Clinical Trial Results:
26-Week Open-Label Extension Study Evaluating The Safety And Tolerability Of Flexible Doses Of Oral Ziprasidone In Children And Adolescents With Bipolar I Disorder (Manic Or Mixed)
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Summary
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EudraCT number |
2015-000607-15 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
24 Jan 2008
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Results information
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Results version number |
v2(current) |
This version publication date |
26 Mar 2016
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First version publication date |
20 Jun 2015
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
A1281133
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00265330 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Pfizer Inc.
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Sponsor organisation address |
235 E 42nd Street, New York, United States, NY 10017
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Public contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 800-718-1021, ClinicalTrials.govCallCenter@pfizer.com
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Scientific contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 800-718-1021, ClinicalTrials.govCallCenter@pfizer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
10 Jul 2008
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
24 Jan 2008
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the safety and tolerability of oral ziprasidone (40-80 milligram [mg] twice a day [BID]) during long-term, open-label administration in children and adolescents with Bipolar I Disorder - Single Manic Episode; Bipolar I Disorder – Most Recent Episode Manic, or Bipolar I Disorder – Most Recent Episode Mixed.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Mar 2006
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 162
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Worldwide total number of subjects |
162
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
41
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Adolescents (12-17 years) |
120
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Adults (18-64 years) |
1
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The number of subjects entering this trial was determined by the number of subjects electing to continue treatment after completing or withdrawing from the preceding double-blind study (A1281132: NCT00257166; 2015-000606-20). | ||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 169 subjects from the parent study were assigned to the extension study and 162 continued on and received study treatment in the extension study. | ||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||
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Arms
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Arm title
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Ziprasidone | ||||||||||||||||||||||||||||||||
Arm description |
Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. | ||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Ziprasidone
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Investigational medicinal product code |
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Other name |
Geodon
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
For subjects having a body weight of 45 kilograms (kg) or greater, the target dosage range was 40-80 milligrams (mg) twice per day (BID) (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID).
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Baseline characteristics reporting groups
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Reporting group title |
Ziprasidone
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Reporting group description |
Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Ziprasidone
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Reporting group description |
Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. | ||
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End point title |
Young Mania Rating Scale (YMRS) Total Score Change from Baseline [1] | ||||||||||||||||||||
End point description |
YMRS: 11-item instrument with scales 0 (normal) to 4 (highest abnormal)for 7 items and 0 (normal) to 8 (highest abnormal) for 4 items. Total possible 0 - 60. Baseline is from parent study A1281132. The Safety Analysis Set includes all subjects who took at least one dose of study medication in this open-label extension study. (Row: n=number subjects with observation).
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End point type |
Primary
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End point timeframe |
Baseline and 26 Weeks; 26 Weeks Last Observation Carried Forward (LOCF)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Clinical Global Impression of Severity (CGI-S) Change from Baseline [2] | ||||||||||||||||||||||||||||
End point description |
CGI-S Scale:standardized assessment tool to rate severity of subject’s illness; assesses investigator’s impression of subject’s current illness state. Change: score at observation minus score at baseline. Score: 1 (not ill at all) to 7 (among most extremely ill). Baseline = last available observation from parent double-blind study(A1281132). The Safety Analysis Set includes all subjects who took at least one dose of study medication in this open-label extension study. (Row: n=number subjects with observation).
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End point type |
Primary
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End point timeframe |
Baseline and 26 Weeks; 26 Weeks LOCF
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Incidence of Lab Abnormalities [3] | ||||||||||||||||||||||||||||
End point description |
Number of subjects with an abnormal lab value for those parameters with 5 percent (%) or greater incidence of abnormality. Total number of subjects with given laboratory test at given visit. Range: N=136-134, with the exception of Insulin (N=115).
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End point type |
Primary
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End point timeframe |
Week 26
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Change in Low-Density Lipoprotein (LDL) Cholesterol and Fasting Cholesterol [4] | ||||||||||||||||||||
End point description |
Mean Change: lab value at observation minus lab value at baseline. The Safety Analysis Set includes all subjects who took at least one dose of study medication in this open-label extension study. (Row: n= total number of subjects with at least 1 observation of the given laboratory test).
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End point type |
Primary
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End point timeframe |
Week 6, Week 26
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Change in Hormones [5] | ||||||||||||||||||||||||||
End point description |
Mean Change: lab value at observation minus lab value at baseline. The Safety Analysis Set includes all subjects who took at least one dose of study medication in this open-label extension study. (Row: n= total number of subjects with at least 1 observation of the given laboratory test).
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End point type |
Primary
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End point timeframe |
Week 6, Week 26
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||
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End point title |
Mean Change from Baseline in Supine Systolic Blood Pressure [6] | ||||||||||||||||||||||||||||
End point description |
Mean Change: vital sign value at observation minus vital sign value at baseline.
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End point type |
Primary
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End point timeframe |
Week 1 through Week 26
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| Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Mean Change from Baseline in Supine Diastolic Blood Pressure [7] | ||||||||||||||||||||||||||||
End point description |
Mean Change: vital sign value at observation minus vital sign value at baseline.
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End point type |
Primary
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End point timeframe |
Week 1 through Week 26
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Mean Change from Baseline in Supine Pulse Rates [8] | ||||||||||||||||||||||||||||
End point description |
Mean Change: vital sign value at observation minus vital sign value at baseline.
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End point type |
Primary
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End point timeframe |
Week 1 through Week 26
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| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Mean Change from Baseline in Standing Systolic Blood Pressure [9] | ||||||||||||||||||||||||||||
End point description |
Mean Change: vital sign value at observation minus vital sign value at baseline.
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End point type |
Primary
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End point timeframe |
Week 1 through Week 26
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| Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Mean Change from Baseline in Standing Diastolic Blood Pressure [10] | ||||||||||||||||||||||||||||
End point description |
Mean Change: vital sign value at observation minus vital sign value at baseline.
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End point type |
Primary
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End point timeframe |
Week 1 through Week 26
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| Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Mean Change from Baseline in Standing Pulse Rates [11] | ||||||||||||||||||||||||||||
End point description |
Mean Change: vital sign value at observation minus vital sign value at baseline.
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End point type |
Primary
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End point timeframe |
Week 1 through Week 26
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| Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Mean Change from Baseline for Body Weight [12] | ||||||||||||||
End point description |
Mean change; body weight value at observation minus body weight value at baseline.
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End point type |
Primary
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End point timeframe |
Week 6, Week 26
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| Notes [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Mean Change from Baseline for Body Mass Index (BMI) Z-Score [13] | ||||||||||||||
End point description |
Mean change in body weight BMI -Z score calculated by subtracting median reference value of the population from observed value and dividing by standard deviation of reference population (kg/m squared). 0=no change.
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End point type |
Primary
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End point timeframe |
Week 6, 26, early termination
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| Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Body Mass Index (BMI) Z-score frequency [14] | ||||||||||||||||||||||||||
End point description |
Change in body weight BMI -Z score calculated by subtracting median reference value of the population from observed value and dividing by standard deviation of reference population (kg/m squared). 0=no change.
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End point type |
Primary
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End point timeframe |
Week 6
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| Notes [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||
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End point title |
Body Mass Index (BMI) Z-score frequency [15] | ||||||||||||||||||||||||||
End point description |
Change in body weight BMI -Z score calculated by subtracting median reference value of the population from observed value and dividing by standard deviation of reference population (kg/m squared). 0=no change.
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End point type |
Primary
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End point timeframe |
Week 26
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| Notes [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||
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End point title |
Mean Change from Baseline for QTcF intervals [16] | ||||||||||||||||||||||||||||
End point description |
QT intervals (observed in an electrocardiogram) corrected using Fridericia’s formula (QTcF). Mean change: mean change of observation minus baseline. Baseline: last available observation in the parent double-blind study.
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End point type |
Primary
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End point timeframe |
Baseline to Week 26 (end of study)
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| Notes [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Frequency of largest categorical increases in QTcF for males [17] | ||||||||||||||||
End point description |
QT intervals (observed in an electrocardiogram) corrected with Fridericia's Formula (QTcF). Number of subjects with corresponding categorical increase in QTcF.
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End point type |
Primary
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End point timeframe |
Week 26 (end of study)
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| Notes [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Frequency of largest categorical increases in QTcF for females [18] | ||||||||||||||||
End point description |
QT interval (observed in an electrocardiogram) corrected using Fridericia Formula (QTcF). Number of subjects with corresponding categorical increase in QTcF.
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End point type |
Primary
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End point timeframe |
Week 26 (end of study)
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| Notes [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Frequency of largest categorical increases in QTcF - all subjects [19] | ||||||||||||||||
End point description |
QT intervals (observed in an electrocardiogram)corrected using Fridericia Formula (QTcF). Number of subjects with corresponding categorical increase in QTcF.
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End point type |
Primary
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End point timeframe |
Week 26 (end of study)
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| Notes [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Treatment emergent adverse events are reported from time of first dose of study treatment up to 6 days after last dose of study treatment.
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Adverse event reporting additional description |
Safety population = all randomized subjects with at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
Ziprasidone
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Reporting group description |
Dosing was flexible, with dosing adjustments made at the discretion of the investigator to maintain optimal efficacy and tolerability. For subjects having a body weight of 45 kg or greater, the target dosage range was 40-80 mg BID (80-160 mg/day). For subjects having a body weight under 45 kg, the maximum permitted dose was 80 mg/day (40 mg BID). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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06 Dec 2006 |
1- In assessments, fasting glucose and glycosylated hemoglobin (HbA1c) were added to clinical laboratory testing.
2- Daily dose of study medication for subjects with a body weight of ≥ 45 kg changed to 40-80 mg/day from 60-80 mg/day.
3- In trial design, minimum dose of the preceding double-blind study was decided for the dose reduction in subjects ≥45 kg, who cannot tolerate a dose of 80 mg/day.
4- In Trial Treatment, inhaled steroids were also added along with the topical steroids in the category of medicines for which use is allowed only if taken during preceding double-blind study with stable dose and clinical condition; and benzhexol and other anticholinergics were added in the category of medicines which are allowed without condition.
5- An additional category (≥460 msec) was used in QTcF reporting.
6- A change was made in the reporting priorities of AEs. A decision was made to report the treatment-emergent AEs as the main safety output, and “All AEs” were reported as additional tables. Combined data are the main analyses and consist of all subjects, regardless of the treatment assignment in the preceding double-blind study (A1281132). |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The AE tables were amended to incorporate previously unreported AEs that were found during an independent audit and verified by the investigators. | |||
