| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| patients with schizophrenia |
|
| MedDRA Classification |
| 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 effect on patient weight of adjunctive therapy of aripiprazole with clozapine versus clozapine mono-therapy, in schizophrenic patients who are not optimally controlled on clozapine. |
|
| E.2.2 | Secondary objectives of the trial |
To assess the effect of adding aripiprazole to clozapine in terms of :
• Efficacy, as measured on
- Positive and Negative Syndrome Scale
- Clinical Global Impression-Severity and Clinical Global Impression-Improvement
• Effectiveness as measured on
- Investigator Assessment Questionnaire
- Global Assessment of Functioning
• Patient reported outcomes for
- Social cognition
- Subjective well-being
- Alertness
- Fatigue
• Safety measures
- Simpson-Angus Scale
- Metabolic Laboratory Parameters
- AE/SAE
- Waist circumference
- BMI
- ECG
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Patients must be competent to understand the nature of the study, sign the informed consent, agree to comply with prescribed dosage regimens, report for regularly scheduled visits with their caring physician, able to provide reliable information for safety, efficacy and Quality of life assessments and communicate to the psychiatrist about adverse events and concomitant medication use (see Protocol Section 9.2.2, Appendix 1);
2) The informed consent process must be documented by signing the informed consent form prior to any study-related procedures including alteration in medications in preparation for study entry;
3) Patients with a diagnosis of schizophrenia as defined by DSM-IV-TR6 criteria (see Protocol Appendix 2);
4) Outpatients (including outpatients in a day or night program) who in the clinical
judgment of the treating psychiatrist, would benefit from the addition of another
antipsychotic (AP) medication;
5) Patients who have been taking a stable dose (variation within 100 mg dose range) of clozapine for a minimum of 3 months, within the range of 200 - 900 mg/day, and who are not optimally controlled, but can benefit from continuing with clozapine treatment, as per investigator judgment;
6) Patients who experienced weight gain of at least 2.5 kg while taking clozapine;
7) Men and women, aged 18 to 65 years.
8) Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the study.
WOCBP must have a negative serum or urine pregnancy test within 72 hours prior to the start of study medication. |
|
| E.4 | Principal exclusion criteria |
1) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the study.
2) WOCBP using a prohibited contraceptive method.
3) Women who are pregnant or breastfeeding;
4) Women with a positive pregnancy test on enrollment or prior to study drug administration;
5) Patients who are at risk for committing suicide; either having active suicidal ideation considered clinically significant or recently attempted suicide;
6) Patients with a diagnosis of schizoaffective disorder, bipolar disorder, depression
with psychotic symptoms, or organic brain syndromes;
7) Patients who have met DSM-IV-TR criteria for any significant Psychoactive
Substance Use Disorder within the 3 months prior to Screening;
8) Patients with a history of neuroleptic malignant syndrome;
9) Patients with epilepsy, a history of seizures (except for a single childhood febrile seizure), a history of stroke or who have a history or evidence of other medical conditions that would expose them to an undue risk of a significant adverse event or
interfere with assessments of safety or efficacy during the course of the trial;
10) Patients with thyroid pathology, which has not been stabilized on medication for at least 3 months;
11) Patients with detectable levels of cocaine in the drug screen. Patients with a positive drug screen for stimulants, opioids or other drugs of abuse are to be discussed with BMS and approval granted prior to treatment;
12) Blood alcohol level ≥50 mg/dL
13) The following laboratory test results, vital sign and ECG findings are exclusionary:
- QTc > 475 msec
- Platelets ≤ 75,000/mm3
- Hemoglobin ≤ 9 g/dL
- WBC ≤ 3500/mm3
- Absolute Neutrophil Count (ANC) ≤ 2000/mm3
- AST (SGOT) or ALT (SGPT) > 3x upper limit of normal
- Creatinine ≥ 2 mg/dL or ≥ 177 umol/l
- Diastolic blood pressure > 105 mmHg
In addition, patients should be excluded if they have any other abnormal laboratory test result, vital sign result or ECG finding that in the investigator’s judgment is medically significant, in that it would impact the safety of the patient or the interpretation of the study results.
14) Experiencing weight loss greater than 10% of total body weight within 3 months
prior to Screening;
15) Patients who are known to be allergic or hypersensitive to aripiprazole or other
dihydrocarbostyrils;
16) Patients who would be likely to require prohibited concomitant therapy during the trial (see Protocol Section 5.4);
17) Patients who have previously received study medication in an aripiprazole clinical study or who have participated in any clinical trial with an investigational agent within the past month;
18) Patients previously treated with aripiprazole, who showed a poor response in terms of efficacy or tolerability;
19) Use of medications for the purpose of weight loss;
20) Treatment with a long acting antipsychotic in which the last dose was less than one full cycle plus one week prior to entering the Double-blind Phase;
21) ECT treatment within 3 months prior to randomization;
22) Prisoners or subjects who are compulsorily detained. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Mean change from baseline in patient weight at Week 16 (LOCF) in patients who received at least 4 weeks of double-blind study medication. |
|
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| tolerability, outcomes for social cognition, subjective well-being, alertness and fatigue |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| optional 12-week open-label extension phase for subjects completing the 16-week double-blind phase |
|
| 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 | 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 65 |
| 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 | 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
|
|
| 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 | 8 |
| 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 | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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