Efficacy Study on Cognitive Functions in Schizophrenic Patients (AMIMIND)

Comparative Efficacy of Amisulpride vs Risperidone on Cognitive Functions in Patients With Chronic Schizophrenia

Primary objectives

• To compare neurocognitive effects of amisulpride with those of risperidone in patients with chronic schizophrenia, as assessed by the general cognitive index, a measure of overall cognitive functioning in schizophrenia

Secondary objectives

• Secondary analyses will be conducted to determine how the two atypical agents' neurocognitive effects compare with regard to their profile of therapeutic action (based on individual cognitive domain scores in seven cognitive domains, including speed of processing, attention/vigilance, working memory, verbal learning and memory, visual learning and memory, reasoning and problem solving and social cognition);
• Investigate whether amisulpride elicits more improvement on negative symptoms compared to risperidone treatment, as measured by the total score on the Scale of the Assessment of Negative Symptoms (SANS) 8 and by the Negative Symptom Subscale of the Positive and Negative Symptom Scale (PANSS);
• Assess whether amisulpride improves overall functioning and individual domains of psychotic symptoms compared to risperidone as measured by the Clinical Global Impression (CGI), and the total and positive and general psychopathology subscale scores of PANSS and by the individual domains of SANS, respectively;
• Evaluate the safety and tolerability of amisulpride and risperidone based on the study completion rates, and frequency of abnormal laboratory values, prolactin serum concentrations and on the Simpson Angus Scale for Extrapyramidal Symptoms (SAS) 10 and the Abnormal Involuntary Movement Scale (AIMS).

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: amisulpride and risperidone

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 4

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary
    • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis: DSM-IV schizophrenia (any subtype)
• Duration of illness: ≥ 5 years
• Concomitant standing or prn medications (except other antipsychotics and those contraindicated in the respective package inserts [amisulpride or risperidone]) are permitted during treatment phase, if they were present at a stable dose for at least 6 weeks prior to the start of initial treatment with study medication
• Overall symptom severity: patients must evidence a total score of 60 or higher on the PANSS scale
• Clinical Symptoms: A score of 4 (moderate) or greater on any of the 7 items of the PANSS Positive Symptom Subscale is present
• Cognitive status (minimum performance level): subject must be able to validly complete the baseline MATRICS assessment
• Clinical judgment by the investigator that treatments with amisulpride or risperidone are warranted due to suboptimal clinical outcome despite previous treatments

Exclusion Criteria:

• Past or current intolerance of amisulpride or risperidone side effects that are judged by the investigator to be unsafe, dose-limiting, or likely to result in study discontinuation.
• Any contraindication for amisulpride or risperidone therapy as indicated in the drug description.
• Presence of any unstable or untreated medical disorder.
• Any history of seizures or seizure disorder other than febrile seizures of childhood;
• History of positive hepatitis B surface antigen.
• Any abnormal laboratory test that is judged to be clinically significant by the investigator.
• A history of significant head injury/trauma, as defined by:

A. loss of consciousness (LOC) for more than 1 hour B. recurring seizures resulting from the head injury C. clear cognitive sequelae of the injury D. cognitive rehabilitation following the injury

• Alcohol or substance dependence within the past 12 months or abuse within the past 3 months. Any subject with positive urine toxicology or alcohol use that is considered abnormal at baseline.
• Clinically significant suicidal or homicidal behavior or attempts within past 6 months.
• Pregnant or breast-feeding women
• Absence of medically approved contraceptive methods for female of childbearing potential.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 2	Drug: amisulpride and risperidone; amisulpride tablet 400-800 mg/day risperidone tablet 4-8 mg/day
Active Comparator: 1	Drug: amisulpride and risperidone; amisulpride tablet 400-800 mg/day risperidone tablet 4-8 mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
General cognitive index, as assessed by the overall average z-score based on the neurocognitive test (MATRICS) battery	Day 0, Day 28, Day 56

Secondary Outcome Measures

Outcome Measure	Time Frame
Cognitive measures assessed by individual subscales scores in seven cognitive domains	Day 0, Day 28, Day 56
Overall Clinical Effects assessed by the Clinical Global Impression (CGI)	Day -21 to -1, Day 0, Day 7, Day 28, Day 56
Clinical symptoms Ratings of psychopathology assessed by the PANSS (positive and negative symptoms, general psychopathology), and the SANS (Attention, Affect, Alogia, asociality/Anhedonia;Avolition)	Day -21 to -1, Day 0, Day 7, Day 28, Day 56
Ratings of potential side affects assessed by the Simpson-Angus Scale (SAS)and the Abnormal Involuntary Movement Scale (AIMS)	Day 0, Day 7, Day 28, Day 56
General safety/tolerability assessed by vital signs measures, treatment emergent adverse events record, and frequency of abnormal laboratory measures	Day -21 to -1, Day 0, Day 28, Day 56

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: László Erős, MD, sanofi-aventis Hungary

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: September 26, 2008
• First Submitted That Met QC Criteria: September 26, 2008
• First Posted (Estimate): September 29, 2008

Study Record Updates

• Last Update Posted (Estimate): December 9, 2010
• Last Update Submitted That Met QC Criteria: December 8, 2010
• Last Verified: December 1, 2010

More Information

Terms related to this study

• 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; Antidepressive Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Antidepressive Agents, Second-Generation; Risperidone; Amisulpride
• Other Study ID Numbers: AMISU_L_01008; EudraCT #: 2007-005772-13