| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Bipolar I disorder, most recent maniac or mixed episode |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10004939 |
|
| 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 objectives of this study are to evaluate the efficacy of extended-release paliperidone (paliperidone ER) compared with placebo in the prevention of the recurrence of any mood symptoms (i.e., manic or depressive) associated with Bipolar I Disorder and to assess the safety and tolerability of paliperidone ER in subjects who maintain clinical stability after an acute manic or mixed episode. |
|
| E.2.2 | Secondary objectives of the trial |
-efficacy of paliperidone ER compared with placebo in the prevention of manic symptoms associated with Bipolar I Disorder
-efficacy of paliperidone ER compared with placebo in the prevention of depressive symptoms associated with Bipolar I Disorder |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
· Man or woman, between 18 (or the minimum age to provide informed consent in the jurisdiction in which the study is taking place, whichever is older) and 65 years of age, inclusive
· Signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. NOTE: It is acceptable to have additional signatures if required by local regulations.
· Subjects must have signed the informed consent form for genetic research indicating whether they do or do not agree to participate in the genetic component of the study (where local regulations permit). NOTE: Participation in the genetic testing component is not required for participation in the study.
· Meet DSM-IV criteria for Bipolar I Disorder, Most Recent Episode Manic or Mixed (with or without psychotic features) at the time of screening (Days -7 to -1). Subjects with other Axis I and II disorders, except those listed in the exclusion criteria, are also acceptable. All diagnoses will be confirmed by the MINI.
· History of at least 2 previously documented mood episodes associated with Bipolar I Disorder (1 of which must be a manic or mixed episode) that required medical treatment within the 3 years before screening.
· Total score of at least 20 on the YMRS at screening and at baseline (Day 1).
· Women must be postmenopausal for at least 1 year, surgically sterile, abstinent, or agree to practice an effective method of birth control if they are sexually active before entry and throughout the study (effective methods of birth control include prescription hormonal contraceptives, contraceptive injections, intrauterine devices, double barrier method, contraceptive patch, and male partner sterilization). Female subjects must also have a negative urine pregnancy test at screening and baseline (Day 1).
· Able and willing to comply with self-administration of study drug, or have consistent help or support available.
· Able to meet study requirements (e.g., answer self-administered questionnaires). NOTE: If a subject is unable to read study information or answer study questions, study personnel may read the questions to the subject and the subject may then mark his or her choice.
|
|
| E.4 | Principal exclusion criteria |
Potential subjects who meet any of the following criteria will be excluded from the participation in the study:
- Meet DSM-IV criteria for any type of episode associated with bipolar disorder other than Bipolar I Disorder, Most Recent Episode Manic or Mixed (with or without psychotic features)
- Meet DSM-IV criteria for rapid cycling
- Meet DSM-IV criteria for schizoaffective disorder
- Known or suspected borderline or antisocial personality disorder
- In the opinion of the investigator, are at significant immediate risk for suicidal or violent behaviour during the course of the study based on current status or prior history (e.g., suicide attempts during previous episodes)
- Known or suspected history of substance dependence (excluding nicotine and caffeine) according to DSM-IV criteria, with DSM-IV duration criteria modified to "at anytime within the previous 3 months"
- Serious or unstable medical illness (e.g., cardiovascular disease, neurologic, hematologic, renal, hepatic, immunologic, endocrine, or other systemic illness), or have a history of cerebrovascular disease or uncontrolled or insulin-dependent diabetes mellitus. Subjects with chronic illness may be included but must be stable and otherwise physically healthy on the basis of a physical examination, medical history, ECG, and the results of chemistry, hematology, and urinalysis testing.
- Known or suspected seizure disorder or require treatment with anticonvulsants for another indication (e.g., migraine prophylaxis)
- History of severe pre-existing gastrointestinal narrowing (pathologic or iatrogenic) or inability to swallow oral study drug whole with the aid of water
- Results at screening or baseline (Day 1) for alanine aminotransferase or aspartate aminotransferase greater than twice the upper limit of the central laboratory's reference range. If the results for any other chemistry, hematology, or urinalysis testing are not within the central laboratory's reference ranges, the subject can be enrolled only if, in the opinion of the investigator, the deviations are not clinically significant.
- Have active hypo- or hyperthyreoidism unless stabilized on appropriate medication for at least 3 months before the screening phase
- History of neuroleptic malignant syndrome or similar encephalopathic syndrome
- Have a moderate to severe degree of tardive dyskinesia at screening
- Known or suspected history of hypersensitivity or intolerance to paliperidone, risperidone, or olanzapine, or suspected history of lifethreatening drug allergy or hypersensitivity to any drug
- Have received benzodiazepines at dosages equivalent to 4 mg/day of lorazepam or higher for a period of 3 months or longer immediately before the screening phase
- have received clozapine, aripiprazole, or fluoxetine within 1 month before the screening phase
- Have received antidepressant therapy (other than fluoxetine) within 7 days (or 5 times the half-life of the product, whichever is longer) before study drug administration on Day 1. Antidepressant medications include known antidepressants used for other indications (e.g., anxiety disorders, sleep disturbance, and smoking cessation) as well as St. John's Wort, SAM-e, and other over-the-counter antidepressants.
- Use of antiparkinsonian drugs or ß-adrenergic blockers (for any indication other than hypertension) within 3 days before study drug administration on Day 1
- Have recently used cocaine, phencyclidine, amphetamine, methylphenidate, pemoline, an opioid (excluding low-dose codeine), hallucinogen, or any other drug that may be associated with manic symptoms, as evidenced by a positive urine drug screen at screening or baseline (Day 1)
- Documented or suspected alcohol intoxication within 3 days before study drug administration on Day 1
- Have had an injection of RISPERDAL CONSTA within 5 weeks before the screening phase, or have received another depot antipsychotic within 1 treatment cycle before the screening phase
- Have received an experimental drug or used an experimental medical device within 3 months before study drug administration on Day 1
- Electroconvulsive therapy within 6 months before study drug administration on Day 1
- Women who are pregnant or nursing
- Have an anticipated life expectancy of 12 months or less
- Unable to provide their own consent
- Previous participation in this study
- Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of the investigator or study center, including family members of the employees or the investigator
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Time to first recurrence of any mood symptoms associated with Bipolar I Disorder |
|
| 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 | Yes |
| 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 | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| 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 | 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 | Yes |
| E.8.2.3.1 | Comparator description |
|
| 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 | 18 |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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
| |
| 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 | 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 | 8 |
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