL004	Lublin		Poland
34	PL002	Pruszcz Gdanski		Poland

Sponsors and Collaborators

• H. Lundbeck A/S

Investigators

• Study Director: Email contact via H. Lundbeck A/S, [e-mail]

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: H. Lundbeck A/S
• ClinicalTrials.gov Identifier: NCT02400346
• Other Study ID Numbers: 16160A; 2014-003547-35
• First Posted: Mar 27, 2015
• Last Update Posted: Aug 10, 2017
• Last Verified: Jul 1, 2017

• Additional relevant MeSH terms: Depressive Disorder; Depressive Disorder, Major; Brexpiprazole

Study Results

Participant Flow

Arm/Group Title	Adjunct Brexpiprazole
Arm/Group Description	All patients continued their current antidepressant treatment and received brexpiprazole open-label in addition. Adjunct brexpiprazole administration was flexible and included a titration period: Weeks 1-4 titration from 0.5 up to 2 mg once daily, in weekly steps. For the rest of the 26 treatment weeks, maintenance with 1-3 mg once daily. Tablets for oral use once daily during 26 weeks. Tablet strengths: 0.5 mg, 1 mg, 2 mg and 3 mg.
Period Title: Overall Study
STARTED	132
COMPLETED	88
NOT COMPLETED	44

Baseline Characteristics

Arm/Group Title	Adjunct Brexpiprazole
Arm/Group Description	All patients continued their current antidepressant treatment and received brexpiprazole open-label in addition. Adjunct brexpiprazole administration was flexible and included a titration period: Weeks 1-4 titration from 0.5 up to 2 mg once daily, in weekly steps. For the rest of the 26 treatment weeks, maintenance with 1-3 mg once daily. Tablets for oral use once daily during 26 weeks. Tablet strengths: 0.5 mg, 1 mg, 2 mg and 3 mg.
Overall Participants	132
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.4 (5.3)
Sex: Female, Male (Count of Participants)
Female	107 81.1%
Male	25 18.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 1.5%
White	130 98.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	52 39.4%
Finland	27 20.5%
Poland	17 12.9%
Germany	15 11.4%
Estonia	21 15.9%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Treatment-Emergent Adverse Events
Description	Treatment-emergent adverse event is an adverse event that started or increased in intensity at or after baseline visit
Time Frame	Baseline to 30 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Adjunct Brexpiprazole
Arm/Group Description	All patients continued their current antidepressant treatment and received brexpiprazole open-label in addition. Adjunct brexpiprazole administration was flexible and included a titration period: Weeks 1-4 titration from 0.5 up to 2 mg once daily, in weekly steps. For the rest of the 26 treatment weeks, maintenance with 1-3 mg once daily. Tablets for oral use once daily during 26 weeks. Tablet strengths: 0.5 mg, 1 mg, 2 mg and 3 mg.
Measure Participants	132
Count of Participants [Participants]	102 77.3%

Adverse Events

Time Frame	Baseline to end of study (30 weeks)
Adverse Event Reporting Description	Treatment-Emergent Adverse Events are reported in this section
Arm/Group Title	Brex + ADT
Arm/Group Description
All Cause Mortality
	Brex + ADT
	Affected / at Risk (%)	# Events
Total	1/132 (0.8%)
Serious Adverse Events
	Brex + ADT
	Affected / at Risk (%)	# Events
Total	6/132 (4.5%)
Cardiac disorders
Acute myocardial infarction	1/132 (0.8%)
Myocardial rupture	1/132 (0.8%)
Infections and infestations
Postoperative wound infection	1/132 (0.8%)
Injury, poisoning and procedural complications
Eye contusion	1/132 (0.8%)
Facial bones fracture	1/132 (0.8%)
Fall	1/132 (0.8%)
Nervous system disorders
Transient ischaemic attack	1/132 (0.8%)
Psychiatric disorders
Depression	1/132 (0.8%)
Major depression	1/132 (0.8%)
Panic attack	1/132 (0.8%)
Vascular disorders
Hypotension	1/132 (0.8%)
Other (Not Including Serious) Adverse Events
	Brex + ADT
	Affected / at Risk (%)	# Events
Total	79/132 (59.8%)
General disorders
Fatigue	20/132 (15.2%)
Infections and infestations
Nasopharyngitis	8/132 (6.1%)
Investigations
Weight increased	11/132 (8.3%)
Metabolism and nutrition disorders
Increased appetite	13/132 (9.8%)
Musculoskeletal and connective tissue disorders
Back pain	7/132 (5.3%)
Nervous system disorders
Akathisia	11/132 (8.3%)
Dizziness	10/132 (7.6%)
Headache	7/132 (5.3%)
Tremor	9/132 (6.8%)
Psychiatric disorders
Anxiety	10/132 (7.6%)
Insomnia	8/132 (6.1%)
Restlessness	17/132 (12.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.