Safety Study of Sertindole Versus Risperidone Under Normal Conditions of Use (SCoP)

This study has been completed.
Sponsor:
Information provided by:
H. Lundbeck A/S
ClinicalTrials.gov Identifier:
NCT00856583
First received: March 5, 2009
Last updated: August 18, 2011
Last verified: August 2011
  Purpose

The purpose of the study is to determine whether there is an increased all-cause mortality in sertindole-treated patients in comparison to patients treated with a well-known antipsychotic (risperidone) when used under normal marketed conditions in the treatment of schizophrenia.


Condition Intervention Phase
Schizophrenia
Drug: Sertindole
Drug: Risperidone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Sertindole Versus Risperidone Safety Outcome Study: a Randomised, Partially-blinded, Parallel-group, Active-controlled, Post-marketing Study

Resource links provided by NLM:


Further study details as provided by H. Lundbeck A/S:

Primary Outcome Measures:
  • Number of Participants With All-cause Mortality [ Time Frame: As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months ] [ Designated as safety issue: Yes ]
    The analysis was based on all deaths from the Whole Randomised Treatment (WRT)+30 days period and the Only Randomised Treatment (ORT) period, respectively

  • Second Primary Outcome: Number of Participants With Cardiac Events, Including Arrhythmias, Requiring Hospitalisation [ Time Frame: As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months ] [ Designated as safety issue: Yes ]
    Second primary endpoint: a serious adverse event where the patient was hospitalised and for which the Independent Safety Committee (ISC) classified the event as a cardiac event with documented arrhythmia. The analysis of this outcome was not performed due to low number of events. The presented analysis is a replacement analysis using all cardiac events, including arrhythmias, that required hospitalisation


Secondary Outcome Measures:
  • Cause-specific Mortality: Number of Participants With Cardiac Deaths - ISC [ Time Frame: As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months ] [ Designated as safety issue: Yes ]

    The analysis was based on all deaths from the WRT+30 days period using the classification performed by the ISC.

    The ISC reviewed and classified those adverse events which resulted in death or hospitalisation or were possible suicide attempts and this review was blinded to exposure. The definition of cardiac death was intentionally wide; sudden or unexplained deaths were assumed to be cardiac if there was no non-cardiac explanation. To ensure consistent evaluation and classification, the ISC decided a priori to classify all instances of self harm as possible suicide.


  • Cause-specific Mortality: Number of Participants With Completed Suicides - ISC [ Time Frame: As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months ] [ Designated as safety issue: Yes ]

    The analysis was based on all deaths from the WRT+30 days period using the classification performed by the ISC.

    The ISC reviewed and classified those adverse events which resulted in death or hospitalisation or were possible suicide attempts and this review was blinded to exposure. The definition of cardiac death was intentionally wide; sudden or unexplained deaths were assumed to be cardiac if there was no non-cardiac explanation. To ensure consistent evaluation and classification, the ISC decided a priori to classify all instances of self harm as possible suicide.


  • Cause-specific Mortality: Number of Participants With Other Than Cardiac Deaths and Completed Suicides - ISC [ Time Frame: As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months ] [ Designated as safety issue: Yes ]

    The analysis was based on all deaths from the WRT+30 days period using the classification performed by the ISC.

    The ISC reviewed and classified those adverse events which resulted in death or hospitalisation or were possible suicide attempts and this review was blinded to exposure. The definition of cardiac death was intentionally wide; sudden or unexplained deaths were assumed to be cardiac if there was no non-cardiac explanation. To ensure consistent evaluation and classification, the ISC decided a priori to classify all instances of self harm as possible suicide.


  • Cause-specific Mortality: Number of Participants With Cardiac Deaths - MedDRA [ Time Frame: As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months ] [ Designated as safety issue: Yes ]
    The analysis was based on all deaths from the WRT+30 days period using the classification based upon the Medical Dictionary for Regulatory Activities (MedDRA) terminology, that is, as reported by the investigator

  • Cause-specific Mortality: Number of Participants With Completed Suicides - MedDRA [ Time Frame: As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months ] [ Designated as safety issue: Yes ]
    The analysis was based on all deaths from the WRT+30 days period using the classification based upon MedDRA terminology, that is, as reported by the investigator

  • Cause-specific Mortality: Number of Participants With Other Than Cardiac Deaths and Completed Suicides - MedDRA [ Time Frame: As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months ] [ Designated as safety issue: Yes ]
    The analysis was based on all deaths from the WRT+30 days period using the classification based upon MedDRA terminology, that is, as reported by the investigator

  • Number of Participants With Suicide Attempts (Fatal and Non-fatal) - ISC [ Time Frame: As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months ] [ Designated as safety issue: Yes ]

    The analysis was based on all suicides and suicide attempts from the WRT+30 days period using the classification performed by the ISC.

    The ISC reviewed and classified those adverse events which resulted in death or hospitalisation or were possible suicide attempts and this review was blinded to exposure. The definition of cardiac death was intentionally wide; sudden or unexplained deaths were assumed to be cardiac if there was no non-cardiac explanation. To ensure consistent evaluation and classification, the ISC decided a priori to classify all instances of self harm as possible suicide.


  • Number of Participants With Suicide Attempts (Fatal and Non-fatal) - MedDRA [ Time Frame: As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months ] [ Designated as safety issue: Yes ]
    The analysis was based on all suicides and suicide attempts from the WRT+30 days period using the classification based upon MedDRA terminology, that is, as reported by the investigator

  • Number of Participants With Hospitalisations, Excluding Hospitalisations Related to the Primary Psychiatric Disease [ Time Frame: As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months ] [ Designated as safety issue: Yes ]
    The analysis was based on time from start of study drug to first hospitalisation during the WRT+30 days period

  • Number of Participants With Discontinuation of Treatment for Any Reason Other Than Study Closure [ Time Frame: As study design allowed patients to continue study drug until the study was closed, many patients were followed for several years, with an overall median time period of approximately 14 months ] [ Designated as safety issue: Yes ]
    The analysis was based on time from start of study drug until stop of study drug for any reason other than sponsor closure of the study


Enrollment: 9809
Study Start Date: July 2002
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sertindole
Normally in the range of 4 to 20 mg/day
Drug: Sertindole
Sertindole was supplied as 4, 12, 16, and 20 mg tablets. The start and maintenance dosages as well as dose titration were set by the investigator, in accordance with the national Summary of Product Characteristics (SPC) for sertindole; in countries where sertindole was not marketed, the European Union (EU) SPC applied (all national and EU SPCs were essentially identical). Recommended dose range: 12 to 20 mg/day. The investigators were instructed to contact H. Lundbeck A/S if they deemed it necessary to increase the dose of sertindole to 24 mg/day, which was allowed in exceptional cases
Other Name: Serdolect
Active Comparator: Risperidone
Normally in the range of 2 to 8 mg/day
Drug: Risperidone
Risperidone was supplied as 1, 2, 3, and 4 mg tablets. The start and maintenance dosages as well as dose titration were set by the investigator, in accordance with the national SPC for risperidone. Recommended dose range: 2 to 8 mg/day
Other Name: Risperdal

Detailed Description:

The Committee for Medicinal Products for Human Use (CHMP) requested a post-marketing study to ascertain that the favourable benefit-risk profile and low mortality rates seen in the clinical studies with sertindole would not be offset by higher mortality rates when sertindole was used under more normal conditions of use. It was recognised that, in a clinical trial setting, strict patient selection and monitoring could lead to higher compliance in patient management and thereby to a lower mortality rate. Study 99824 was therefore designed in collaboration with the CHMP as an open-label, randomised study with minimum study management that focused on mortality and general patient safety. The duration of the treatment period was not fixed. No efficacy measures were included.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient has signed the Informed Consent Form or, if he/she is not able to sign it (according to the ICH GCP guidelines and the Declaration of Helsinki), the patient's legal representative has signed the Informed Consent Form
  • The patient has been diagnosed with schizophrenia
  • Based on the patient's clinical status, new or change of antipsychotic treatment is indicated
  • The patient is at least 18 years of age
  • The patient meets the criteria set out in the national SPCs for sertindole and risperidone. For those countries in which sertindole was not marketed, the EU SPC applied

Exclusion Criteria:

  • The last treatment taken by the patient was sertindole or risperidone
  • The patient has never previously received any antipsychotic drug therapy
  • The patient has contraindications to treatment with either sertindole or risperidone
  • In addition to sertindole/risperidone, treatment with another antipsychotic is indicated
  • The patient is homeless
  • The patient has previously been included in one of the two H. Lundbeck A/S post-marketing studies, 99823 or 99824
  • The patient is, in the opinion of the investigator, unlikely to comply with the study protocol or unsuitable for any other reason
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00856583

Sponsors and Collaborators
H. Lundbeck A/S
Investigators
Study Director: Email contact via H. Lundbeck A/S LundbeckClinicalTrials@lundbeck.com
  More Information

Publications:
Responsible Party: H. Lundbeck A/S
ClinicalTrials.gov Identifier: NCT00856583     History of Changes
Other Study ID Numbers: 99824, 2004-000213-19
Study First Received: March 5, 2009
Results First Received: May 4, 2011
Last Updated: August 18, 2011
Health Authority: Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
Bulgaria: Bulgarian Drug Agency
Croatia: Agency for Medicinal Product and Medical Devices
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Estonia: The State Agency of Medicine
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: Ministry of Health and Welfare
Hong Kong: Department of Health
Hungary: National Institute of Pharmacy
India: Drugs Controller General of India
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Luxembourg: Ministère de la Santé
Malaysia: Ministry of Health
Netherlands: Medicines Evaluation Board (MEB)
Norway: Norwegian Medicines Agency
Philippines: Bureau of Food and Drugs
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency
Russia: FSI Scientific Center of Expertise of Medical Application
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Singapore: Clinical Trials & Epidemiology Research Unit (CTERU)
Slovakia: State Institute for Drug Control
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
Taiwan: National Bureau of Controlled Drugs
Thailand: Food and Drug Administration
Turkey: Ministry of Health
Ukraine: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Risperidone
Sertindole
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents

ClinicalTrials.gov processed this record on September 18, 2014