OSKIRA - 1: Evaluation of Effectiveness of Two Dosing Regimens of Fostamatinib Compared to Placebo in Patients With Rheumatoid Arthritis (RA) Who Are Taking Methotrexate But Not Responding.
Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT01197521
Collaborator
(none)
923
127
3
26
7.3
0.3
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 methotrexate 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
:
923 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
(OSKIRA-1): 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 Methotrexate
Study Start Date
:
Sep 1, 2010
Actual Primary Completion Date
:
Nov 1, 2012
Actual Study Completion Date
:
Nov 1, 2012
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. Non-responder imputation has been applied by carrying the baseline observation forward. BID=twice daily, CRP=C-reactive protein, DMARD=disease-modifying anti-rheumatic drug, 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 have been excluded from the analysis. ANCOVA=analysis of covariance, BID=twice daily, DMARD=disease-modifying anti-rheumatic drug, IP=investigational product, PO=orally, QD=once a day.
Secondary Outcome Measures
- ACR20 - 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. Non-responder imputation has been applied by carrying the baseline observation forward. BID=twice daily, CRP=C-reactive protein, DMARD=Disease-modifying anti-rheumatic drug, PO=orally.
- Proportion of Patients Achieving ACR50 up to 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. Non-responder imputation has been applied by carrying the baseline observation forward. BID=twice daily, CRP=C-reactive protein, DMARD=Disease-modifying anti-rheumatic drug, PO=orally, QD=once a day.
- Proportion of Patients Achieving ACR70 up to 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. Non-responder imputation has been applied by carrying the baseline observation forward. 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 [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, RA=rheumatoid arthritis. Mean refers to change at Week 24.
- Proportion of Patients Achieving DAS28-CRP <2.6 at Week 12 [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 [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-CRP 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. Non-responder imputation has been applied by carrying the baseline observation forward. BID=twice daily, CRP=C-reactive protein, 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 calculated by summing 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 higher score indicating greater disability. HAQ-DI response: a reduction from baseline in HAQ-DI 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.
- 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 QoL. Scores for 8 sub-domains (Physical Functioning, Role-physical, Bodily Pain, General Health, Vitality, Social Function, Role-emotional & Mental Health) are derived & normalised to a scale of 0-100. Physical Component Scores (PCS) are derived by multiplying each of these 8 scores by a constant, summing them & standardising against a population with mean of 50, standard deviation of 10. Higher scores represent a better QoL. Mean changes from baseline score are presented at each visit 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 drug, PO=orally, QD=once daily, QoL=quality of life.
- 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 QoL. Scores for 8 sub-domains (Physical Functioning, Role-physical, Bodily Pain, General Health, Vitality, Social Function, Role-emotional & Mental Health) are derived & normalised to a scale of 0-100. Mental Component Scores (MCS) are derived by multiplying each of these 8 scores by a constant, summing them & standardising against a population with mean of 50, standard deviation of 10. Higher scores represent a better QoL. Mean changes from baseline score are presented at each visit 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 drug, PO=orally, QD=once daily, QoL=quality of life.
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
-
Currently taking methotrexate
-
6 or more swollen joints and 6 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 | Anniston | Alabama | United States | |
| 2 | Research Site | Huntsville | Alabama | United States | |
| 3 | Research Site | Tuscaloosa | Alabama | United States | |
| 4 | Research Site | Tucson | Arizona | United States | |
| 5 | Research Site | Huntington Beach | California | United States | |
| 6 | Research Site | Long Beach | California | United States | |
| 7 | Research Site | Santa Maria | California | United States | |
| 8 | Research Site | Santa Monica | California | United States | |
| 9 | Research Site | Colorado Springs | Colorado | United States | |
| 10 | Research Site | Bridgeport | Connecticut | United States | |
| 11 | Research Site | Lewes | Delaware | United States | |
| 12 | Research Site | Daytona Beach | Florida | United States | |
| 13 | Research Site | Ocala | Florida | United States | |
| 14 | Research Site | Atlanta | Georgia | United States | |
| 15 | Research Site | Marietta | Georgia | United States | |
| 16 | Research Site | Idaho Falls | Idaho | United States | |
| 17 | Research Site | Springfield | Illinois | United States | |
| 18 | Research Site | Wichita | Kansas | United States | |
| 19 | Research Site | Bowling Green | Kentucky | United States | |
| 20 | Research Site | Flowood | Mississippi | United States | |
| 21 | Research Site | Florissant | Missouri | United States | |
| 22 | Research Site | Richmond Heights | Missouri | United States | |
| 23 | Research Site | St Louis | Missouri | United States | |
| 24 | Research Site | Kalispell | Montana | United States | |
| 25 | Research Site | Albuquerque | New Mexico | United States | |
| 26 | Research Site | Albany | New York | United States | |
| 27 | Research Site | Brooklyn | New York | United States | |
| 28 | Research Site | Olean | New York | United States | |
| 29 | Research Site | Asheville | North Carolina | United States | |
| 30 | Research Site | Greensboro | North Carolina | United States | |
| 31 | Research Site | Perrysburg | Ohio | United States | |
| 32 | Research Site | Lake Oswego | Oregon | United States | |
| 33 | Research Site | Erie | Pennsylvania | United States | |
| 34 | Research Site | Waxford | Pennsylvania | United States | |
| 35 | Research Site | Charleston | South Carolina | United States | |
| 36 | Research Site | Hixson | Tennessee | United States | |
| 37 | Research Site | Memphis | Tennessee | United States | |
| 38 | Research Site | Dallas | Texas | United States | |
| 39 | Research Site | Houston | Texas | United States | |
| 40 | Research Site | Mesquite | Texas | United States | |
| 41 | Research Site | San Antonio | Texas | United States | |
| 42 | Research Site | Reading | Berkshire | Argentina | |
| 43 | Research Site | Buenos Aires | Caba | Argentina | |
| 44 | Research Site | Ciudad Autonoma Bs As | CBA | Argentina | |
| 45 | Research Site | Cordoba | CRD | Argentina | |
| 46 | Research Site | Rosario | Santa Fe | Argentina | |
| 47 | Research Site | San Miguel de Tucuman | TUC | Argentina | |
| 48 | Research Site | Caba | Argentina | ||
| 49 | Research Site | Quilmes | Argentina | ||
| 50 | Research Site | San Juan | Argentina | ||
| 51 | Research Site | Camperdown | New South Wales | Australia | |
| 52 | Research Site | Cairns | Queensland | Australia | |
| 53 | Research Site | Southport | Queensland | Australia | |
| 54 | Research Site | Brussels | Belgium | ||
| 55 | Research Site | Yvoir | Belgium | ||
| 56 | Research Site | Vitoria | ES | Brazil | |
| 57 | Research Site | Recife | PE | Brazil | |
| 58 | Research Site | Curitiba | PR | Brazil | |
| 59 | Research Site | Sao Paulo | SP | Brazil | |
| 60 | Research Site | Rio de Janeiro | Brazil | ||
| 61 | Research Site | Plovdiv | Bulgaria | ||
| 62 | Research Site | Sevlievo | Bulgaria | ||
| 63 | Research Site | Sofia | Bulgaria | ||
| 64 | Research Site | Veliko Tarnovo | Bulgaria | ||
| 65 | Research Site | Osorno | X Region | Chile | |
| 66 | Research Site | Santiago | Chile | ||
| 67 | Research Site | Parnu | Estonia | ||
| 68 | Research Site | Tallinn | Estonia | ||
| 69 | Research Site | Tartu | Estonia | ||
| 70 | Research Site | Orleans Cedex 1 | France | ||
| 71 | Research Site | Paris Cedex 13 | France | ||
| 72 | Research Site | Balatonfured | Hungary | ||
| 73 | Research Site | Bekescsaba | Hungary | ||
| 74 | Research Site | Budapest | Hungary | ||
| 75 | Research Site | Debrecen | Hungary | ||
| 76 | Research Site | Mako | Hungary | ||
| 77 | Research Site | Sopron | Hungary | ||
| 78 | Research Site | Szentes | Hungary | ||
| 79 | Research Site | Zalaegerszeg-pozva | Hungary | ||
| 80 | Research Site | Secunderabad | Andhra Pradesh | India | |
| 81 | Research Site | Vishakhapatnam | Andhra Pradesh | India | |
| 82 | Research Site | Ahmedabad | Gujarat | India | |
| 83 | Research Site | Bangalore | Karnataka | India | |
| 84 | Research Site | Mangalore | Karnataka | India | |
| 85 | Research Site | Udupi | Karnataka | India | |
| 86 | Research Site | Nagpur | Maharshtra | India | |
| 87 | Research Site | Lucknow | Uttar Pradesh | India | |
| 88 | Research Site | Calcutta | India | ||
| 89 | Research Site | Hyderabad | India | ||
| 90 | Research Site | Saltillo | Coahuila | Mexico | |
| 91 | Research Site | Mexico | Distrito Federal | Mexico | |
| 92 | Research Site | Guadalajara | JAL | Mexico | |
| 93 | Research Site | Monterrey | Nuevo Leon | Mexico | |
| 94 | Research Site | Obrergon | SON | Mexico | |
| 95 | Research Site | Chihuahua | Mexico | ||
| 96 | Research Site | Mexicali | Mexico | ||
| 97 | Research Site | San Luis Potosi | Mexico | ||
| 98 | Research Site | Pueblo Libre | Lima | Peru | |
| 99 | Research Site | Arequipa | Peru | ||
| 100 | Research Site | Lima | Peru | ||
| 101 | Research Site | Bytom | Poland | ||
| 102 | Research Site | Chelm Slaski | Poland | ||
| 103 | Research Site | Grodzisk Mazowiecki | Poland | ||
| 104 | Research Site | Katowice | Poland | ||
| 105 | Research Site | Krakow | Poland | ||
| 106 | Research Site | Warszawa | Poland | ||
| 107 | Research Site | Wroclaw | Poland | ||
| 108 | Research Site | Zyrardow | Poland | ||
| 109 | Research Site | Bratislava | Slovakia | ||
| 110 | Research Site | Poprad | Slovakia | ||
| 111 | Research Site | Rimavska Sobota | Slovakia | ||
| 112 | Research Site | Zilina | Slovakia | ||
| 113 | Research Site | Donetsk | Ukraine | ||
| 114 | Research Site | Ivano-frankivsk | Ukraine | ||
| 115 | Research Site | Kharkiv | Ukraine | ||
| 116 | Research Site | Kiev | Ukraine | ||
| 117 | Research Site | Kyiv | Ukraine | ||
| 118 | Research Site | Lviv | Ukraine | ||
| 119 | Research Site | Odessa | Ukraine | ||
| 120 | Research Site | Vinnytsya | Ukraine | ||
| 121 | Research Site | Zaporyzhzhya | Ukraine | ||
| 122 | Research Site | Warrington | Cheshire | United Kingdom | |
| 123 | Research Site | Christchurch | United Kingdom | ||
| 124 | Research Site | Ipswich | United Kingdom | ||
| 125 | Research Site | London | United Kingdom | ||
| 126 | Research Site | Westcliff-on-the Sea | United Kingdom | ||
| 127 | Research Site | Wirral | United Kingdom |
Sponsors and Collaborators
- AstraZeneca
Investigators
- Study Director: Neil MacKillop, MD PhD, AstraZeneca
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01197521
Other Study ID Numbers:
- D4300C00001
- 2010-020743-12
First Posted:
Sep 9, 2010
Last Update Posted:
Apr 7, 2014
Last Verified:
Feb 1, 2014
Keywords provided by AstraZeneca
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | A total of 1475 patients were enrolled: 311, 306 & 306 were randomised to Groups A, B & C, respectively (310, 304 & 304 received at least 1 dose of IP). |
|---|---|
| Pre-assignment Detail | A total of 552 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 | 310 | 304 | 304 |
| Randomised But Did Not Receive Treatment | 1 | 2 | 2 |
| COMPLETED | 207 | 191 | 161 |
| NOT COMPLETED | 103 | 113 | 143 |
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 | 310 | 304 | 304 | 918 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
52
(12.2)
|
52
(12.0)
|
53
(11.9)
|
52
(12.0)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
263
84.8%
|
254
83.6%
|
253
83.2%
|
770
83.9%
|
| Male |
47
15.2%
|
50
16.4%
|
51
16.8%
|
148
16.1%
|
| Race/Ethnicity, Customized (Number) [Number] | ||||
| White |
218
70.3%
|
213
70.1%
|
209
68.8%
|
640
69.7%
|
| Black or African American |
9
2.9%
|
5
1.6%
|
11
3.6%
|
25
2.7%
|
| Asian |
3
1%
|
10
3.3%
|
5
1.6%
|
18
2%
|
| American Indian or Alaska Native |
14
4.5%
|
12
3.9%
|
11
3.6%
|
37
4%
|
| Indian or Pakistani |
20
6.5%
|
14
4.6%
|
19
6.3%
|
53
5.8%
|
| Other |
46
14.8%
|
50
16.4%
|
49
16.1%
|
145
15.8%
|
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. Non-responder imputation has been applied by carrying the baseline observation forward. 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 | 310 | 304 | 304 |
| Number [Percentage of responders] |
49.0
|
44.4
|
34.2
|
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 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 | Week 24 | |
| Method | Mantel Haenszel | |
| Comments | Treatment difference in proportion of responders with a Mantel Haenszel approach stratified by 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 | ||
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 | 0.006 |
| Comments | Week 24 | |
| Method | Mantel Haenszel | |
| Comments | Treatment difference in proportion of responders with a Mantel Haenszel approach stratified by pooled country. | |
| Method of Estimation | Estimation Parameter | Weighted difference in proportions |
| Estimated Value | 0.10 | |
| Confidence Interval |
(2-Sided) 95% 0.03 to 0.18 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| 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 have been excluded from the analysis. ANCOVA=analysis of covariance, BID=twice daily, DMARD=disease-modifying anti-rheumatic drug, IP=investigational product, 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 IP. Patients were analysed by randomised treatment. Measurements at 2 timepoints are required in order 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 | 285 | 277 | 278 |
| Mean (Standard Deviation) [Units on a scale] |
0.45
(2.201)
|
1.29
(13.380)
|
0.13
(2.142)
|
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, 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 | 0.252 |
| Comments | Week 24 | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | The residuals from the ANCOVA are analysed using a Cochran-Mantel-Haenszel approach, adjusting for the effects of 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 | This analysis is performed using an ANCOVA model on the ranks of the change from baseline, by pooled country, 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 | 0.170 |
| Comments | Week 24 | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | The residuals from the ANCOVA are analysed using a Cochran-Mantel-Haenszel approach, adjusting for the effects of pooled country. | |
| Title | ACR20 - 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. Non-responder imputation has been applied by carrying the baseline observation forward. BID=twice daily, CRP=C-reactive protein, DMARD=Disease-modifying anti-rheumatic drug, PO=orally. |
| 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 (Combined) | PLACEBO (24 WKS) THEN FOSTA 100 MG BID PO |
|---|---|---|
| Arm/Group Description | Dosing Group A and B combined | Dosing Group C |
| Measure Participants | 614 | 304 |
| Number [Percentage of responders] |
18.2
|
4.9
|
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 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-values presented. Formal statistical testing could not be carried out due to the predefined multiplicity procedure (as the primary variable comparisons were non-significant). | |
| Method | Mantel Haenszel | |
| Comments | 95% confidence intervals and p-values are calculated using a Mantel Haenszel approach stratified by pooled country. | |
| Method of Estimation | Estimation Parameter | Weighted difference in proportion |
| Estimated Value | 0.13 | |
| Confidence Interval |
(2-Sided) 95% 0.10 to 0.17 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Proportion of Patients Achieving ACR50 up to 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. Non-responder imputation has been applied by carrying the baseline observation forward. 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 | 310 | 304 | 304 |
| Number [Percentage of responders] |
26.1
|
18.4
|
9.9
|
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 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-values presented. Formal statistical testing could not be carried out due to the predefined multiplicity procedure (as the primary variable comparisons were non-significant). | |
| Method | Mantel Haenszel | |
| Comments | 95% confidence intervals and p-values are calculated using a Mantel Haenszel approach stratified by pooled country. | |
| Method of Estimation | Estimation Parameter | Weighted difference in proportions |
| Estimated Value | 0.16 | |
| Confidence Interval |
(2-Sided) 95% 0.11 to 0.22 |
|
| 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 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 | 0.002 |
| Comments | Nominal p-values presented. Formal statistical testing could not be carried out due to the predefined multiplicity procedure (as the primary variable comparisons were non-significant). | |
| Method | Mantel Haenszel | |
| Comments | 95% confidence intervals and p-values are calculated using a Mantel Haenszel approach stratified by pooled country. | |
| Method of Estimation | Estimation Parameter | Weighted difference in proportions |
| Estimated Value | 0.09 | |
| Confidence Interval |
(2-Sided) 95% 0.03 to 0.14 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Proportion of Patients Achieving ACR70 up to 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. Non-responder imputation has been applied by carrying the baseline observation forward. 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 | 310 | 304 | 304 |
| Number [Percentage of responders] |
10.3
|
5.6
|
2.0
|
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 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-values presented. Formal statistical testing could not be carried out due to the predefined multiplicity procedure (as the primary variable comparisons were non-significant). | |
| Method | Mantel Haenszel | |
| Comments | 95% confidence intervals and p-values are calculated using a Mantel Haenszel approach stratified by pooled country. | |
| Method of Estimation | Estimation Parameter | Weighted difference in proportions |
| Estimated Value | 0.08 | |
| Confidence Interval |
(2-Sided) 95% 0.05 to 0.12 |
|
| 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 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 | 0.015 |
| Comments | Nominal p-values presented. Formal statistical testing could not be carried out due to the predefined multiplicity procedure (as the primary variable comparisons were non-significant). | |
| Method | Mantel Haenszel | |
| Comments | 95% confidence intervals and p-values are calculated using a Mantel Haenszel approach stratified by pooled country. | |
| Method of Estimation | Estimation Parameter | Weighted difference in proportions |
| Estimated Value | 0.04 | |
| Confidence Interval |
(2-Sided) 95% 0.01 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, RA=rheumatoid arthritis. Mean refers to change at Week 24. |
| 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 | 310 | 304 | 304 |
| Mean (Standard Deviation) [Percentage improvement from baseline] |
26.13
(30.833)
|
20.06
(28.599)
|
12.92
(26.611)
|
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 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. ACRn 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 | The treatment differences, 95% CIs and p-values are estimated using the Van Elteren test stratified by 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 | 0.002 |
| Comments | Nominal p-value presented for treatment comparison. ACRn 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 | The treatment differences, 95% CIs and p-values are estimated using the Van Elteren test stratified by pooled country. | |
| Title | Proportion of Patients Achieving DAS28-CRP <2.6 at Week 12 |
|---|---|
| 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 | 310 | 304 | 304 |
| Number [Percentage of responders] |
10.3
|
7.9
|
2.0
|
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 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-values presented. Formal statistical testing could not be carried out due to the predefined multiplicity procedure (as the primary variable comparisons were non-significant). | |
| Method | Regression, Logistic | |
| Comments | Odds ratio and 95% confidence intervals are calculated using Logistic Regression with treatment and pooled country as factors. | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 6.0 | |
| Confidence Interval |
(2-Sided) 95% 2.44 to 14.64 |
|
| 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 | 0.002 |
| Comments | Nominal p-values presented. Formal statistical testing could not be carried out due to the predefined multiplicity procedure (as the primary variable comparisons were non-significant). | |
| Method | Regression, Logistic | |
| Comments | Odds ratio and 95% confidence intervals are calculated using Logistic Regression with treatment and pooled country as factors. | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 4.4 | |
| Confidence Interval |
(2-Sided) 95% 1.76 to 11.02 |
|
| 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 |
|---|---|
| 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 | 310 | 304 | 304 |
| Number [Percentage of responders] |
13.2
|
8.6
|
4.9
|
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 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-values presented. Formal statistical testing could not be carried out due to the predefined multiplicity procedure (as the primary variable comparisons were non-significant). | |
| Method | Regression, Logistic | |
| Comments | Odds ratio and 95% confidence intervals are calculated using Logistic Regression with treatment and pooled country as factors. | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 3.0 | |
| Confidence Interval |
(2-Sided) 95% 1.63 to 5.67 |
|
| 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 | 0.083 |
| Comments | Nominal p-values presented. Formal statistical testing could not be carried out due to the predefined multiplicity procedure (as the primary variable comparisons were non-significant). | |
| Method | Regression, Logistic | |
| Comments | Odds ratio and 95% confidence intervals are calculated using Logistic Regression with treatment and pooled country as factors. | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.8 | |
| Confidence Interval |
(2-Sided) 95% 0.93 to 3.50 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | An odds ratio >1 indicates a benefit towards Fostamatinib. | |
| Title | Proportion of Patients Achieving DAS28-CRP 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. Non-responder imputation has been applied by carrying the baseline observation forward. BID=twice daily, CRP=C-reactive protein, 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 | 310 | 304 | 304 |
| No response |
34.8
(1.46)
|
41.1
(1.34)
|
53.0
(1.30)
|
| Moderate response |
39.0
|
44.4
|
36.2
|
| Good response |
26.1
|
14.5
|
10.9
|
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 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. This 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 proportional odds model with treatment and pooled country as factors. | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.43 | |
| Confidence Interval |
(2-Sided) 95% 1.79 to 3.30 |
|
| 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 | 0.004 |
| Comments | Nominal p-value presented for treatment comparison. This 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 proportional odds model with treatment and pooled country as factors. | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.57 | |
| Confidence Interval |
(2-Sided) 95% 1.16 to 2.14 |
|
| 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 calculated by summing 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 higher score indicating greater disability. HAQ-DI response: a reduction from baseline in HAQ-DI 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 | 310 | 304 | 304 |
| Number [Percentage of responders] |
54.8
|
50.3
|
35.2
|
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 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-values presented. Formal statistical testing could not be carried out due to the predefined multiplicity procedure (as the primary variable comparisons were non-significant). | |
| Method | Regression, Logistic | |
| Comments | Odds ratio and 95% confidence intervals are calculated using Logistic Regression with treatment and pooled country as factors. | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.3 | |
| Confidence Interval |
(2-Sided) 95% 1.68 to 3.26 |
|
| 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 | Nominal p-values presented. Formal statistical testing could not be carried out due to the predefined multiplicity procedure (as the primary variable comparisons were non-significant). | |
| Method | Regression, Logistic | |
| Comments | Odds ratio and 95% confidence intervals are calculated using Logistic Regression with treatment and pooled country as factors. | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.9 | |
| Confidence Interval |
(2-Sided) 95% 1.38 to 2.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | An odds ratio >1 indicates a benefit towards Fostamatinib. | |
| 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 QoL. Scores for 8 sub-domains (Physical Functioning, Role-physical, Bodily Pain, General Health, Vitality, Social Function, Role-emotional & Mental Health) are derived & normalised to a scale of 0-100. Physical Component Scores (PCS) are derived by multiplying each of these 8 scores by a constant, summing them & standardising against a population with mean of 50, standard deviation of 10. Higher scores represent a better QoL. Mean changes from baseline score are presented at each visit 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 drug, PO=orally, QD=once daily, QoL=quality of life. |
| 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 | 310 | 304 | 303 |
| Mean (Standard Deviation) [Units on a scale] |
6
(8.0)
|
5
(6.7)
|
3
(6.2)
|
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 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. This was not formally tested within the predefined multiplicity procedure. | |
| Method | ANCOVA | |
| Comments | Including terms for baseline as a continuous covariate and treatment and pooled country as factors. | |
| Method of Estimation | Estimation Parameter | Treatment difference |
| Estimated Value | 2.24 | |
| Confidence Interval |
() 95% 1.16 to 3.31 |
|
| 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 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 | 0.020 |
| Comments | Nominal p-value presented for treatment comparison. This was not formally tested within the predefined multiplicity procedure. | |
| Method | ANCOVA | |
| Comments | Including terms for baseline as a continuous covariate and treatment and pooled country as factors. | |
| Method of Estimation | Estimation Parameter | Treatment difference |
| Estimated Value | 1.27 | |
| Confidence Interval |
() 95% 0.20 to 2.35 |
|
| 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 QoL. Scores for 8 sub-domains (Physical Functioning, Role-physical, Bodily Pain, General Health, Vitality, Social Function, Role-emotional & Mental Health) are derived & normalised to a scale of 0-100. Mental Component Scores (MCS) are derived by multiplying each of these 8 scores by a constant, summing them & standardising against a population with mean of 50, standard deviation of 10. Higher scores represent a better QoL. Mean changes from baseline score are presented at each visit 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 drug, PO=orally, QD=once daily, QoL=quality of life. |
| 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 | 310 | 304 | 303 |
| Mean (Standard Deviation) [Units on a scale] |
4
(9.5)
|
4
(8.6)
|
2
(8.1)
|
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 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 | 0.005 |
| Comments | Nominal p-value presented for treatment comparison. This was not formally tested within the predefined multiplicity procedure. | |
| Method | ANCOVA | |
| Comments | Including terms for baseline as a continuous covariate and treatment and pooled country as factors. | |
| Method of Estimation | Estimation Parameter | Treatment difference |
| Estimated Value | 1.80 | |
| Confidence Interval |
() 95% 0.54 to 3.07 |
|
| 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 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 | 0.017 |
| Comments | Nominal p-value presented for treatment comparison. This was not formally tested within the predefined multiplicity procedure. | |
| Method | ANCOVA | |
| Comments | Including terms for baseline as a continuous covariate and treatment and pooled country as factors. | |
| Method of Estimation | Estimation Parameter | Treatment difference |
| Estimated Value | 1.56 | |
| Confidence Interval |
() 95% 0.28 to 2.83 |
|
| 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. 5 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 | 24/310 (7.7%) | 24/304 (7.9%) | 12/304 (3.9%) | 5/304 (1.6%) | ||||
| Blood and lymphatic system disorders | ||||||||
| ANAEMIA | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| Cardiac disorders | ||||||||
| ACUTE MYOCARDIAL INFARCTION | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| ATRIAL FIBRILLATION | 0/310 (0%) | 0 | 2/304 (0.7%) | 2 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 |
| ATRIAL FLUTTER | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| CARDIAC FAILURE | 0/310 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 1/304 (0.3%) | 1 |
| CARDIAC FAILURE ACUTE | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| CARDIOPULMONARY FAILURE | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| ATRIAL THROMBOSIS | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| Eye disorders | ||||||||
| CHORIORETINOPATHY | 0/310 (0%) | 0 | 0/304 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| COLITIS | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| COLONIC OBSTRUCTION | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| DUODENAL ULCER HAEMORRHAGE | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| GASTRITIS ATROPHIC | 0/310 (0%) | 0 | 0/304 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 |
| PANCREATITIS | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| REFLUX GASTRITIS | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| Hepatobiliary disorders | ||||||||
| BILE DUCT OBSTRUCTION | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| BILIARY COLIC | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| CHOLECYSTITIS | 1/310 (0.3%) | 1 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| CHOLELITHIASIS | 2/310 (0.6%) | 2 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| Immune system disorders | ||||||||
| ANAPHYLACTIC REACTION | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| Infections and infestations | ||||||||
| APPENDICITIS | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| BACTERIAL DIARRHOEA | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| BRONCHITIS | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 |
| CELLULITIS | 2/310 (0.6%) | 2 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| ESCHERICHIA URINARY TRACT INFECTION | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| GASTROENTERITIS | 1/310 (0.3%) | 1 | 3/304 (1%) | 3 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| GASTROENTERITIS VIRAL | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| PANCREATITIS VIRAL | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| PNEUMONIA | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| PULMONARY TUBERCULOSIS | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| SEPSIS | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| SEPTIC SHOCK | 0/310 (0%) | 0 | 0/304 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 |
| UPPER RESPIRATORY TRACT INFECTION | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| URINARY TRACT INFECTION | 0/310 (0%) | 0 | 0/304 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| ACCIDENTAL OVERDOSE | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| CONTUSION | 0/310 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 1/304 (0.3%) | 1 |
| FEMORAL NECK FRACTURE | 0/310 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 1/304 (0.3%) | 1 |
| FEMUR FRACTURE | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| FIBULA FRACTURE | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| HIP FRACTURE | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| HUMERUS FRACTURE | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| SPINAL FRACTURE | 0/310 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 1/304 (0.3%) | 1 |
| TIBIA FRACTURE | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| DEHYDRATION | 0/310 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 1/304 (0.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||
| FOOT DEFORMITY | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| OSTEOARTHRITIS | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 |
| PATHOLOGICAL FRACTURE | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| RHEUMATOID ARTHRITIS | 2/310 (0.6%) | 2 | 0/304 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 |
| SPONDYLOLISTHESIS | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| SYSTEMIC LUPUS ERYTHEMATOSUS | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| BASAL CELL CARCINOMA | 0/310 (0%) | 0 | 0/304 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 |
| GANGLIONEUROMA | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| GASTRIC CANCER | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| RENAL CANCER | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| THYROID CANCER | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| UTERINE LEIOMYOMA | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| Nervous system disorders | ||||||||
| ISCHAEMIC STROKE | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| MULTIPLE SCLEROSIS | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| TRANSIENT GLOBAL AMNESIA | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| Pregnancy, puerperium and perinatal conditions | ||||||||
| ABORTION SPONTANEOUS | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| Psychiatric disorders | ||||||||
| CONFUSIONAL STATE | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| CALCULUS URINARY | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| NEPHROLITHIASIS | 0/310 (0%) | 0 | 0/304 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 |
| RENAL ARTERY STENOSIS | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| RENAL FAILURE ACUTE | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| HAEMORRHAGIC OVARIAN CYST | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| METRORRHAGIA | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| ACUTE RESPIRATORY FAILURE | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| CHRONIC OBSTRUCTIVE PULMONARY DISEASE | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| DYSPNOEA | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| INTERSTITIAL LUNG DISEASE | 0/310 (0%) | 0 | 0/304 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 |
| PULMONARY EMBOLISM | 0/310 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 1/304 (0.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||
| ANGIOEDEMA | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| VITILIGO | 1/310 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| Vascular disorders | ||||||||
| CIRCULATORY COLLAPSE | 0/310 (0%) | 0 | 0/304 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 |
| HYPOTENSION | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| HYPOVOLAEMIC SHOCK | 0/310 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (0%) | 0 | 0/304 (0%) | 0 |
| PERIPHERAL ISCHAEMIA | 0/310 (0%) | 0 | 0/304 (0%) | 0 | 1/304 (0.3%) | 1 | 0/304 (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 | 169/310 (54.5%) | 191/304 (62.8%) | 64/304 (21.1%) | 80/304 (26.3%) | ||||
| Gastrointestinal disorders | ||||||||
| ABDOMINAL PAIN UPPER | 12/310 (3.9%) | 12 | 16/304 (5.3%) | 17 | 3/304 (1%) | 3 | 10/304 (3.3%) | 10 |
| DIARRHOEA | 60/310 (19.4%) | 84 | 63/304 (20.7%) | 87 | 18/304 (5.9%) | 26 | 12/304 (3.9%) | 14 |
| NAUSEA | 19/310 (6.1%) | 20 | 27/304 (8.9%) | 31 | 8/304 (2.6%) | 9 | 11/304 (3.6%) | 11 |
| VOMITING | 18/310 (5.8%) | 18 | 8/304 (2.6%) | 9 | 5/304 (1.6%) | 6 | 5/304 (1.6%) | 5 |
| Infections and infestations | ||||||||
| NASOPHARYNGITIS | 22/310 (7.1%) | 29 | 28/304 (9.2%) | 34 | 6/304 (2%) | 7 | 11/304 (3.6%) | 14 |
| URINARY TRACT INFECTION BACTERIAL | 18/310 (5.8%) | 23 | 14/304 (4.6%) | 19 | 6/304 (2%) | 6 | 6/304 (2%) | 6 |
| Investigations | ||||||||
| ALANINE AMINOTRANSFERASE INCREASED | 22/310 (7.1%) | 27 | 22/304 (7.2%) | 23 | 8/304 (2.6%) | 10 | 5/304 (1.6%) | 6 |
| ASPARTATE AMINOTRANSFERASE INCREASED | 16/310 (5.2%) | 18 | 13/304 (4.3%) | 15 | 4/304 (1.3%) | 7 | 5/304 (1.6%) | 7 |
| BLOOD PRESSURE INCREASED | 17/310 (5.5%) | 18 | 16/304 (5.3%) | 23 | 4/304 (1.3%) | 4 | 5/304 (1.6%) | 5 |
| Musculoskeletal and connective tissue disorders | ||||||||
| BACK PAIN | 18/310 (5.8%) | 19 | 8/304 (2.6%) | 8 | 2/304 (0.7%) | 3 | 2/304 (0.7%) | 2 |
| RHEUMATOID ARTHRITIS | 16/310 (5.2%) | 18 | 8/304 (2.6%) | 9 | 6/304 (2%) | 6 | 12/304 (3.9%) | 13 |
| Nervous system disorders | ||||||||
| HEADACHE | 15/310 (4.8%) | 20 | 20/304 (6.6%) | 29 | 7/304 (2.3%) | 7 | 12/304 (3.9%) | 12 |
| Vascular disorders | ||||||||
| HYPERTENSION | 59/310 (19%) | 72 | 58/304 (19.1%) | 76 | 11/304 (3.6%) | 13 | 12/304 (3.9%) | 12 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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
| Name/Title | Dave Goldstraw |
|---|---|
| Organization | AstraZeneca |
| Phone | +44 (0)1625 512415 |
| dave.goldstraw@astrazeneca.com |
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01197521
Other Study ID Numbers:
- D4300C00001
- 2010-020743-12
First Posted:
Sep 9, 2010
Last Update Posted:
Apr 7, 2014
Last Verified:
Feb 1, 2014