Study of Safety & Tolerability of OPC-34712 as Adjunctive Therapy in Treatment of Adult Patients With Major Depressive Disorder

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01447576
• Collaborator: (none)
• Enrollment: 1,036
• Locations: 32
• Arm: 1
• Duration (Months): 39
• Patients Per Site: 32.4
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the long-term safety, tolerability and efficacy of oral OPC-34712 as adjunctive therapy in the treatment of adult patients with Major Depressive Disorder (MDD).

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: ADT; Drug: OPC-34712	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 1036 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter, Open-label Study to Assess the Safety and Tolerability of Oral OPC-34712 as Adjunctive Therapy in Adult Patients With Major Depressive Disorder
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OPC-34712 + ADT Experimental: OPC-34712, Oral Tablets, 0.25 - 3 mg; Antidepressant drug treatment	Drug: ADT; Once daily dosing during the duration of the study.; Other Names: Anti-depressant Drug Therapy ; Drug: OPC-34712; OPC-34712, Oral Tablets, 0.25 - 3 mg

Outcome Measures

Primary Outcome Measures

1. Participants With Adverse Events (AEs). [After the Informed Consent Form (ICF) was signed, through Follow up 30 (+2) days after last visit]

   An AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug-related by the physician. The severity was assessed as mild, moderate, or severe. A treament-emergent AE (TEAE) was defined as any AE that started after start of open-label brexpiprazole; or if the event was continuous from baseline and was worsening, serious, study drug-related, or resulted in death, discontinuation, interruption, or reduction of study drug.

Secondary Outcome Measures

1. Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score. [Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and 52 (last-observation-carried-forward [LOCF])]

   The CGI-S is a 7-point scale from 1 through 7. The items on CGI-S scale are: 0 = not assessed, 1 = normal, not at all ill, 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = among the most extremely ill participants. The score 0 (= not assessed) was set to missing.

2. Mean Clinical Global Impression - Improvement (CGI-I) Scale Score. [Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and 52 (LOCF)]

   The items on CGI-I scale are 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. The score of 0 (= not assessed) was set to missing. The CGI-I is therefore a 7-point scale from 1 through 7. CGI improvement was compared to the participants condition at Baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female subjects between 18 and 65 years of age, with a diagnosis of a single or recurrent, non-psychotic episode of major depressive disorder, as defined by DSM-IV-TR criteria and confirmed by the Mini International Neuropsychiatric Interview (M.I.N.I.) which is equal to or greater than 8 weeks in duration.

• Subjects must currently be taking allowable antidepressant therapy at an adequate dose for a minimum of six weeks by the end of the screening period (ie at the time of the Baseline visit).

• Subjects must report a history for the current depressive episode of an inadequate response to at least one and no more than four adequate antidepressant treatments.

Exclusion Criteria:

• Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving study drug.

• Subjects who report an inadequate response to more than three adequate trials of antidepressant treatments during current depressive episode at a therapeutic dose for an adequate duration.

• Subjects with a current Axis I (DSM-IV-TR) 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, post-traumatic stress disorder.

• Subjects with a clinically significant current Axis II (DSM-IV-TR) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pacific Clinical Research Medical Group	Arcadia	California	United States	91007
2	Artemis Institute for Clinical Research	San Diego	California	United States	92123
3	California Neuroscience Research Medical Group, Inc.	Sherman Oaks	California	United States	91403
4	Gulfcoast Clinical Research Center	Fort Myers	Florida	United States	33912
5	Clinical Neuroscience Solutions	Jacksonville	Florida	United States	32216
6	Florida Clinical Research Center	Maitland	Florida	United States	32751
7	Clinical Neurosciences Solutions	Orlando	Florida	United States	32806
8	Stedman Clinical Trials	Tampa	Florida	United States	33613
9	Carman Research	Smyrna	Georgia	United States	30080
10	Goldpoint Clinical Research, LLC	Indianapolis	Indiana	United States	46240
11	Pharmasite Research	Baltimore	Maryland	United States	91208
12	Clinical Insights	Glen Burnie	Maryland	United States	21061
13	Rochester Center for Behavioral Medicine	Rochester Hills	Michigan	United States	48307
14	Center for Psychiatry and Behavioral Medicine, Inc.	Las Vegas	Nevada	United States	89128
15	Center for Emotional Fitness	Cherry Hill	New Jersey	United States	08002
16	Brooklyn Medical Institute	Brooklyn	New York	United States	11214
17	Medical & Behavioral Health Research	New York	New York	United States	10023
18	The Medical Research Network, LLC	New York	New York	United States	10128
19	Finger Lakes Clinical Research	Rochester	New York	United States	14618
20	Midwest Clinical Research Center	Dayton	Ohio	United States	45417
21	Oregon Center for Clinical Investigations, Inc.	Portland	Oregon	United States	97210
22	Oregon Center for Clinical Investigations	Salem	Oregon	United States	97301
23	Carolina Clinical Research Services	Columbia	South Carolina	United States	29201
24	FutureSearch Trials of Dallas	Dallas	Texas	United States	75231
25	Bayou City Research, Ltd.	Houston	Texas	United States	77007
26	Radiant Research	Murray	Utah	United States	84123
27	Psychiatric Alliance of the Blue Ridge	Charlottesville	Virginia	United States	22903
28	Neuroscience, Inc.	Herndon	Virginia	United States	20170
29	Northwest Clinical Research Center	Bellevue	Washington	United States	98007
30	Summit Research Network	Seattle	Washington	United States	98104
31	Northbrooke Research Center	Brown Deer	Wisconsin	United States	53223
32	Dean Foundation	Middleton	Wisconsin	United States	53562

Sponsors and Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT01447576
• Other Study ID Numbers: 331-08-212
• First Posted: Oct 6, 2011
• Last Update Posted: Nov 6, 2015
• Last Verified: Oct 1, 2015

• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Antidepressive Agents

Study Results

Participant Flow

Recruitment Details	1036 participants entered trial, including 792 who had rolled over from previous studies and 244 de novo participants. Of the 792 rollovers, 337 were 6-week enrollers and the 52-week enrollers consisted of 699 enrolled participants (455 rollover and 244 de novo). This was a single arm study and all participants received the same treatment.
Pre-assignment Detail	Eligible participants received daily treatment with open-label brexpiprazole (0.25 up to 3.0 milligrams (mg)/day) and commercially marketed ADT.

Arm/Group Title	Brexpiprazole +ADT
Arm/Group Description	All participants received brexpiprazole 0.25 to 3.0 mg/day plus ADT.
Period Title: Overall Study
STARTED	1036
COMPLETED	560
NOT COMPLETED	476

Baseline Characteristics

Arm/Group Title	Brexpiprazole+ADT
Arm/Group Description	All participants received brexpiprazole 0.25 to 3.0 mg/day plus ADT.
Overall Participants	1036
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	44.0 (11.0)
Sex: Female, Male (Count of Participants)
Female	702 67.8%
Male	334 32.2%

Outcome Measures

1. Primary Outcome

Title	Participants With Adverse Events (AEs).
Description	An AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug-related by the physician. The severity was assessed as mild, moderate, or severe. A treament-emergent AE (TEAE) was defined as any AE that started after start of open-label brexpiprazole; or if the event was continuous from baseline and was worsening, serious, study drug-related, or resulted in death, discontinuation, interruption, or reduction of study drug.
Time Frame	After the Informed Consent Form (ICF) was signed, through Follow up 30 (+2) days after last visit

Outcome Measure Data

Analysis Population Description

The primary safety dataset included all participants exposed to at least 1 dose of brexpiprazole.

Arm/Group Title	Brexpiprazole+ADT
Arm/Group Description	All participants received brexpiprazole 0.25 to 3.0 mg/day plus ADT.
Measure Participants	1034
Participants with TEAEs	851 82.1%
Participants with serious TEAEs	30 2.9%

2. Secondary Outcome

Title	Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score.
Description	The CGI-S is a 7-point scale from 1 through 7. The items on CGI-S scale are: 0 = not assessed, 1 = normal, not at all ill, 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = among the most extremely ill participants. The score 0 (= not assessed) was set to missing.
Time Frame	Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and 52 (last-observation-carried-forward [LOCF])

Outcome Measure Data

Analysis Population Description

Efficacy dataset had participants who received at least 1 dose of brexpiprazole and had a baseline and at least 1 postbaseline efficacy evaluation for CGI-S. LOCF dataset included data recorded at a given visit in treatment phase or, if no observation was recorded at that visit, data carried forward from the previous visit in the Treatment Phase.

Arm/Group Title	Brexpiprazole+ADT
Arm/Group Description	All participants received brexpiprazole 0.25 to 3.0 mg/day plus ADT.
Measure Participants	1032
Week 1	-0.09 (0.60)
Week 2	-0.35 (0.82)
Week 4	-0.63 (0.96)
Week 6	-0.79 (1.03)
Week 8	-0.92 (1.12)
Week 14	-0.93 (1.14)
Week 20	-1.08 (1.17)
Week 26	-1.13 (1.24)
Week 32	-1.24 (1.24)
Week 38	-1.37 (1.28)
Week 44	-1.46 (1.27)
Week 52	-1.52 (1.34)
Week 52-LOCF	-0.81 (1.24)

3. Secondary Outcome

Title	Mean Clinical Global Impression - Improvement (CGI-I) Scale Score.
Description	The items on CGI-I scale are 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. The score of 0 (= not assessed) was set to missing. The CGI-I is therefore a 7-point scale from 1 through 7. CGI improvement was compared to the participants condition at Baseline.
Time Frame	Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and 52 (LOCF)

Outcome Measure Data

Analysis Population Description

Efficacy dataset had participants who received at least 1 dose of brexpiprazole and had a baseline and atleast 1 postbaseline efficacy evaluation for CGI-S. LOCF dataset included data recorded at a given visit in treatment phase or, if no observation was recorded at that visit, data carried forward from the previous visit in the Treatment Phase.

Arm/Group Title	Brexpiprazole+ADT
Arm/Group Description	All participants received brexpiprazole 0.25 to 3.0 mg/day plus ADT.
Measure Participants	1023
Week 1	3.38 (0.94)
Week 2	3.04 (1.06)
Week 4	2.67 (1.09)
Week 6	2.46 (1.10)
Week 8	2.36 (1.10)
Week 14	2.36 (1.23)
Week 20	2.22 (1.17)
Week 26	2.16 (1.12)
Week 32	2.08 (1.13)
Week 38	1.97 (1.11)
Week 44	1.91 (1.14)
Week 52	1.92 (1.15)
Week 52-LOCF	2.57 (1.31)

Adverse Events

Time Frame	After the ICF was signed, through the treatment period and through Follow-up (telephone contact or in-clinic visit) 30 (+ 2) days after the last visit.
Adverse Event Reporting Description	The safety sample consisted of participants who received at least 1 dose of brexpiprazole. Serious adverse event data were available for 697 participants (52 Week enrollers). Non-serious AE data were available for 1034 participants.
Arm/Group Title	Brexpiprazole+ADT
Arm/Group Description	Participants received brexpiprazole 0.25 to 3.0mg/day plus ADT.
All Cause Mortality
	Brexpiprazole+ADT
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Brexpiprazole+ADT
	Affected / at Risk (%)	# Events
Total	29/697 (4.2%)
Gastrointestinal disorders
Pancreatitis	1/697 (0.1%)
General disorders
Non-cardiac chest pain	1/697 (0.1%)
Hepatobiliary disorders
Cholecystitis	1/697 (0.1%)
Cholelithiasis	1/697 (0.1%)
Infections and infestations
Pneumonia	1/697 (0.1%)
Pyelonephritis	1/697 (0.1%)
Injury, poisoning and procedural complications
Intentional overdose	2/697 (0.3%)
Musculoskeletal and connective tissue disorders
Back pain	1/697 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of the cervix	1/697 (0.1%)
Metastatic malignant melanoma	1/697 (0.1%)
Nervous system disorders
Convulsion	1/697 (0.1%)
Cranial nerve paralysis	1/697 (0.1%)
Dizziness	1/697 (0.1%)
Sciatica	1/697 (0.1%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/697 (0.1%)
Psychiatric disorders
Anxiety	2/697 (0.3%)
Depression	3/697 (0.4%)
Depression suicidal	1/697 (0.1%)
Depressive symptom	1/697 (0.1%)
Suicidal ideation	3/697 (0.4%)
Suicide attempt	3/697 (0.4%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/697 (0.1%)
Pneumothorax	1/697 (0.1%)
Pulmonary embolism	1/697 (0.1%)
Other (Not Including Serious) Adverse Events
	Brexpiprazole+ADT
	Affected / at Risk (%)	# Events
Total	684/1034 (66.2%)
Gastrointestinal disorders
Constipation	41/1034 (4%)
Diarrhoea	42/1034 (4.1%)
Dry mouth	40/1034 (3.9%)
Nausea	50/1034 (4.8%)
General disorders
Fatigue	95/1034 (9.2%)
Infections and infestations
Upper respiratory tract infection	67/1034 (6.5%)
Nasopharyngitis	47/1034 (4.5%)
Investigations
Weight increased	217/1034 (21%)
Metabolism and nutrition disorders
Increased appetite	87/1034 (8.4%)
Musculoskeletal and connective tissue disorders
Back pain	33/1034 (3.2%)
Nervous system disorders
Akathisia	102/1034 (9.9%)
Dizziness	60/1034 (5.8%)
Headache	87/1034 (8.4%)
Sedation	54/1034 (5.2%)
Somnolence	94/1034 (9.1%)
Tremor	42/1034 (4.1%)
Psychiatric disorders
Anxiety	67/1034 (6.5%)
Insomnia	91/1034 (8.8%)
Restlessness	59/1034 (5.7%)
Abnormal dreams	41/1034 (4%)
Middle insomnia	24/1034 (2.3%)

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.