Oskira ABPM: Study of the Effect of Fostamatinib Twice Daily on Blood Pressure in Patients With Rheumatoid Arthritis
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the effect of fostamatinib compared to placebo on ambulatory blood pressure in patients with active rheumatoid arthritis who are taking a disease-modifying anti-rheumatic drug (DMARD).
The study will last for 57 days.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
OSKIRA-ABPM: A Multi-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study of the Effect of Fostamatinib 100 mg Twice Daily on 24-hour Ambulatory Blood Pressure in Patients with Rheumatoid Arthritis
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Dosing Regimen A Oral treatment |
Drug: fostamatinib
fostamatinib 100 mg twice daily
|
Placebo Comparator: Dosing Regimen B Oral treatment |
Drug: placebo
placebo
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in 24-hour Mean Ambulatory SBP [4 weeks]
ANCOVA=analysis of covariance, BID=twice daily, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure.
Secondary Outcome Measures
- Change From Baseline in 24-hour Mean Ambulatory DBP [4 weeks]
ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product.
- Change From Baseline in Mean Daytime and Night-time SBP and DBP by Ambulatory Blood Pressure Monitoring [4 weeks]
ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure.
- Change From Baseline in Mean Awake SBP and DBP by Ambulatory Blood Pressure Monitoring [4 weeks]
ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure.
- Change From Baseline in Mean Sleeping SBP and DBP by Ambulatory Blood Pressure Monitoring [4 weeks]
ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure.
- Mean Change From Baseline in Clinic SBP and DBP [4 weeks]
Blood pressure was measured in the clinic using an automated blood pressure machine (oscillometric method). Three separate measurements were taken 2 to 5 minutes apart and the mean of the 2nd and 3rd measurements calculated. ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure.
- Mean Change From Baseline in Morning Pre-dose Home SBP and DBP [4 weeks]
ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure.
- Mean Change From Baseline in Evening Post-dose Home SBP and DBP [4 weeks]
ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure.
- Mean Change From Completion/Discontinuation to Follow-up in Clinical Measurement of SBP and DBP [Day 29 to Day 36]
BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure.
- DAS28-CRP Improvement [4 weeks]
ANCOVA=analysis of covariance, BID=twice daily, DAS28-CRP=Disease Activity Score based on a count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (C-reactive protein [CRP]) and the patient's own assessment, FAS=full analysis set, IP=investigational product. Scores can take any positive value with a lower value indicative of a better clinical condition. Mean changes from baseline in DAS28-CRP score are shown at each visit and are presented as decreases from baseline (defined as baseline minus post-baseline) with larger changes indicating a better clinical condition.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male and female patients aged 18 or over diagnosed with rheumatoid arthritis after the age of 16
-
Active rheumatoid arthritis defined as: ≥4 swollen joints and ≥4 tender/painful joints (from 28 joint count) and either erythrocyte sedimentation rate ≥28 mm/h, or C-reactive protein ≥10 mg/L.
-
Currently taking one of the following disease-modifying anti-rheumatic drugs: methotrexate, sulfasalazine, hydroxychloroquine or chloroquine.
-
Patients without essential hypertension or with essential hypertension if their blood pressure is controlled (<140/90 mmHg) with anti-hypertensive medications being stable at least 4 weeks prior to randomisation.
Exclusion Criteria:
-
Females who are pregnant or breastfeeding.
-
Certain inflammatory conditions (other than rheumatoid arthritis), connective tissue diseases or chronic pain disorders
-
History of liver problems that have required previous investigations
-
Evidence of tuberculosis infection
-
Conditions that preclude or render difficult the 24-hour ambulatory blood pressure monitoring technique.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Research Site | Huntsville | Alabama | United States | |
2 | Research Site | Huntington Beach | California | United States | |
3 | Research Site | Santa Maria | California | United States | |
4 | Research Site | Trumbull | Connecticut | United States | |
5 | Research Site | Boca Raton | Florida | United States | |
6 | Research Site | Brandon | Florida | United States | |
7 | Research Site | Orlando | Florida | United States | |
8 | Research Site | Tampa | Florida | United States | |
9 | Research Site | Venice | Florida | United States | |
10 | Research Site | Decatur | Georgia | United States | |
11 | Research Site | South Bend | Indiana | United States | |
12 | Research Site | Cumberland | Maryland | United States | |
13 | Research Site | Frederick | Maryland | United States | |
14 | Research Site | Hagerstown | Maryland | United States | |
15 | Research Site | Florissant | Missouri | United States | |
16 | Research Site | Richmond Heights | Missouri | United States | |
17 | Research Site | Freehold | New Jersey | United States | |
18 | Research Site | Albuquerque | New Mexico | United States | |
19 | Research Site | Brooklyn | New York | United States | |
20 | Research Site | Charlotte | North Carolina | United States | |
21 | Research Site | Greensboro | North Carolina | United States | |
22 | Research Site | Lake Oswego | Oregon | United States | |
23 | Research Site | Duncansville | Pennsylvania | United States | |
24 | Research Site | Memphis | Tennessee | United States | |
25 | Research Site | Austin | Texas | United States | |
26 | Research Site | Dallas | Texas | United States | |
27 | Research Site | Houston | Texas | United States | |
28 | Research Site | Lubbock | Texas | United States | |
29 | Research Site | Nassau Bay | Texas | United States | |
30 | Research Site | Tacoma | Washington | United States | |
31 | Research Site | Sevlievo | Bulgaria | ||
32 | Research Site | Sofia | Bulgaria | ||
33 | Research Site | Brno | Czech Republic | ||
34 | Research Site | Hlucin | Czech Republic | ||
35 | Research Site | Hostivice | Czech Republic | ||
36 | Research Site | Kladno | Czech Republic | ||
37 | Research Site | Ostrava-Trebovice | Czech Republic | ||
38 | Research Site | Praha 11 | Czech Republic | ||
39 | Research Site | Praha 2 | Czech Republic | ||
40 | Research Site | Praha 4 | Czech Republic | ||
41 | Research Site | Aachen | Germany | ||
42 | Research Site | Halle | Germany | ||
43 | Research Site | Gdynia | Poland | ||
44 | Research Site | Grodzisk Mazowiecki | Poland | ||
45 | Research Site | Kalisz | Poland | ||
46 | Research Site | Katowice | Poland | ||
47 | Research Site | Poznan | Poland | ||
48 | Research Site | Sroda Wielkopolska | Poland | ||
49 | Research Site | Wroclaw | Poland | ||
50 | Research Site | Łódź | Poland | ||
51 | Research Site | Bloemfontein | South Africa | ||
52 | Research Site | Cape Town | South Africa | ||
53 | Research Site | Durban | South Africa | ||
54 | Research Site | Kempron Park | South Africa | ||
55 | Research Site | Donetsk | Ukraine | ||
56 | Research Site | Kyiv | Ukraine | ||
57 | Research Site | Vinnytsia | Ukraine | ||
58 | Research Site | Zaporizhzhya | Ukraine | ||
59 | Research Site | Zaporozhye | Ukraine |
Sponsors and Collaborators
- AstraZeneca
Investigators
- Study Director: Chris O'Brien, MD PhD, AstraZeneca
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- D4300C00033
- 2011-006070-73
Study Results
Participant Flow
Recruitment Details | A total of 266 patients were enrolled. |
---|---|
Pre-assignment Detail | A total of 131 patients failed screening. |
Arm/Group Title | FOSTA 100 MG BID | PLACEBO |
---|---|---|
Arm/Group Description | Fostamatinib 100 mg bid, oral treatment | Oral treatment |
Period Title: Overall Study | ||
STARTED | 68 | 67 |
Randomised But Did Not Receive Treatment | 0 | 0 |
COMPLETED | 64 | 65 |
NOT COMPLETED | 4 | 2 |
Baseline Characteristics
Arm/Group Title | FOSTA 100 MG BID | PLACEBO | Total |
---|---|---|---|
Arm/Group Description | Fostamatinib 100 mg bid, oral treatment | Oral treatment | Total of all reporting groups |
Overall Participants | 68 | 67 | 135 |
Age (Years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [Years] |
54
(12.0)
|
54
(13.0)
|
54
(12.5)
|
Sex: Female, Male (Count of Participants) | |||
Female |
57
83.8%
|
57
85.1%
|
114
84.4%
|
Male |
11
16.2%
|
10
14.9%
|
21
15.6%
|
Race/Ethnicity, Customized (Number) [Number] | |||
White |
63
92.6%
|
58
86.6%
|
121
89.6%
|
Black or African American |
3
4.4%
|
8
11.9%
|
11
8.1%
|
Indian or Pakistani |
2
2.9%
|
1
1.5%
|
3
2.2%
|
Outcome Measures
Title | Change From Baseline in 24-hour Mean Ambulatory SBP |
---|---|
Description | ANCOVA=analysis of covariance, BID=twice daily, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure. |
Time Frame | 4 weeks |
Outcome Measure Data
Analysis Population Description |
---|
The FAS includes those randomised patients who received at least 1 dose of IP. Patients were analysed by randomised treatment in accordance with the intention to treat principle.The analysis population for each endpoint includes patients from the FAS still on IP at 4 weeks and with a valid measurement for this type of blood pressure assessment. |
Arm/Group Title | FOSTA 100 MG BID | PLACEBO |
---|---|---|
Arm/Group Description | Fostamatinib 100 mg bid, oral treatment | Oral treatment |
Measure Participants | 64 | 62 |
Mean (Standard Deviation) [mmHg] |
4.3
(7.34)
|
1.3
(7.87)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | FOSTA 100 MG BID, PLACEBO |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.023 |
Comments | ||
Method | ANCOVA | |
Comments | Inc. baseline (covariate); treatment, region, prior failure to biologic disease modifying antirheumatic drug & baseline antihypertensive use (factors) | |
Method of Estimation | Estimation Parameter | Least squares mean treatment difference |
Estimated Value | 2.93 | |
Confidence Interval |
(2-Sided) 95% 0.40 to 5.45 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline in 24-hour Mean Ambulatory DBP |
---|---|
Description | ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product. |
Time Frame | 4 weeks |
Outcome Measure Data
Analysis Population Description |
---|
The FAS includes those randomised patients who received at least 1 dose of IP. Patients were analysed by randomised treatment in accordance with the intention to treat principle.The analysis population for each endpoint includes patients from the FAS still on IP at 4 weeks and had a valid measurement for this type of blood pressure assessment. |
Arm/Group Title | FOSTA 100 MG BID | PLACEBO |
---|---|---|
Arm/Group Description | Fostamatinib 100 mg bid, oral treatment | Oral treatment |
Measure Participants | 64 | 62 |
Mean (Standard Deviation) [mmHg] |
4.4
(4.67)
|
0.7
(4.41)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | FOSTA 100 MG BID, PLACEBO |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.001 |
Comments | ||
Method | ANCOVA | |
Comments | Inc. baseline (covariate); treatment, region, prior failure to biologic disease modifying antirheumatic drug & baseline antihypertensive use (factors) | |
Method of Estimation | Estimation Parameter | Least squares mean treatment difference |
Estimated Value | 3.53 | |
Confidence Interval |
(2-Sided) 95% 2.04 to 5.03 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline in Mean Daytime and Night-time SBP and DBP by Ambulatory Blood Pressure Monitoring |
---|---|
Description | ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure. |
Time Frame | 4 weeks |
Outcome Measure Data
Analysis Population Description |
---|
The FAS includes those randomised patients who received at least 1 dose of IP. Patients were analysed by randomised treatment in accordance with the intention to treat principle.The analysis population for each endpoint includes patients from the FAS still on IP at 4 weeks and with a valid measurement for this type of blood pressure assessment. |
Arm/Group Title | FOSTA 100 MG BID | PLACEBO |
---|---|---|
Arm/Group Description | Fostamatinib 100 mg bid, oral treatment | Oral treatment |
Measure Participants | 64 | 62 |
Day 28 daytime SBP |
4.9
(8.44)
|
1.6
(8.45)
|
Day 28 daytime DBP |
4.7
(5.20)
|
0.8
(4.89)
|
Day 28 night-time SBP |
3.0
(8.59)
|
0.9
(9.75)
|
Day 28 night-time DBP |
3.7
(6.04)
|
0.8
(6.46)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | FOSTA 100 MG BID, PLACEBO |
---|---|---|
Comments | Change from baseline in mean daytime SBP (Day 28) | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.020 |
Comments | ||
Method | ANCOVA | |
Comments | Inc. baseline (covariate); treatment, region, prior failure to biologic disease modifying antirheumatic drug & baseline antihypertensive use (factors) | |
Method of Estimation | Estimation Parameter | Least square means treatment difference |
Estimated Value | 3.30 | |
Confidence Interval |
(2-Sided) 95% 0.53 to 6.08 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | FOSTA 100 MG BID, PLACEBO |
---|---|---|
Comments | Change from baseline in mean daytime DBP (Day 28) | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.001 |
Comments | ||
Method | ANCOVA | |
Comments | Inc. baseline (covariate); treatment, region, prior failure to biologic disease modifying antirheumatic drug & baseline antihypertensive use (factors) | |
Method of Estimation | Estimation Parameter | Least square means treatment difference |
Estimated Value | 3.75 | |
Confidence Interval |
(2-Sided) 95% 2.08 to 5.42 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | FOSTA 100 MG BID, PLACEBO |
---|---|---|
Comments | Change from baseline in mean night-time SBP (Day 28) | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.179 |
Comments | ||
Method | ANCOVA | |
Comments | Inc. baseline (covariate); treatment, region, prior failure to biologic disease modifying antirheumatic drug & baseline antihypertensive use (factors) | |
Method of Estimation | Estimation Parameter | Least square means treatment difference |
Estimated Value | 2.07 | |
Confidence Interval |
(2-Sided) 95% -0.96 to 5.11 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | FOSTA 100 MG BID, PLACEBO |
---|---|---|
Comments | Change from baseline in mean night-time DBP (Day 28) | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.002 |
Comments | ||
Method | ANCOVA | |
Comments | Inc. baseline (covariate); treatment, region, prior failure to biologic disease modifying antirheumatic drug & baseline antihypertensive use (factors) | |
Method of Estimation | Estimation Parameter | Least square means treatment difference |
Estimated Value | 3.14 | |
Confidence Interval |
(2-Sided) 95% 1.13 to 5.14 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline in Mean Awake SBP and DBP by Ambulatory Blood Pressure Monitoring |
---|---|
Description | ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure. |
Time Frame | 4 weeks |
Outcome Measure Data
Analysis Population Description |
---|
The FAS includes those randomised patients who received at least 1 dose of IP. Patients were analysed by randomised treatment in accordance with the intention to treat principle.The analysis population for each endpoint includes patients from the FAS still on IP at 4 weeks and with a valid measurement for this type of blood pressure assessment. |
Arm/Group Title | FOSTA 100 MG BID | PLACEBO |
---|---|---|
Arm/Group Description | Fostamatinib 100 mg bid, oral treatment | Oral treatment |
Measure Participants | 63 | 62 |
Day 28 awake SBP |
4.8
(8.24)
|
1.4
(8.37)
|
Day 28 awake DBP |
4.8
(4.80)
|
0.8
(4.69)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | FOSTA 100 MG BID, PLACEBO |
---|---|---|
Comments | Change from baseline in mean awake SBP (Day 28) | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.024 |
Comments | ||
Method | ANCOVA | |
Comments | Inc. baseline (covariate); treatment, region, prior failure to biologic disease modifying antirheumatic drug & baseline antihypertensive use (factors) | |
Method of Estimation | Estimation Parameter | Least square means treatment difference |
Estimated Value | 3.11 | |
Confidence Interval |
(2-Sided) 95% 0.41 to 5.81 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | FOSTA 100 MG BID, PLACEBO |
---|---|---|
Comments | Change from baseline in mean awake DBP (Day 28) | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.001 |
Comments | ||
Method | ANCOVA | |
Comments | Inc. baseline (covariate); treatment, region, prior failure to biologic disease modifying antirheumatic drug & baseline antihypertensive use (factors) | |
Method of Estimation | Estimation Parameter | Least square means treatment difference |
Estimated Value | 3.66 | |
Confidence Interval |
(2-Sided) 95% 2.10 to 5.22 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline in Mean Sleeping SBP and DBP by Ambulatory Blood Pressure Monitoring |
---|---|
Description | ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure. |
Time Frame | 4 weeks |
Outcome Measure Data
Analysis Population Description |
---|
The FAS includes those randomised patients who received at least 1 dose of IP. Patients were analysed by randomised treatment in accordance with the intention to treat principle.The analysis population for each endpoint includes patients from the FAS still on IP at 4 weeks and with a valid measurement for this type of blood pressure assessment. |
Arm/Group Title | FOSTA 100 MG BID | PLACEBO |
---|---|---|
Arm/Group Description | Fostamatinib 100 mg bid, oral treatment | Oral treatment |
Measure Participants | 58 | 60 |
Day 28 sleeping SBP |
2.4
(8.86)
|
0.7
(10.12)
|
Day 28 sleeping DBP |
2.8
(6.28)
|
0.5
(6.72)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | FOSTA 100 MG BID, PLACEBO |
---|---|---|
Comments | Change from baseline in mean sleeping SBP | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.223 |
Comments | ||
Method | ANCOVA | |
Comments | Inc. baseline (covariate); treatment, region, prior failure to biologic disease modifying antirheumatic drug & baseline antihypertensive use (factors) | |
Method of Estimation | Estimation Parameter | Least squares mean treatment difference |
Estimated Value | 1.99 | |
Confidence Interval |
(2-Sided) 95% -1.22 to 5.20 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | FOSTA 100 MG BID, PLACEBO |
---|---|---|
Comments | Change from baseline in mean sleeping DBP | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.007 |
Comments | ||
Method | ANCOVA | |
Comments | Inc. baseline (covariate); treatment, region, prior failure to biologic disease modifying antirheumatic drug & baseline antihypertensive use (factors) | |
Method of Estimation | Estimation Parameter | Least square means treatment difference |
Estimated Value | 2.87 | |
Confidence Interval |
(2-Sided) 95% 0.81 to 4.93 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Mean Change From Baseline in Clinic SBP and DBP |
---|---|
Description | Blood pressure was measured in the clinic using an automated blood pressure machine (oscillometric method). Three separate measurements were taken 2 to 5 minutes apart and the mean of the 2nd and 3rd measurements calculated. ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure. |
Time Frame | 4 weeks |
Outcome Measure Data
Analysis Population Description |
---|
The FAS includes those randomised patients who received at least 1 dose of IP. Patients were analysed by randomised treatment in accordance with the intention to treat principle.The analysis population for each endpoint includes patients from the FAS still on IP at 4 weeks and with a valid measurement for this type of blood pressure assessment. |
Arm/Group Title | FOSTA 100 MG BID | PLACEBO |
---|---|---|
Arm/Group Description | Fostamatinib 100 mg bid, oral treatment | Oral treatment |
Measure Participants | 64 | 64 |
Day 29 SBP |
3.8
(11.53)
|
2.9
(9.61)
|
Day 29 DBP |
2.7
(7.88)
|
0.7
(6.72)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | FOSTA 100 MG BID, PLACEBO |
---|---|---|
Comments | Change from baseline in clinic SBP (Day 29) | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.200 |
Comments | ||
Method | ANCOVA | |
Comments | Inc. baseline (covariate); treatment, region, prior failure to biologic disease modifying antirheumatic drug & baseline antihypertensive use (factors) | |
Method of Estimation | Estimation Parameter | Least square means treatment difference |
Estimated Value | 2.24 | |
Confidence Interval |
(2-Sided) 95% -1.20 to 5.69 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | FOSTA 100 MG BID, PLACEBO |
---|---|---|
Comments | Change from baseline in clinic DBP (Day 29) | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.046 |
Comments | ||
Method | ANCOVA | |
Comments | Inc. baseline (covariate); treatment, region, prior failure to biologic disease modifying antirheumatic drug & baseline antihypertensive use (factors) | |
Method of Estimation | Estimation Parameter | Least square means treatment difference |
Estimated Value | 2.36 | |
Confidence Interval |
(2-Sided) 95% 0.05 to 4.68 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Mean Change From Baseline in Morning Pre-dose Home SBP and DBP |
---|---|
Description | ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure. |
Time Frame | 4 weeks |
Outcome Measure Data
Analysis Population Description |
---|
The FAS includes those randomised patients who received at least 1 dose of IP. Patients were analysed by randomised treatment in accordance with the intention to treat principle.The analysis population for each endpoint includes patients from the FAS still on IP at 4 weeks and with a valid measurement for this type of blood pressure assessment. |
Arm/Group Title | FOSTA 100 MG BID | PLACEBO |
---|---|---|
Arm/Group Description | Fostamatinib 100 mg bid, oral treatment | Oral treatment |
Measure Participants | 62 | 59 |
Weekly average pre-dose SBP (Week 4) |
5.1
(8.53)
|
-1.3
(6.50)
|
Weekly average pre-dose DBP (Week 4) |
4.0
(5.82)
|
-0.4
(3.78)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | FOSTA 100 MG BID, PLACEBO |
---|---|---|
Comments | Change from baseline in weekly average pre-dose home SBP (Week 4) | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.001 |
Comments | ||
Method | ANCOVA | |
Comments | Inc. baseline (covariate); treatment, region, prior failure to biologic disease modifying antirheumatic drug & baseline antihypertensive use (factors) | |
Method of Estimation | Estimation Parameter | Least square means treatment difference |
Estimated Value | 6.31 | |
Confidence Interval |
(2-Sided) 95% 3.60 to 9.03 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | FOSTA 100 MG BID, PLACEBO |
---|---|---|
Comments | Change from baseline in weekly average pre-dose home DBP (Week 4) | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.001 |
Comments | ||
Method | ANCOVA | |
Comments | Inc. baseline (covariate); treatment, region, prior failure to biologic disease modifying antirheumatic drug & baseline antihypertensive use (factors) | |
Method of Estimation | Estimation Parameter | Least square means treatment difference |
Estimated Value | 4.58 | |
Confidence Interval |
(2-Sided) 95% 2.91 to 6.25 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Mean Change From Baseline in Evening Post-dose Home SBP and DBP |
---|---|
Description | ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure. |
Time Frame | 4 weeks |
Outcome Measure Data
Analysis Population Description |
---|
The FAS includes those randomised patients who received at least 1 dose of IP. Patients were analysed by randomised treatment in accordance with the intention to treat principle.The analysis population for each endpoint includes patients from the FAS still on IP at 4 weeks and with a valid measurement for this type of blood pressure assessment. |
Arm/Group Title | FOSTA 100 MG BID | PLACEBO |
---|---|---|
Arm/Group Description | Fostamatinib 100 mg bid, oral treatment | Oral treatment |
Measure Participants | 61 | 59 |
Weekly average post-dose SBP (Week 4) |
5.3
(9.11)
|
-1.6
(7.71)
|
Weekly average post-dose DBP (Week 4) |
3.7
(5.69)
|
-1.0
(4.95)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | FOSTA 100 MG BID, PLACEBO |
---|---|---|
Comments | Change from baseline in weekly average post-dose home SBP (Week 4) | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.001 |
Comments | ||
Method | ANCOVA | |
Comments | Inc. baseline (covariate); treatment, region, prior failure to biologic disease modifying antirheumatic drug & baseline antihypertensive use (factors) | |
Method of Estimation | Estimation Parameter | Least square means treatment difference |
Estimated Value | 7.22 | |
Confidence Interval |
(2-Sided) 95% 4.29 to 10.16 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | FOSTA 100 MG BID, PLACEBO |
---|---|---|
Comments | Change from baseline in weekly average post-dose home DBP (Week 4) | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.001 |
Comments | ||
Method | ANCOVA | |
Comments | Inc. baseline (covariate); treatment, region, prior failure to biologic disease modifying antirheumatic drug & baseline antihypertensive use (factors) | |
Method of Estimation | Estimation Parameter | Least square means treatment difference |
Estimated Value | 4.74 | |
Confidence Interval |
(2-Sided) 95% 2.90 to 6.59 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Mean Change From Completion/Discontinuation to Follow-up in Clinical Measurement of SBP and DBP |
---|---|
Description | BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure. |
Time Frame | Day 29 to Day 36 |
Outcome Measure Data
Analysis Population Description |
---|
The FAS includes those randomised patients who received at least 1 dose of IP. Patients were analysed by randomised treatment in accordance with the intention to treat principle. The analysis population for each endpoint includes patients from the FAS still on IP at Day 36 and with a valid measurement for this type of blood pressure assessment. |
Arm/Group Title | FOSTA 100 MG BID | PLACEBO |
---|---|---|
Arm/Group Description | Fostamatinib 100 mg bid, oral treatment | Oral treatment |
Measure Participants | 64 | 64 |
SBP |
-3.3
(12.32)
|
-0.5
(9.25)
|
DBP |
-1.8
(9.56)
|
-0.6
(6.38)
|
Title | DAS28-CRP Improvement |
---|---|
Description | ANCOVA=analysis of covariance, BID=twice daily, DAS28-CRP=Disease Activity Score based on a count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (C-reactive protein [CRP]) and the patient's own assessment, FAS=full analysis set, IP=investigational product. Scores can take any positive value with a lower value indicative of a better clinical condition. Mean changes from baseline in DAS28-CRP score are shown at each visit and are presented as decreases from baseline (defined as baseline minus post-baseline) with larger changes indicating a better clinical condition. |
Time Frame | 4 weeks |
Outcome Measure Data
Analysis Population Description |
---|
The FAS includes those randomised patients who received at least 1 dose of IP. Patients were analysed by randomised treatment in accordance with the intention to treat principle. The analysis population for each endpoint includes those patients from the FAS who were still on IP at 4 weeks and had a valid measurement for this type of assessment. |
Arm/Group Title | FOSTA 100 MG BID | PLACEBO |
---|---|---|
Arm/Group Description | Fostamatinib 100 mg bid, oral treatment | Oral treatment |
Measure Participants | 67 | 67 |
Day 8 |
0.8
(0.77)
|
0.3
(0.61)
|
Day 15 |
1.0
(1.06)
|
0.3
(0.77)
|
Day 29 |
1.2
(1.06)
|
0.5
(1.00)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | FOSTA 100 MG BID, PLACEBO |
---|---|---|
Comments | Improvement from baseline at Day 29. Non-responder imputation has been applied following premature withdrawal, or any dose of background disease modifying antirheumatic drug increased or any other RA treatment initiated including DMARDs, anti-TNFs or other biologics, or receiving 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 | Inc. baseline (covariate); treatment, region, prior failure to biologic disease modifying antirheumatic drug & baseline antihypertensive use (factors) | |
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Least square means treatment difference |
Estimated Value | 0.74 | |
Confidence Interval |
(2-Sided) 95% 0.40 to 1.08 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Adverse Events
Time Frame | ||||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | FOSTA 100 MG BID | PLACEBO | ||
Arm/Group Description | ||||
All Cause Mortality |
||||
FOSTA 100 MG BID | PLACEBO | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
FOSTA 100 MG BID | PLACEBO | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/68 (0%) | 0/67 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
FOSTA 100 MG BID | PLACEBO | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 2/68 (2.9%) | 4/67 (6%) | ||
Gastrointestinal disorders | ||||
DIARRHOEA | 2/68 (2.9%) | 3 | 4/67 (6%) | 4 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The disclosure restriction on the PI is that the sponsor can review and comment on results communications prior to publication or presentation. Sponsor will be allowed a review period of at least 60 days from submission but can request that the submission be delayed for an additional 90 days from the date of Sponsor's request.
Results Point of Contact
Name/Title | Dave Goldstraw |
---|---|
Organization | AstraZeneca Pharmaceuticals |
Phone | +44-1625-512415 |
dave.goldstraw@astrazeneca.com |
- D4300C00033
- 2011-006070-73