Study of the Safety and Efficacy of OPC-34712 as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder

Major Depressive Disorder Clinical Trial

Official title:

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of OPC-34712 as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00797966
• Other study ID #: 331-08-211
• Status: Completed
• Phase: Phase 2
• First received: November 24, 2008
• Last updated: February 2, 2016
• Start date: May 2009
• Est. completion date: July 2010

Study information

• Verified date: February 2016
• Source: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Primary: To compare the efficacy of OPC-34712 to placebo as adjunctive treatment to an assigned open-label marketed antidepressant treatment (ADT)in patients who demonstrate an incomplete response to a prospective eight week trial of the same assigned open-label marketed ADT.

Description:

A comparison of the Fixed dose arm (OPC-31712, 0.15 mg) verses placebo was included as a general secondary efficacy variable and results for this dose group comparison are included under each of the Outcome Measures.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 850
• Est. completion date: July 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Male or female subjects between 18 and 65 years of age, with diagnosis of major depressive disorder, as defined by DSM-IV-TR criteria

• The current depressive episode must be equal to or greater than 8 weeks in duration

• Subjects must report a history for the current depressive episode of an inadequate response to at least one and no more than three 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

• Subjects with a clinically significant current Axis II (DSM-IV-TR)

• diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• OPC-34712
Tablets, Oral, 1 - 4 mg OPC-34712 variable dose once daily, 14 weeks
• Placebo
Tablets, Oral, 1- 4 mg OPC-34712 once daily, 14 weeks
• ADT
Tablets, 10 - 225 mgs, dose once daily, 14 weeks

Locations

Country	Name	City	State
United States	Pacific Clinical Research Medical Group	Arcadia	California
United States	Community Clinical Research, Inc.	Austin	Texas
United States	FutureSearch Clinical Trials	Austin	Texas
United States	Pharmasite Research, Inc.	Baltimore	Maryland
United States	NorthCoast Clinical Trials, Inc	Beachwood	Ohio
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Southwestern Research	Beverly Hills	California
United States	Florida Clinical Research Center, LLC	Bradenton	Florida
United States	Northbrooke Research Center	Brown Deer	Wisconsin
United States	Neuro-Behavioral Clinical Research, Inc	Canton	Ohio
United States	Carolinas HealthCare - Behavioral Heath Center	Charlotte	North Carolina
United States	Psychiatric Alliance of the Blue Ridge	Charlottesville	Virginia
United States	Uptown Research Institute	Chicago	Illinois
United States	Patient Priority Clinical Sites, LLC	Cinncinnati	Ohio
United States	USC School of Medicine- Department of Neuropsychiatry and Behavioral Science	Columbia	South Carolina
United States	CNS Clinical Research Group	Coral Springs	Florida
United States	Midwest Clinical Research Center	Dayton	Ohio
United States	Radiant Research Center	Denver	Colorado
United States	Synergy Escondido	Escondido	California
United States	Gulfcoast Clinical Research Center	Fort Myers	Florida
United States	Collaborative Neuroscience Network Inc.	Garden Grove	California
United States	NeuroScience, Inc.	Herndon	Virginia
United States	The Davis Clinic, PC	Indianapolis	Indiana
United States	Clinical Neuroscience Solutions, Inc.	Jacksonville	Florida
United States	Accurate Clinical Trials	Kissimee	Florida
United States	Suburban Research Associates	Media	Pennsylvania
United States	Clinical Neurosciences Solutions, Inc.	Memphis	Tennessee
United States	NorthStar Medical Research, LLC	Middleburg Heights	Ohio
United States	Dean Foundation	Middleton	Wisconsin
United States	Dominion Clinical Research	Midlothian	Virginia
United States	Bioscience Research	Mount Kisco	New York
United States	Synergy Clinical Research Center	National City	California
United States	Medical & Behavioral Health Research, PC	New York	New York
United States	Eastside Comprehensive Medical Center	New York City	New York
United States	Midwest Center for Neurobehavioral Medicine	Oakbrook Terrace	Illinois
United States	Excell Research	Oceanside	California
United States	Clinical Neurosciences Solutions	Orlando	Florida
United States	Vince & Associates Clinical Research	Overland Park	Kansas
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Summitt Research Network (Oregon)	Portland	Oregon
United States	Finger Lakes Clinical Research	Rochester	New York
United States	Mood Disorders Clinic	Salt Lake City	Utah
United States	Radiant Research	Salt Lake City	Utah
United States	Affiliated Research Institute	San Diego	California
United States	Summit Research Network (Seattle) LLC	Seattle	Washington
United States	California Neuroscience Research Medical Group, Inc.	Sherman Oaks	California
United States	Carman Research	Smyrna	Georgia
United States	Stedman Clinical Trials	Tampa	Florida
United States	University of South Florida College of Medicine Psychiatry Center	Tampa	Florida
United States	Janus Center	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Development & Commercialization, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From the End of Phase A (Week 8 Visit) to the End of Phase B (Week 14 Visit) in Montgomery Asberg Depression Rating Scale (MADRS) Total Score.	The MADRS is utilized as the primary efficacy assessment of a participant's level of depression. The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the "best" rating and 6 being the "worst" rating. The MADRS Total Score is the sum of ratings for all 10 items. The possible Total scores are from 0 to 60. The MADRS Total Score was unevaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items were recorded, the MADRS Total Score was the mean of the recorded items multiplied by 10 and then rounded to the first decimal place.	Week 8 to Week 14	No
Secondary	Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Mean Clinical Global Impression - Severity of Illness Scale (CGI-S) Score.	CGI-S items 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 patients. The score 0 (= not assessed) was set to missing. The CGI-S was therefore a 7-point scale from 1 through 7. CGI-S was assessed at screening, baseline and each subsequent visit from Week 1 through Week 14.	Week 8 to Week 14	No
Secondary	Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Mean Quality of Life, Enjoyment, and Satisfaction Questionnaire - Short Form (QLES-Q-SF) Subscale Score - the Overall General Subscore (Sum of First 14 Items).	The Q-LES-Q is a self-report measure to enable physicians to obtain sensitive measures of the degree of enjoyment and satisfaction experienced by participants in various areas of daily functioning. Each item is scored on a five-point scale, with 1= Very Poor; 2=Poor; 3=Fair; 4=Good; 5=Very Good. Lower scores indicating less enjoyment or satisfaction with the activity. The Overall-General Subscore will be defined by summing the scores on all 14 items and expressing it as the percent of the maximum possible score. When expressing the total score as a percentage, if items are left blank the range will be modified to reflect the number of items scored. Raw score is sum of non-missing ratings from items 1 to 14. Minimum score is number of non-missing items. Maximum score is 5*(minimum score). Range is maximum score minus minimum score. Total score is 100*(Raw score minus minimum score)/ Range, rounded to nearest integer.	Week 8 to Week 14	No
Secondary	Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Sheehan Disability Scale (SDS) Mean Score (the Mean of 3 Individual Item Scores).	The Sheehan Disability Scale (SDS) is a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0 = not at all, to 10 = extremely. For the work/school item, no response was to be entered if the participant did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS Score will be calculated over the three item scores. All three item scores need to be available with the exception of the work/school item score when this item is not applicable.	Week 8 to Week 14	No
Secondary	Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than the Week 14 Visit.	The MADRS is utilized as the primary efficacy assessment of a patient's level of depression. The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the "best" rating and 6 being the "worst" rating. The MADRS Total Score is the sum of ratings for all 10 items. The possible Total scores are from 0 to 60. The MADRS Total Score was unevaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items were recorded, the MADRS Total Score was the mean of the recorded items multiplied by 10 and then rounded to the first decimal place.	Week 8 to each of Week 9, 10, 11, 12 and 13.	No
Secondary	Change From End of Phase A (Week 8 Visit) in Mean CGI-S Score for Every Study Week Visit in Phase B Other Than the Week 14 Visit.	CGI-S items 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 patients. The score 0 (= not assessed) was set to missing. The CGI-S was therefore a 7-point scale from 1 through 7. CGI-S was assessed at screening, baseline and each subsequent visit from Week 1 through Week 14.	Week 8 to each of Week 9, 10, 11, 12 and 13.	No
Secondary	Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Mean Q-LES-Q-SF Item 15 Score (Satisfaction With Medication).	The Q-LES-Q (Short Form) is a self-report measure designed to enable physicians to easily obtain sensitive measures of the degree of enjoyment and satisfaction experienced by participants in various areas of daily functioning. Each item is scored on a five-point scale, with 1= Very Poor; 2=Poor; 3=Fair; 4=Good; 5=Very Good. Lower scores indicating less enjoyment or satisfaction with the activity. According to the scoring system suggested for this questionnaire, item 15 (Satisfaction with Medication) will yield a separate subscore.	Week 8 to Week 14	No
Secondary	Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Mean Q-LES-Q-SF Item 16 Score (Overall Life Satisfaction).	The Q-LES-Q (Short Form) is a self-report measure designed to enable physicians to easily obtain sensitive measures of the degree of enjoyment and satisfaction experienced by participants in various areas of daily functioning. Each item is scored on a five-point scale, with 1= Very Poor; 2=Poor; 3=Fair; 4=Good; 5=Very Good. Lower scores indicating less enjoyment or satisfaction with the activity. According to the scoring system suggested for this questionnaire, item 16 (Overall Life Satisfaction) will yield a separate subscore.	Week 8 to Week 14	No
Secondary	Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score.	The IDS-SR is a 30-item self-report measure used to assess core diagnostic depressive symptoms as well as atypical and melancholic symptom features of major depressive disorders. The IDS-SR consists of 30 items, all rated on a 0 to 3 scale with 0 being the "best" rating and 3 being the "worst" rating. The IDS-SR Total Score is the sum of ratings of 28 item scores. The possible IDS-SR Total Score ranges from 0 to 84. The IDS-SR Total Score was un-evaluable if less than 23 of the 28 items are recorded. If the number of items was at least 23 and at most 27, the IDS-SR Total Score will be the mean of the recorded items multiplied by 28 and then rounded to the first decimal place.	Week 8 to each of Week 9, 10, 11, 12, 13 and 14	No
Secondary	Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Hamilton Depression Rating Scale (HAM-D17) Score.	The HAM-D17 is utilized as a secondary assessment of a participant's level of depression. The HAM-D (17-Item) consists of 17 items. Eight items are rated on a 0 to 2 scale (items 4, 5, 6, 12, 13, 14, 16 and 17), while nine items (items 1, 2, 3, 7, 8, 9, 10, 11, and 15) are rated on a 0 to 4 scale (twice the weight of the other items). For all of these items, 0 is the "best" rating and the highest score (2 or 4) is the "worst" rating. The possible total scores are from 0 to 52.	Week 8 to Week 14	No
Secondary	Clinical Global Impression-Improvement Scale (CGI-I) Score at Each Study Week Visit in Phase B.	CGI-I items 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) will be set to missing. The CGI-I is therefore a 7-point scale from 1 through 7. CGI-I was assessed at each visit in Phase B, and improvement is judged with respect to the participant's condition at baseline. CGI-I was also assessed at each visit in Phase B, but in that phase improvement is judged with respect to the partcipant's condition at the end of Phase A.	Week 8 to each of Week 9, 10, 11, 12, 13 and 14.	No
Secondary	Percentage of Participants With MADRS Response From End of Phase A (Week 8 Visit).	A MADRS response was defined as >/= 50% reduction in MADRS Total Score from end of Phase A (Week 8 visit).	Week 8 to each of Week 9, 10, 11, 12, 13 and 14.	No
Secondary	Percentage of Participants With MADRS Remission From End of Phase A (Week 8 Visit).	A MADRS remission was defined as MADRS Total Score	Week 8 to each of Week 9, 10, 11, 12, 13 and 14.	No
Secondary	Percentage of Participants With CGI-I Response From End of Phase A (Week 8 Visit).	CGI-I response is defined as CGI-I of 1 [very much improved] or 2 [much improved].	Week 9, 10, 11, 12, 13 and 14.	No