Safety and Efficacy of Zicronapine in Patients With Schizophrenia

A 6-month, Randomised, Double-blind, Parallel-group, Risperidone-controlled, Fixed-dose Study Evaluating the Safety and Efficacy of Zicronapine in Patients With Schizophrenia

To assess the effect of zicronapine versus risperidone on metabolic parameters comprising body weight, body mass index (BMI), waist circumference, levels of fasting blood lipids and glucose during 6 months of treatment.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Zicronapine; Drug: Risperidone

Detailed Description

Schizophrenia is a serious and disabling mental disorder that affects approximately 1% of the world's population. Antipsychotic drugs remain the cornerstone in the pharmacotherapy of schizophrenia. There are a number of antipsychotic drugs in use but none is ideal, in particular because their safety profile is complex and their effectiveness is limited.

Thus, present treatment options leave room for improvement and call for new, more effective pharmacotherapies for the treatment of schizophrenia. In the current study, non-acute patients with schizophrenia will be randomised to blinded treatment with either zicronapine or a standard antipsychotic treatment for 24 weeks. The safety (with focus on metabolic parameters) and efficacy of zicronapine will be evaluated in comparison to risperidone.

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czech Republic
  • Brno, Czech Republic, 602 00
    • CZ004
  • Brno, Czech Republic, 625 00
    • CZ001
  • Kladno, Czech Republic, 27201
    • CZ007
  • Liberec, Czech Republic, 460 63
    • CZ003
  • Olomouc, Czech Republic, 771 11
    • CZ002
  • Praha, Czech Republic, 100 00
    • CZ008
  • Praha, Czech Republic, 110 00
    • CZ006
  • Sternberk, Czech Republic, 785 17
    • CZ005
• Estonia
  • Pärnu, Estonia, 80012
    • EE003
  • Tallinn, Estonia, 10614
    • EE001
  • Tallinn, Estonia, 10617
    • EE002
  • Tartu, Estonia, 50406
    • EE004
• Finland
  • Helsinki, Finland, 00250
    • FI001
  • Kellokoski, Finland, 04500
    • FI002
• France
  • Clermont Ferrand, France, 63003
    • FR001
  • Nimes, France, 30900
    • FR002
  • Strasbourg, France, 67091
    • FR004
  • Toulon, France, 83000
    • FR003
• Poland
  • Bełchatów, Poland, 97-400
    • PL004
  • Gdańsk, Poland, 80-542
    • PL002
  • Kielce, Poland, 25-317
    • PL003
  • Lublin, Poland, 20-109
    • PL001
  • Łódź, Poland, 91-229
    • PL006
  • Żuromin, Poland, 93-00
    • PL005

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The patient meets the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) criteria for schizophrenia
• The patient is a man or woman, ≥18 and ≤65 years old
• The patient has a PANSS total score ≥60 and ≤100 (extremes included) at screening and baseline

Exclusion Criteria:

• The patient has a current, predominant Axis I psychiatric disorder other than schizophrenia as defined in the DSM-IV-TR
• The patient has a current diagnosis or a history of substance dependence (except nicotine) or substance abuse (except cannabis) according to the DSM-IV-TR criteria ≤6 months prior to screening
• The patient is at significant risk of harming him/herself or others according to the investigator's judgement (assisted by the assessment of suicidal ideation and behaviour using the C-SSRS)
• The patient is resistant to antipsychotic treatment according to the investigator's judgement or has been treated with clozapine ≤3 months prior to screening
• The patient has experienced an acute exacerbation requiring hospitalisation ≤3 months prior to screening or between screening and baseline
• The patient has been treated with risperidone or paliperidone ≤6 months prior to screening

Other inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Risperidone	Drug: Risperidone; 5 mg/day; orally; Other Names: Risperdal®
Experimental: Zicronapine	Drug: Zicronapine; 7.5 mg/day; orally; Other Names: Past name: Lu 31-130

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess the effect of zicronapine versus risperidone on body weight (and BMI)	6 months
To assess the effect of zicronapine versus risperidone on waist circumference	6 months
To assess the effect of zicronapine versus risperidone on levels of fasting blood lipids	6 months
To assess the effect of zicronapine versus risperidone on levels of fasting blood glucose	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the overall safety and tolerability of zicronapine versus risperidone during 6 months of treatment by comparing the frequencies of adverse events sorted by system organ class and preferred term.		6 months
To assess the potential of zicronapine versus risperidone to induce extrapyramidal symptoms using change from baseline to each assessment in the AIMS, BARS, and SAS total scores	Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Scale (BARS), and Simpson Angus Scale (SAS) total scores	6 months
To assess the effect of zicronapine versus risperidone on serum prolactin levels		6 months
To assess the effect of zicronapine on suicidal ideation and behaviour using the Columbia Suicide-Severity Rating Scale (C-SSRS)		6 months
To assess the effect of zicronapine versus risperidone on electrocardiogram (ECG) parameters		6 months
To assess the efficacy of zicronapine versus risperidone following 6 months of treatment using change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score		6 months
To assess the efficacy of zicronapine versus risperidone using change from baseline to each assessment in the PANSS total score and PANSS subscale scores (Positive Symptoms, Negative Symptoms, and General Psychopathology)		6 months
To assess the efficacy of zicronapine versus risperidone by comparing the proportions of responders (using two definitions of response: ≥20% and ≥50% decrease from baseline in PANSS total score)		6 months
To assess the efficacy of zicronapine versus risperidone on global improvement using change from baseline to each assessment in the Clinical Global Impression - Severity of Illness (CGI-S) score		6 months
To assess the effect of zicronapine versus risperidone on personal and social functioning using the Personal and Social Performance Scale (PSP)		6 months
To assess the effect of zicronapine versus risperidone on functioning using the Global Assessment of Functioning scale (GAF)		6 months
To assess the effect of zicronapine versus risperidone on quality of life using the disease-specific Schizophrenia Quality of Life scale (S-QoL)		6 months
To assess the effect of zicronapine versus risperidone on the patient's satisfaction with treatment using the Medication Satisfaction Questionnaire (MSQ)		6 months

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: February 3, 2011
• First Submitted That Met QC Criteria: February 11, 2011
• First Posted (Estimate): February 14, 2011

Study Record Updates

• Last Update Posted (Estimate): November 8, 2016
• Last Update Submitted That Met QC Criteria: November 7, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Schizophrenia; Risperidone; Antipsychotic; Lu 31-130
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Risperidone
• Other Study ID Numbers: 13639A; 2010-022181-28 (EudraCT Number)

Plan for Individual participant data (IPD)

Study Data/Documents

1. EudraCT Results
   Information identifier: 2010-022181-28