Clinical Trial Results:
A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Study of Fostamatinib Disodium in the Treatment of Persistent/Chronic Immune Thrombocytopenic Purpura
Summary
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EudraCT number |
2013-005452-15 |
Trial protocol |
GB IT HU NL DK |
Global end of trial date |
21 Apr 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Apr 2021
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First version publication date |
08 Apr 2021
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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 |
C-935788-047
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02076399 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Rigel Pharmaceuticals, Inc.
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Sponsor organisation address |
1180 Veterans Blvd , South San Francisco, CA, United States, 94080
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Public contact |
Clinical trials, Rigel Pharmaceuticals, Inc., +1 650-624-1100, clinicaltrials@rigel.com
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Scientific contact |
Clinical trials, Rigel Pharmaceuticals, Inc., +1 650-624-1100, clinicaltrials@rigel.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 |
03 Mar 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 Apr 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Apr 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 primary objective of this study was to establish the efficacy of fostamatinib as compared with placebo in achieving a stable platelet response in subjects with persistent/chronic ITP.
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Protection of trial subjects |
The study was conducted in accordance with Good Clinical Practice (GCP) and the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
Placebo OFC tablets were provided to match the appearance of fostamatinib 100 mg and 150 mg OFC tablets. Tablets were administered orally bid using the same escalation scheme as fostamatinib tablets over the course of 24 weeks. | ||
Actual start date of recruitment |
14 Jul 2014
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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 |
Netherlands: 1
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Country: Number of subjects enrolled |
United Kingdom: 25
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Country: Number of subjects enrolled |
Denmark: 2
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Country: Number of subjects enrolled |
Hungary: 3
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Country: Number of subjects enrolled |
Italy: 7
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Country: Number of subjects enrolled |
United States: 20
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Country: Number of subjects enrolled |
Canada: 5
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Country: Number of subjects enrolled |
Australia: 13
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Worldwide total number of subjects |
76
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EEA total number of subjects |
13
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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) |
50
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From 65 to 84 years |
22
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85 years and over |
4
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Recruitment
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Recruitment details |
Approximately 75 subjects were planned to be enrolled at multiple sites. Seventy-six subjects were enrolled, and all enrolled subjects were included in the efficacy and safety analyses. 76 patients were enrolled from July 2014 to April 2016. | |||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 117 subjects were screened, 41 subjects failed screening (primarily they did not meet inclusion criteria or did meet one or more exclusion criterion), and the remaining 76 subjects were randomized; 51 to the fostamatinib group and 25 to the placebo group (ITT population). One subject (1.3% overall) was lost to follow-up. | |||||||||||||||||||||||||||||||||
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 |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Fostamatinib Recipient | |||||||||||||||||||||||||||||||||
Arm description |
Fostamatinib (100 mg PO bid or 150 mg PO bid) | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Fostamatinib Disodium
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Investigational medicinal product code |
R935788
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Other name |
R788, Fostamatinib
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects begin with Fostamatinib Disodium tablet 100 mg PO bid and increase to 150 mg big after week 4 based on platelet count and tolerability.
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Arm title
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Placebo Recipient | |||||||||||||||||||||||||||||||||
Arm description |
Placebo | |||||||||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo tablet PO bid (morning and evening) over the course of 24 weeks
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Baseline characteristics reporting groups
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Reporting group title |
Fostamatinib Recipient
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Reporting group description |
Fostamatinib (100 mg PO bid or 150 mg PO bid) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo Recipient
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Reporting group description |
Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Fostamatinib Recipient
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Reporting group description |
Fostamatinib (100 mg PO bid or 150 mg PO bid) | ||
Reporting group title |
Placebo Recipient
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Reporting group description |
Placebo |
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End point title |
Number of Participants With Stable Platelet Response (Count of ≥50,000/µL on at Least 4 of the Last 6 Scheduled Visits Between Weeks 14 and 24) | |||||||||
End point description |
A stable platelet response by Week 24 defined as a platelet count of at least 50,000/μL on at least 4 of the last 6 scheduled visits between Weeks 14 and 24.
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End point type |
Primary
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End point timeframe |
From Week 14 to Week 24
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Statistical analysis title |
Analysis for primary endpoint | |||||||||
Comparison groups |
Fostamatinib Recipient v Placebo Recipient
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Number of subjects included in analysis |
76
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.0261 | |||||||||
Method |
Fisher exact | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
17.6
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
7.2 | |||||||||
upper limit |
28.1 |
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End point title |
Number of Participants With Platelet Count ≥ 50,000/µL at Week 12 | |||||||||
End point description |
Platelet Count ≥ 50,000/µL at Week 12
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End point type |
Secondary
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End point timeframe |
Week 12
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No statistical analyses for this end point |
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End point title |
Number of Participants With Platelet Count ≥ 50,000/µL at Week 24 | |||||||||
End point description |
Platelet Count ≥ 50,000/µL at Week 24
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End point type |
Secondary
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End point timeframe |
Week 24
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No statistical analyses for this end point |
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End point title |
Platelet Count ≥ 30,000/μL and ≥ 20,000/μL Above Baseline in Subjects With Baseline Platelet Count of <15,000/μL at Week 24. | |||||||||
End point description |
Number of subjects with baseline platelet count <15,000/μL who showed platelet count increase to ≥30,000/μL and ≥20,000/μL from baseline count at Week 24.
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End point type |
Secondary
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End point timeframe |
Baseline to Week 24
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No statistical analyses for this end point |
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End point title |
Mean of the ITP Bleeding Score (IBLS) | ||||||||||||
End point description |
The ITP Bleeding Scale (IBLS) is an immune thrombocytopenic purpura (ITP)-specific bleeding score used to analyze the correlation of clinical and laboratory platelet variables with bleeding. The IBLS comprises of 11 grades from 0 (none) to 2 (marked bleeding) by history over the previous week or by exam; 2 being worse. These 11 grades include: skin by physical exam, oral by physical exam, skin by history, oral by history, epistaxis, gastrointestinal, urinary, gynecological, pulmonary, intracranial hemorrhage, and subconjunctival hemorrhage. After each grade is scored, the mean value for all 11 grades is calculated (lowest score being 0 and highest score being 2) for each subject visit. LOCF method was used to impute any missing data.
The mean of the IBLS scores across visits during the 24-week treatment period was summarized by treatment group using descriptive statistics. A 2-sided, 2-sample t-test was used to test for a difference in means between treatments for this endpoint.
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End point type |
Secondary
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End point timeframe |
Assessed over the 24-week study period
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Statistical analysis title |
Analysis for mean of the ITP bleeding score (IBLS) | ||||||||||||
Comparison groups |
Fostamatinib Recipient v Placebo Recipient
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Number of subjects included in analysis |
76
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.6642 [1] | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||
Point estimate |
-0.01
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.01 | ||||||||||||
upper limit |
0 | ||||||||||||
Notes [1] - P-value from a two-sided two-sample t-test, testing for a difference in means between fostamatinib and placebo. |
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End point title |
Mean of World Health Organization (WHO) Bleeding Scale | ||||||||||||
End point description |
The World Health Organization (WHO) bleeding scale is a standardized grading scale created to measure the severity of bleeding. The scale is a clinical investigator-assessed five-point scale with a score range starting at the lowest 0=No bleeding, 1 = Petechiae, 2=Mild blood loss, 3=Gross blood loss, to the worse 4=Debilitating blood loss. The WHO bleeding scale is scored by history over the previous-week or by exam. After each grade is scored, the mean value is calculated (lowest score being 0 [no bleeding] to the highest score being 4 [debilitating blood loss]) for each visit. LOCF method was used to impute any missing data.
The mean of the WHO bleeding scale across visits during the 24-week treatment period was summarized by treatment group using descriptive statistics. A 2-sided, 2-sample t-test was used to test for a difference in means between treatments for this endpoint.
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End point type |
Secondary
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End point timeframe |
Assessed over the 24-week study period
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Statistical analysis title |
Analysis for mean of WHO Bleeding Scale | ||||||||||||
Comparison groups |
Placebo Recipient v Fostamatinib Recipient
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Number of subjects included in analysis |
76
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.3365 [2] | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||
Point estimate |
0.15
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.2 | ||||||||||||
upper limit |
0.5 | ||||||||||||
Notes [2] - P-value from a two-sided two-sample t-test, testing for a difference in means between fostamatinib and placebo. |
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End point title |
Platelet Count ≥ 30,000/μL and ≥ 20,000/μL Above Baseline in Subjects With Baseline Platelet Count of <15,000/μL at Week 12 | |||||||||
End point description |
Number of subjects with baseline platelet count <15,000/μL who showed platelet count increase to ≥30,000/μL and ≥20,000/μL from baseline count at Week 12.
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End point type |
Secondary
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End point timeframe |
Baseline to Week 12
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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 |
24 Weeks
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.1
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Reporting groups
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Reporting group title |
Fostamatinib Recipient
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Reporting group description |
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Reporting group title |
Placebo Recipient
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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08 Apr 2014 |
Notable changes made between Version 1.0 (16Dec2013) and Version 2.0 (08Apr2014) of the protocol were as follows:
• Inclusion criterion #2 has been revised to clarify the amount of time a subject who is participating in the study must have had a diagnosis of ITP prior to being randomized.
• Exclusion criterion #6 has been revised and #7 has been added in an effort to exclude only subjects at significant risk of deep vein thrombosis (DVT). Thus, the timeframe has been shortened to thrombosis within the 6 months prior to randomization and, for subjects who have a more distant history of DVT, results of a D-dimer test must be within the normal range as a measure of low risk for DVT recurrence.
• Exclusion criterion #8 has been revised to specify that the IBLS score cannot be greater than 2 at any of the 11 sites evaluated.
• D-dimer testing has been added to Screening Visit A (V1). D-dimer test should be performed at the local lab and is only required for subjects who have a history of DVT greater than 6 months prior to randomization.
• An ECG has been added to the Visit 15 assessment for subjects going onto the extension study.
• To assure that subjects sign an ICF prior to any study related procedures, text was added to clarify that subjects who require a washout period greater than 30 days should sign the ICF at a prescreening visit prior to beginning washout.
• When Visit 2 and Visit 3 occur on the same day, following clarification added: Visit 3 SF-36 assessment will be administered after Visit 2 assessments are complete.
• Section 7.4.2: subjects who have a dose reduction due to adverse events may be allowed to have their dose reescalated after the adverse event has resolved following consultation with the Medical Monitor (if clinical benefit of study drug is shown).
• Measurement of IgD and IgE levels has been removed from the protocol.
• The D-dimer test was added to the list of laboratory tests that will be performed during the study. |
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21 Nov 2014 |
Notable changes made between Version 2.0 (08Apr2014) and Version 3.0 (21Nov2014) of the protocol were as follows:
• Inclusion criterion #4 was revised to clarify a typical treatment regimen for ITP (Master protocol and 3 country-specific protocols).
• Exclusion criterion #18 was added to exclude subjects who had major surgery within 28 days prior to randomization.
• Prior ITP treatments were defined as including therapies granted market authorization, and examples of typical prior ITP treatments were provided. Washout requirements were revised to clarify that subjects must discontinue all therapeutic agents other than those allowed as concomitant ITP therapy.
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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. | |||
None reported |