A Phase 3 Trial Investigating the Safety and Effectiveness of OPC-34712 in the Treatment of Adults with Major Depressive Disorder
- Conditions
- Major Depressive Disorder (MDD)MedDRA version: 14.1Level: LLTClassification code 10025454Term: Major depressive disorder, recurrent episodeSystem Organ Class: 100000004873Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]
- Registration Number
- EUCTR2011-001349-33-HU
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1653
Subjects are required to meet the following inclusion criteria:
1. Subjects who are able to provide written informed consent and/or consent obtained from a legally acceptable representative (as required by IRB/IEC) prior to the initiation of any protocol-required procedures.
2. Ability, in the opinion of the principal investigator, to understand the nature of the trial and follow protocol requirements, including the prescribed dosage regimens, tablet/capsule ingestion, and discontinuation of prohibited concomitant medication; to read and understand the written word in order to complete subject-reported outcomes measures; and to be reliably rated on assessment scales.
3. Male and female outpatients 18 to 65 years of age, inclusive, at the time of informed consent.
4. Subjects with both a diagnosis of MDD, and in a current Major Depressive Episode, as defined by DSM-IV-TR criteria and confirmed by both the MINI and an adequate clinical psychiatric evaluation. The current Major Depressive Episode must be >= 8 weeks in duration. In addition, subjects must have a history for the current Major Depressive Episode of an inadequate response to at least one and no more than three adequate antidepressant treatments. An inadequate response is defined as < 50% reduction in depressive symptom severity, as assessed by the ATRQ. Adequate treatment is defined as an antidepressant treatment for at least 6 weeks in duration at a minimum dose (or higher) as specified in the ATRQ. If the subject showed >= 50% improvement on any antidepressant treatment in the current episode, then the subject must have had an inadequate response to a subsequent adequate antidepressant treatment (as defined above by the ATRQ) of another antidepressant drug prior to entry into the trial. For the most recent antidepressant treatment, the subject must not report >= 50% improvement (as defined above by the ATRQ).
5. Subjects with a HAM-D17 Total Score >= 18 at the Screening and Baseline visits.
6. Subjects willing to discontinue all prohibited psychotropic medications to meet protocol-required washouts prior to and during the trial period.
Inclusion Criteria Required for Entry into Phase B (Double-blind Randomization Phase):
7. HAM-D17 Total Score >= 14 at the Week 8 visit
8. HAM-D17 Total Score at the Week 8 visit that is less than a 50% reduction from baseline value
9. CGI-I score >= 3 at the Week 8 visit
10. As evaluated by the investigator, the subject is suitable for randomization based on all available clinical, efficacy, and safety data collected during Phase A in addition to HAM-D17 and CGI-I scores.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1587
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 66
For full details on exclusion criteria please refer to Section 3.4.3 of the trial protocol.
Details of the exclusion criteria around the target population are included below.
Subjects will be excluded if they meet any of the following exclusion criteria:
• Subjects who report an inadequate response (less than 50% reduction in depressive symptom severity) to more than three monotherapy antidepressant treatments during the current Major Depressive Episode at a therapeutic dose and for an adequate duration (minimum duration of six weeks), including any antidepressant that the subject may be taking at screening if it meets the criteria for adequate treatment.
• Subjects who report treatment with adjunctive antipsychotic medication with an antidepressant for a minimum of three weeks during the current Major Depressive Episode
• Subjects who have received ECT for the current Major Depressive Episode.
• Subjects who have had an inadequate response to ECT at any time in the past or who have had a vagus nerve stimulation or deep brain stimulation device implanted for management of treatment-resistant depression
• Subjects with a current need for involuntary commitment or who have been hospitalized within four weeks of screening for the current Major Depressive Episode.
• 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 current Axis II (DSM-IV-TR) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder.
• Subjects experiencing hallucinations, delusions or any psychotic symptomatology in the current Major Depressive Episode.
• Subjects who answer Yes” on the C-SSRS either Suicidal Ideation Item 4 or C-SSRS Suicidal Ideation Item 5 whose most recent episode meeting criteria was within the past 6 months or Subjects who answer Yes” on any of the 5 C-SSRS Suicidal Behavior Items and whose most recent episode meeting criteria for any of the occurred within the last 2 years
• Subjects who have met DSM-IV-TR criteria for substance abuse or dependence within the past 180 days; including alcohol and benzodiazepines, but excluding caffeine and nicotine.
Exclusion Criteria Assessed at the Week 8 Visit
• Subjects who do not met predetermined blinded criteria for incomplete response according to the MST and/or the IVRS/IWRS.
• Subjects who, in the opinion of the investigator or medical monitor, are not suitable for randomization for other reasons.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare the efficacy of OPC-34712 (1.0 and 3.0 mg/day) to placebo as adjunctive therapy to an assigned open-label antidepressant therapy (ADT) in subjects who demonstrate an incomplete response after 8 weeks of prospective treatment with the same assigned open-label ADT.;Secondary Objective: To evaluate the safety and tolerability of OPC 34712 (1.0 and 3.0 mg/day) as adjunctive therapy to ADT in the proposed subject population with MDD.;Primary end point(s): The primary efficacy endpoint is the change from the end of Phase A (Week 8 visit) to the end of Phase B (Week 14 visit, LOCF) in MADRS Total Score. The trial will compare the 1.0 mg/day OPC-34712-plus-ADT arm and the 3.0 mg/day OPC-34712-plus-ADT arm to the placebo-plus-ADT arm, with an overall alpha of 0.05 for the primary endpoint.;Timepoint(s) of evaluation of this end point: The primary efficacy endpoint is evaluated as the change from the Week 8 visit to the Week 14 visit.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): The key secondary efficacy variable is the change from end of Phase A (Week 8 visit) to end of Phase B (Week 14 visit, LOCF) in Sheehan Disability Scale (SDS) Mean Score (the mean of 3 individual item scores). ;Timepoint(s) of evaluation of this end point: The secondary efficacy endpoint is evaluated as the change from the Week 8 visit to the Week 14 visit.