Efficacy Study Exploring the Effects on Cognition of Sertindole Versus Comparator in Patients With Schizophrenia

A Randomised, Double-Blind, Parallel-Group, Flexible-Dose Study Exploring the Neurocognitive Effect of Sertindole Versus Comparator in Patients With Schizophrenia Using the MATRICS Consensus Cognitive Battery (MCCB)

The objective of this study is to explore the neurocognitive efficacy of Sertindole versus comparator in patients with schizophrenia using the MCCB.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Cognition
• Intervention / Treatment: Drug: Sertindole; Drug: Quetiapine

Detailed Description

Sertindole is an atypical antipsychotic approved in the European Union (EU) for use in patients with schizophrenia who are intolerant to at least one other antipsychotic agent. During clinical development sertindole was found to be as effective in the treatment of schizophrenia as the first-generation antipsychotic haloperidol and as the second-generation antipsychotic risperidone.

Sertindole is generally well tolerated and has a benign side-effect profile, including an absence of sedation, no effect on plasma prolactin levels, moderate weight gain, no anticholinergic-mediated cognitive impairment and a low rate of extrapyramidal symptoms (EPS). Sertindole has been shown to prolong the QT interval and is contraindicated in patients with prolonged QT interval and in patients receiving drugs known to significantly prolong the QT interval.

The study is designed to provide data on the neurocognitive properties of sertindole versus quetiapine in patients with schizophrenia. Efficacy for cognitive impairment is assessed in patients who are in a stable phase of their illness, with a predefined maximum level of symptoms that will allow them to be included in the study. Prior antipsychotic medication will be withdrawn (down-tapered) and patients will be randomly assigned to one of the study drugs.

Cognitive deficiencies are an important feature of schizophrenia and correlate strongly with functional impairment. Improving functional outcomes in schizophrenia has a high priority and has resulted in the initiation of a program called Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) leading to the development of a neuropsychological test battery, the MCCB which is used in this study.

• Study Type: Interventional
• Enrollment (Actual): 264
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Garden Grove, California, United States, 92845
      • US017
    • National City, California, United States, 91950
      • US008
    • Pasadena, California, United States, 91107
      • US001
    • Pico Rivera, California, United States, 90660
      • US006
    • San Diego, California, United States, 92126
      • US011
    • Stanford, California, United States, 94305
      • US014
    • Torrance, California, United States, 90502
      • US026
  • Colorado
    • Aurora, Colorado, United States, 80045
      • US016
  • Florida
    • Orange City, Florida, United States, 32763
      • US015
    • Tampa, Florida, United States, 33613
      • US010
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • US007
  • Illinois
    • Chicago, Illinois, United States, 60640
      • US024
    • Joliet, Illinois, United States, 60435
      • US002
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • US012
    • Glen Burnie, Maryland, United States, 21061
      • US027
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • US019
  • New Jersey
    • Clementon, New Jersey, United States, 08021
      • US021
  • New York
    • Brooklyn, New York, United States, 11203
      • US013
    • Staten Island, New York, United States, 10305
      • US025
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • US005
    • Durham, North Carolina, United States, 27705
      • US018
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19139
      • US022
  • Texas
    • Austin, Texas, United States, 78754
      • US023
    • Dallas, Texas, United States, 75235
      • US020
    • Desoto, Texas, United States, 75115
      • US004
    • Houston, Texas, United States, 77008
      • US028

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Primary diagnosis of schizophrenia
• Man or woman, aged between 18 and 55 years

Exclusion Criteria:

• Current Axis I primary psychiatric diagnosis other than schizophrenia
• Not previously received antipsychotic drugs for schizophrenia
• Acute exacerbation requiring hospitalisation within the last 3 months
• Clinically significant extrapyramidal symptoms
• Clinically significant cardiovascular disease, congestive heart failure, cardiac hypertrophy, arrhythmia or bradycardia
• Congenital long QT syndrome or a family history of this disease, or known acquired QT interval prolongation
• Significant ECG abnormalities
• Hypokalaemia or hypomagnesaemia
• In concurrent treatment with drugs inhibiting the P450 enzymes system CYP3A

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: Quetiapine	Drug: Quetiapine; Twice daily oral dose. Day 1-20: 50-500 mg/day (titration period). Day 21-84: 400, 500 or 600 mg/day (flexible treatment period).
Experimental: Sertindole	Drug: Sertindole; Once daily oral dose. Day 1-20: 4-16 mg/day (titration period). Day 21-84: 12, 16 or 20 mg/day (flexible treatment period).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Neurocognitive effect of treatment based on the overall composite score on the MCCB	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Domain specific scores on MCCB; PANSS total score, PANSS positive symptom subscale score, PANSS negative symptom subscale score, and PANSS general psychopathology subscale score; CGI-S, CDSS and GAF scores; QLS and UPSA total and subscale scores; ECGs	12 weeks

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S

Publications and helpful links

General Publications

• Nielsen J, Matz J, Mittoux A, Polcwiartek C, Struijk JJ, Toft E, Kanters JK, Graff C. Cardiac effects of sertindole and quetiapine: analysis of ECGs from a randomized double-blind study in patients with schizophrenia. Eur Neuropsychopharmacol. 2015 Mar;25(3):303-11. doi: 10.1016/j.euroneuro.2014.12.005. Epub 2015 Jan 3.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: April 3, 2008
• First Submitted That Met QC Criteria: April 3, 2008
• First Posted (Estimate): April 9, 2008

Study Record Updates

• Last Update Posted (Estimate): May 28, 2014
• Last Update Submitted That Met QC Criteria: May 14, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Schizophrenia; Cognition; MATRICS Consensus Cognitive Battery
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Quetiapine Fumarate; Sertindole
• Other Study ID Numbers: 11723A