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 |
mental disease called schizophrenia |
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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 | 17.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009134 |
E.1.2 | Term | Chronic 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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039632 |
E.1.2 | Term | Schizophrenia NOS |
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 characterize the safety of ALKS 9072 during long-term treatment of subjects with stable
schizophrenia. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the durability of effect of ALKS 9072 during long-term treatment of subjects with
stable schizophrenia |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects Who Participated in ALK9072-003
1. Subject completed the ALK9072-003 Day 85 visit
2. Subject continues to require chronic treatment with an antipsychotic medication, in the opinion of the investigator
3. Subject continues to meet the contraceptive requirements of the study (see Section 7.5.1)
4. Subject is willing to continue, and has provided informed consent before initiation of any study specific procedures
New Subjects (Not Participated in ALK9072-003)
1. Subject is between 18 and 70 years old, inclusive, at screening
2. Subject is on a stable dose of oral antipsychotic medication and would potentially benefit from conversion to an extended release injectable, in the opinion of the investigator
3. Subject has a diagnosis of chronic schizophrenia (based on DSM-IV-TR criteria) that is clinically stable as evidenced by:
- No hospitalizations for acute exacerbations of schizophrenia within 3 months before
screening
- CGI-S score of ≤ 3 (mild) at screening
4. Subject has previously had a clinically significant beneficial response (improvement in
schizophrenia symptoms), as determined by the investigator, to treatment with an antipsychotic medication other than clozapine
5. Subject has been able to achieve outpatient status for more than 3 consecutive months in the past year
6. Subject has a PANSS total score of less than 70 at screening
7. Subject has a BMI of 18.5 to 40.0 kg/m2 (inclusive) at screening
8. Subject resides in a stable living situation, in the opinion of the investigator
9. Subject has an identified reliable informant, in the opinion of the investigator
10. Subject meets contraceptive requirements defined in the protocol (see Section 7.5.1)
11. Subject is fluent (oral and written) in the language in which standardized tests will be administered, and can be reliably rated
12. Subject is willing and able to provide informed consent and subject has signed the informed consent form before initiation of any study specific procedures |
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E.4 | Principal exclusion criteria |
Subjects Who Participated in ALK9072-003
1. Subject had an abnormal clinical laboratory, vital sign, or ECG finding during participation in
study ALK9072-003 that was clinically relevant and related to study drug, in the opinion of the
investigator
2. Subject was withdrawn from study ALK9072-003 due to a severe AE or a SAE, or
because of development of a serious medical condition or serious tolerability issues
3. Subject missed more than 1 scheduled study visit during participation in study ALK9072-003
4. Subject has a significant or unstable medical condition that would preclude safe completion of the current study
5. Subject requires use of a prohibited concomitant medication
6. Subject is pregnant or breastfeeding
New Subjects (Not Participated in ALK9072-003)
1. Subject has a history of poor or inadequate clinical response to treatment with aripiprazole
2. Subject has a history of treatment resistance, defined as failure to respond to 2 adequate trials of different antipsychotic medications (a minimum of 4 weeks at the subject's maximum tolerated dose)
3. Subject has a history of neuroleptic malignant syndrome, clinically significant tardive dyskinesia, tardive dystonia, or other medical condition that would convey undue risk or interfere with study assessments
4. Subject has clinically significant extrapyramidal symptoms at screening or baseline
5. Subject is at significant risk of suicidal, homicidal or violent ideation or behavior, by history or as clinically assessed by the investigator
6. Subject answers “Yes” on items 4 or 5 of the C-SSRS (ideation) with the most recent episode occurring within the past 2 months, or answers “Yes” to any of the 5 items (behavior) with an episode occurring within the last year
7. Subject has a diagnosis (according to DSM-IV-TR criteria) of substance (including alcohol)
dependence currently or within 6 months before screening or abuse within 3 months before
screening (exception: nicotine and caffeine dependence are allowed)
8. Subject has comorbid schizoaffective disorder, bipolar disorder, major depressive disorder,
dementia, delirium, amnestic or any other cognitive disorder currently or within the past 2 years
9. Subject has a clinically significant or unstable medical illness/condition/disorder that would be
anticipated, in the investigator’s opinion, to potentially compromise subject safety or adversely
affect the evaluation of durability of effect
10. Subject has clinically significant cardiac arrhythmia, cardiomyopathy, or cardiac conduction
defect, history of myocardial infarction or unstable angina within the last 3 months before
screening, or clinically significant abnormality on screening or baseline ECG including but not
limited to the following: QTcF > 465 msec for
11. Subject has a laboratory abnormality that, in the opinion of the investigator, would compromise the well-being of the subject, or any of the following laboratory abnormalities at screening or baseline:
AST or ALT value ≥ 2 times the upper limit of the laboratory normal reference range
HbA1c > 9%
Absolute neutrophil count </=1.5 x 1000/L
Platelet count </=75 x 1000/L
Serum creatinine > 2.5 mg/dL
Positive test result for HIV, Hbs-Ag, or antihepatitis C virus antibody
Urine drug screen at screening or baseline indicates illicit substance use with a positive
result for any of the tested substances
Exception: results positive for benzodiazepines, opiates, or barbiturates may not be
exclusionary if the investigator confirms that such medication was medically indicated
and consults the INC Research medical monitor before enrolling a subject with such a
finding
12. Subject is pregnant, lactating, or breastfeeding
13. Subject has inadequate gluteal muscle or excessive gluteal fat, as determined by the investigator, that would interfere with gluteal IM injection using a 1.5 or 2-inch needle
14. Subject has received any long-acting IM antipsychotic medication within 2 injection cycles before screening
15. Subject has used a prohibited medication
16. Subject is currently under involuntary hospitalization
17. Subject is currently incarcerated, expects to be incarcerated in the next 12 months, or has pendinglegal action which may impact compliance with participation in this study or study procedures
18. Subject is currently participating in or has recently participated in another clinical trial in which the
subject received an experimental or investigational drug or agent within 3 months before screening
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety evaluations: will include the number and percentage of subjects with treatment-emergent AEs (TEAEs), as well as changes from baseline in and/or development of potentially clinically significant findings pertaining to the following during the treatment period: vital signs (blood pressure, pulse rate, respiratory rate, and body temperature) and weight, laboratory test results (hematology panel, serum chemistry panel [including glucose, high- and low-density lipoproteins, total cholesterol, and HbA1c] and urinalysis), 12-lead ECG, abnormal movement scales (AIMS, BARS, and SAS), physical examinations, and development of injection site reactions. Furthermore, the C-SSRS will be performed and concomitant medications will be recorded. |
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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) |
Durability of effect evaluations will include the following: Positive and Negative Syndrome Scale
(PANSS) total score and positive, negative, and general psychopathology subscale scores; CGI-I score and CGI-S score; PANSS response (PANSS total score ≥ 30% decrease [improvement of symptoms] from baseline); overall response (PANSS total score ≥ 30% decrease [improvement of symptoms] from baseline or CGI-I score of 2 [much improved] or 1 [very much improved]); relapse (PANSS total score increase of ≥ 30% from baseline or rehospitalization for psychotic symptoms or use of adjunctive antipsychotic medication after stabilization); remitters (defined as the simultaneous attainment of a score of ≤ 3 for 6 months or more on 8 main items of the PANSS); and time to discontinuation.
Other evaluations include PSP, EQ-5D-5L, SF-36v2, and concomitant antipsychotic medication use. |
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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 | 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 | 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 | No |
E.8.1.1 | Randomised | No |
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 |
extension study; for pts rolling over from ALK9072-003 study -double blinded;new pts - open label |
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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.8.2.4 | 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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 |
Malaysia |
Philippines |
Romania |
Russian Federation |
Serbia |
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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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 | 4 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |