SCoP: Safety Study of Sertindole Versus Risperidone Under Normal Conditions of Use
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
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:
|
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:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
- 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.
- 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.
- 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.
- 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
- 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
- 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
- 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.
- 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
- 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
- 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
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.- 99824
- 2004-000213-19
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
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). |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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
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 | |
LundbeckClinicalTrials@lundbeck.com |
- 99824
- 2004-000213-19