E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with Treatment Resistant Major Depression |
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E.1.1.1 | Medical condition in easily understood language |
Subjects with Treatment Resistant Major Depression |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057840 |
E.1.2 | Term | Major depression |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate that monotherapy with flexibly dosed BMS-820836 (0.5 mg - 2 mg/day) versus continuing a standard antidepressant treatment (duloxetine 60 mg/day) to which inadequate response has been shown, significantly reduces depressive symptoms in patients with MDD. A reduction in depressive symptoms will be quantified using the change in Montgomery Asberg Depression Rating Scale (MADRS) total score over 6-weeks from the end of the Prospective Treatment Phase (Phase B, Week 8) to end of the Randomization Phase (Phase C, Week 14) in patients with treatment resistant depression (TRD). Thus, patients entering the randomized comparison (Phase C) have demonstrated an incomplete response to a prospective eight week trial of duloxetine 60 mg/day (Phase B) in addition to a documented history of inadequate response to at least one (but not more than 3) antidepressant from a different class for the current major depressive episode (Phase A). |
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E.2.2 | Secondary objectives of the trial |
1) To compare the CGI-I score at end of Phase C in TRD patients treated with flexibly
dosed BMS-820836 versus continuing fixed dose duloxetine.
2) To compare the Sheehan Disability Scale (SDS) total score change from Week 8 to
Week 14 (end of Phase B to end of Phase C) in TRD patients treated with flexibly
dosed BMS-820836 versus continuing fixed-dose duloxetine.
3) To evaluate the safety and tolerability of flexibly dosed BMS-820836
(0.5 - 2 mg/day) in the TRD patient population compared with continuing fixed-dose
duloxetine over 6-weeks (in Phase C).
4) To evaluate the change from Week 8 to Week 14 (end of Phase B to the end of Phase C) in the MADRS anhedonia factor score |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a) Patients must be able to understand the nature of the study, agree to comply with the prescribed dosage regimens, report for regularly scheduled office visits, and communicate to study personnel about adverse events and concomitant medication use.
b) Patients with a diagnosis of Major Depressive Disorder, currently experiencing a Major Depressive Episode, as defined by DSM IV TR criteria. The current depressive episode must be > 8 weeks in duration and < 3 years duration;
c) In the current MDD episode, patients should report a history of inadequate response to 1 - 3 adequate trials of antidepressant treatment.
d) Patients must have a HAM-D17 total score >= 18 at Screening;
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E.4 | Principal exclusion criteria |
1) Patients who report an inadequate response (less than 50% reduction in depressive symptom severity) to more than three adequate trials of antidepressant treatments during the current depressive episode
2) Patients who have failed duloxetine at an adequate dose and for an adequate duration in their current episode unless, in the judgment of the
investigator, the patient could benefit from treatment with this medication
3) Patients whose only inadequate response to an antidepressant in the current MDE is to an SNRI (duloxetine, venlafaxine, desvenlafaxine or milnacipran
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for this study is the change from end of Phase B (Week 8) to the end of Phase C (Week 14, LOCF) in the MADRS total score. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1) CGI-Improvement Score at end of Phase C (Week 14, LOCF);
2) Change from end of Phase B (Week 8) to the end of Phase C (Week 14, LOCF) in mean Sheehan Disability Scale (SDS) score.
3) Change from Week 8 to Week 14 (end of Phase B to the end of Phase C) in the MADRS anhedonia factor score |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Weeks 2, 4, 6 , 8, 9, 10, 11, 12, 13, 14
2) Baseline, week 8, week 14
3) Week 8, and Week 14 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
there is an initial single blind phase of the study (prospective phase) |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
South Africa |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |