E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.1 |
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.1.3 | 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 overall efficacy of aripiprazole IM depot as acute treatment in subjects with schizophrenia. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of aripiprazole IM depot as acute treatment in subjects with schizophrenia |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female subjects 18 to 65 years of age, inclusive, at the time of informed consent.
2. Subjects with a diagnosis of schizophrenia for at least 1 year as defined by DSM-IV-TR criteria and confirmed by the MINI for Schizophrenia and Psychotic Disorders Studies.
3. Subjects with a stable living environment when not in hospital, as demonstrated by the ability to provide contact information for themselves and/or family/friend(s)/caregiver(s).
4. Subjects who would benefit from hospitalization or continued hospitalization for treatment of a current acute relapse of schizophrenia at trial entry. Note: The screening visit (ie, signing the informed consent) must occur no more than 5 days after the date of hospital admission.
5. Subjects who are experiencing an acute exacerbation of psychotic symptoms and marked deterioration of usual function as demonstrated by meeting BOTH of the following at screening and baseline:
• Currently experiencing an acute exacerbation of psychotic symptoms accompanied by significant deterioration in the subject’s clinical and/or functional status from their baseline clinical presentation with a Positive and Negative Syndrome Scale (PANSS) Total Score ≥ 80 AND
• Specific psychotic symptoms on the PANSS as measured by a score of > 4 on each of the following items (possible scores of 1 to 7 for each item)
• Conceptual disorganization (P2)
• Hallucinatory behavior (P3)
• Suspiciousness/persecution (P6)
• Unusual thought content (G9)
6. Subjects who have received previous outpatient antipsychotic treatment at an adequate dose (minimal recommended dose for the treatment of schizophrenia according to the manufacturer labeling) for an adequate duration (at least 6 weeks) and who showed a previous good response to such antipsychotic treatment (other than clozapine) in the last 12 months, according to the investigator’s opinion.
7. Subjects with a history of relapse and/or exacerbation of symptoms when they are not receiving antipsychotic treatment, excluding the current episode.
8. Subjects willing to discontinue all prohibited psychotropic medications to meet protocol-required washouts prior to and during the trial period.
9. BMI ≤ 40 kg/m2 (morbid obesity) at screening.
10. Subjects who are able to provide written informed consent (as required by IRB/IEC) prior to the initiation of any protocol-required procedures.
11. Ability, in the opinion of the investigator, to understand the nature of the trial and follow protocol requirements, including the prescribed dosage regimens, tablet ingestion, and discontinuation of prohibited concomitant medication, and to be reliably rated on assessment scales. |
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E.4 | Principal exclusion criteria |
Sexually active males of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 180 days after the last dose of trial medication. Sexually active females of childbearing potential who do not agree to practice 2
different methods of birth control or remain abstinent during the trial and for 150 days after the last dose of trial medication.
Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving IMP in this trial.
Subjects with improvement of ≥ 30% in total PANSS score between the screening and baseline assessments. -Subjects presenting with a first episode of schizophrenia- Subjects hospitalized for ≥ 30 days out of the last 90 days prior to screening visit. Subjects who have been hospitalized > 5 days for the current acute episode at the time of the screening visit.
Subjects with schizophrenia who are considered resistant/refractory to antipsychotic treatment.
Subjects who have a history of response to clozapine treatment only.
Subjects with a current DSM-IV-TR Axis I diagnosis other than schizophrenia. Also, subjects with borderline,
paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder or mental retardation.
Subjects experiencing acute depressive symptoms within the past 30 days, that require treatment with an antidepressant.
Subjects with a significant risk of violent behavior; who represent a risk of committing suicide as indicated by any suicidal ideation within the last 1 month or any suicidal behaviors within the last
year; or who present a serious risk of suicide.
Subjects with clinically significant tardive dyskinesia
Subjects with severe akathisia.
Subjects who have met DSM-IV-TR criteria for substance abuse with the past 3 months prior to screening or dependence within the past 6 months; including alcohol and benzodiazepines, but excluding caffeine and nicotine. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Outcome Variable:
• Mean change from baseline to endpoint in PANSS Total
Score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Key Secondary Outcome Variable:
• Mean change from baseline to endpoint in Clinical Global
Impression - Severity scale (CGI-S)
Other Secondary Outcome Variables:
Efficacy:
• Mean change from baseline to endpoint in PANSS positive
and negative subscales
• Mean change from baseline to endpoint in Personal and
Social Performance Scale (PSP)
• Mean Clinical Global Impression - Improvement
scale (CGI-I) score at endpoint
• Responder rate at endpoint (defined by ≥ 30% reduction in
Total PANSS score) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | 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 | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
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 |
Bulgaria |
Colombia |
Croatia |
Egypt |
India |
Indonesia |
Latvia |
Philippines |
Poland |
Romania |
Russian Federation |
Serbia |
Slovakia |
Turkey |
Ukraine |
United States |
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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 Date is defined as the last Date of Contact or the Date of Final Contact Attempt from the Post-treatment Follow-up eCRF page for the last subject completing or withdrawing from 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 | 14 |
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 | 14 |
E.8.9.2 | In all countries concerned by the trial days | 0 |