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 |
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 | 16.0 |
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 |
The primary objective of the study is to evaluate the longer term safety and tolerability of lurasidone flexibly dosed at 20, 40, 60 or 80 mg/day over a 12-week period in subjects with bipolar I disorder who have previously been treated with lurasidone. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to evaluate the longer-term effectiveness of lurasidone flexibly dosed at 20, 40, 60 or 80 mg/day over a 12-week period in subjects with bipolar I disorder who have previously been treated with lurasidone. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject provides written informed consent and is willing and able to comply with the protocol, in the opinion of the Investigator.
2. Subject has completed the 28 week Double-blind Phase of Study D1050296 and all required assessments on the final study visit (Week 28, Visit 28); OR Subject has experienced a protocol-defined recurrence of any mood event during the Double-blind Phase of Study D1050296 and has completed all required assessments on the final study visit; OR Subject had at least entered the Open-label Phase of Study D1050296 when the Sponsor stopped the study and has completed all required assessments on the final study visit.
3. Subject is judged by the Investigator to be suitable for participation in a 12-week clinical study involving open-label lurasidone treatment.
4. Subject is not pregnant at the extension baseline visit (must have a negative urine pregnancy test at the final study visit in Study D1050296) or nursing (must not be lactating) and is not planning pregnancy within the projected duration of the study.
5. Males and female subjects who are of reproductive potential agree to remain abstinent or use adequate and reliable contraception throughout the study and for at least 30 days after the last dose of lurasidone has been taken. In the Investigator’s judgment, the subject will adhere to this requirement. - Adequate contraception is defined as continuous use of either two barrier methods (eg, condom and spermicide or diaphragm with spermicide) or acceptable hormonal contraceptive. Acceptable hormonal contraceptives include the following: a) contraceptive implant (such as Norplant®); b) injectable contraception (such as medroxyprogesterone acetate injection); or c) oral contraception. - Female subjects who are of non-reproductive potential, ie, a subject who is surgically sterile, has undergone tubal ligation, or is postmenopausal (defined as at least 12 months of spontaneous amenorrhea or between 6 and 12 months of spontaneous amenorrhea with follicle stimulating hormone concentrations within postmenopausal range as determined by laboratory analysis) are not required to remain abstinent or use adequate contraception.
6. Subject is in good physical health on the basis of physical examination at the extension baseline visit (performed at the final study visit in Study D1050296). |
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E.4 | Principal exclusion criteria |
1. Subject is considered by the Investigator to be at imminent risk of suicide, injury to self or to others, or damage to property.
2. Subject answers "yes" to "Suicidal Ideation" item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) on the Columbia Suicide Severity Rating Scale (C-SSRS) at the extension baseline visit (final study visit in Study D1050296). Subjects who answer "yes" to this question must be referred to the Investigator for follow-up evaluation.
3. Subject requires treatment with any potent CYP3A4 inhibitors or inducers during the study. Subject requires treatment with a drug that consistently prolongs the QTc interval.
4. Subject currently has a clinically significant neurological, metabolic (including type 1 diabetes), hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological disorder such as unstable angina, congestive heart failure (uncontrolled), or central nervous system (CNS) infection that would pose a risk to the subject if they were to participate in the study or that might confound the results of the study. Subjects with human immunodeficiency virus (HIV) seropositivity (or history of seropositivity) will be excluded. Note: Active medical conditions that are minor or well-controlled are not exclusionary if they do not affect risk to the subject or the study results. In cases in which the impact of the condition upon risk to the subject or study results is unclear, the Medical Monitor should be consulted. Any subject with a known cardiovascular disease or condition (even if under control) must be discussed with the Medical Monitor before being enrolled in the study.
5. Subject exhibits evidence of severe tardive dyskinesia, severe dystonia, or any other severe movement disorder. Severity is to be determined by the Investigator.
6. Subject has presence of abnormal electrocardiogram (ECG) at the extension baseline visit (final study visit in Study D1050296), which in the Investigator’s opinion is clinically significant (Medical Monitor may be consulted to determine clinical significance). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability will be assessed by the proportion of subjects with the following: - Clinical and laboratory treatment-emergent adverse events (TEAEs) - TEAEs leading to discontinuation - Serious AEs (SAEs).
Safety and tolerability will further be assessed by the following parameters; - Clinical review of TEAEs and laboratory values (including serum prolactin) - ECG findings - Physical examination - Weight - Vital signs - Columbia Suicide Severity Rating Scale (C-SSRS). - Movement disorders, as assessed by Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), and the Simpson-Angus Scale (SAS). |
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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) |
Effectiveness endpoints will be assessed by the following parameters: - YMRS total score. - MADRS total score. - Quick Inventory of Depressive Symptomatology ¡V Self Report (QIDS-SR16) total score. - Positive and Negative Syndrome Scale Positive Subscale (PANSS-P) score. - Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) score (overall, depression, mania). - Sheehan Disability Scale (SDS) total score and SDS subscales. -Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF). - Pittsburgh Insomnia Rating Scale (PIRS-2). -Health Services Utilization Questionnaire (HSUQ) (US sites only). - SF-12 Health Survey. - Medication Satisfaction Questionnaire (MSQ). - Intend to attend assessment. |
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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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
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 |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |