Clinical Trial Results:
Radium-223 Dichloride (Alpharadin) in Castration-Resistant (Hormone-Refractory) Prostate Cancer Patients with Bone Metastasis
Summary
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EudraCT number |
2012-000075-16 |
Trial protocol |
SE DE NO FI BE ES CZ IE GB IT DK NL AT |
Global end of trial date |
28 Feb 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Mar 2017
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First version publication date |
01 Mar 2017
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Other versions |
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 |
BAY88-8223/16216
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01618370 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Bayer AG
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Sponsor organisation address |
Kaiser-Wilhelm-Allee, D-51368 Leverkusen, Germany,
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Public contact |
Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
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Scientific contact |
Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
28 Feb 2016
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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 |
28 Feb 2016
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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 |
The main objectives of the study were to:
•assess the acute and long-term safety of radium-223 dichloride
•assess the overall survival of this subject population.
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Protection of trial subjects |
The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent form was read by and explained to all subjects. Participating subjects signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
22 Jul 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Poland: 10
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Country: Number of subjects enrolled |
Netherlands: 16
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Country: Number of subjects enrolled |
Spain: 90
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Country: Number of subjects enrolled |
Sweden: 95
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Country: Number of subjects enrolled |
United Kingdom: 31
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Country: Number of subjects enrolled |
Belgium: 11
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Country: Number of subjects enrolled |
Finland: 38
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Country: Number of subjects enrolled |
Germany: 124
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Country: Number of subjects enrolled |
Ireland: 26
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Country: Number of subjects enrolled |
Italy: 48
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Country: Number of subjects enrolled |
Russian Federation: 12
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Country: Number of subjects enrolled |
Canada: 21
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Country: Number of subjects enrolled |
Switzerland: 48
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Country: Number of subjects enrolled |
Israel: 84
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Country: Number of subjects enrolled |
Norway: 54
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Worldwide total number of subjects |
708
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EEA total number of subjects |
543
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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) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
138
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From 65 to 84 years |
522
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85 years and over |
48
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Recruitment
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Recruitment details |
Study was conducted at 115 study centers in 15 countries, between 22 July 2012 (first subject first visit) and 28 February 2016 (last subject last visit). | ||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Overall, 852 subjects were screened. Of these, 143 subjects failed screening and one subject did not receive any study drug, remaining 708 subjects were allocated to treatment. | ||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||
Arms
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Arm title
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Radium-223 dichloride (Xofigo; BAY88-8223) 50 kBg/kg | ||||||||||||||||||||||||||||||||||||
Arm description |
Subjects received a slow bolus intravenous (iv) injection of Radium-223 dichloride (Xofigo; BAY88-8223), at a dose of 50 kilobecquerel per kilogram (kBq/kg) body weight, based on National Institute of Standards and Technology (NIST) 2010 standardization, at intervals of every 4 weeks for up to 6 cycles. Follow-up assessments for safety were conducted every 6 months until the subject died or until the program was terminated by the sponsor. | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Radium-223 dichloride
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Investigational medicinal product code |
BAY88-8223
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Other name |
Xofigo, Alpharadin
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects received a slow bolus iv injection of Radium-223 dichloride (Xofigo; BAY88-8223), at a dose of 50 kBq/kg body weight, based on NIST 2010 standardization, at intervals of every 4 weeks for up to 6 cycles.
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Baseline characteristics reporting groups
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Reporting group title |
Radium-223 dichloride (Xofigo; BAY88-8223) 50 kBg/kg
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Reporting group description |
Subjects received a slow bolus intravenous (iv) injection of Radium-223 dichloride (Xofigo; BAY88-8223), at a dose of 50 kilobecquerel per kilogram (kBq/kg) body weight, based on National Institute of Standards and Technology (NIST) 2010 standardization, at intervals of every 4 weeks for up to 6 cycles. Follow-up assessments for safety were conducted every 6 months until the subject died or until the program was terminated by the sponsor. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Radium-223 dichloride (Xofigo; BAY88-8223) 50 kBg/kg
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Reporting group description |
Subjects received a slow bolus intravenous (iv) injection of Radium-223 dichloride (Xofigo; BAY88-8223), at a dose of 50 kilobecquerel per kilogram (kBq/kg) body weight, based on National Institute of Standards and Technology (NIST) 2010 standardization, at intervals of every 4 weeks for up to 6 cycles. Follow-up assessments for safety were conducted every 6 months until the subject died or until the program was terminated by the sponsor. | ||
Subject analysis set title |
Safety Analysis Set (SAF)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
SAF (N=708) included all subjects who received at least one dose of the study drug.
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End point title |
Overall Survival [1] | ||||||||
End point description |
Overall survival was defined as time from the start of therapy to death due to any cause. Subjects alive at the time of analysis were censored at the last date known to be alive. Median, percentiles and 95% confidence interval were computed using Kaplan-Meier estimates. ‘99999’ indicates that data were not calculated.
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End point type |
Primary
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End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
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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: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [2] - SAF |
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No statistical analyses for this end point |
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End point title |
Eastern Cooperative Oncology Group (ECOG): Shift Change From Baseline Performance Status During Treatment Period [3] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
ECOG PS was measured in a scale from 0 (best) to grade 4 (worst), where 0= Fully active, able to carry on all pre-diseases performance without restriction, 1= Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, 2= Ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% waking hours, 3= Capable of only limited self-care, confined to bed/chair, more than 50% waking hours, and 4= Completely disabled, cannot carry on any self-care, totally confined to bed/chair. In the below table only those category has been reported for which shift from baseline were occurred. ‘n’= evaluable subjects for the respective category.
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End point type |
Primary
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End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
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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: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [4] - SAF |
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No statistical analyses for this end point |
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End point title |
Time to Skeletal-Related Events (SRE) - Overall Study [5] | ||||||||
End point description |
SRE were defined as the use of external beam radiotherapy to relieve skeletal symptoms or the occurrence of new symptomatic pathological bone fractures (vertebral or nonvertebral); or the occurrence of spinal cord compression; or a tumor-related orthopedic surgical intervention. The median time to SRE could not be fully computed because of the small number of events recorded due to the short follow-up. “99999” signifies value cannot be estimated due to censored data or data were not available.
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End point type |
Primary
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End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
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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: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [6] - SAF |
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Treatment-Emergent Adverse Events of Grade 3-5 (TEAEs) During Treatment Period [7] | ||||||||||||||||||
End point description |
An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Treatment emergent AEs were classified in to five grades based upon their severity. On the basis of that grade 3 AEs are severe or medically significant but not immediately life-threatening; which may leads hospitalization or prolongation of hospitalization; disabling; limiting self-care activities of daily living. Grade 4 AEs are life-threatening consequences; urgent intervention. Grade 5 AE is related to Death.
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End point type |
Primary
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End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
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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: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [8] - SAF |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Alkaline Phosphatase (ALP) at Specified Time Point [9] | ||||||||||||||||||
End point description |
Changes in total-ALP from the last value collected prior to the first injection of study drug in each cycle was determined. Median and range (minimum-maximum) were reported. ‘n’= evaluable subjects for the respective category.
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End point type |
Primary
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End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
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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: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [10] - SAF |
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) of Any Grade Leading to Drug Discontinuation During Treatment and Follow up Period [11] | ||||||||||
End point description |
An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events that started or worsened after the start of study drug administration up to 30 days after last drug administration during the follow-up period. Drug discontinuation occurred due to any AE were reported in this endpoint.
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End point type |
Primary
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End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
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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: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [12] - SAF |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Alanine Aminotransferase (ALT) at Specified Time Point [13] | ||||||||||||||||||
End point description |
Changes in total-ALT from the last value collected prior to the first injection of study drug in each cycle was determined. Median and range (minimum-maximum) were reported. ‘n’= evaluable subjects for the respective category.
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End point type |
Primary
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End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
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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: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [14] - SAF |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Aspartate Aminotransferase (AST) at Specified Time Point [15] | ||||||||||||||||||
End point description |
Changes in total-AST from the last value collected prior to the first injection of study drug in each cycle was determined. Median and range (minimum-maximum) were reported. ‘n’= evaluable subjects for the respective category.
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End point type |
Primary
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End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
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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: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [16] - SAF |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Basophils at Specified Time Point [17] | ||||||||||||||||||
End point description |
Changes in total-basophils count from the last value collected prior to the first injection of study drug in each cycle was determined. Median and range (minimum-maximum) were reported. ‘n’= evaluable subjects for the respective category.
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End point type |
Primary
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End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
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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: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [18] - SAF |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Bilirubin at Specified Time Point [19] | ||||||||||||||||||
End point description |
Changes in total-bilirubin count from the last value collected prior to the first injection of study drug in each cycle was determined. Median and range (minimum-maximum) were reported.
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End point type |
Primary
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End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
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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: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [20] - SAF |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Serum Creatinine at Specified Time Point [21] | ||||||||||||||||||
End point description |
Changes in total-serum creatinine count from the last value collected prior to the first injection of study drug in each cycle was determined. Median and range (minimum-maximum) were reported. ‘n’= evaluable subjects for the respective category.
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End point type |
Primary
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End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
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Notes [21] - 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: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [22] - SAF |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Eosinophils at Specified Time Point [23] | ||||||||||||||||||
End point description |
Changes in total-eosinophils count from the last value collected prior to the first injection of study drug in each cycle was determined. Median and range (minimum-maximum) were reported. ‘n’= evaluable subjects for the respective category.
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End point type |
Primary
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End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
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Notes [23] - 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: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [24] - SAF |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Hematocrit at Specified Time Point [25] | ||||||||||||||||||
End point description |
Changes in total-hematocrit count from the last value collected prior to the first injection of study drug in each cycle was determined. Median and range (minimum-maximum) were reported. ‘n’= evaluable subjects for the respective category.
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End point type |
Primary
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End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
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Notes [25] - 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: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [26] - SAF |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Hemoglobin at Specified Time Point [27] | ||||||||||||||||||
End point description |
Changes in total-hemoglobin count from the last value collected prior to the first injection of study drug in each cycle was determined. Median and range (minimum-maximum) were reported. ‘n’= evaluable subjects for the respective category.
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End point type |
Primary
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End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
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Notes [27] - 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: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [28] - SAF |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Lymphocytes at Specified Time Point [29] | ||||||||||||||||||
End point description |
Changes in total-lymphocytes count from the last value collected prior to the first injection of study drug in each cycle was determined. Median and range (minimum-maximum) were reported. ‘n’= evaluable subjects for the respective category.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
|
||||||||||||||||||
Notes [29] - 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: Descriptive statistics were done, no inferential statistical analyses were performed. |
|||||||||||||||||||
|
|||||||||||||||||||
Notes [30] - SAF |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Change from Baseline in Monocytes at Specified Time Point [31] | ||||||||||||||||||
End point description |
Changes in total-monocytes count from the last value collected prior to the first injection of study drug in each cycle was determined. Median and range (minimum-maximum) were reported.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
|
||||||||||||||||||
Notes [31] - 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: Descriptive statistics were done, no inferential statistical analyses were performed. |
|||||||||||||||||||
|
|||||||||||||||||||
Notes [32] - SAF |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Change from Baseline in Neutrophils at Specified Time Point [33] | ||||||||||||||||||
End point description |
Changes in total-neutrophils count from the last value collected prior to the first injection of study drug in each cycle was determined. Median and range (minimum-maximum) were reported.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
|
||||||||||||||||||
Notes [33] - 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: Descriptive statistics were done, no inferential statistical analyses were performed. |
|||||||||||||||||||
|
|||||||||||||||||||
Notes [34] - SAF |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Change from Baseline in Platelets at Specified Time Point [35] | ||||||||||||||||||
End point description |
Changes in total-platelets count from the last value collected prior to the first injection of study drug in each cycle was determined. Median and range (minimum-maximum) were reported.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
|
||||||||||||||||||
Notes [35] - 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: Descriptive statistics were done, no inferential statistical analyses were performed. |
|||||||||||||||||||
|
|||||||||||||||||||
Notes [36] - SAF |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Change from Baseline in Prostate Specific Antigen (PSA) at Specified Time Point [37] | ||||||||||||||||||
End point description |
Changes in PSA level from the last value collected prior to the first injection of study drug in each cycle was determined. Median and range (minimum-maximum) were reported.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
|
||||||||||||||||||
Notes [37] - 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: Descriptive statistics were done, no inferential statistical analyses were performed. |
|||||||||||||||||||
|
|||||||||||||||||||
Notes [38] - SAF |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Change from Baseline in Erythrocytes at Specified Time Point [39] | ||||||||||||||||||
End point description |
Changes in total-erythrocytes count from the last value collected prior to the first injection of study drug in each cycle was determined. Median and range (minimum-maximum) were reported.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
|
||||||||||||||||||
Notes [39] - 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: Descriptive statistics were done, no inferential statistical analyses were performed. |
|||||||||||||||||||
|
|||||||||||||||||||
Notes [40] - SAF |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Change from Baseline in Sodium at Specified Time Point [41] | ||||||||||||||||||
End point description |
Changes in sodium level from the last value collected prior to the first injection of study drug in each cycle was determined. Median and range (minimum-maximum) were reported.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
|
||||||||||||||||||
Notes [41] - 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: Descriptive statistics were done, no inferential statistical analyses were performed. |
|||||||||||||||||||
|
|||||||||||||||||||
Notes [42] - SAF |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Change from Baseline in Leukocytes at Specified Time Point [43] | ||||||||||||||||||
End point description |
Changes in total-leukocytes count from the last value collected prior to the first injection of study drug in each cycle was determined. Median and range (minimum-maximum) were reported.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
|
||||||||||||||||||
Notes [43] - 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: Descriptive statistics were done, no inferential statistical analyses were performed. |
|||||||||||||||||||
|
|||||||||||||||||||
Notes [44] - SAF |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||
End point title |
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Treatment Emergent Serious Adverse Events (TESAEs) – During Follow up Period [45] | ||||||||||
End point description |
An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events that started or worsened after the start of study drug administration up to 30 days after last drug administration during the follow-up period. An serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly and another med important serious event as judged by the investigator. In the below table data was provided for the follow-up period.
|
||||||||||
End point type |
Primary
|
||||||||||
End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
|
||||||||||
Notes [45] - 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: Descriptive statistics were done, no inferential statistical analyses were performed. |
|||||||||||
|
|||||||||||
Notes [46] - SAF |
|||||||||||
No statistical analyses for this end point |
|
|||||||||||
End point title |
Number of Subjects With Treatment Emergent Adverse Events (TEAE) Treatment Emergent Serious Adverse Events (TESAE) – During Treatment Period [47] | ||||||||||
End point description |
An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly and another med important serious event as judged by the investigator. Treatment-emergent adverse events were defined as adverse events that started or worsened after the start of study drug administration up to 30 days after last drug administration during the treatment period.
|
||||||||||
End point type |
Primary
|
||||||||||
End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
|
||||||||||
Notes [47] - 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: Descriptive statistics were done, no inferential statistical analyses were performed. |
|||||||||||
|
|||||||||||
Notes [48] - SAF |
|||||||||||
No statistical analyses for this end point |
|
|||||||
End point title |
Number of Subjects With Secondary Malignancies [49] | ||||||
End point description |
Number of subjects with secondary or additional malignancies including acute myeloid leukemia, and hematological conditions such as myelodysplastic syndrome, aplastic anemia, myelofibrosis et cetera (etc), as well as information on additional anticancer treatments received were analyzed.
|
||||||
End point type |
Primary
|
||||||
End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
|
||||||
Notes [49] - 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: Descriptive statistics were done, no inferential statistical analyses were performed. |
|||||||
|
|||||||
Notes [50] - SAF |
|||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in BPI-SF Questionnaire (Brief Pain Inventory-Short Form) Score | ||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
BPI-SF was a 15-item, self-administered, clinically valid, reliable and responsive measure developed to assess severity of pain related to cancer. The worst pain in last 24 hours was scored by averaging the scores. The pain severity score was established by the developers of the instrument and it is the average of the four pain questions (worst pain in last 24 hours, least pain in last 24 hours, average pain, and pain experienced right now). The pain interference questionnaire were based on the average of seven question designed to assess the degree of pain which interferes common feeling and function (general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Scores ranges from 0-10, higher score indicates a higher level of pain/interference. In the below table ‘n’=evaluable subjects whose last value were collected prior to the first injection of radium-223 dichloride; EOT=End of treatment; FU=Follow-up.
|
||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From start of study drug administration up to 30 days of last study drug administration
|
||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [51] - SAF |
|||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse event data were collected From start of study drug administration up to 30 days of last study drug administration
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
|
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Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Radium-223 DiChloride 50 kBq/kg
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Reporting group description |
Subjects received Radium-223 dichloride, at a dose of 50 kBq/kg body weight, based on NIST 2010 standardization, at every 4 weeks up to 6 cycles. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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30 Oct 2012 |
-Changed Radium-223 Chloride and Ra223 Cl to Radium-223 Dichloride and radium-223 dichloride respectively, following receipt of the official United States Adopted Name for the product
-Clarification on the inclusion/exclusion criteria particularly the definition of progressive disease and acceptable diagnostic procedures
-Inclusion of subjects with history of spinal cord compression who have completely recovered
-Clarification regarding inclusion of subjects who received prior radiotherapy
-Inclusion of allowed concomitant treatments, abiraterone and denosumab
-Provided additional guidance on the collection of safety data
-Provided additional guidance on safety protection during dose preparation
-Extension of the screening period from 21 days to 28 days and extension of the timeframe for laboratory assessments from 24 hours to within 72 hours
-Substituted follow-up visits with phone call follow-ups for deteriorating subjects
-Addition of long-term follow-up section
-Clarification regarding AEs that lead to discontinuation
-Clarification on AEs/SAEs documentation and reporting
-In addition, administrative changes were made, corrected Bone Pain Index terminology to Brief Pain Inventory, and minor editorial changes and clarifications |
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02 Apr 2013 |
-Exclusion from the active follow up of subjects who receive further anticancer treatment including radium 223 dichloride administered either within a clinical study or as commercially available drug, and to follow them up for survival status only.
-Addition of a time window of 3 months for bone scan due to differences in the standard of care in the involved sites
-Provide clarifications and guidance on:
a. Washout period of 4 weeks applicable for all prior anticancer therapies
b. Anticancer therapies allowed during the study treatment period
c. Guidance on when rescreening is allowed
d. Definition of end of screening period
-Reconfirmation of eligibility
-Active follow-up Sections were updated to allow collection by means of phone follow-up of long-term safety data in all study subjects, including those who are no longer fit to travel to the investigational site due to deteriorating conditions.
-In addition, administrative changes were made, including the change of the Sponsor’s medical expert as well as minor editorial changes and abbreviations were added. |
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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. | |||
Occurrence of "±” in relation with geometric CV is auto-generated. Decimal places were automatically truncated if last decimal equals zero. ‘99999’ indicates that data were not calculated. |