Clinical trial NCT00654706: Efficacy Study Exploring the Effects on Cognition of Sertindole Versus Comparator in Patients With Schizophrenia
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Cognition
Keywords: Schizophrenia
Cognition
MATRICS Consensus Cognitive Battery
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2008-04-09
Enrollment: 264
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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 Prior antipsychotic medication will be withdrawn (down-tapered) and patients will be randomly assigned to one of the study drugs.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.

Eligibility criteria: 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

Primary outcomes:
measure: Neurocognitive effect of treatment based on the overall composite score on the MCCB
timeFrame: 12 weeks
Secondary outcomes:
measure: 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
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Garden Grove
country: United States
facility: US017
state: California
city: National City
country: United States
facility: US008
state: California
city: Pasadena
country: United States
facility: US001
state: California
city: Pico Rivera
country: United States
facility: US006
state: California
city: San Diego
country: United States
facility: US011
state: California
city: Stanford
country: United States
facility: US014
state: California
city: Torrance
country: United States
facility: US026
state: California
city: Aurora
country: United States
facility: US016
state: Colorado
city: Orange City
country: United States
facility: US015
state: Florida
city: Tampa
country: United States
facility: US010
state: Florida
city: Atlanta
country: United States
facility: US007
state: Georgia
city: Chicago
country: United States
facility: US024
state: Illinois
city: Joliet
country: United States
facility: US002
state: Illinois
city: Baltimore
country: United States
facility: US012
state: Maryland
city: Glen Burnie
country: United States
facility: US027
state: Maryland
city: Lebanon
country: United States
facility: US019
state: New Hampshire
city: Clementon
country: United States
facility: US021
state: New Jersey
city: Brooklyn
country: United States
facility: US013
state: New York
city: Staten Island
country: United States
facility: US025
state: New York
city: Charlotte
country: United States
facility: US005
state: North Carolina
city: Durham
country: United States
facility: US018
state: North Carolina
city: Philadelphia
country: United States
facility: US022
state: Pennsylvania
city: Austin
country: United States
facility: US023
state: Texas
city: Dallas
country: United States
facility: US020
state: Texas
city: Desoto
country: United States
facility: US004
state: Texas
city: Houston
country: United States
facility: US028
state: Texas
Study officials:
affiliation: LundbeckClinicalTrials@lundbeck.com
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References:
citation: 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.