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 | 14.1 |
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 |
The primary objective of this study is 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, 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 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 the global severity score as 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 65 years of age, 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 (eg, family member or caregiver) 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)
- Lithium or divalproex levels must be within the protocol-defined therapeutic range (0.6-1.2 mEq/L for lithium or 50-125 μg/mL for divalproex) at screening. Although the lower limit for lithium serum concentration is 0.6 mEq/L at screening and during the study, lithium levels ≥ 0.4 mEq/L will be permitted with Medical Monitor approval if 0.6 mEq/L or higher is judged to be intolerable or unsafe for an individual subject. The investigator will verify that the subject has had continuous treatment with either medication for a minimum of 28 days prior to the screening visit based on confirmation from a reliable informant (eg, family member or other caregiver) or treating health professional. All preparations of lithium, divalproex (including extended-release formulations), or valproic acid will be permitted. |
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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) trial of three or more antidepressants (with or without mood stabilizers) during the current episode
- Imminent risk of suicide or injury to self, others, or property
- Subject has been hospitalized for a manic or mixed episode within the 60 days prior to randomization |
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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 | 14 |
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 |
Czech Republic |
France |
Germany |
India |
Poland |
Romania |
Russian Federation |
South Africa |
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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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 | 1 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |