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

Study Overview
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Brief Summary
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This is a Double-blind study wherein patients with Major Depressive Disorder (MDD) will receive either from 1 to 3 mg a day of study medication (OPC-34712)or placebo (an inactive substance) in addition to an FDA approved antidepressant in order to determine if the study medication is effective as an add on treatment of MDD.

Official Title
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A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of OPDC-34712 (1 to 3 mg/Day) as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder.

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: OPC-34712
* Drug: Placebo
* Drug: ADT


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brexipiprazole + ADT<br>OPC-34712 Tablets, Oral, 1 - 3 mg OPC-34712 + ADT | Drug: OPC-34712<br>* Tablets, Oral, 1 - 3 mg OPC-34712<br>Drug: Placebo<br>* Placebo<br>Drug: ADT<br> <br> * Other names: FDA Approved Antidepressant (ADT);|
| Placebo Comparator: Placebo + ADT<br>Placebo + ADT | Drug: Placebo<br>* Placebo<br>Drug: ADT<br> <br> * Other names: FDA Approved Antidepressant (ADT);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From the End of Phase A (Week 8 Visit) to the End of Phase B (Week 14 Visit) in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score. | The MADRS was utilized as the primary efficacy assessment of a participants level of depression. The MADRS consisted 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; therefore, possible total scores range from 0 to 60. The MADRS total score were to be unevaluable if less than 8 of the 10 items were 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 of to the first decimal place. | Baseline (end of week 8) to Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From End of Phase A (Week 8) to Phase B in Sheehan Disability Scale (SDS) Score. | The SDS was a self-rated instrument used to measure the effect of the participants symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores ranged from 0 through 10. The number most representative of how much each area was disrupted by symptoms was marked along the line from 0= not at all, to 10= extremely. Scores of 5 and above are associated with significant functional impairment. The SDS total score ranges from 0 to 30, with higher values indicating greater disruption in the participant's work/social/family life. 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 were calculated over the three item scores. All three item scores were needed to be available with the exception of the work/school item score when this item was not applicable. | Baseline (end of week 8) to Week 14 | 
| Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B. | The MADRS was utilized as the primary efficacy assessment of a participants level of depression. The MADRS consisted 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; therefore, possible total scores range from 0 to 60. The MADRS total score were to be unevaluable if less than 8 of the 10 items were 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 of to the first decimal place. | Baseline (end of week 8) to Week 14 | 
| Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression- Severity Illness Scale (CGI-S) Score. | The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the investigator had to answer the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time? Response choices included: 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; and 7 = among the most extremely ill participants. | Baseline (end of week 8) to Week 14 | 
| Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score. | The IDS-SR was a 30-item self-report measure, that was used to assess core diagnostic depressive symptoms as well as atypical and melancholic symptom features of major depressive disorder (MDD). For individual items, the scores range from 0 to 3. The IDS-SR are scored by summing responses to 28 of the 30 items to obtain a total score ranging from 0 to 84, higher values indicate greater disruption in the depressive symptoms. | Baseline (end of week 8) to Week 14 | 
| Change From End of Phase A (Week 8) to End of Phase B (Week 14) in the Hamilton Depression Rating Scale 17-item Version (HAM-D17) Total Score. | The HAM-D17 was utilized as a secondary assessment of a participants level of depression. The HAM-D (17-Item) consisted of 17 items. Eight items were 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) were rated on a 0 to 4 scale (twice the weight of the other items). For all of these items, 0 was the best rating and the highest score (2 or 4) was the worst rating. The possible total scores were from 0 to 52. | Baseline (end of week 8) to Week 14 | 
| Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A. | The efficacy of study medication was rated for each participant using the CGI-I. The study physician would rate the participants total improvement whether or not it is due entirely to drug treatment. Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. | Baseline (end of week 8) to Week 14 | 
| Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit. | A MADRS response was defined as >=50 percent reduction in MADRS Total Score from end of Phase A (Week 8 visit). The MADRS consisted 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; therefore, possible total scores range from 0 to 60. The MADRS total score were to be unevaluable if less than 8 of the 10 items were 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 of to the first decimal place. | Baseline (end of week 8) to Week 14 | 
| Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit. | A MADRS remission was defined as MADRS Total Score =< 10 and >= 50 percent reduction in MADRS Total Score from end of Phase A (Week 8 visit). The MADRS consisted 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; therefore, possible total scores range from 0 to 60. The MADRS total score were to be unevaluable if less than 8 of the 10 items were 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 of to the first decimal place. | Baseline (end of week 8) to Week 14 | 
| Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8). | CGI-I Response was defined as a CGI-I score of 1 (very much improved) or 2 (much improved). | Baseline (end of week 8) to Week 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OPC-34712, Major Depressive Disorder, Adjunctive Treatment