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Evaluation of Effectiveness of Two Dosing Regimens of Fostamatinib Compared to Placebo in Patients With Rheumatoid Arthritis (RA) Who Are Taking Disease Modifying Anti-rheumatic Drug (DMARD) But Not Responding. (OSKIRA - 2)

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ClinicalTrials.gov Identifier: NCT01197534
Recruitment Status : Completed
First Posted : September 9, 2010
Results First Posted : April 17, 2014
Last Update Posted : April 17, 2014
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: fostamatinib
Drug: placebo, fostamatinib
Enrollment 913
Recruitment Details A total of 1632 patients were enrolled: 308, 300 & 305 were randomised to Groups A, B & C, respectively (308, 298 & 302 received at least 1 dose of investigational product).
Pre-assignment Details A total of 719 patients failed screening.
Arm/Group Title FOSTA 100 MG BID PO FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Hide Arm/Group Description Dosing Group A Dosing Group B Dosing Group C
Period Title: Overall Study
Started 308 [1] 298 [1] 302 [1]
Randomised But Did Not Receive Treatment 0 2 [2] 3 [3]
Completed 174 [4] 168 [4] 129 [4]
Not Completed 134 130 173
Reason Not Completed
Not reported             16             10             16
Enrolment in long term extension             57             66             119
Severe non-compliance to protocol             3             4             1
Lack of therapeutic response             9             4             9
Dev. of study specific discont. criteria             13             6             2
Lost to Follow-up             1             4             2
Adverse Event             35             36             24
[1]
Patients who received treatment
[2]
Adverse event / Other
[3]
Eligibility criteria not fulfilled / Severe non-compliance to protocol
[4]
Number of patients who completed treatment includes patients who had a dose reduction.
Arm/Group Title FOSTA 100 MG BID PO FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO Total
Hide Arm/Group Description Dosing Group A Dosing Group B Dosing Group C Total of all reporting groups
Overall Number of Baseline Participants 308 298 302 908
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 308 participants 298 participants 302 participants 908 participants
53  (12.3) 54  (11.6) 53  (11.8) 53  (11.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 308 participants 298 participants 302 participants 908 participants
Female
245
  79.5%
245
  82.2%
252
  83.4%
742
  81.7%
Male
63
  20.5%
53
  17.8%
50
  16.6%
166
  18.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 308 participants 298 participants 302 participants 908 participants
White 254 235 241 730
Black or African American 6 15 8 29
Asian 16 13 20 49
American Indian or Alaska Native 0 2 1 3
Indian or Pakistani 25 31 28 84
Other 7 2 4 13
1.Primary Outcome
Title Proportion of Patients With ACR20 at Week 24, Comparison Between Fostamatinib and Placebo
Hide Description ACR20: American College of Rheumatology 20% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
Arm/Group Title FOSTA 100 MG BID PO FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Hide Arm/Group Description:
Dosing Group A
Dosing Group B
Dosing Group C
Overall Number of Participants Analyzed 308 298 302
Measure Type: Number
Unit of Measure: Percentage of responders
39.6 39.6 24.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID PO, FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of DMARD or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Week 24
Method Mantel Haenszel
Comments Treatment difference in proportion of responders using a Mantel Haenszel approach stratified by background use of DMARD and pooled country.
Method of Estimation Estimation Parameter Weighted difference in proportions
Estimated Value 0.15
Confidence Interval (2-Sided) 95%
0.08 to 0.22
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Proportion of Patients Achieving ACR20, Comparison Between Fostamatinib and Placebo at Week 1
Hide Description ACR20: American College of Rheumatology 20% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, CRP = C-reactive protein, DMARD = Disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.
Time Frame 1 week
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
Arm/Group Title FOSTA 100 MG BID PO (Combined) PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Hide Arm/Group Description:
Dosing Group A and B combined
Dosing Group C
Overall Number of Participants Analyzed 606 302
Measure Type: Number
Unit of Measure: Percentage of responders
16.0 8.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID PO (Combined), PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of DMARD or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mantel Haenszel
Comments 95% confidence intervals and p-values are calculated using a Mantel Haenszel approach stratified by background use of DMARD and pooled country.
Method of Estimation Estimation Parameter Weighted difference in proportion
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
0.04 to 0.12
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Proportion of Patients Achieving ACR50, Comparison Between Fostamatinib and Placebo at Week 24
Hide Description ACR50: American College of Rheumatology 50% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, CRP = C-reactive protein, DMARD = Disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
Arm/Group Title FOSTA 100 MG BID PO FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Hide Arm/Group Description:
Dosing Group A
Dosing Group B
Dosing Group C
Overall Number of Participants Analyzed 308 298 302
Measure Type: Number
Unit of Measure: Percentage of responders
20.8 18.1 8.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of DMARD or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mantel Haenszel
Comments 95% confidence intervals and p-values are calculated using a Mantel Haenszel approach stratified by background use of DMARD and pooled country.
Method of Estimation Estimation Parameter Weighted difference in proportions
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
0.07 to 0.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of DMARD or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mantel Haenszel
Comments 95% confidence intervals and p-values are calculated using a Mantel Haenszel approach stratified by background use of DMARD and pooled country.
Method of Estimation Estimation Parameter Weighted difference in proportions
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
0.05 to 0.15
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Proportion of Patients Achieving ACR70, Comparison Between Fostamatinib and Placebo at Week 24
Hide Description ACR70: American College of Rheumatology 70% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, CRP = C-reactive protein, DMARD = Disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
Arm/Group Title FOSTA 100 MG BID PO FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Hide Arm/Group Description:
Dosing Group A
Dosing Group B
Dosing Group C
Overall Number of Participants Analyzed 308 298 302
Measure Type: Number
Unit of Measure: Percentage of responders
9.1 6.0 2.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of DMARD or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mantel Haenszel
Comments 95% confidence intervals and p-values are calculated using a Mantel Haenszel approach stratified by background use of DMARD and pooled country.
Method of Estimation Estimation Parameter Weighted difference in proportions
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
0.03 to 0.10
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of DMARD or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments [Not Specified]
Method Mantel Haenszel
Comments 95% confidence intervals and p-values are calculated using a Mantel Haenszel approach stratified by background use of DMARD and pooled country.
Method of Estimation Estimation Parameter Weighted difference in proportions
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
0.00 to 0.07
Estimation Comments [Not Specified]
5.Secondary Outcome
Title ACRn - Comparison Between Fostamatinib and Placebo at Week 24
Hide Description ACRn: American College of Rheumatology index of RA improvement, based on smallest percentage improvement in the count of swollen joints (out of 28 joints), count of tender joints (out of 28 joints), or in blood test measures of inflammation (such as CRP) or the physician or patient's own assessments of disease activity, pain and physical function. Scores are reported as a percentage improvement on a scale of -100 to +100, with larger values representing a better clinical outcome. BID = twice daily, CI = confidence interval, CRP = C-reactive protein, DMARD = Disease-modifying anti-rheumatic drug, PO = orally, QD = once a day. Mean refers to change at Week 24.
Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
Arm/Group Title FOSTA 100 MG BID PO FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Hide Arm/Group Description:
Dosing Group A
Dosing Group B
Dosing Group C
Overall Number of Participants Analyzed 308 298 302
Mean (Standard Deviation)
Unit of Measure: Percentage improvement from baseline
20.75  (31.203) 18.31  (28.427) 9.84  (23.219)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of DMARD or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Nominal p-value presented for treatment comparison. Outcome was not formally tested within the predefined multiplicity procedure. As this is a non-parametric test, p-values alone are presented rather than an estimated treatment difference.
Method Van Elteren
Comments P-values are estimated using the Van Elteren test stratified by background use of DMARD and pooled country.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Nominal p-value presented for treatment comparison. Outcome was not formally tested within the predefined multiplicity procedure. As this is a non-parametric test, p-values alone are presented rather than an estimated treatment difference.
Method Van Elteren
Comments P-values are estimated using the Van Elteren test stratified by background use of DMARD and pooled country.
6.Secondary Outcome
Title Proportion of Patients Achieving DAS28-CRP <2.6 at Week 12, Comparison Between Fostamatinib and Placebo
Hide Description DAS28-CRP: Disease Activity Score based on a count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (CRP) and the patient's own assessment. Scores can take any positive value with a lower value indicating a better clinical condition. A DAS28-CRP score of <2.6 is indicative of remission of RA symptoms. BID = twice daily, CRP = C-reactive protein, DMARD = Disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once a day.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
Arm/Group Title FOSTA 100 MG BID PO FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Hide Arm/Group Description:
Dosing Group A
Dosing Group B
Dosing Group C
Overall Number of Participants Analyzed 308 298 302
Measure Type: Number
Unit of Measure: Percentage of responders
17.2 10.7 3.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of DMARD or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments Odds ratio and 95% confidence intervals calculated using Logistic Regression with treatment, background use of DMARD and pooled country as factors.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 7.1
Confidence Interval (2-Sided) 95%
3.42 to 14.80
Estimation Comments An odds ratio >1 indicates a benefit towards fostamatinib.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of DMARD or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments Odds ratio and 95% confidence intervals calculated using Logistic Regression with treatment, background use of DMARD and pooled country as factors.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.0
Confidence Interval (2-Sided) 95%
1.88 to 8.65
Estimation Comments An odds ratio >1 indicates a benefit towards fostamatinib.
7.Secondary Outcome
Title Proportion of Patients Achieving DAS28-CRP <2.6 at Week 24, Comparison Between Fostamatinib and Placebo
Hide Description DAS28-CRP: Disease Activity Score based on a count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (CRP) and the patient's own assessment. Scores can take any positive value with a lower value indicating a better clinical condition. A DAS28-CRP score of <2.6 is indicative of remission of RA symptoms. BID = twice daily, CRP = C-reactive protein, DMARD = Disease-modifying anti-rheumatic drug, OR=odds ratio, PO = orally, QD=once a day.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
Arm/Group Title FOSTA 100 MG BID PO FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Hide Arm/Group Description:
Dosing Group A
Dosing Group B
Dosing Group C
Overall Number of Participants Analyzed 308 298 302
Measure Type: Number
Unit of Measure: Percentage of responders
41.3 12.8 2.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of DMARD or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments Odds ratio and 95% confidence intervals calculated using Logistic Regression with treatment, background use of DMARD and pooled country as factors.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 7.3
Confidence Interval (2-Sided) 95%
3.23 to 16.65
Estimation Comments An odds ratio >1 indicates a benefit towards fostamatinib.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of DMARD or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments Odds ratio and 95% confidence intervals calculated using Logistic Regression with treatment, background use of DMARD and pooled country as factors.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.4
Confidence Interval (2-Sided) 95%
2.81 to 14.71
Estimation Comments An odds ratio >1 indicates a benefit towards fostamatinib.
8.Secondary Outcome
Title Proportion of Patients Achieving DAS28 EULAR Response at Week 24
Hide Description Change in DAS28 was derived for each post baseline scheduled assessment and categorised using the European League Against Rheumatism (EULAR) response criteria. BID = twice daily, DAS28 = Disease Activity Score based on a 28-joint count, DMARD = disease-modifying anti-rheumatic drug, OR=odds ratio, PO = orally, QD = once a day.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
Arm/Group Title FOSTA 100 MG BID PO FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Hide Arm/Group Description:
Dosing Group A
Dosing Group B
Dosing Group C
Overall Number of Participants Analyzed 308 298 302
Measure Type: Number
Unit of Measure: Percentage of responders
No response 42.9 45.3 64.6
Moderate response 33.8 34.9 29.1
Good response 23.4 19.8 6.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of DMARD or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Nominal p-value presented for treatment comparison. Outcome was not formally tested within the predefined multiplicity procedure.
Method Proportional odds model
Comments No Response, moderate response and good response are included in the model, with treatment, background use of DMARD and pooled country as factors.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.84
Confidence Interval (2-Sided) 95%
2.06 to 3.91
Estimation Comments An odds ratio > 1 indicates a benefit towards fostamatinib.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of DMARD or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Nominal p-value presented for treatment comparison. Outcome was not formally tested within the predefined multiplicity procedure.
Method Proportional odds model
Comments No Response, moderate response and good response are included in the model, with treatment, background use of DMARD and pooled country as factors.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.44
Confidence Interval (2-Sided) 95%
1.77 to 3.37
Estimation Comments An odds ratio > 1 indicates a benefit towards fostamatinib.
9.Secondary Outcome
Title HAQ-DI Response - Comparison of the Change(>=0.22) From Baseline Between Fostamatinib and Placebo at Week 24
Hide Description HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is then calculated by summing the category scores from 8 sub-categories (ie, scores for patient ability in dressing and grooming, rising, eating, walking, hygiene, reach, grip and common daily activities) and dividing by the number of categories completed. The HAQ-DI score takes values between 0 and 3, with a higher score indicating greater disability. The HAQ-DI response is a reduction from baseline in HAQ-DI score greater than or equal to the minimally important difference (0.22). BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once a day.
Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
Arm/Group Title FOSTA 100 MG BID PO FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Hide Arm/Group Description:
Dosing Group A
Dosing Group B
Dosing Group C
Overall Number of Participants Analyzed 308 298 302
Measure Type: Number
Unit of Measure: Percentage of responders
46.1 42.3 26.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of DMARD or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments Odds ratio and 95% confidence intervals calculated using Logistic Regression with treatment, background use of DMARD and pooled country as factors.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.4
Confidence Interval (2-Sided) 95%
1.73 to 3.46
Estimation Comments An odds ratio >1 indicates a benefit towards fostamatinib.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments Odds ratio and 95% confidence intervals calculated using Logistic Regression with treatment, background use of DMARD and pooled country as factors.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.1
Confidence Interval (2-Sided) 95%
1.46 to 2.94
Estimation Comments An odds ratio >1 indicates a benefit towards fostamatinib.
10.Secondary Outcome
Title Change From Baseline to Week 24 in mTSS, Comparison Between Fostamatinib and Placebo
Hide Description mTSS: modified total sharp score, a measure of structural progression based upon X-rays. Hand and foot joints are scored for erosions and joint space narrowing and the results summed to give a value between 0 and 448. A higher value represents more serious progression of the disease. After disregarding ineligible records, patients with 2 or more non-missing values have had missing data imputed via linear extrapolation/interpolation methods. Patients with only 1 result were excluded from the analysis. ANCOVA = analysis of covariance, BID = twice daily, IP = investigational product, QD = once a day.
Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set includes patients who received at least 1 dose of IP. Patients were analysed by randomised treatment in accordance with the intention to treat principle. Measurements at 2 timepoints are required for a patient to be included in the analysis; therefore patients with only 1 result have been excluded from the analysis population.
Arm/Group Title FOSTA 100 MG BID PO FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Hide Arm/Group Description:
Dosing Group A
Dosing Group B
Dosing Group C
Overall Number of Participants Analyzed 308 298 302
Mean (Standard Deviation)
Unit of Measure: Units on a scale
0.64  (3.130) 0.37  (3.095) 1.16  (5.849)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments This analysis is performed using an ANCOVA model on the ranks of the change from baseline, by pooled country and background use of DMARD, including a term for the ranks of the baseline score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.904
Comments As this is a non-parametric test, p-values alone are presented rather than an estimated treatment difference.
Method Cochran-Mantel-Haenszel
Comments Residuals from ANCOVA are analysed using a Cochran-Mantel-Haenszel approach, adjusting for the effects of pooled country and background use of DMARD.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments This analysis is performed using an ANCOVA model on the ranks of the change from baseline, by pooled country and background use of DMARD, including a term for the ranks of the baseline score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.342
Comments As this is a non-parametric test, p-values alone are presented rather than an estimated treatment difference.
Method Cochran-Mantel-Haenszel
Comments Residuals from ANCOVA are analysed using a Cochran-Mantel-Haenszel approach, adjusting for the effects of pooled country and background use of DMARD.
11.Secondary Outcome
Title SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Placebo at Week 24
Hide Description SF-36: 36-item Short Form Health Survey, a measure of health related quality of life. Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional and Mental Health) are derived and normalised to a scale of 0-100. Physical and mental component scores (PCS and MCS) are derived by multiplying each of these 8 scores by a constant, summing them and standardising against a population with mean of 50+/- 10. Higher scores represent a better quality of life. Mean changes from baseline score are presented as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease modifying antirheumatic drugs, PO = orally, QD = once a day.
Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
Arm/Group Title FOSTA 100 MG BID PO FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Hide Arm/Group Description:
Dosing Group A
Dosing Group B
Dosing Group C
Overall Number of Participants Analyzed 308 298 302
Mean (Standard Deviation)
Unit of Measure: Units on a scale
5  (7.2) 4  (6.6) 2  (5.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of DMARD or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Nominal p-value presented for treatment comparison. Outcome was not formally tested within the predefined multiplicity procedure.
Method ANCOVA
Comments Including terms for baseline as continuous covariate and treatment, background use of DMARD and pooled country as factors.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 2.47
Confidence Interval (2-Sided) 95%
1.47 to 3.48
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of DMARD or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments Nominal p-value presented for treatment comparison. Outcome was not formally tested within the predefined multiplicity procedure.
Method ANCOVA
Comments Including terms for baseline as continuous covariate and treatment, background use of DMARD and pooled country as factors.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 1.64
Confidence Interval (2-Sided) 95%
0.63 to 2.65
Estimation Comments [Not Specified]
12.Secondary Outcome
Title SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Placebo at Week 24
Hide Description SF-36: 36-item Short Form Health Survey, a measure of health related quality of life. Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional and Mental Health) are derived and normalised to a scale of 0-100. Physical and mental component scores (PCS and MCS) are derived by multiplying each of these 8 scores by a constant, summing them and standardising against a population with mean of 50+/- 10. Higher scores represent a better quality of life. Mean changes from baseline score are presented as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease modifying antirheumatic drugs, PO = orally, QD = once a day.
Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.
Arm/Group Title FOSTA 100 MG BID PO FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Hide Arm/Group Description:
Dosing Group A
Dosing Group B
Dosing Group C
Overall Number of Participants Analyzed 308 298 302
Mean (Standard Deviation)
Unit of Measure: Units on a scale
3  (7.5) 3  (8.4) 1  (6.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of DMARD or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Nominal p-value presented for treatment comparison. Outcome was not formally tested within the predefined multiplicity procedure.
Method ANCOVA
Comments Including terms for baseline as continuous covariate and treatment, background use of DMARD and pooled country as factors.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 2.09
Confidence Interval (2-Sided) 95%
0.97 to 3.20
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO, PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO
Comments Non-responder imputation has been applied following premature withdrawal, or increased dose of DMARD or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Nominal p-value presented for treatment comparison. Outcome was not formally tested within the predefined multiplicity procedure.
Method ANCOVA
Comments Including terms for baseline as continuous covariate and treatment, background use of DMARD and pooled country as factors.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 1.96
Confidence Interval (2-Sided) 95%
0.83 to 3.08
Estimation Comments [Not Specified]
Time Frame 52 weeks
Adverse Event Reporting Description For placebo treated patients time frame includes both placebo (24 weeks) and fostamatinib (28 weeks) treatment. 11 SAEs occurred during the 24 week placebo treated period.
 
Arm/Group Title FOSTA 100 MG BID FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PLACEBO (24 WKS) THEN FOSTA 100 MG BID - FOSTA Period PLACEBO (24 WKS) THEN FOSTA 100 MG BID - Placebo Period
Hide Arm/Group Description Dosing Group A Dosing Group B Dosing Group C [Not Specified]
All-Cause Mortality
FOSTA 100 MG BID FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PLACEBO (24 WKS) THEN FOSTA 100 MG BID - FOSTA Period PLACEBO (24 WKS) THEN FOSTA 100 MG BID - Placebo Period
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Hide Serious Adverse Events
FOSTA 100 MG BID FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PLACEBO (24 WKS) THEN FOSTA 100 MG BID - FOSTA Period PLACEBO (24 WKS) THEN FOSTA 100 MG BID - Placebo Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   30/308 (9.74%)      25/298 (8.39%)      10/302 (3.31%)      10/302 (3.31%)    
Blood and lymphatic system disorders         
LEUKOPENIA  1  0/308 (0.00%)  0 0/298 (0.00%)  0 1/302 (0.33%)  1 0/302 (0.00%)  0
Cardiac disorders         
ANGINA PECTORIS  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
ATRIAL FIBRILLATION  1  2/308 (0.65%)  2 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
ATRIAL FLUTTER  1  0/308 (0.00%)  0 0/298 (0.00%)  0 1/302 (0.33%)  1 0/302 (0.00%)  0
CARDIAC ARREST  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
LEFT VENTRICULAR FAILURE  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
MYOCARDIAL INFARCTION  1  1/308 (0.32%)  1 0/298 (0.00%)  0 1/302 (0.33%)  1 0/302 (0.00%)  0
VENTRICULAR FIBRILLATION  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
Eye disorders         
MACULAR HOLE  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
Gastrointestinal disorders         
COLITIS  1  1/308 (0.32%)  1 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
COLITIS ULCERATIVE  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
DIARRHOEA  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
GASTRITIS  1  2/308 (0.65%)  2 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
GASTRITIS EROSIVE  1  0/308 (0.00%)  0 0/298 (0.00%)  0 1/302 (0.33%)  1 0/302 (0.00%)  0
GASTRITIS HAEMORRHAGIC  1  0/308 (0.00%)  0 0/298 (0.00%)  0 1/302 (0.33%)  1 0/302 (0.00%)  0
LOWER GASTROINTESTINAL HAEMORRHAGE  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
OESOPHAGITIS ULCERATIVE  1  0/308 (0.00%)  0 0/298 (0.00%)  0 1/302 (0.33%)  1 0/302 (0.00%)  0
PANCREATITIS CHRONIC  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
STOMATITIS  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
VOMITING  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
General disorders         
NON-CARDIAC CHEST PAIN  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
Hepatobiliary disorders         
CHOLECYSTITIS ACUTE  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
CHOLELITHIASIS  1  0/308 (0.00%)  0 2/298 (0.67%)  2 0/302 (0.00%)  0 0/302 (0.00%)  0
HEPATOCELLULAR INJURY  1  0/308 (0.00%)  0 0/298 (0.00%)  0 0/302 (0.00%)  0 1/302 (0.33%)  1
NON-ALCOHOLIC STEATOHEPATITIS  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
Infections and infestations         
ACUTE SINUSITIS  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
ARTHRITIS BACTERIAL  1  0/308 (0.00%)  0 0/298 (0.00%)  0 1/302 (0.33%)  1 0/302 (0.00%)  0
ATYPICAL PNEUMONIA  1  0/308 (0.00%)  0 0/298 (0.00%)  0 1/302 (0.33%)  1 0/302 (0.00%)  0
BRONCHITIS  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
BRONCHITIS BACTERIAL  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
BRONCHITIS VIRAL  1  0/308 (0.00%)  0 0/298 (0.00%)  0 1/302 (0.33%)  1 0/302 (0.00%)  0
BURSITIS INFECTIVE  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
DENGUE FEVER  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
DEVICE RELATED INFECTION  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
ENTEROCOLITIS BACTERIAL  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
ESCHERICHIA INFECTION  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
GASTROENTERITIS  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
GASTROENTERITIS BACTERIAL  1  1/308 (0.32%)  1 1/298 (0.34%)  1 1/302 (0.33%)  1 0/302 (0.00%)  0
GASTROINTESTINAL BACTERIAL INFECTION  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
HERPES SIMPLEX  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
INFLUENZA  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
PNEUMOCOCCAL SEPSIS  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
PNEUMONIA  1  0/308 (0.00%)  0 0/298 (0.00%)  0 0/302 (0.00%)  0 1/302 (0.33%)  1
PNEUMONIA STREPTOCOCCAL  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
URINARY TRACT INFECTION BACTERIAL  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
Injury, poisoning and procedural complications         
CLAVICLE FRACTURE  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
FEMORAL NECK FRACTURE  1  0/308 (0.00%)  0 0/298 (0.00%)  0 1/302 (0.33%)  1 0/302 (0.00%)  0
HIP FRACTURE  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
HUMERUS FRACTURE  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
OVERDOSE  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
ULNA FRACTURE  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
Investigations         
ALANINE AMINOTRANSFERASE INCREASED  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
ASPARTATE AMINOTRANSFERASE INCREASED  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
BLOOD CREATINE PHOSPHOKINASE INCREASED  1  0/308 (0.00%)  0 0/298 (0.00%)  0 0/302 (0.00%)  0 1/302 (0.33%)  1
Metabolism and nutrition disorders         
HYPOCALCAEMIA  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
HYPOKALAEMIA  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
OBESITY  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
Musculoskeletal and connective tissue disorders         
MYOSITIS  1  0/308 (0.00%)  0 0/298 (0.00%)  0 0/302 (0.00%)  0 1/302 (0.33%)  1
OSTEOARTHRITIS  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
PATHOLOGICAL FRACTURE  1  0/308 (0.00%)  0 0/298 (0.00%)  0 1/302 (0.33%)  1 0/302 (0.00%)  0
RHEUMATOID ARTHRITIS  1  1/308 (0.32%)  1 2/298 (0.67%)  2 0/302 (0.00%)  0 2/302 (0.66%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
BONE NEOPLASM MALIGNANT  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
METASTASES TO CENTRAL NERVOUS SYSTEM  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
METASTATIC BRONCHIAL CARCINOMA  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
PARATHYROID TUMOUR BENIGN  1  0/308 (0.00%)  0 0/298 (0.00%)  0 0/302 (0.00%)  0 1/302 (0.33%)  1
RENAL ONCOCYTOMA  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
SQUAMOUS CELL CARCINOMA OF SKIN  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
Nervous system disorders         
CAROTID ARTERY STENOSIS  1  0/308 (0.00%)  0 0/298 (0.00%)  0 0/302 (0.00%)  0 1/302 (0.33%)  1
CONVULSION  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
LUMBAR RADICULOPATHY  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
SYNCOPE  1  1/308 (0.32%)  1 1/298 (0.34%)  1 0/302 (0.00%)  0 1/302 (0.33%)  1
Psychiatric disorders         
ANXIETY  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
Renal and urinary disorders         
RENAL FAILURE ACUTE  1  1/308 (0.32%)  1 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
URINARY RETENTION  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
Reproductive system and breast disorders         
ENDOMETRIOSIS  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
MENORRHAGIA  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
UTERINE HAEMORRHAGE  1  0/308 (0.00%)  0 0/298 (0.00%)  0 0/302 (0.00%)  0 1/302 (0.33%)  1
UTERINE POLYP  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
ACUTE RESPIRATORY DISTRESS SYNDROME  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 0/302 (0.00%)  0
ALLERGIC BRONCHITIS  1  0/308 (0.00%)  0 0/298 (0.00%)  0 1/302 (0.33%)  1 0/302 (0.00%)  0
ASTHMA  1  1/308 (0.32%)  1 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
PULMONARY EMBOLISM  1  1/308 (0.32%)  1 0/298 (0.00%)  0 0/302 (0.00%)  0 1/302 (0.33%)  1
PULMONARY TOXICITY  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
RESPIRATORY FAILURE  1  1/308 (0.32%)  1 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
Vascular disorders         
DEEP VEIN THROMBOSIS  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
MALIGNANT HYPERTENSION  1  0/308 (0.00%)  0 1/298 (0.34%)  1 0/302 (0.00%)  0 0/302 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
FOSTA 100 MG BID FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PLACEBO (24 WKS) THEN FOSTA 100 MG BID - FOSTA Period PLACEBO (24 WKS) THEN FOSTA 100 MG BID - Placebo Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   170/308 (55.19%)      152/298 (51.01%)      42/302 (13.91%)      77/302 (25.50%)    
Gastrointestinal disorders         
DIARRHOEA  1  44/308 (14.29%)  44 47/298 (15.77%)  47 15/302 (4.97%)  15 13/302 (4.30%)  13
NAUSEA  1  20/308 (6.49%)  20 17/298 (5.70%)  17 5/302 (1.66%)  5 7/302 (2.32%)  7
Infections and infestations         
NASOPHARYNGITIS  1  37/308 (12.01%)  37 29/298 (9.73%)  29 2/302 (0.66%)  2 16/302 (5.30%)  16
Investigations         
ALANINE AMINOTRANSFERASE INCREASED  1  21/308 (6.82%)  21 14/298 (4.70%)  14 2/302 (0.66%)  2 4/302 (1.32%)  4
ASPARTATE AMINOTRANSFERASE INCREASED  1  17/308 (5.52%)  17 13/298 (4.36%)  13 3/302 (0.99%)  3 4/302 (1.32%)  4
BLOOD PRESSURE INCREASED  1  15/308 (4.87%)  15 15/298 (5.03%)  15 1/302 (0.33%)  1 10/302 (3.31%)  10
Musculoskeletal and connective tissue disorders         
RHEUMATOID ARTHRITIS  1  19/308 (6.17%)  19 23/298 (7.72%)  23 1/302 (0.33%)  1 10/302 (3.31%)  10
Nervous system disorders         
HEADACHE  1  19/308 (6.17%)  19 12/298 (4.03%)  12 5/302 (1.66%)  5 9/302 (2.98%)  9
Vascular disorders         
HYPERTENSION  1  68/308 (22.08%)  68 55/298 (18.46%)  55 17/302 (5.63%)  17 16/302 (5.30%)  16
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dave Goldstraw
Organization: AstraZeneca Pharmaceuticals
Phone: +44 (0)1625 512415
EMail: dave.goldstraw@astrazeneca.com
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01197534    
Other Study ID Numbers: D4300C00002
2010-020744-35 ( EudraCT Number )
First Submitted: September 8, 2010
First Posted: September 9, 2010
Results First Submitted: November 22, 2013
Results First Posted: April 17, 2014
Last Update Posted: April 17, 2014