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 | 19.0 |
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 |
Evaluate the long-term efficacy and safety of SM-13496 (20-120 mg/day) in patients with bipolar I disorder. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients who completed the prior study D1002001:
1) Patients who were fully informed of and understand the objectives, procedures, and possible benefits and risks of the study and who provided written voluntary consent to participate in the study. If the patient is a minor at the time of
consent, written consent should be obtained from a legally acceptable representative (guardian) in addition to the patient him/herself
2) Patients who completed the prior study and who are considered by the investigator to be eligible and without safety concerns
3) Patients who agree to use appropriate contraception to prevent pregnancy in female patients or the female partners of patients, when the patients or their partners are of childbearing potential
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E.4 | Principal exclusion criteria |
Patients who completed the prior study:
1) Patients with a score > 4 on the Montgomery-Ǻsberg Depression Rating Scale (MADRS) item 10 (suicidal thoughts) at Week 6 in the prior study
2) Patients with a “Yes” response to the Columbia-Suicide Severity Rating Scale (C-SSRS) item 4 (active suicidal ideation with some intent to act, without a specific plan) or item 5 (active suicidal ideation with specific plan and intent) at
Week 6 in the prior study
3) Patients with imminent risk of suicide or injury to self, others, or property
4) Patients who are otherwise considered ineligible for the study by the investigator
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E.5 End points |
E.5.1 | Primary end point(s) |
SAFETY ENDPOINTS:
- Incidence of adverse events (AEs) and adverse drug reactions (ADRs)
- Incidence of extrapyramidal AEs and ADRs
- Proportion of patients with concomitant use of antiparkinson medication
- Change from baseline in the prior study (D1002001) and the present study (D1002002) in the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) total score (except for the overall severity score) at the final assessment and at
each assessment point
- Change from baseline in the prior study and the present study in the individual DIEPSS symptoms scores at the final assessment and at each assessment
- Change from baseline in the prior study and the present study in the serum prolactin concentration at the final assessment and at each assessment point
- Change from baseline in the prior study and the present study in the ECG parameter (QTc) at the final measurement
- Change from baseline in the prior study and the present study in the fasting blood glucose, HbA1c (NGSP), glycoalbumin, total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides at the final measurement
- Change from baseline in the prior study and the present study in the body weight at the final measurement
- Laboratory measures and vital signs
- Proportion of patients with any instance of suicide attempt or suicidal ideation based on the Columbia Suicide Severity Rating Scale (C-SSRS)
EFFICACY ENDPOINTS:
1) Change from baseline in the prior study (D1002001) and the present study (D1002002) in the MADRS total score at the final assessment and each assessment point
2) Change from baseline in the prior study and the present study in the Young Mania Rating Scale (YMRS) total score at the final assessment and each assessment point
3) Change from baseline in the prior study and the present study in the Clinical Global Impressions: Bipolar Version - Severity of Illness (CGI-BP-S) (overall, depression, mania) scores at the final assessment and each assessment point
4) Change from baseline in the prior study and the present study in the Sheehan Disability Scale (SDS) score at the final assessment and each assessment point
5) Change from baseline in the prior study and the present study in the Hamilton Rating Scale for Anxiety (HAM-A) total score at the final assessment and each assessment point
6) The time to recurrence/relapse of any mood event from clinical stability of bipolar disorder. Clinical stability is defined as total scores of ≤ 12 on the MADRS and the YMRS over at least 12 weeks, with the allowance of 2 excursions (the YMRS and/or MADRS total scores up to 13 or 14, respectively) except during the last 4 weeks before achieving clinical stability.
7) Time to all cause discontinuation |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, 1, 2, 4, 8, 12, 16, 20, 24 and 28 weeks |
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E.5.2 | Secondary end point(s) |
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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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 |
Japan |
Malaysia |
Philippines |
Russian Federation |
Taiwan |
Ukraine |
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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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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 | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |