OSKIRA - 2: 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.
Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT01197534
Collaborator
(none)
913
154
3
30
5.9
0.2
Study Details
Study Description
Brief Summary
The purpose of the study is to evaluate the 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. The study will last for 1 year.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Sub-study:
Full title: Optional Genetic Research
Date: 18 June 2010
Version: 1
Objectives: To collect and store, with appropriate consent ,DNA samples for future exploratory research into genes/genetic variation that may influence response (ie, absorption, distribution, metabolism and excretion, safety, tolerability and efficacy) to fostamatinib disodium and/or methotrexate; and/or susceptibility to, progression of and prognosis of RA
Study Design
Study Type:
Interventional
Actual Enrollment
:
913 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
(OSKIRA-2): A Phase III, Multi-centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study of Two Dosing Regimens of Fostamatinib Disodium in Rheumatoid Arthritis Patients With an Inadequate Response to DMARDs
Study Start Date
:
Sep 1, 2010
Actual Primary Completion Date
:
Mar 1, 2013
Actual Study Completion Date
:
Mar 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dosing Regimen A Oral Treatment |
Drug: fostamatinib
fostamatinib 100 mg twice daily
|
| Experimental: Dosing Regimen B Oral Treatment |
Drug: fostamatinib
fostamatinib 100 mg twice daily/ 150 mg once daily
|
| Placebo Comparator: Dosing Regimen C Oral Treatment |
Drug: placebo, fostamatinib
Placebo for 24 weeks followed by fostamatinib 100 mg twice daily.
|
Outcome Measures
Primary Outcome Measures
- Proportion of Patients With ACR20 at Week 24, Comparison Between Fostamatinib and Placebo [24 weeks]
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.
Secondary Outcome Measures
- Proportion of Patients Achieving ACR20, Comparison Between Fostamatinib and Placebo at Week 1 [1 week]
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.
- Proportion of Patients Achieving ACR50, Comparison Between Fostamatinib and Placebo at Week 24 [24 weeks]
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.
- Proportion of Patients Achieving ACR70, Comparison Between Fostamatinib and Placebo at Week 24 [24 weeks]
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.
- ACRn - Comparison Between Fostamatinib and Placebo at Week 24 [Baseline and 24 weeks]
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.
- Proportion of Patients Achieving DAS28-CRP <2.6 at Week 12, Comparison Between Fostamatinib and Placebo [12 weeks]
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.
- Proportion of Patients Achieving DAS28-CRP <2.6 at Week 24, Comparison Between Fostamatinib and Placebo [24 weeks]
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.
- Proportion of Patients Achieving DAS28 EULAR Response at Week 24 [24 weeks]
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.
- HAQ-DI Response - Comparison of the Change(>=0.22) From Baseline Between Fostamatinib and Placebo at Week 24 [Baseline and 24 weeks]
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.
- Change From Baseline to Week 24 in mTSS, Comparison Between Fostamatinib and Placebo [Baseline and 24 weeks]
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.
- SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Placebo at Week 24 [Baseline and 24 weeks]
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.
- SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Placebo at Week 24 [Baseline and 24 weeks]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Active rheumatoid arthritis (RA) diagnosed after the age of 16
-
Treatment with one the following disease modifying anti-rheumatic drug: methotrexate, sulfasalazine, hydroxychloroquine or chloroquine
-
4 or more swollen joints and 4 or more tender/painful joints (from 28 joint count)and either Erythrocyte Sedimentation Rate (ESR) blood result of 28mm/h or more, or C-Reactive Protein (CRP) blood result of 10mg/L or more
-
At least one of the following: documented history of positive rheumatoid factor (blood test), current presence of rheumatoid factor (blood test), radiographic erosion within 12 months prior to study enrolment, presence of serum anti-cyclic citrullinated peptide antibodies (blood test)
Exclusion Criteria:
-
Females who are pregnant or breast feeding
-
Poorly controlled hypertension
-
Liver disease or significant liver function test abnormalities
-
Certain inflammatory conditions (other than rheumatoid arthritis), connective tissue diseases or chronic pain disorders
-
Recent or significant cardiovascular disease
-
Significant active or recent infection including tuberculosis
-
Previous failure to respond to a TNF alpha antagonist, anakinra or previous treatment with other biological agent
-
Severe renal impairment
-
Neutropenia
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Birmingham | Alabama | United States | |
| 2 | Research Site | Glendale | Arizona | United States | |
| 3 | Research Site | Mesa | Arizona | United States | |
| 4 | Research Site | Phoenix | Arizona | United States | |
| 5 | Research Site | Scottsdale | Arizona | United States | |
| 6 | Research Site | Tucson | Arizona | United States | |
| 7 | Research Site | Hot Springs | Arkansas | United States | |
| 8 | Research Site | Huntington Beach | California | United States | |
| 9 | Research Site | Torrance | California | United States | |
| 10 | Research Site | Trumbull | Connecticut | United States | |
| 11 | Research Site | Washington | District of Columbia | United States | |
| 12 | Research Site | Boca Raton | Florida | United States | |
| 13 | Research Site | Brandon | Florida | United States | |
| 14 | Research Site | Jacksonville | Florida | United States | |
| 15 | Research Site | Miami | Florida | United States | |
| 16 | Research Site | Orlando | Florida | United States | |
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| 18 | Research Site | Venice | Florida | United States | |
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| 102 | Research Site | Ramat Gan | Israel | ||
| 103 | Research Site | Ramat-gan | Israel | ||
| 104 | Research Site | Rehovot | Israel | ||
| 105 | Research Site | Tel Aviv | Israel | ||
| 106 | Research Site | Jesi | AN | Italy | |
| 107 | Research Site | Legnano | MI | Italy | |
| 108 | Research Site | Udine | UD | Italy | |
| 109 | Research Site | Varese | VA | Italy | |
| 110 | Research Site | Liepaja | Latvia | ||
| 111 | Research Site | Riga | Latvia | ||
| 112 | Research Site | Valmiera | Latvia | ||
| 113 | Research Site | Kaunas | Lithuania | ||
| 114 | Research Site | Klaipeda | Lithuania | ||
| 115 | Research Site | Siauliai | Lithuania | ||
| 116 | Research Site | Aveiro | Portugal | ||
| 117 | Research Site | Lisboa | Portugal | ||
| 118 | Research Site | Porto | Portugal | ||
| 119 | Research Site | Baia Mare | Romania | ||
| 120 | Research Site | Brailari | Romania | ||
| 121 | Research Site | Bucharest | Romania | ||
| 122 | Research Site | Bucuresti | Romania | ||
| 123 | Research Site | Ploiesti | Romania | ||
| 124 | Research Site | Belgrade | Serbia | ||
| 125 | Research Site | Kragujevac | Serbia | ||
| 126 | Research Site | Niska Banja | Serbia | ||
| 127 | Research Site | Novi Sad | Serbia | ||
| 128 | Research Site | Kempron Park | Gauteng | South Africa | |
| 129 | Research Site | Pretoria | Gauteng | South Africa | |
| 130 | Research Site | Durban | Kz-natal | South Africa | |
| 131 | Research Site | Cape Town | W Cape | South Africa | |
| 132 | Research Site | Port Elizabeth | South Africa | ||
| 133 | Research Site | Stellenbosch | South Africa | ||
| 134 | Research Site | La Laguna (tenerife) | Canarias | Spain | |
| 135 | Research Site | Merida | Extremadura | Spain | |
| 136 | Research Site | Barcelona | Spain | ||
| 137 | Research Site | Getafe | Spain | ||
| 138 | Research Site | Kharkiv | Ukraine | ||
| 139 | Research Site | Kyiv | Ukraine | ||
| 140 | Research Site | Lutsk | Ukraine | ||
| 141 | Research Site | Lviv | Ukraine | ||
| 142 | Research Site | Simferopol | Ukraine | ||
| 143 | Research Site | Vinnytsia | Ukraine | ||
| 144 | Research Site | Zaporizhzhya | Ukraine | ||
| 145 | Research Site | Zaporyzhzhya | Ukraine | ||
| 146 | Research Site | Maidstone | Kent | United Kingdom | |
| 147 | Research Site | Eastbourne | Sussex | United Kingdom | |
| 148 | Research Site | Solihull | West Midlands | United Kingdom | |
| 149 | Research Site | Basingstoke | United Kingdom | ||
| 150 | Research Site | Cambridge | United Kingdom | ||
| 151 | Research Site | London | United Kingdom | ||
| 152 | Research Site | Newcastle Upon Tyne | United Kingdom | ||
| 153 | Research Site | Stoke on Trent | United Kingdom | ||
| 154 | Research Site | Swindon | United Kingdom |
Sponsors and Collaborators
- AstraZeneca
Investigators
- Study Director: Neil MacKillop, MD PhD, AstraZeneca
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01197534
Other Study ID Numbers:
- D4300C00002
- 2010-020744-35
First Posted:
Sep 9, 2010
Last Update Posted:
Apr 17, 2014
Last Verified:
Mar 1, 2014
Keywords provided by AstraZeneca
Additional relevant MeSH terms:
Study Results
Participant Flow
| 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 Detail | 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 |
|---|---|---|---|
| Arm/Group Description | Dosing Group A | Dosing Group B | Dosing Group C |
| Period Title: Overall Study | |||
| STARTED | 308 | 298 | 302 |
| Randomised But Did Not Receive Treatment | 0 | 2 | 3 |
| COMPLETED | 174 | 168 | 129 |
| NOT COMPLETED | 134 | 130 | 173 |
Baseline Characteristics
| 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 |
|---|---|---|---|---|
| Arm/Group Description | Dosing Group A | Dosing Group B | Dosing Group C | Total of all reporting groups |
| Overall Participants | 308 | 298 | 302 | 908 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
53
(12.3)
|
54
(11.6)
|
53
(11.8)
|
53
(11.9)
|
| Sex: Female, Male (Count of 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 (Number) [Number] | ||||
| White |
254
82.5%
|
235
78.9%
|
241
79.8%
|
730
80.4%
|
| Black or African American |
6
1.9%
|
15
5%
|
8
2.6%
|
29
3.2%
|
| Asian |
16
5.2%
|
13
4.4%
|
20
6.6%
|
49
5.4%
|
| American Indian or Alaska Native |
0
0%
|
2
0.7%
|
1
0.3%
|
3
0.3%
|
| Indian or Pakistani |
25
8.1%
|
31
10.4%
|
28
9.3%
|
84
9.3%
|
| Other |
7
2.3%
|
2
0.7%
|
4
1.3%
|
13
1.4%
|
Outcome Measures
| Title | Proportion of Patients With ACR20 at Week 24, Comparison Between Fostamatinib and Placebo |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| Arm/Group Description | Dosing Group A | Dosing Group B | Dosing Group C |
| Measure Participants | 308 | 298 | 302 |
| Number [Percentage of responders] |
39.6
|
39.6
|
24.5
|
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 | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Proportion of Patients Achieving ACR20, Comparison Between Fostamatinib and Placebo at Week 1 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| Arm/Group Description | Dosing Group A and B combined | Dosing Group C |
| Measure Participants | 606 | 302 |
| Number [Percentage of responders] |
16.0
|
8.3
|
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 |
|---|---|---|
| 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 | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Proportion of Patients Achieving ACR50, Comparison Between Fostamatinib and Placebo at Week 24 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| Arm/Group Description | Dosing Group A | Dosing Group B | Dosing Group C |
| Measure Participants | 308 | 298 | 302 |
| Number [Percentage of responders] |
20.8
|
18.1
|
8.3
|
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 | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
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 | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Proportion of Patients Achieving ACR70, Comparison Between Fostamatinib and Placebo at Week 24 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| Arm/Group Description | Dosing Group A | Dosing Group B | Dosing Group C |
| Measure Participants | 308 | 298 | 302 |
| Number [Percentage of responders] |
9.1
|
6.0
|
2.6
|
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 | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
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 | ||
| Statistical Test of Hypothesis | p-Value | 0.033 |
| Comments | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | ACRn - Comparison Between Fostamatinib and Placebo at Week 24 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| Arm/Group Description | Dosing Group A | Dosing Group B | Dosing Group C |
| Measure Participants | 308 | 298 | 302 |
| Mean (Standard Deviation) [Percentage improvement from baseline] |
20.75
(31.203)
|
18.31
(28.427)
|
9.84
(23.219)
|
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 | ||
| 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. | |
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 | ||
| 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. | |
| Title | Proportion of Patients Achieving DAS28-CRP <2.6 at Week 12, Comparison Between Fostamatinib and Placebo |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| Arm/Group Description | Dosing Group A | Dosing Group B | Dosing Group C |
| Measure Participants | 308 | 298 | 302 |
| Number [Percentage of responders] |
17.2
|
10.7
|
3.0
|
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 | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | An odds ratio >1 indicates a benefit towards fostamatinib. | |
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 | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | An odds ratio >1 indicates a benefit towards fostamatinib. | |
| Title | Proportion of Patients Achieving DAS28-CRP <2.6 at Week 24, Comparison Between Fostamatinib and Placebo |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| Arm/Group Description | Dosing Group A | Dosing Group B | Dosing Group C |
| Measure Participants | 308 | 298 | 302 |
| Number [Percentage of responders] |
41.3
|
12.8
|
2.3
|
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 | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | An odds ratio >1 indicates a benefit towards fostamatinib. | |
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 | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | An odds ratio >1 indicates a benefit towards fostamatinib. | |
| Title | Proportion of Patients Achieving DAS28 EULAR Response at Week 24 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| Arm/Group Description | Dosing Group A | Dosing Group B | Dosing Group C |
| Measure Participants | 308 | 298 | 302 |
| No response |
42.9
(1.46)
|
45.3
(1.34)
|
64.6
(1.30)
|
| Moderate response |
33.8
|
34.9
|
29.1
|
| Good response |
23.4
|
19.8
|
6.3
|
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 | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | An odds ratio > 1 indicates a benefit towards fostamatinib. | |
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 | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | An odds ratio > 1 indicates a benefit towards fostamatinib. | |
| Title | HAQ-DI Response - Comparison of the Change(>=0.22) From Baseline Between Fostamatinib and Placebo at Week 24 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| Arm/Group Description | Dosing Group A | Dosing Group B | Dosing Group C |
| Measure Participants | 308 | 298 | 302 |
| Number [Percentage of responders] |
46.1
|
42.3
|
26.5
|
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 | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | An odds ratio >1 indicates a benefit towards fostamatinib. | |
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 | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | An odds ratio >1 indicates a benefit towards fostamatinib. | |
| Title | Change From Baseline to Week 24 in mTSS, Comparison Between Fostamatinib and Placebo |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| Arm/Group Description | Dosing Group A | Dosing Group B | Dosing Group C |
| Measure Participants | 308 | 298 | 302 |
| Mean (Standard Deviation) [Units on a scale] |
0.64
(3.130)
|
0.37
(3.095)
|
1.16
(5.849)
|
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 | ||
| 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. | |
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 | ||
| 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. | |
| Title | SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Placebo at Week 24 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| Arm/Group Description | Dosing Group A | Dosing Group B | Dosing Group C |
| Measure Participants | 308 | 298 | 302 |
| Mean (Standard Deviation) [Units on a scale] |
5
(7.2)
|
4
(6.6)
|
2
(5.7)
|
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 | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
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 | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Placebo at Week 24 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| Arm/Group Description | Dosing Group A | Dosing Group B | Dosing Group C |
| Measure Participants | 308 | 298 | 302 |
| Mean (Standard Deviation) [Units on a scale] |
3
(7.5)
|
3
(8.4)
|
1
(6.3)
|
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 | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
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 | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| 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 | ||||
| Arm/Group Description | Dosing Group A | Dosing Group B | Dosing Group C | |||||
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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
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 (9.7%) | 25/298 (8.4%) | 10/302 (3.3%) | 10/302 (3.3%) | ||||
| Blood and lymphatic system disorders | ||||||||
| LEUKOPENIA | 0/308 (0%) | 0 | 0/298 (0%) | 0 | 1/302 (0.3%) | 1 | 0/302 (0%) | 0 |
| Cardiac disorders | ||||||||
| ANGINA PECTORIS | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| ATRIAL FIBRILLATION | 2/308 (0.6%) | 2 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| ATRIAL FLUTTER | 0/308 (0%) | 0 | 0/298 (0%) | 0 | 1/302 (0.3%) | 1 | 0/302 (0%) | 0 |
| CARDIAC ARREST | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| LEFT VENTRICULAR FAILURE | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| MYOCARDIAL INFARCTION | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 1/302 (0.3%) | 1 | 0/302 (0%) | 0 |
| VENTRICULAR FIBRILLATION | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| Eye disorders | ||||||||
| MACULAR HOLE | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| COLITIS | 1/308 (0.3%) | 1 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| COLITIS ULCERATIVE | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| DIARRHOEA | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| GASTRITIS | 2/308 (0.6%) | 2 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| GASTRITIS EROSIVE | 0/308 (0%) | 0 | 0/298 (0%) | 0 | 1/302 (0.3%) | 1 | 0/302 (0%) | 0 |
| GASTRITIS HAEMORRHAGIC | 0/308 (0%) | 0 | 0/298 (0%) | 0 | 1/302 (0.3%) | 1 | 0/302 (0%) | 0 |
| LOWER GASTROINTESTINAL HAEMORRHAGE | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| OESOPHAGITIS ULCERATIVE | 0/308 (0%) | 0 | 0/298 (0%) | 0 | 1/302 (0.3%) | 1 | 0/302 (0%) | 0 |
| PANCREATITIS CHRONIC | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| STOMATITIS | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| VOMITING | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| General disorders | ||||||||
| NON-CARDIAC CHEST PAIN | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| Hepatobiliary disorders | ||||||||
| CHOLECYSTITIS ACUTE | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| CHOLELITHIASIS | 0/308 (0%) | 0 | 2/298 (0.7%) | 2 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| HEPATOCELLULAR INJURY | 0/308 (0%) | 0 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 1/302 (0.3%) | 1 |
| NON-ALCOHOLIC STEATOHEPATITIS | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| Infections and infestations | ||||||||
| ACUTE SINUSITIS | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| ARTHRITIS BACTERIAL | 0/308 (0%) | 0 | 0/298 (0%) | 0 | 1/302 (0.3%) | 1 | 0/302 (0%) | 0 |
| ATYPICAL PNEUMONIA | 0/308 (0%) | 0 | 0/298 (0%) | 0 | 1/302 (0.3%) | 1 | 0/302 (0%) | 0 |
| BRONCHITIS | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| BRONCHITIS BACTERIAL | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| BRONCHITIS VIRAL | 0/308 (0%) | 0 | 0/298 (0%) | 0 | 1/302 (0.3%) | 1 | 0/302 (0%) | 0 |
| BURSITIS INFECTIVE | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| DENGUE FEVER | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| DEVICE RELATED INFECTION | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| ENTEROCOLITIS BACTERIAL | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| ESCHERICHIA INFECTION | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| GASTROENTERITIS | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| GASTROENTERITIS BACTERIAL | 1/308 (0.3%) | 1 | 1/298 (0.3%) | 1 | 1/302 (0.3%) | 1 | 0/302 (0%) | 0 |
| GASTROINTESTINAL BACTERIAL INFECTION | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| HERPES SIMPLEX | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| INFLUENZA | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| PNEUMOCOCCAL SEPSIS | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| PNEUMONIA | 0/308 (0%) | 0 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 1/302 (0.3%) | 1 |
| PNEUMONIA STREPTOCOCCAL | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| URINARY TRACT INFECTION BACTERIAL | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| CLAVICLE FRACTURE | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| FEMORAL NECK FRACTURE | 0/308 (0%) | 0 | 0/298 (0%) | 0 | 1/302 (0.3%) | 1 | 0/302 (0%) | 0 |
| HIP FRACTURE | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| HUMERUS FRACTURE | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| OVERDOSE | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| ULNA FRACTURE | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| Investigations | ||||||||
| ALANINE AMINOTRANSFERASE INCREASED | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| ASPARTATE AMINOTRANSFERASE INCREASED | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| BLOOD CREATINE PHOSPHOKINASE INCREASED | 0/308 (0%) | 0 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 1/302 (0.3%) | 1 |
| Metabolism and nutrition disorders | ||||||||
| HYPOCALCAEMIA | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| HYPOKALAEMIA | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| OBESITY | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| MYOSITIS | 0/308 (0%) | 0 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 1/302 (0.3%) | 1 |
| OSTEOARTHRITIS | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| PATHOLOGICAL FRACTURE | 0/308 (0%) | 0 | 0/298 (0%) | 0 | 1/302 (0.3%) | 1 | 0/302 (0%) | 0 |
| RHEUMATOID ARTHRITIS | 1/308 (0.3%) | 1 | 2/298 (0.7%) | 2 | 0/302 (0%) | 0 | 2/302 (0.7%) | 2 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| BONE NEOPLASM MALIGNANT | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| METASTASES TO CENTRAL NERVOUS SYSTEM | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| METASTATIC BRONCHIAL CARCINOMA | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| PARATHYROID TUMOUR BENIGN | 0/308 (0%) | 0 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 1/302 (0.3%) | 1 |
| RENAL ONCOCYTOMA | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| SQUAMOUS CELL CARCINOMA OF SKIN | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| Nervous system disorders | ||||||||
| CAROTID ARTERY STENOSIS | 0/308 (0%) | 0 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 1/302 (0.3%) | 1 |
| CONVULSION | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| LUMBAR RADICULOPATHY | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| SYNCOPE | 1/308 (0.3%) | 1 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 1/302 (0.3%) | 1 |
| Psychiatric disorders | ||||||||
| ANXIETY | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| RENAL FAILURE ACUTE | 1/308 (0.3%) | 1 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| URINARY RETENTION | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| ENDOMETRIOSIS | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| MENORRHAGIA | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| UTERINE HAEMORRHAGE | 0/308 (0%) | 0 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 1/302 (0.3%) | 1 |
| UTERINE POLYP | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| ACUTE RESPIRATORY DISTRESS SYNDROME | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| ALLERGIC BRONCHITIS | 0/308 (0%) | 0 | 0/298 (0%) | 0 | 1/302 (0.3%) | 1 | 0/302 (0%) | 0 |
| ASTHMA | 1/308 (0.3%) | 1 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| PULMONARY EMBOLISM | 1/308 (0.3%) | 1 | 0/298 (0%) | 0 | 0/302 (0%) | 0 | 1/302 (0.3%) | 1 |
| PULMONARY TOXICITY | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| RESPIRATORY FAILURE | 1/308 (0.3%) | 1 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| Vascular disorders | ||||||||
| DEEP VEIN THROMBOSIS | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
| MALIGNANT HYPERTENSION | 0/308 (0%) | 0 | 1/298 (0.3%) | 1 | 0/302 (0%) | 0 | 0/302 (0%) | 0 |
Other (Not Including 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 | 170/308 (55.2%) | 152/298 (51%) | 42/302 (13.9%) | 77/302 (25.5%) | ||||
| Gastrointestinal disorders | ||||||||
| DIARRHOEA | 44/308 (14.3%) | 44 | 47/298 (15.8%) | 47 | 15/302 (5%) | 15 | 13/302 (4.3%) | 13 |
| NAUSEA | 20/308 (6.5%) | 20 | 17/298 (5.7%) | 17 | 5/302 (1.7%) | 5 | 7/302 (2.3%) | 7 |
| Infections and infestations | ||||||||
| NASOPHARYNGITIS | 37/308 (12%) | 37 | 29/298 (9.7%) | 29 | 2/302 (0.7%) | 2 | 16/302 (5.3%) | 16 |
| Investigations | ||||||||
| ALANINE AMINOTRANSFERASE INCREASED | 21/308 (6.8%) | 21 | 14/298 (4.7%) | 14 | 2/302 (0.7%) | 2 | 4/302 (1.3%) | 4 |
| ASPARTATE AMINOTRANSFERASE INCREASED | 17/308 (5.5%) | 17 | 13/298 (4.4%) | 13 | 3/302 (1%) | 3 | 4/302 (1.3%) | 4 |
| BLOOD PRESSURE INCREASED | 15/308 (4.9%) | 15 | 15/298 (5%) | 15 | 1/302 (0.3%) | 1 | 10/302 (3.3%) | 10 |
| Musculoskeletal and connective tissue disorders | ||||||||
| RHEUMATOID ARTHRITIS | 19/308 (6.2%) | 19 | 23/298 (7.7%) | 23 | 1/302 (0.3%) | 1 | 10/302 (3.3%) | 10 |
| Nervous system disorders | ||||||||
| HEADACHE | 19/308 (6.2%) | 19 | 12/298 (4%) | 12 | 5/302 (1.7%) | 5 | 9/302 (3%) | 9 |
| Vascular disorders | ||||||||
| HYPERTENSION | 68/308 (22.1%) | 68 | 55/298 (18.5%) | 55 | 17/302 (5.6%) | 17 | 16/302 (5.3%) | 16 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Dave Goldstraw |
|---|---|
| Organization | AstraZeneca Pharmaceuticals |
| Phone | +44 (0)1625 512415 |
| dave.goldstraw@astrazeneca.com |
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01197534
Other Study ID Numbers:
- D4300C00002
- 2010-020744-35
First Posted:
Sep 9, 2010
Last Update Posted:
Apr 17, 2014
Last Verified:
Mar 1, 2014