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 | 17.0 |
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 of lurasidone (20 - 80 mg/day flexibly dosed) compared with placebo in children and adolescent subjects with bipolar I disorder, most recent episode depressed, with or without rapid cycling disease course, and without psychotic features (diagnosed by Diagnostic and Statistical Manual of Mental Disorders, 5th Ed. [DSM-V] criteria) as measured by the change from Baseline in the Children's Depression Rating Scale, Revised (CDRS-R) total score. |
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E.2.2 | Secondary objectives of the trial |
Global severity as assessed by the Clinical Global Impression-Bipolar Version, Severity of Illness (CGI-BP-S) score (depression).
Other secondary objectives of this study include evaluation of the following:
Change in anxiety symptoms;
Change in quality of life;
Change in social and psychiatric functioning
Treatment response;
Symptom remission;
Change in attention-deficit/hyperactivity symptoms;
Safety and tolerability of lurasidone 20 - 80 mg/day flexibly dosed;
Treatment-emergent mania. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female subjects 10 to 17 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-V criteria, and confirmation of the bipolar I disorder diagnosis by an adequately trained clinician at the time of screening, by means of the Schedule for Affective Disorders and Schizophrenia for School-age Children [K-SADS-PL]). Children's Depression Rating Scale, Revised (CDRS-R) total score ≥ 45 at screening and Baseline. Young Mania Rating Scale (YMRS) score ≤ 15 (with YMRS Item 1 [elevated mood] score ≤ 2) at screening and Baseline. |
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E.4 | Principal exclusion criteria |
Has an Axis I or Axis II diagnosis other than bipolar I disorder and/or concomitant ADHD that has been the primary focus of treatment within 3 months of screening. Has a history or current diagnosis of intellectual disability, Autism Spectrum Disorder, neuroleptic malignant syndrome, or any neurologic disorder, severe head trauma, or any unstable medical condition. CDRS-R total score > 85 at screening or Baseline. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in the Children Depression Rating Scale, Revised (CDRS-R) total score as compared to placebo from Double-Blind Baseline to Week 6 (Day 43). |
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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) |
Change in Clinical Global Impression-Bipolar Version, Severity of Illness (CGI-BP-S) score (depression) as compared to placebo from Double-Blind Baseline to Week 6 (Day 43).
Other Secondary Efficacy Endpoints:
Change from Baseline in Pediatric Anxiety Rating Scale (PARS) score as compared to placebo.
Change from Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) score as compared to placebo.
Change from Baseline in Clinician-rated Children’s Global Assessment Scale (CGAS) score as compared to placebo.
Proportion of responders, where response is defined as ≥ 50% reduction from Baseline in adjusted CDRS-R total score at last observation carried forward (LOCF) Endpoint as compared to placebo.
Proportion of subjects achieving remission, where remission is defined as post-baseline CDRS-R Total Score ≤ 28 and Young Mania Rating Scale (YMRS) total score ≤ 8 and Clinical Global Impressions-Bipolar Version Severity (CGI-BP-S) depression score ≤ 3.
Change from Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS) score as compared to placebo. |
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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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
Bulgaria |
China |
Colombia |
Croatia |
France |
Germany |
Hungary |
Korea, Republic of |
Malaysia |
Mexico |
Philippines |
Poland |
Puerto Rico |
Romania |
Russian Federation |
Serbia |
Spain |
Ukraine |
United Kingdom |
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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LVLS (last visit last subject) |
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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 | 8 |
E.8.9.1 | In the Member State concerned days | |
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 | 2 |