| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Acute Manic or Mixed Episodes Associated with Bipolar I Disorder |
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| E.1.1.1 | Medical condition in easily understood language |
Bipolar disorder is a psychiatric diagnosis where patients have one or more episodes of abnormally elevated energy levels, cognition and mood (mania) with or without one or more depressive episodes.
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| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10068455 |
| E.1.2 | Term | Bipolar I disorder, hypomanic |
| 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 |
| To collect safety data of long-term treatment with asenapine in pediatric subjects (12 to 17 years) with a manic or mixed episode associated with bipolar I disorder. |
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| E.2.2 | Secondary objectives of the trial |
To collect exploratory efficacy data of long-term treatment with asenapine in
pediatric subjects (12 to 17 years) with a manic or mixed episode associated with
bipolar I disorder.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Each subject’s parent(s) or legal representative must be willing and able to provide written informed consent for the trial and each subject must indicate assent before trial participation;
2. Each subject must have completed the 3-week (P06107) efficacy and safety trial and, according to the investigator’s judgment, may benefit from long-term treatment;
3. Each subject must have demonstrated an acceptable degree of compliance with trial medication, visits, and other requirements in trial P06107 in the opinion of the investigator;
4. Each subject must be ≥12 years and ≤18 years of age; A subject may be of either sex, and of any race/ethnicity;
5. Each subject must be a male, or a female who is not of childbearing potential (eg, surgically sterile) or who is non-pregnant, non-lactating, and is using a medically accepted method of contraception. If a female subject of childbearing potential, must agree to use a medically
accepted method of contraception while receiving protocol specified medication and for 1 month after stopping the medication;
6. Each subject must have a caregiver, or an identified responsible person, living with the subject, who is considered reliable by the investigator and who has agreed to provide support to the subject to ensure compliance with trial treatment, outpatient visits, and protocol procedures;
Refer to protocol for complete list
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| E.4 | Principal exclusion criteria |
1. The subject has a positive urine pregnancy test at Baseline, or the intention to become pregnant during the course of the trial;
2. The subject is at imminent risk of self-harm or harm to others, in the investigator’s opinion based on clinical interview and responses provided on the Columbia Suicide Severity Rating Scale (C-SSRS);
3. The subject is under involuntary inpatient commitment;
4. A subject has known serological evidence of human immunodeficiencyvirus (HIV) antibody.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary objective of the trial is to investigate safety and tolerability of long-term asenapine treatment in pediatrics, which will rely on descriptive safety endpoints.
There are no pre-specified key safety endpoints. Events and parameters specified as “Tier 1,” “Tier 2,” and “Tier 3,” which are exploratory.
Tier 1 Events:
• Akathisia (preferred term [PT])
• Dizziness (PT)
• Insomnia (PT)
• Combined somnolence (PT), hypersomnia (PT) and sedation (PT)
• Combined oral hypoesthesia (PT) and dysgeusia (PT)
• EPS (standardized Medical Dictionary for Regulatory Activities [MedDRA] queries [SMQ] [narrow]), and
• Incidence of weight gain ≥7% increase from baseline to endpoint.
Tier 2 Events:
Specific AEs (incidence ≥4 subjects overall).
• Change from baseline to endpoint in the laboratory variables:
- Fasting glucose
- Fasting triglycerides
- Fasting cholesterol
- Prolactin
- Fasting insulin, and
- HbA1c.
The Tier 2 fasting laboratory endpoints may be included regardless of whether fasting can be definitively achieved in certain outpatient trials. Subjects will report whether they were fasting and this will be evident in the database.
Tier 3 Events:
• All other specific AEs occurring in <4 subjects overall (not in Tier 1 or Tier 2)
• Change or shift from baseline results (Laboratory parameters, Vital Signs,
ECGs, ESRS, C-SSRS, menstrual cycle, growth, Tanner staging)
• Laboratory parameters, vital signs, ECGs, ESRS, C-SSRS, menstrual cycle,
growth, Tanner staging.
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Continuously throughout the study |
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| E.5.2 | Secondary end point(s) |
• Change in Y-MRS total score from baseline(s);
• Proportion of Y-MRS total score remitters (Y-MRS ≤12);
• Proportion of sustained remitter of the Y-MRS;
• Proportion of Y-MRS total score responders ≥50%;
• Time to first total Y-MRS 50% response;
• Time to failure to maintain effect;
• Change in CGI-BPoverall, CGI-BPdepression, and CGI-BPmania from baseline(s)
(calculated from severity);
• Change in CDRS-R total score from baseline(s)
• Proportion of CDRS-R responders;
• Proportion of subjects with emergent depression based on CDRS-R;
• Change in CGAS from baseline(s);
• Proportion of subjects with CGAS total score >=70 (ie, indicating normal
functioning);
• Change in PQ-LES-Q total score from baseline(s);
• Change in PQ-LES-Q overall score from baseline(s).
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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 | Yes |
| 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 | No |
| 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.8.3 |
Will this trial be conducted at a single site globally?
| No |
| E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
| 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.8.9.2 | In all countries concerned by the trial years | 2 |
| 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 | 18 |
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