E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
SCHIZOPHRENIA AND BIPOLAR DISORDER |
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E.1.1.1 | Medical condition in easily understood language |
psychotic disorder and mood disorder |
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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 | PT |
E.1.2 | Classification code | 10039626 |
E.1.2 | Term | Schizophrenia |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057667 |
E.1.2 | Term | Bipolar disorder |
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 evaluate the efficacy, defined as time to response (where response is defined as a Clinical Global Impression of Improvement [CGI I] score of 1 [“Very much improved”] or 2 [“Much improved”]), of inhaled loxapine 9.1 mg as compared with aripiprazole 9.75 mg administered as an intramuscular (IM) injection in acutely agitated patients with schizophrenia or bipolar disorder. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate efficacy, defined as percentage of responders at 10, 20, 30, 50, 60, 90 and 120 minutes of inhaled loxapine 9.1 mg as compared with aripiprazole 9.75 mg IM. • To assess the proportion of patients who needed an additional dose of study medication. • To assess the proportion of patients who needed rescue medication. • To assess patient satisfaction with inhaled loxapine compared with aripiprazole. • To evaluate and compare the safety and tolerability of study medication. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female patients between the ages of 18 to 65 years, inclusive. 2. Patients who met Diagnostic and Statistical Manual of Mental Disorders (DSM-5 criteria for schizophrenia or bipolar disorder I. 3. Patients judged to be clinically agitated at baseline with a value of ≥ 4 out of the 7 items on the CGI S scale. 4. Written informed consent from patients with documented adequate consent capacity per the Investigator’s judgement. 5. Patients in good general health prior to study participation as judged by the Investigator and stated in the patient’s record.
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E.4 | Principal exclusion criteria |
1. Patients with agitation caused primarily by acute intoxication (as per Investigator’s judgment). 2. Patients with acute alcohol or psychoactive drugs intoxication/withdrawal symptoms incompatible with their participation in the study as judged by the Investigator. 3. Patients judged to be at serious risk for suicide as per the Investigator’s judgement. 4. Patients treated with benzodiazepines or other hypnotics or oral or short-acting IM antipsychotics within 1 hour prior to study drug administration (however, those patients may be subsequently reassessed for inclusion). 5.Patients with a history of allergy or intolerance to loxapine or amoxapine and/or aripiprazole. 6. Female patients of childbearing potential who have a positive urine pregnancy test at screening or breastfeeding or inpatients who previously had a positive serum pregnancy test upon admission. 7. Patients with previous laboratory or electrocardiogram abnormalities considered relevant by the Investigator that may have clinical implications for the patient's participation in the study. 8. Patients with significant hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease and congestive heart failure), endocrinologic, neurologic or hematologic disease. 9. Patients with acute respiratory signs/symptoms (e.g., wheezing) or with active airways disease (such as patients with asthma or chronic obstructive pulmonary disease). 10. Patients who received an investigational drug within 30 days prior to screening. 11. Patients who are considered by the Investigator, for any reason, to be unsuitable candidates for receiving inhaled loxapine, or are likely to be unable to use the inhalation device.
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Endpoint: • Time to response, where response is defined as a CGI I score of 1 (“Very much improved”) or 2 (“Much improved”).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Post treatment Evaluation Period, which will start with the administration of Dose 1 of the study medication and will continue for at least 4 hours and for a maximum of 24 hours after Dose 1 or the end of the agitation episode as per the Investigator’s judgement, whichever occurs first. |
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E.5.2 | Secondary end point(s) |
Exploratory Endpoints: • The proportion of responders, as defined by a CGI I score of 1 or 2 at 10, 20, 30, 50, 60, 90 and 120 minutes after the first dose of study drug administration. • The value of the CGI-I score at 10, 20, 30, 50, 60, 90 and 120 minutes following Dose 1 of inhaled loxapine compared with aripiprazole. • Total number of patients per group who received 1 or 2 doses of study medication with and without rescue medication by 4 hours and 24 hours after Dose 1 or the end of the agitation episode as per the Investigator’s judgement, whichever occurs first. • Time to rescue medication during the entire Post-treatment Evaluation Period. • Time to Dose 2 (PRN) of study medication during the Post-treatment Evaluation Period as compared between groups. • Satisfaction with study treatment (based on Item 14 of the TSQM) as compared between groups. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Berween 10 minutes and 24 hours after the first dose of study drug administration. |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
•Satisfaction with study treatment |
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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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
Czech Republic |
Germany |
Russian Federation |
Spain |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 36 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 36 |
E.8.9.2 | In all countries concerned by the trial days | 0 |