A Multicenter, Double-Blind, Flexible-Dose, 6-Month Trial Comparing the Efficacy and Safety of Asenapine With Olanzapine in Stable Subjects With Predominant, Persistent Negative Symptoms of Schizophrenia - Aphrodite
- Conditions
- Schizophrenia with predominant, persistent negative symptomsMedDRA version: 7.1Level: LLTClassification code 10039626
- Registration Number
- EUCTR2004-002560-17-DE
- Lead Sponsor
- V Organon
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 444
Subjects are eligible to participate in the study if they:
Demographic
1. are at least 18 years of age;
2. are a male, or a female who is not of childbearing potential (ie, surgically sterile, postmenopausal for at least 1 year) or who is non-pregnant, non-lactating, and using a method of birth control that is acceptable to the investigator;
Procedural
3. sign written informed consent after the scope and nature of the investigation have
been explained to them before screening evaluations. Subjects unable or incapable
of signing may participate if the legal representative provides consent and the subject affirms their participation;
4. are fluent in the language of the investigator, study staff (including raters), and the informed consent;
5. have a caregiver or an identified responsible person (eg, family member, social
worker, caseworker, or nurse) considered reliable by the investigator in providing
support to the subject to ensure compliance with study treatment, outpatient visits
and protocol procedures;
Diagnoses
6. have a documented current diagnosis of schizophrenia of paranoid (295.30),
disorganized (295.10), catatonic (295.20), residual (295.60), or undifferentiated
(295.90) subtype (the Mini International Neuropsychiatric Interview [MINI] interview
will be used);
7. have a minimum PANSS negative subscale score of 20 at screening and baseline,
with a minimum score of 4 (moderate) on at least 3 of the Marder factors for negative
symptoms (blunted affect [N1], emotional withdrawal [N2], poor rapport [N3], passive social withdrawal [N4], lack of spontaneity [N6], motor retardation [G7], active social avoidance [G16]);
8. have a PANSS positive subscale (Marder factor) score < the PANSS negative subscale (Marder factor) score at screening and baseline; and
9. have demonstrated clinical stability for the past 5 months at time of screening,
defined as:
• no significant changes in schizophrenia symptomatology (changes in medication or medication dosing may be acceptable);
• no hospitalizations for the symptoms of schizophrenia during the past 5 months;
• no increase in level of psychiatric care during the past 5 months due to worsening of symptoms of schizophrenia;
• no jailing or imprisonment in the past 5 months due to worsening of symptoms of
schizophrenia.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Potential subjects will be excluded at screening if they:
Medical Status
1. have an uncontrolled, unstable clinically significant medical condition (eg, renal,
hepatic, endocrine, respiratory, cardiovascular, hematologic, immunologic,
cerebrovascular disease, anorexia [body mass index (BMI) <18.5 kg/m2] or obesity
[BMI >35 kg/m2], or malignancy) that may interfere with the interpretation of safety or efficacy evaluations in the opinion of the investigator;
2. have any clinically significant abnormal laboratory, vital sign, physical examination,
or ECG findings at screening and any significant changes by baseline that, in the
opinion of the investigator, may interfere with the interpretation of safety or efficacy
evaluations;
3. have a positive result on the serum pregnancy test or are breast feeding at
screening, or intend to become pregnant during the course of the trial;
4. have narrow angle glaucoma;
5. have a seizure disorder beyond childhood or are taking any anticonvulsants to
prevent seizures;
6. have known serological evidence of human immunodeficiency virus (HIV) antibody;
7. have a history of neuromalignant syndrome (NMS);
Psychiatric
8. have a score of 3 or greater on the global Parkinson item of the ESRS-A;
9. have depressive symptoms as defined by a score of 9 or greater on the CDSS;
10. have a rating of 4 or higher on 2 or more items in the PANSS positive symptom
subscale including items for delusions, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution;
11. have a substance-induced psychotic disorder or behavioral disturbance thought to be due to substance abuse;
12. have current (past 5 months) substance abuse/dependence according to DSM-IV-TRTM criteria (excluding nicotine);
13. have a concurrent psychiatric disorder other than schizophrenia coded on Axis I, a primary diagnosis other than schizophrenia including depression;
14. have a diagnosis of mental retardation or severe organic brain syndromes;
15. present an imminent risk of self-harm or harm to others;
16. Have a score of 2 on items 7, 10, or 11 on the ISST-modified at screening;
Medication
17. have been treated with olanzapine in the previous 5 months (at adequate doses for at least 3 months) and had an inadequate response with respect to treatment of negative symptoms;
18. have a history of hypersensitivity to olanzapine;
19. have been treated with clozapine in the previous 5 months for treatment-resistant schizophrenia (i.e. at least two other antipsychotic treatments have been unsuccessful before clozapine was prescribed);
20. have received antidepressants and/or mood stabilizers to treat a depressive disorder (Axis I) or had antidepressant medication or antidepressant dose changes due to clinically unstable depressive symptomatology, during the 5 month period prior to the Screening visit;
21. have previously been treated in an asenapine trial;
22. have taken an investigational drug within 30 days prior to baseline;
23. require high doses of benzodiazepines (=4 mg per day lorazepam or equivalent); or
24. have been judged by the investigator to be medically non-compliant in the
management of their disease.
Subjects are eligible for randomization if they have:
25. the same CGI-S of Illness scores from screening to baseline; and
26. baseline PANSS total score and PANSS negative subscale (Marder factor) score of ±20% from Screening.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Compare the efficacy of 5-10 mg BID asenapine to that of 5-20 mg QD olanzapine in the treatment of predominant, persistent negative symptoms of schizophrenia.;Secondary Objective: Compare the efficacy of asenapine with olanzapine in psychosocial function in subjects with schizophrenia and predominant, persistent negative symptoms.;Primary end point(s): The change from baseline in the Negative Symptom Assessment (NSA) at 6 months.
- Secondary Outcome Measures
Name Time Method