E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10004939 |
E.1.2 | Term | Bipolar I disorder |
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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 long-term safety, tolerability, and pharmacokinetics of cariprazine in patients with bipolar I disorder. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be eligible to participate in the study, patients must have either documented inadequate response or be intolerant to their current treatment or not be currently receiving any treatment, and they also must meet the following criteria: Criteria to be assessed at Visit 1 (Screening): 1. Provide written (signed or thumbprinted) informed consent before the initiation of any study-specific procedures 2. Male or female, 18 to 65 years of age, inclusive 3. Currently meet the DSM-IV-TR criteria for bipolar I disorder confirmed by the administration of the Structured Clinical Interview (SCID), most recent episode manic or mixed type—with or without psychotic symptoms 4. Young Mania Rating Scale (YMRS) total score ≥ 18 5. Montgomery-Asberg Depression Rating Scale (MADRS) score < 18 6. Experienced a manic or mixed episode that required treatment within 12 months of Visit 1 7. If a female with childbearing potential, have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test 8. Have normal physical examination results, vital signs, clinical laboratory test results, and electrocardiogram (ECG) results or abnormal results that are judged not clinically significant by the Investigator and documented as such in the eCRF. 9. Body mass index (BMI) between 18 and 40 kg/m2, inclusive Criteria to be assessed at Visit 2 (Baseline): 10. Continue to meet the Visit 1 inclusion criteria |
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E.4 | Principal exclusion criteria |
1. Principal DSM-IV-TR–based diagnosis of an axis I disorder, other than bipolar I, or any axis I disorder other than bipolar I that was the primary focus of treatment within 6 months before V1 2. Currently meet DSM-IV-TR criteria for any of the following: • Mental retardation, delirium, dementia, amnesic, or other cognitive disorders • Schizophrenia, schizoaffective, or other psychotic disorders • Rapid cycling (>4 episodes of a mood disturbance in the previous 12 months that meets criteria for major depressive, manic, mixed, or hypomanic episodes per DSM-IV) • Substance-induced manic or hypomanic episode. Mania that is a result of direct psychological effects of a general medical condition • Known or suspected borderline or antisocial personality disorder or other DSM-IV-TR axis II disorder of sufficient severity to interfere with participation in this study • Alcohol and/or substance abuse or dependence (other than nicotine or caffeine) within the prior 3 months. 3. Positive result from the blood alcohol test or urine drug screen for any prohibited Medication 4. History of intolerance or hypersensitivity to cariprazine, other drugs of the same class, rescue medications or any history of severe drug allergy or hypersensitivity. 5. Experiencing first manic episode 6. At imminent risk of injuring self or others or causing significant damage to property, as judged by the PI 7. Suicide risk, as determined by any of the following criteria: • A suicide attempt within the past year • A score of 5 or greater on item 10 of the MADRS • Significant risk judged by the PI based on the psychiatric interview or information collected in the C-SSRS 8. Manic symptoms resulting from initiation of prior antidepressant therapy 9. Electroconvulsive therapy in the 3 months prior to V1 10. Treatment with depot neuroleptic in the 3 months prior to V1 11. Treatment with clozapine in the past 10 years (exception: episodic use of clozapine at doses ≤ 100 mg/d for the treatment of insomnia) 12. Previous resistance to electroconvulsive therapy 13. Requiring concomittant treatment with any of the prohibited medications, supplements, or herbal medications listed in Protocol App.II 14. Female patients who meet the following criteria: Pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study; Not at least 2 years postmenopausal, surgically sterile, or practicing a reliable method of contraception that will continue throughout the study duration. In Germany: not at least 2 years postmenopausal, surgically sterile, or practicing a highly reliable (Pearl Index <1) method of contraception that will continue throughout the study duration. Refer to protocol section 9.3.2, EC #14 for acceptable methods of contraception in Germany. 15. Any concurrent medical condition that, in the judgment of the PI, might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the patient’s well-being 16. Any cardiovascular disease that is clinically significant, unstable, or decompensated. Refer to protocol section 9.3.2., EC#16. 17. Hypothyroidism or hyperthyroidism, unless stabilized on appropriate pharmacotherapy with no change in dosage for at least 3 months before V1 18. Abnormal level of serum vitamin B12 or folate, or psychiatric symptoms possibly secondary to any other organic medical condition 19. Gastric bypass or have any condition that would be expected to affect drug absorption 20. History of seizure disorder, stroke, significant head injury, tumor of the central nervous system, or any other condition that predisposes the patient toward a risk for seizure 21. Known HIV infection 22. Known history or present evidence of hepatitis C infection, unless the patient has had successful definitive treatment for hepatitis C, with documentation of same. 23. Positive test for hepatitis-B surface antigen and/or hepatitis-B core antibody IgM 24. AST and/or ALT > 2 × ULN, confirmed by re-test 25. AST and/or ALT > 1.5 × ULN who have also tested positive for HAV-IgM 26. History of tardive dyskinesia (except for mild cases attributed to use of conventional agents), serotonin syndrome, or neuroleptic malignant syndrome 27. Hystory of syndrome of inappropriate antidiuretic hormone secretion 28. History of cataracts or any of the LOCS III findings at the screening examination noted in protocol section 9.2.3, EC #28. 29.Patients who meet any of the ophtalmologic assessment criteria as per protocol section 9.3.2., EC#29. 30. Treatment with any IP, including cariprazine, within 3 months (or at least 5 half-lives, whichever is longer) prior to V1 31. Inability to speak and understand the local language sufficiently to understand the nature of the study, provide written informed consent (signed or thumbprinted), and allow the completion of all study assessments 32. Requiring pharmacologic treatment for the control of EPS |
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E.5 End points |
E.5.1 | Primary end point(s) |
Collection of long term safety data, including adverse events, ECGs, laboratory parameters and ophthalmology information.
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
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 | 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 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
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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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The end of trial is the last patient last visit which includes the 3 week safety follow up. |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |