SCoP: Safety Study of Sertindole Versus Risperidone Under Normal Conditions of Use

Sponsor
H. Lundbeck A/S (Industry)
Overall Status
Completed
CT.gov ID
NCT00856583
Collaborator
(none)
9,809
2
67.1

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
9809 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Sertindole Versus Risperidone Safety Outcome Study: a Randomised, Partially-blinded, Parallel-group, Active-controlled, Post-marketing Study
Study Start Date :
Jul 1, 2002
Actual Primary Completion Date :
Feb 1, 2008
Actual Study Completion Date :
Feb 1, 2008

Arms and Interventions

Arm Intervention/Treatment
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 Names:
  • 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 Names:
  • Risperdal
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With All-cause Mortality [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]

      The analysis was based on all deaths from the Whole Randomised Treatment (WRT)+30 days period and the Only Randomised Treatment (ORT) period, respectively

    2. Second Primary Outcome: Number of Participants With Cardiac Events, Including Arrhythmias, Requiring Hospitalisation [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]

      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

    1. Cause-specific Mortality: Number of Participants With Cardiac Deaths - ISC [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]

      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.

    2. Cause-specific Mortality: Number of Participants With Completed Suicides - ISC [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]

      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.

    3. Cause-specific Mortality: Number of Participants With Other Than Cardiac Deaths and Completed Suicides - ISC [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]

      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.

    4. Cause-specific Mortality: Number of Participants With Cardiac Deaths - MedDRA [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]

      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

    5. Cause-specific Mortality: Number of Participants With Completed Suicides - MedDRA [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]

      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

    6. Cause-specific Mortality: Number of Participants With Other Than Cardiac Deaths and Completed Suicides - MedDRA [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]

      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

    7. Number of Participants With Suicide Attempts (Fatal and Non-fatal) - ISC [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]

      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.

    8. Number of Participants With Suicide Attempts (Fatal and Non-fatal) - MedDRA [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]

      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

    9. Number of Participants With Hospitalisations, Excluding Hospitalisations Related to the Primary Psychiatric Disease [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]

      The analysis was based on time from start of study drug to first hospitalisation during the WRT+30 days period

    10. Number of Participants With Discontinuation of Treatment for Any Reason Other Than Study Closure [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]

      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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    No locations specified.

    Sponsors and Collaborators

    • H. Lundbeck A/S

    Investigators

    • Study Director: Email contact via H. Lundbeck A/S, LundbeckClinicalTrials@lundbeck.com

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00856583
    Other Study ID Numbers:
    • 99824
    • 2004-000213-19
    First Posted:
    Mar 6, 2009
    Last Update Posted:
    Aug 19, 2011
    Last Verified:
    Aug 1, 2011
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details 593 centres in 38 countries (Europe and Asia). First patient first visit: 11 July 2002. Last patient last visit: 22 February 2008.
    Pre-assignment Detail
    Arm/Group Title Sertindole Risperidone
    Arm/Group Description Normally in the range of 4 to 20 mg/day Normally in the range of 2 to 8 mg/day
    Period Title: Overall Study
    STARTED 4905 4904
    COMPLETED 1768 2307
    NOT COMPLETED 3137 2597

    Baseline Characteristics

    Arm/Group Title Sertindole Risperidone Total
    Arm/Group Description Normally in the range of 4 to 20 mg/day Normally in the range of 2 to 8 mg/day Total of all reporting groups
    Overall Participants 4905 4904 9809
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    38.4
    (11.8)
    38.3
    (11.7)
    38.3
    (11.8)
    Age, Customized (participants) [Number]
    18 to 65 years
    4806
    98%
    4820
    98.3%
    9626
    98.1%
    > 65 years
    99
    2%
    84
    1.7%
    183
    1.9%
    Sex: Female, Male (Count of Participants)
    Female
    2195
    44.8%
    2188
    44.6%
    4383
    44.7%
    Male
    2710
    55.2%
    2716
    55.4%
    5426
    55.3%
    Duration of schizophrenia (participants) [Number]
    Unknown
    125
    2.5%
    87
    1.8%
    212
    2.2%
    < 5 years
    1450
    29.6%
    1468
    29.9%
    2918
    29.7%
    5 to 10 years
    1254
    25.6%
    1278
    26.1%
    2532
    25.8%
    > 10 years
    2076
    42.3%
    2071
    42.2%
    4147
    42.3%
    Reasons for prescription of study drug (participants) [Number]
    Adverse drug reaction
    1121
    22.9%
    1072
    21.9%
    2193
    22.4%
    Lack of efficacy
    2542
    51.8%
    2580
    52.6%
    5122
    52.2%
    None or poor compliance
    161
    3.3%
    169
    3.4%
    330
    3.4%
    Patient's choice
    992
    20.2%
    979
    20%
    1971
    20.1%
    Other
    89
    1.8%
    104
    2.1%
    193
    2%
    Number of previous suicide attempts (participants) [Number]
    Unknown
    17
    0.3%
    11
    0.2%
    28
    0.3%
    0 previous suicide attempts
    4281
    87.3%
    4288
    87.4%
    8569
    87.4%
    1 previous suicide attempt
    378
    7.7%
    377
    7.7%
    755
    7.7%
    2 previous suicide attempts
    125
    2.5%
    126
    2.6%
    251
    2.6%
    3 previous suicide attempts
    52
    1.1%
    53
    1.1%
    105
    1.1%
    4 previous suicide attempts
    18
    0.4%
    13
    0.3%
    31
    0.3%
    >= 5 previous suicide attempts
    34
    0.7%
    36
    0.7%
    70
    0.7%
    Time since last suicide attempt (participants) [Number]
    No previous suicide attempt or unknown
    4298
    87.6%
    4301
    87.7%
    8599
    87.7%
    < 1 year
    122
    2.5%
    117
    2.4%
    239
    2.4%
    1 to 5 years
    226
    4.6%
    218
    4.4%
    444
    4.5%
    > 5 years
    259
    5.3%
    268
    5.5%
    527
    5.4%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With All-cause Mortality
    Description The analysis was based on all deaths from the Whole Randomised Treatment (WRT)+30 days period and the Only Randomised Treatment (ORT) period, respectively
    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

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all patients who took at least one dose of study drug.
    Arm/Group Title Sertindole Risperidone
    Arm/Group Description Normally in the range of 4 to 20 mg/day Normally in the range of 2 to 8 mg/day
    Measure Participants 4905 4904
    Number of deaths (WRT+30 days)
    64
    1.3%
    61
    1.2%
    Number of deaths (ORT)
    40
    0.8%
    44
    0.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sertindole, Risperidone
    Comments The basis for the statistical analysis of the first primary outcome was the null hypothesis of an excess mortality in sertindole-treated patients compared to the mortality in risperidone-treated patients for the WRT+30 days period.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments If the upper limit of the 90% confidence interval (CI) for the estimated all-cause mortality ratio was <1.5 (pre-specified), the null hypothesis was rejected. With this limit, 7,600 patient years of exposure (PYE) were required to ensure 80% power at the 5% significance level of rejecting the null hypothesis when assuming a mortality of 2 deaths per 100 PYE. As the actual mortality was only about half that anticipated, more exposure was necessary and the duration of the study increased markedly.
    Statistical Test of Hypothesis p-Value 0.05
    Comments
    Method Cox Proportional Hazard
    Comments Adjusted for: age, sex, time since last suicide attempt, last previous antipsychotic treatment (mono-/polytherapy), year since start of enrollment.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.117
    Confidence Interval (2-Sided) 90%
    0.831 to 1.500
    Parameter Dispersion Type:
    Value:
    Estimation Comments The hazard ratio is calculated as sertindole (numerator) versus risperidone (denominator).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sertindole, Risperidone
    Comments The basis for the statistical analysis of the first primary outcome was the null hypothesis of an excess mortality in sertindole-treated patients compared to the mortality in risperidone-treated patients for the ORT period.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments If the upper limit of the 90% CI for the estimated all-cause mortality ratio was <1.5 (pre-specified), the null hypothesis was rejected. With this limit, 7,600 PYE were required to ensure 80% power at the 5% significance level of rejecting the null hypothesis when assuming a mortality of 2 deaths per 100 PYE. As the actual mortality was only about half that anticipated, more exposure was necessary and the duration of the study increased markedly.
    Statistical Test of Hypothesis p-Value <0.05
    Comments
    Method Cox Proportional Hazard
    Comments Adjusted for: age, sex, time since last suicide attempt, last previous antipsychotic treatment (mono-/polytherapy), year since start of enrollment.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.980
    Confidence Interval (2-Sided) 90%
    0.684 to 1.405
    Parameter Dispersion Type:
    Value:
    Estimation Comments The hazard ratio is calculated as sertindole (numerator) versus risperidone (denominator).
    2. Secondary Outcome
    Title Cause-specific Mortality: Number of Participants With Cardiac Deaths - ISC
    Description 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.
    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

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all patients who took at least one dose of study drug.
    Arm/Group Title Sertindole Risperidone
    Arm/Group Description Normally in the range of 4 to 20 mg/day Normally in the range of 2 to 8 mg/day
    Measure Participants 4905 4904
    Number [participants]
    31
    0.6%
    12
    0.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sertindole, Risperidone
    Comments The basis for the statistical analysis of this secondary outcome was the null hypothesis of mortality hazard ratio equal to 1 for the sertindole-treated patients versus risperidone-treated patients during the WRT+30 days period.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0022
    Comments
    Method Cox Proportional Hazard
    Comments Adjusted: age, sex, time since last suicide attempt, last previous antipsychotic treatment (mono-/polytherapy), region, year since start of enrollment
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 2.84
    Confidence Interval (2-Sided) 95%
    1.45 to 5.55
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Primary Outcome
    Title Second Primary Outcome: Number of Participants With Cardiac Events, Including Arrhythmias, Requiring Hospitalisation
    Description 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
    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

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all patients who took at least one dose of study drug.
    Arm/Group Title Sertindole Risperidone
    Arm/Group Description Normally in the range of 4 to 20 mg/day Normally in the range of 2 to 8 mg/day
    Measure Participants 4905 4904
    Number [participants]
    10
    0.2%
    6
    0.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sertindole, Risperidone
    Comments The basis for the statistical analysis of time to 1st occurence of the secondary primary outcome (one patient in the risperidone group reported more than one occurrence of this event) was the null hypothesis of hazard ratio equal to 1 for the sertindole-treated patients versus risperidone-treated patients during the WRT+30 days period.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.29
    Comments
    Method Cox Proportional Hazard
    Comments Adjusted for: age and sex.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.73
    Confidence Interval (2-Sided) 95%
    0.63 to 4.78
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Cause-specific Mortality: Number of Participants With Completed Suicides - ISC
    Description 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.
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Sertindole Risperidone
    Arm/Group Description Normally in the range of 4 to 20 mg/day Normally in the range of 2 to 8 mg/day
    Measure Participants 4905 4904
    Number [participants]
    14
    0.3%
    21
    0.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sertindole, Risperidone
    Comments The basis for the statistical analysis of this secondary outcome was the null hypothesis of mortality hazard ratio equal to 1 for the sertindole-treated patients versus risperidone-treated patients during the WRT+30 days period.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.34
    Comments
    Method Cox Proportional Hazard
    Comments Adjusted for: age, sex, time since last suicide attempt, last previous antipsychotic treatment (mono-/polytherapy), year since start of enrollment.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.72
    Confidence Interval (2-Sided) 95%
    0.36 to 1.41
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Cause-specific Mortality: Number of Participants With Other Than Cardiac Deaths and Completed Suicides - ISC
    Description 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.
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Sertindole Risperidone
    Arm/Group Description Normally in the range of 4 to 20 mg/day Normally in the range of 2 to 8 mg/day
    Measure Participants 4905 4904
    Number [participants]
    19
    0.4%
    28
    0.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sertindole, Risperidone
    Comments The basis for the statistical analysis of this secondary outcome was the null hypothesis of mortality hazard ratio equal to 1 for the sertindole-treated patients versus risperidone-treated patients during the WRT+30 days period.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.26
    Comments
    Method Cox Proportional Hazard
    Comments Adjusted for: age, sex, last previous antipsychotic treatment (mono-/polytherapy), year since start of enrollment.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.715
    Confidence Interval (2-Sided) 95%
    0.40 to 1.28
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Cause-specific Mortality: Number of Participants With Cardiac Deaths - MedDRA
    Description 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
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Sertindole Risperidone
    Arm/Group Description Normally in the range of 4 to 20 mg/day Normally in the range of 2 to 8 mg/day
    Measure Participants 4905 4904
    Number [participants]
    17
    0.3%
    8
    0.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sertindole, Risperidone
    Comments The basis for the statistical analysis of this secondary outcome was the null hypothesis of mortality hazard ratio equal to 1 for the sertindole-treated patients versus risperidone-treated patients during the WRT+30 days period.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.081
    Comments
    Method Cox Proportional Hazard
    Comments Adjusted for: age, sex, last previous antipsychotic treatment (mono-/polytherapy).
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 2.13
    Confidence Interval (2-Sided) 95%
    0.91 to 4.98
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Cause-specific Mortality: Number of Participants With Completed Suicides - MedDRA
    Description 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
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Sertindole Risperidone
    Arm/Group Description Normally in the range of 4 to 20 mg/day Normally in the range of 2 to 8 mg/day
    Measure Participants 4905 4904
    Number [participants]
    13
    0.3%
    21
    0.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sertindole, Risperidone
    Comments The basis for the statistical analysis of this secondary outcome was the null hypothesis of mortality hazard ratio equal to 1 for the sertindole-treated patients versus risperidone-treated patients during the WRT+30 days period.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.24
    Comments
    Method Cox Proportional Hazard
    Comments Adjusted for: age, sex, time since last suicide attempt, last previous antipsychotic treatment (mono-/polytherapy), year since start of enrollment.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.66
    Confidence Interval (2-Sided) 95%
    0.33 to 1.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Cause-specific Mortality: Number of Participants With Other Than Cardiac Deaths and Completed Suicides - MedDRA
    Description 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
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Sertindole Risperidone
    Arm/Group Description Normally in the range of 4 to 20 mg/day Normally in the range of 2 to 8 mg/day
    Measure Participants 4905 4904
    Number [participants]
    34
    0.7%
    32
    0.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sertindole, Risperidone
    Comments The basis for the statistical analysis of this secondary outcome was the null hypothesis of mortality hazard ratio equal to 1 for the sertindole-treated patients versus risperidone-treated patients during the WRT+30 days period.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.59
    Comments
    Method Cox Proportional Hazard
    Comments Adjusted for: age, sex, last previous antipsychotic treatment (mono-/polytherapy), year since start of enrollment.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.14
    Confidence Interval (2-Sided) 95%
    0.70 to 1.85
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Number of Participants With Suicide Attempts (Fatal and Non-fatal) - ISC
    Description 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.
    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

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all patients who took at least one dose of study drug.
    Arm/Group Title Sertindole Risperidone
    Arm/Group Description Normally in the range of 4 to 20 mg/day Normally in the range of 2 to 8 mg/day
    Measure Participants 4905 4904
    Number [participants]
    68
    1.4%
    76
    1.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sertindole, Risperidone
    Comments The basis for the statistical analysis of time to 1st occurence of this secondary outcome was the null hypothesis of hazard ratio equal to 1 for the sertindole-treated patients versus risperidone-treated patients during the WRT+30 days period.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.65
    Comments
    Method Cox Proportional Hazard
    Comments Adjusted for: age, sex, duration of schizophrenia, time since last suicide attempt, year since start of enrollment.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.93
    Confidence Interval (2-Sided) 95%
    0.66 to 1.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title Number of Participants With Suicide Attempts (Fatal and Non-fatal) - MedDRA
    Description 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
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Sertindole Risperidone
    Arm/Group Description Normally in the range of 4 to 20 mg/day Normally in the range of 2 to 8 mg/day
    Measure Participants 4905 4904
    Number [participants]
    43
    0.9%
    65
    1.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sertindole, Risperidone
    Comments The basis for the statistical analysis of time to 1st occurence of this secondary outcome was the null hypothesis of hazard ratio equal to 1 for the sertindole-treated patients versus risperidone-treated patients during the WRT+30 days period.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.044
    Comments
    Method Cox Proportional Hazard
    Comments Adjusted for: age, sex, duration of schizophrenia, time since last suicide attempt, year since start of enrollment.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.67
    Confidence Interval (2-Sided) 95%
    0.45 to 0.99
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Secondary Outcome
    Title Number of Participants With Hospitalisations, Excluding Hospitalisations Related to the Primary Psychiatric Disease
    Description The analysis was based on time from start of study drug to first hospitalisation during the WRT+30 days period
    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

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all patients who took at least one dose of study drug.
    Arm/Group Title Sertindole Risperidone
    Arm/Group Description Normally in the range of 4 to 20 mg/day Normally in the range of 2 to 8 mg/day
    Measure Participants 4905 4904
    Number [participants]
    174
    3.5%
    149
    3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sertindole, Risperidone
    Comments The basis for the statistical analysis of time to 1st occurence of this secondary outcome was the null hypothesis of hazard ratio equal to 1 for the sertindole-treated patients versus risperidone-treated patients during the WRT+30 days period.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.040
    Comments
    Method Cox Proportional Hazard
    Comments Adjusted for: age, sex, time since last suicide attempt, last antipsychotic medication (a-/typicals/both), region, year since start of enrollment.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.26
    Confidence Interval (2-Sided) 95%
    1.01 to 1.57
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    12. Secondary Outcome
    Title Number of Participants With Discontinuation of Treatment for Any Reason Other Than Study Closure
    Description 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
    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

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all patients who took at least one dose of study drug.
    Arm/Group Title Sertindole Risperidone
    Arm/Group Description Normally in the range of 4 to 20 mg/day Normally in the range of 2 to 8 mg/day
    Measure Participants 4905 4904
    Number [participants]
    3136
    (430 PET?) 63.9%
    2597
    (433) 53%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sertindole, Risperidone
    Comments The basis for the statistical analysis of this secondary outcome was the null hypothesis of hazard ratio equal to 1 for the sertindole-treated patients versus risperidone-treated patients during the WRT+30 days period.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cox Proportional Hazard
    Comments Adjusted: disease duration, time since last suicide attempt, last antipsychotic medication (a-/typicals/both), region, year since start of enrollment.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.35
    Confidence Interval (2-Sided) 95%
    1.28 to 1.43
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    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.
    Adverse Event Reporting Description Data on all serious adverse events and non-serious cardiac adverse events were collected.
    Arm/Group Title Sertindole Risperidone
    Arm/Group Description Normally in the range of 4 to 20 mg/day Normally in the range of 2 to 8 mg/day
    All Cause Mortality
    Sertindole Risperidone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Sertindole Risperidone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 266/4905 (5.4%) 217/4904 (4.4%)
    Blood and lymphatic system disorders
    Anaemia 2/4905 (0%) 2 3/4904 (0.1%) 3
    Blood disorder 1/4905 (0%) 1 0/4904 (0%) 0
    Leukopenia 2/4905 (0%) 2 0/4904 (0%) 0
    Normochromic normocytic anaemia 0/4905 (0%) 0 1/4904 (0%) 1
    Cardiac disorders
    Acute myocardial infarction 2/4905 (0%) 2 1/4904 (0%) 1
    Angina unstable 0/4905 (0%) 0 1/4904 (0%) 2
    Arrhythmia 3/4905 (0.1%) 3 0/4904 (0%) 0
    Atrial flutter 1/4905 (0%) 1 0/4904 (0%) 0
    Cardiac arrest 2/4905 (0%) 2 0/4904 (0%) 0
    Cardiac failure 1/4905 (0%) 1 2/4904 (0%) 2
    Cardiac failure acute 4/4905 (0.1%) 4 1/4904 (0%) 1
    Cardiac failure congestive 1/4905 (0%) 1 0/4904 (0%) 0
    Cardio-respiratory arrest 3/4905 (0.1%) 3 2/4904 (0%) 2
    Cardiomyopathy 1/4905 (0%) 1 0/4904 (0%) 0
    Cardiopulmonary failure 1/4905 (0%) 1 1/4904 (0%) 1
    Conduction disorder 1/4905 (0%) 1 0/4904 (0%) 0
    Myocardial infarction 4/4905 (0.1%) 4 2/4904 (0%) 2
    Myocardial ischaemia 4/4905 (0.1%) 4 2/4904 (0%) 2
    Palpitations 1/4905 (0%) 1 0/4904 (0%) 0
    Torsade de pointes 2/4905 (0%) 2 0/4904 (0%) 0
    Ventricular tachycardia 1/4905 (0%) 1 0/4904 (0%) 0
    Ear and labyrinth disorders
    Vertigo 0/4905 (0%) 0 1/4904 (0%) 1
    Endocrine disorders
    Hyperprolactinaemia 3/4905 (0.1%) 3 3/4904 (0.1%) 3
    Inappropriate antidiuretic hormone secretion 0/4905 (0%) 0 2/4904 (0%) 2
    Eye disorders
    Eyelid disorder 1/4905 (0%) 1 0/4904 (0%) 0
    Meibomianitis 1/4905 (0%) 1 0/4904 (0%) 0
    Retinal detachment 1/4905 (0%) 1 1/4904 (0%) 1
    Gastrointestinal disorders
    Abdominal discomfort 1/4905 (0%) 1 0/4904 (0%) 0
    Abdominal distension 1/4905 (0%) 1 0/4904 (0%) 0
    Abdominal pain 2/4905 (0%) 2 0/4904 (0%) 0
    Abdominal pain upper 1/4905 (0%) 1 1/4904 (0%) 1
    Abdominal strangulated hernia 1/4905 (0%) 1 0/4904 (0%) 0
    Acute abdomen 1/4905 (0%) 1 0/4904 (0%) 0
    Anal fistula 1/4905 (0%) 1 0/4904 (0%) 0
    Ascites 1/4905 (0%) 1 0/4904 (0%) 0
    Crohn's disease 0/4905 (0%) 0 1/4904 (0%) 1
    Duodenal ulcer 2/4905 (0%) 2 0/4904 (0%) 0
    Duodenitis 0/4905 (0%) 0 1/4904 (0%) 1
    Gastric haemorrhage 1/4905 (0%) 1 1/4904 (0%) 1
    Gastric polyps 1/4905 (0%) 1 0/4904 (0%) 0
    Gastric ulcer 1/4905 (0%) 1 0/4904 (0%) 0
    Gastric ulcer perforation 1/4905 (0%) 1 1/4904 (0%) 1
    Gastritis 0/4905 (0%) 0 4/4904 (0.1%) 4
    Gastrointestinal disorder 2/4905 (0%) 2 0/4904 (0%) 0
    Gastrointestinal haemorrhage 0/4905 (0%) 0 1/4904 (0%) 1
    Haematemesis 1/4905 (0%) 1 1/4904 (0%) 1
    Inguinal hernia 1/4905 (0%) 1 0/4904 (0%) 0
    Nausea 1/4905 (0%) 1 0/4904 (0%) 0
    Oesophageal stenosis 1/4905 (0%) 1 0/4904 (0%) 0
    Oesophageal ulcer 1/4905 (0%) 1 0/4904 (0%) 0
    Oesophageal ulcer haemorrhage 1/4905 (0%) 1 0/4904 (0%) 0
    Oesophagitis 1/4905 (0%) 1 0/4904 (0%) 0
    Pancreatic mass 0/4905 (0%) 0 1/4904 (0%) 1
    Pancreatitis acute 2/4905 (0%) 2 1/4904 (0%) 1
    Peritonitis 0/4905 (0%) 0 1/4904 (0%) 1
    Rectal haemorrhage 0/4905 (0%) 0 1/4904 (0%) 1
    Rectal prolapse 1/4905 (0%) 1 0/4904 (0%) 0
    Vomiting 2/4905 (0%) 2 0/4904 (0%) 0
    General disorders
    Asthenia 1/4905 (0%) 1 1/4904 (0%) 1
    Chest pain 2/4905 (0%) 2 1/4904 (0%) 1
    Condition aggravated 1/4905 (0%) 1 0/4904 (0%) 0
    Death 12/4905 (0.2%) 12 2/4904 (0%) 2
    Drowning 0/4905 (0%) 0 2/4904 (0%) 2
    Generalised oedema 1/4905 (0%) 1 0/4904 (0%) 0
    Oedema peripheral 1/4905 (0%) 1 0/4904 (0%) 0
    Pyrexia 1/4905 (0%) 1 3/4904 (0.1%) 3
    Sudden death 1/4905 (0%) 1 2/4904 (0%) 2
    Hepatobiliary disorders
    Bile duct obstruction 1/4905 (0%) 1 0/4904 (0%) 0
    Cholecystitis 2/4905 (0%) 2 1/4904 (0%) 1
    Cholelithiasis 2/4905 (0%) 2 0/4904 (0%) 0
    Hepatic cirrhosis 0/4905 (0%) 0 1/4904 (0%) 1
    Hepatocellular damage 1/4905 (0%) 1 0/4904 (0%) 0
    Immune system disorders
    Hypersensitivity 1/4905 (0%) 1 0/4904 (0%) 0
    Infections and infestations
    Amoebic dysentery 0/4905 (0%) 0 1/4904 (0%) 1
    Appendicitis 3/4905 (0.1%) 3 3/4904 (0.1%) 3
    Bronchitis 3/4905 (0.1%) 3 0/4904 (0%) 0
    Bronchopneumonia 1/4905 (0%) 1 2/4904 (0%) 2
    Dengue fever 0/4905 (0%) 0 1/4904 (0%) 1
    Gangrene 1/4905 (0%) 1 0/4904 (0%) 0
    Gastroenteritis 1/4905 (0%) 1 1/4904 (0%) 1
    Gastroenteritis bacterial 1/4905 (0%) 1 0/4904 (0%) 0
    Helicobacter infection 0/4905 (0%) 0 1/4904 (0%) 1
    Infection 0/4905 (0%) 0 1/4904 (0%) 1
    Infection in an immunocompromised host 0/4905 (0%) 0 1/4904 (0%) 1
    Laryngitis 1/4905 (0%) 1 0/4904 (0%) 0
    Liver abscess 0/4905 (0%) 0 1/4904 (0%) 1
    Meningitis tuberculous 0/4905 (0%) 0 1/4904 (0%) 1
    Obstructive chronic bronchitis with acute exacerbation 1/4905 (0%) 1 1/4904 (0%) 1
    Osteomyelitis 0/4905 (0%) 0 1/4904 (0%) 1
    Parasitic gastroenteritis 1/4905 (0%) 1 0/4904 (0%) 0
    Pneumonia 7/4905 (0.1%) 9 7/4904 (0.1%) 7
    Pneumonia chlamydial 1/4905 (0%) 1 0/4904 (0%) 0
    Postoperative wound infection 2/4905 (0%) 2 0/4904 (0%) 0
    Pulmonary tuberculosis 4/4905 (0.1%) 4 2/4904 (0%) 2
    Pyelonephritis acute 1/4905 (0%) 1 0/4904 (0%) 0
    Sepsis 1/4905 (0%) 1 2/4904 (0%) 2
    Sinusitis 0/4905 (0%) 0 1/4904 (0%) 1
    Tuberculosis 0/4905 (0%) 0 2/4904 (0%) 3
    Upper respiratory tract infection 0/4905 (0%) 0 1/4904 (0%) 1
    Urinary tract infection 1/4905 (0%) 1 3/4904 (0.1%) 3
    Vaginal candidiasis 1/4905 (0%) 1 0/4904 (0%) 0
    Injury, poisoning and procedural complications
    Accidental exposure 1/4905 (0%) 1 0/4904 (0%) 0
    Accidental overdose 2/4905 (0%) 2 0/4904 (0%) 0
    Acetabulum fracture 1/4905 (0%) 1 0/4904 (0%) 0
    Alcohol poisoning 0/4905 (0%) 0 2/4904 (0%) 2
    Ankle fracture 1/4905 (0%) 1 0/4904 (0%) 0
    Burns third degree 1/4905 (0%) 1 0/4904 (0%) 0
    Carbon monoxide poisoning 0/4905 (0%) 0 1/4904 (0%) 1
    Contusion 1/4905 (0%) 1 0/4904 (0%) 0
    Drug toxicity 2/4905 (0%) 2 6/4904 (0.1%) 6
    Excoriation 0/4905 (0%) 0 1/4904 (0%) 1
    Face injury 1/4905 (0%) 1 0/4904 (0%) 0
    Fall 2/4905 (0%) 2 1/4904 (0%) 1
    Femoral neck fracture 1/4905 (0%) 1 1/4904 (0%) 1
    Femur fracture 1/4905 (0%) 1 0/4904 (0%) 0
    Fracture 0/4905 (0%) 0 1/4904 (0%) 1
    Head injury 2/4905 (0%) 2 2/4904 (0%) 2
    Heat stroke 1/4905 (0%) 1 0/4904 (0%) 0
    Hip fracture 1/4905 (0%) 1 1/4904 (0%) 1
    Intentional overdose 21/4905 (0.4%) 23 14/4904 (0.3%) 16
    Joint injury 0/4905 (0%) 0 1/4904 (0%) 1
    Joint sprain 1/4905 (0%) 1 0/4904 (0%) 0
    Ligament injury 0/4905 (0%) 0 1/4904 (0%) 1
    Lower limb fracture 3/4905 (0.1%) 3 0/4904 (0%) 0
    Medication error 1/4905 (0%) 2 0/4904 (0%) 0
    Meniscus lesion 0/4905 (0%) 0 1/4904 (0%) 1
    Multiple drug overdose intentional 0/4905 (0%) 0 1/4904 (0%) 1
    Multiple fractures 1/4905 (0%) 1 1/4904 (0%) 1
    Multiple injuries 1/4905 (0%) 1 0/4904 (0%) 0
    Overdose 15/4905 (0.3%) 16 8/4904 (0.2%) 8
    Pneumothorax traumatic 0/4905 (0%) 0 1/4904 (0%) 1
    Poisoning 3/4905 (0.1%) 3 1/4904 (0%) 1
    Road traffic accident 4/4905 (0.1%) 4 3/4904 (0.1%) 3
    Self mutilation 1/4905 (0%) 1 1/4904 (0%) 1
    Skull fracture 0/4905 (0%) 0 1/4904 (0%) 1
    Thermal burn 1/4905 (0%) 1 0/4904 (0%) 0
    Tibia fracture 0/4905 (0%) 0 1/4904 (0%) 1
    Traumatic brain injury 1/4905 (0%) 1 0/4904 (0%) 0
    Ulna fracture 0/4905 (0%) 0 1/4904 (0%) 1
    Upper limb fracture 0/4905 (0%) 0 1/4904 (0%) 1
    Investigations
    Alanine aminotransferase increased 1/4905 (0%) 1 0/4904 (0%) 0
    Aspartate aminotransferase increased 1/4905 (0%) 1 0/4904 (0%) 0
    Blood triglycerides increased 1/4905 (0%) 1 0/4904 (0%) 0
    Electrocardiogram QT prolonged 17/4905 (0.3%) 18 0/4904 (0%) 0
    Electrocardiogram repolarisation abnormality 1/4905 (0%) 1 0/4904 (0%) 0
    Hepatic enzyme increased 1/4905 (0%) 1 0/4904 (0%) 0
    Medical observation 0/4905 (0%) 0 1/4904 (0%) 1
    Weight increased 1/4905 (0%) 1 0/4904 (0%) 0
    Metabolism and nutrition disorders
    Diabetes mellitus 4/4905 (0.1%) 4 1/4904 (0%) 1
    Diabetes mellitus inadequate control 0/4905 (0%) 0 1/4904 (0%) 1
    Diabetic ketoacidosis 0/4905 (0%) 0 1/4904 (0%) 1
    Electrolyte imbalance 0/4905 (0%) 0 1/4904 (0%) 1
    Hyperglycaemia 0/4905 (0%) 0 1/4904 (0%) 1
    Hyperlipidaemia 1/4905 (0%) 1 0/4904 (0%) 0
    Hypoglycaemia 0/4905 (0%) 0 1/4904 (0%) 1
    Hypokalaemia 2/4905 (0%) 2 0/4904 (0%) 0
    Hyponatraemia 0/4905 (0%) 0 2/4904 (0%) 2
    Type 2 diabetis mellitus 3/4905 (0.1%) 3 0/4904 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain 1/4905 (0%) 1 1/4904 (0%) 2
    Intervertebral disc protrusion 1/4905 (0%) 1 0/4904 (0%) 0
    Muscle spasms 1/4905 (0%) 1 0/4904 (0%) 0
    Osteoarthritis 2/4905 (0%) 2 0/4904 (0%) 0
    Osteoporosis postmenopausal 1/4905 (0%) 1 0/4904 (0%) 0
    Pain in extremity 0/4905 (0%) 0 1/4904 (0%) 1
    Rhabdomyolysis 1/4905 (0%) 1 0/4904 (0%) 0
    Systemic lupus erythematosus 1/4905 (0%) 1 0/4904 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adrenal carcinoma 1/4905 (0%) 1 0/4904 (0%) 0
    Benign neoplasm of testis 1/4905 (0%) 1 0/4904 (0%) 0
    Brain neoplasm 0/4905 (0%) 0 2/4904 (0%) 2
    Breast cancer 1/4905 (0%) 1 3/4904 (0.1%) 3
    Colon cancer 0/4905 (0%) 0 1/4904 (0%) 1
    Gammopathy 0/4905 (0%) 0 1/4904 (0%) 1
    Gastric cancer 1/4905 (0%) 1 1/4904 (0%) 1
    Gastric neoplasm 0/4905 (0%) 0 1/4904 (0%) 1
    Hepatic neoplasm malignant 0/4905 (0%) 0 1/4904 (0%) 1
    Lung neoplasm malignant 1/4905 (0%) 1 0/4904 (0%) 0
    Metastases to central nervous system 0/4905 (0%) 0 3/4904 (0.1%) 3
    Non-Hodgkin's lymphoma 0/4905 (0%) 0 1/4904 (0%) 1
    Non-small cell lung cancer 0/4905 (0%) 0 1/4904 (0%) 1
    Ovarian cancer 0/4905 (0%) 0 1/4904 (0%) 1
    Scrotal cancer 0/4905 (0%) 0 1/4904 (0%) 1
    Squamous cell carcinoma of the cervix 1/4905 (0%) 1 0/4904 (0%) 0
    Uterine cancer 0/4905 (0%) 0 1/4904 (0%) 1
    Uterine leiomyoma 3/4905 (0.1%) 3 0/4904 (0%) 0
    Nervous system disorders
    Brain damage 1/4905 (0%) 1 0/4904 (0%) 0
    Cerebral haemorrhage 2/4905 (0%) 2 1/4904 (0%) 1
    Cerebral infarction 0/4905 (0%) 0 1/4904 (0%) 1
    Cerebrovascular accident 3/4905 (0.1%) 3 0/4904 (0%) 0
    Cerebrovascular disorder 0/4905 (0%) 0 1/4904 (0%) 1
    Coma 0/4905 (0%) 0 1/4904 (0%) 1
    Convulsion 4/4905 (0.1%) 4 5/4904 (0.1%) 6
    Diabetic coma 1/4905 (0%) 1 1/4904 (0%) 1
    Dizziness 3/4905 (0.1%) 3 1/4904 (0%) 1
    Dyskinesia 0/4905 (0%) 0 2/4904 (0%) 2
    Epilepsy 5/4905 (0.1%) 5 3/4904 (0.1%) 3
    Extrapyramidal disorder 0/4905 (0%) 0 1/4904 (0%) 1
    Grand mal convulsion 5/4905 (0.1%) 5 3/4904 (0.1%) 3
    Headache 0/4905 (0%) 0 2/4904 (0%) 2
    Hypoxic encephalopathy 0/4905 (0%) 0 1/4904 (0%) 1
    Loss of consciousness 2/4905 (0%) 2 2/4904 (0%) 2
    Neuroleptic malignant syndrome 0/4905 (0%) 0 2/4904 (0%) 2
    Status epilepticus 1/4905 (0%) 1 1/4904 (0%) 1
    Syncope 2/4905 (0%) 2 1/4904 (0%) 1
    Transient ischaemic attack 1/4905 (0%) 1 0/4904 (0%) 0
    Pregnancy, puerperium and perinatal conditions
    Blighted ovum 1/4905 (0%) 1 0/4904 (0%) 0
    Intra-uterine death 1/4905 (0%) 1 0/4904 (0%) 0
    Pregnancy 1/4905 (0%) 1 0/4904 (0%) 0
    Psychiatric disorders
    Completed suicide 13/4905 (0.3%) 13 21/4904 (0.4%) 21
    Delirium 2/4905 (0%) 2 1/4904 (0%) 1
    Depression 2/4905 (0%) 2 3/4904 (0.1%) 3
    Depressive symptom 0/4905 (0%) 0 1/4904 (0%) 1
    Drug abuse 0/4905 (0%) 0 1/4904 (0%) 1
    Intentional self-injury 3/4905 (0.1%) 3 3/4904 (0.1%) 3
    Mania 1/4905 (0%) 1 0/4904 (0%) 0
    Psychotic disorder 2/4905 (0%) 2 0/4904 (0%) 0
    Suicidal behaviour 1/4905 (0%) 1 0/4904 (0%) 0
    Suicidal ideation 7/4905 (0.1%) 7 4/4904 (0.1%) 4
    Suicide attempt 29/4905 (0.6%) 30 45/4904 (0.9%) 49
    Renal and urinary disorders
    Calculus urinary 1/4905 (0%) 1 1/4904 (0%) 1
    Renal colic 1/4905 (0%) 1 0/4904 (0%) 0
    Renal disorder 0/4905 (0%) 0 1/4904 (0%) 1
    Renal failure acute 0/4905 (0%) 0 1/4904 (0%) 1
    Urge incontinence 1/4905 (0%) 1 0/4904 (0%) 0
    Reproductive system and breast disorders
    Amenorrhoea 0/4905 (0%) 0 1/4904 (0%) 1
    Galactorrhoea 0/4905 (0%) 0 3/4904 (0.1%) 3
    Haematosalpinx 0/4905 (0%) 0 1/4904 (0%) 1
    Menorrhagia 1/4905 (0%) 1 0/4904 (0%) 0
    Metrorrhagia 0/4905 (0%) 0 1/4904 (0%) 1
    Ovarian cyst 0/4905 (0%) 0 1/4904 (0%) 1
    Uterovaginal prolapse 0/4905 (0%) 0 1/4904 (0%) 1
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome 1/4905 (0%) 1 0/4904 (0%) 0
    Asphyxia 4/4905 (0.1%) 4 3/4904 (0.1%) 3
    Aspiration 3/4905 (0.1%) 3 0/4904 (0%) 0
    Asthma 3/4905 (0.1%) 5 0/4904 (0%) 0
    Chronic obstructive pulmonary disease 2/4905 (0%) 2 1/4904 (0%) 1
    Cough 0/4905 (0%) 0 1/4904 (0%) 1
    Dyspnoea 2/4905 (0%) 2 0/4904 (0%) 0
    Emphysema 1/4905 (0%) 1 0/4904 (0%) 0
    Haemoptysis 1/4905 (0%) 1 0/4904 (0%) 0
    Hydrothorax 0/4905 (0%) 0 1/4904 (0%) 1
    Lung disorder 0/4905 (0%) 0 1/4904 (0%) 1
    Obstructive airways disorder 0/4905 (0%) 0 1/4904 (0%) 1
    Pneumonia aspiration 1/4905 (0%) 1 1/4904 (0%) 1
    Pulmonary embolism 4/4905 (0.1%) 4 3/4904 (0.1%) 3
    Pulmonary oedema 1/4905 (0%) 1 0/4904 (0%) 0
    Respiratory failure 4/4905 (0.1%) 4 0/4904 (0%) 0
    Status asthmaticus 0/4905 (0%) 0 1/4904 (0%) 1
    Skin and subcutaneous tissue disorders
    Rash pruritic 1/4905 (0%) 1 0/4904 (0%) 0
    Social circumstances
    Alcohol use 1/4905 (0%) 1 0/4904 (0%) 0
    Drug abuser 1/4905 (0%) 1 0/4904 (0%) 0
    Physical assault 1/4905 (0%) 1 1/4904 (0%) 1
    Social problem 0/4905 (0%) 0 1/4904 (0%) 1
    Treatment noncompliance 1/4905 (0%) 1 0/4904 (0%) 0
    Surgical and medical procedures
    Bunion operation 0/4905 (0%) 0 1/4904 (0%) 1
    Cholecystectomy 1/4905 (0%) 1 2/4904 (0%) 2
    Hernia repair 0/4905 (0%) 0 1/4904 (0%) 1
    Mastectomy 0/4905 (0%) 0 1/4904 (0%) 1
    Plastic surgery 1/4905 (0%) 1 0/4904 (0%) 0
    Tonsillectomy 0/4905 (0%) 0 1/4904 (0%) 1
    Varicose vein operation 0/4905 (0%) 0 1/4904 (0%) 1
    Vascular disorders
    Aortic aneurysm rupture 1/4905 (0%) 1 1/4904 (0%) 1
    Deep vein thrombosis 2/4905 (0%) 2 0/4904 (0%) 0
    Haematoma 0/4905 (0%) 0 1/4904 (0%) 1
    Hypertension 2/4905 (0%) 2 1/4904 (0%) 1
    Hypertensive crisis 1/4905 (0%) 1 0/4904 (0%) 0
    Labile hypertension 1/4905 (0%) 1 0/4904 (0%) 0
    Lymphoedema 0/4905 (0%) 0 1/4904 (0%) 1
    Orthostatic hypotension 1/4905 (0%) 1 2/4904 (0%) 2
    Phlebitis 1/4905 (0%) 1 1/4904 (0%) 1
    Shock 1/4905 (0%) 1 0/4904 (0%) 0
    Other (Not Including Serious) Adverse Events
    Sertindole Risperidone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 397/4905 (8.1%) 11/4904 (0.2%)
    Investigations
    Electrocardiogram QT prolonged 397/4905 (8.1%) 11/4904 (0.2%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Publication of the results by the investigator will be subject to mutual agreement between the investigator and H. Lundbeck A/S.

    Results Point of Contact

    Name/Title H. Lundbeck A/S
    Organization H. Lundbeck A/S
    Phone
    Email LundbeckClinicalTrials@lundbeck.com
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00856583
    Other Study ID Numbers:
    • 99824
    • 2004-000213-19
    First Posted:
    Mar 6, 2009
    Last Update Posted:
    Aug 19, 2011
    Last Verified:
    Aug 1, 2011