Study of the Safety, Tolerability, and Pharmacokinetics of Once Weekly Zicronapine in Patients With Schizophrenia

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of once weekly dosing of zicronapine, compared to daily dosing of zicronapine.

Detailed Description
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The study includes 2 treatment periods. The open-label run-in period will begin at patient enrolment and continue for 3 weeks, during which all patients will receive once daily treatment with zicronapine. The double-blind period will begin at patient randomization and continue for 5 weeks, during which the patients will be assigned to one group receiving once daily treatment with zicronapine and 3 groups receiving once weekly treatment with zicronapine.

Official Title
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A Randomised, Double-blind, Parallel-group, Explorative Study of the Safety, Tolerability, and Pharmacokinetics of Daily Dosing Compared to Weekly Dosing of Zicronapine in Patients With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Zicronapine open-label lead-in 10 mg daily
* Drug: Zicronapine 10 mg daily
* Drug: Zicronapine 20 mg once weekly
* Drug: Zicronapine 30 mg once weekly
* Drug: Zicronapine 45 mg once weekly


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) A score of <=4 (moderately ill) on Clinical Global Impression - Severity of Illness (CGI-S) scale A total score >=60 on Positive and Negative Syndrome Scale (PANSS) A score of <=4 (moderate) on PANSS items: P7 (hostility) AND G8 (uncooperativeness) Exclusion Criteria: Acute exacerbation requiring hospitalization within the last 3 months OR requiring change of antipsychotic medication within the last 4 weeks Diagnosis or history of substance dependence or substance abuse according to DSM-IV-TR within the last 3 months Significant risk of harming himself/herself or others Positive serology for hepatitis A, B, C, or HIV Present condition that might compromise liver function Medical or neurological disorder or treatment that could interfere with study treatment or compliance Previous exposure to zicronapine Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zicronapine open-label lead-in 10 mg daily<br> | Drug: Zicronapine open-label lead-in 10 mg daily<br>* Encapsulated tablet ,10 mg, once daily, open-label<br>* Other names: Lu 31-130;|
| Experimental: Zicronapine 10 mg daily<br> | Drug: Zicronapine 10 mg daily<br>* Encapsulated tablet, 10 mg, once daily, double-blind<br>* Other names: Lu 31-130;|
| Experimental: Zicronapine 20 mg once weekly<br> | Drug: Zicronapine 20 mg once weekly<br>* Encapsulated tablet, 20 mg, once weekly (on day 1 of each 7 day cycle), double-blind<br>* Other names: Lu 31-130;|
| Experimental: Zicronapine 30 mg once weekly<br> | Drug: Zicronapine 30 mg once weekly<br>* Encapsulated tablet, 30 mg, once weekly (on day 1 of each 7 day cycle), double-blind<br>* Other names: Lu 31-130;|
| Experimental: Zicronapine 45 mg once weekly<br> | Drug: Zicronapine 45 mg once weekly<br>* Encapsulated tablet, 45 mg, once weekly (on day 1 of each 7 day cycle), double-blind<br>* Other names: Lu 31-130;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Adverse Events as a Measure of Safety and Tolerability | Number of patients with treatment-emergent adverse events during each of the two study periods plus corresponding safety follow-up period. Open-label period: 3 weeks post-baseline plus 8 weeks safety follow-up (11 weeks total); Double-blind period: 5 weeks post-randomization plus 8 weeks safety follow-up (13 weeks total) | 11 weeks for open-label period; 13 weeks for double-blind period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Syndrome Scale (PANSS) Total and Subscales Change From Baseline | The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 that indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. The PANSS total score was the sum of the rating scores for 7 positive subscale items, 7 negative subscale items, and 16 general psychopathology subscale items from the PANSS panel. PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome). | 8 weeks post-baseline (3 weeks open-label period plus 5 weeks double-blind period) | 
| Clinical Global Impression Severity Scale (CGI-S) Change From Baseline | The CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses their clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). | 8 weeks post-baseline (3 weeks open-label period plus 5 weeks double-blind period) | 
| Clinical Global Impression Improvement Scale (CGI-I) | The CGI-I provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). In all cases, the assessment is made independent of whether the rater believes the improvement is drug-related or not. | 8 weeks post-baseline (3 weeks open-label period plus 5 weeks double-blind period) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Antipsychotic, Zicronapine, Lu 31-310