E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bipolar disorder I depression |
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E.1.1.1 | Medical condition in easily understood language |
A mental illness characterized by the occurrence of one or more manic episodes, or mixed episodes. There is also a history of one or more major depressive episodes |
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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 | 100000004873 |
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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 and safety of lurasidone (in combination with lithium or divalproex) for the maintenance treatment of bipolar I disorder in subjects with or without rapid cycling and/or psychotic features. |
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E.2.2 | Secondary objectives of the trial |
Global severity, assessed by the Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) score (overall) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Open-label Phase: a. 18 years of age or older b. Diagnostic and Statistical Manual of Mental Disorders, 4th Ed., Text Revision (DSM-IV-TR) diagnosis of bipolar I disorder c. ≥ 1 manic, mixed manic, or depressed episode in past 2 years d. YMRS or MADRS total score ≥ 14 if on lithium or divalproex; ≥ 18 if not on lithium or divalproex Double-blind Phase: a. Subjects must achieve consistent clinical stability, defined as total scores ≤ 12 on the YMRS and MADRS over at least 12 weeks, with the allowance of two excursions (YMRS and/or MADRS total scores up to 13 or 14, respectively) except during the last 4 weeks before randomization
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E.4 | Principal exclusion criteria |
Open-label Phase: a. Diagnosis of an Axis I or Axis II disorder, other than bipolar I disorder, that is the primary focus of treatment within 3 months of screening b. Subjects for whom diagnostic agreement between the Investigator and United BioSource Corporation (Boston) (UBC) cannot be reached c. Ultra-fast rapid cycling (defined as ≥ 8 mood episodes over the previous 12-month period) d. Subjects who test positive for drugs of abuse at screening. In the event a subject tests positive for cannabinoids (tetrahydrocannabinol), the Investigator will evaluate the subject’s ability to abstain from cannabis during the study e. Unstable/inadequately treated medical illness f. The subject answers “yes” to “Suicidal Ideation” items 4 or 5 on the C-SSRS (at time of evaluation) Double-blind Phase: a. Subjects who in the Investigator’s judgment have not been compliant with study medication during the stabilization phase b. Subjects who have not stabilized during the open-label phase (within 20 weeks) c. Subjects who test positive for drugs of abuse at double-blind phase baseline. In the event a subject tests positive for cannabinoids (tetrahydrocannabinol), the Investigator will evaluate the subject’s ability to abstain from cannabis during the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Time to recurrence of any mood event (from double-blind phase baseline); mood event is defined as any of the following: - Fulfilled DSM-IV-TR criteria for manic, mixed manic, hypomanic, or depressive episode - Required treatment intervention for manic, mixed manic, hypomanic, or depressive symptoms with any antipsychotic (other then study drug), antidepressant, mood stabilizer (other than lithium or divalproex), anxiolytic agents, benzodiazepine (beyond dosage allowed for anxiety, agitation or insomnia) - Psychiatric hospitalization for any bipolar mood episode - YMRS or MADRS total score ≥ 18 or CGI-BP-S score ≥ 4 at two consecutive assessments no more than 10 days apart - Discontinuation from the study because of a mood event (as determined by the Investigator) Subject meeting criteria for a mood event must be discontinued from the study. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visit 13-20 (at every visit; visit schedule – every 4 weeks) |
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E.5.2 | Secondary end point(s) |
1. Time to all-cause discontinuation 2. Time to recurrence of a manic, mixed manic, hypomanic, or depressed episode 3. Proportion of subjects who experience a recurrence of a manic, mixed manic, hypomanic, or depressed episode 4. Change from double-blind phase baseline (final visit in the open-label phase) to endpoint in Global severity, assessed by the Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) score (overall, depression, mania), YMRS, MADRS, Quick Inventory of Depressive Symptomatology – Self Report (QIDS-SR16) total score, and Positive and Negative Syndrome Scale Positive Subscale (PANSS-P) 5. Subject self-report of functional impairment associated with symptoms of bipolar disorder, assessed by the Sheehan Disability Scale (SDS) total score and SDS subscales 6. Quality of life assessed by Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) 7. Sleep quality assessed by the Pittsburgh Insomnia Rating Scale (PIRS-2) 8. Health outcome measures: Health Services Utilization Questionnaire (HSUQ) and the SF-12 Health Survey 9. Medication Satisfaction Questionnaire (MSQ) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Visit 13-20 (at every visit; visit schedule – every 4 weeks) |
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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 | No |
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 | 8 |
E.8.5 | The trial involves multiple Member States | No |
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 |
Argentina |
Australia |
Bulgaria |
Chile |
Croatia |
Czech Republic |
France |
Hungary |
India |
Poland |
Russian Federation |
Serbia |
Slovakia |
Spain |
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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 visit of the last patient 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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |