E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10004936 |
E.1.2 | Term | Bipolar 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 evaluate the efficacy of lurasidone (20-120 mg/day flexibly dosed) in combination with lithium or divalproex compared to placebo (in combination with lithium or divalproex) for the treatment of subjects with bipolar I disorder demonstrating non-response to treatment with lithium or divalproex alone. Subjects most recent episode must be depressed, with or without rapid cycling disease course (≥ 4 episodes of mood disturbance, but < 8 episodes in the previous 12 months), and without psychotic features (diagnosed by Diagnostic and Statistical Manual of Mental Disorders, 4th Ed., Text Revision [DSM-IV-TR] criteria) as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) total score. |
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E.2.2 | Secondary objectives of the trial |
The key secondary objective of this study is to evaluate the efficacy of lurasidone (20-120 mg/day, flexibly dosed) in combination with lithium or divalproex as measured by:
• Global severity, assessed by the Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) score (depression) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subjects 18 to 75 years of age inclusive, with bipolar I disorder, most recent episode depressed with or without rapid cycling disease course (≥ 4 episodes of mood disturbance but < 8 episodes in the previous 12 months) and without psychotic features (diagnosed by DSM-IV-TR criteria, and confirmed by the MINI). The current episode of major depression associated with bipolar I disorder must be confirmed by the investigator and noted in the source records.
• Subjects must have a lifetime history of at least one bipolar manic or mixed manic episode. It is strongly recommended that a reliable informant (e.g., family member, caregiver, or treating health professional), be available to confirm this history.
• Subject’s current major depressive episode is ≥ 4 weeks and less than 12 months in duration.
• MADRS total score ≥ 20 (at both screening and baseline visits)
• YMRS total score ≤ 12 (at both screening and baseline visits)
• Subjects requiring prospective run-in treatment and subjects meeting randomization criteria at the time of screening must be appropriate candidates for lithium or divalproex treatment, in the judgment of the investigator. All subjects are required to have had a minimum of 28 days of treatment with lithium or divalproex and will be required to demonstrate serum levels within the protocol-specified therapeutic range at least once during the 28 days of treatment prior to randomization.
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E.4 | Principal exclusion criteria |
• Diagnosis of an Axis I or Axis II disorder, other than bipolar I disorder, that is the primary focus of treatment within 3 months prior to screening
• Subject scores ≥ 4 on MADRS item number 10 (suicidal thoughts) at screening or baseline
• History of non-response to an adequate (6-week) monotherapy trial of three or more antidepressants administered within the package-defined therapeutic dose-range (with or without mood stabilizers) during the current episode
• Imminent risk of suicide or injury to self, others, or property
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change from baseline in MADRS total score after 6 weeks of treatment (Day 42). |
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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) |
The mean change from baseline to endpoint (Week 6) in:
• Global severity assessed by the CGI-BP-S score (depression) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 |
China |
Colombia |
Czech Republic |
India |
Japan |
Lithuania |
Peru |
Slovakia |
Ukraine |
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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Last patient, last visit. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |