Oskira ABPM: Study of the Effect of Fostamatinib Twice Daily on Blood Pressure in Patients With Rheumatoid Arthritis

Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT01563978
Collaborator
(none)
266
59
2
9
4.5
0.5

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

Study Type:
Interventional
Actual Enrollment :
266 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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 Start Date :
Apr 1, 2012
Actual Primary Completion Date :
Jan 1, 2013
Actual Study Completion Date :
Jan 1, 2013

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

  1. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01563978
Other Study ID Numbers:
  • D4300C00033
  • 2011-006070-73
First Posted:
Mar 27, 2012
Last Update Posted:
May 8, 2014
Last Verified:
Apr 1, 2014
Keywords provided by AstraZeneca
Additional relevant MeSH terms:

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

1. Primary Outcome
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
2. Secondary Outcome
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
3. Secondary Outcome
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
4. Secondary Outcome
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
5. Secondary Outcome
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
6. Secondary Outcome
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
7. Secondary Outcome
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
8. Secondary Outcome
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
9. Secondary Outcome
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)
10. Secondary Outcome
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

[Not Specified]

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
Email dave.goldstraw@astrazeneca.com
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01563978
Other Study ID Numbers:
  • D4300C00033
  • 2011-006070-73
First Posted:
Mar 27, 2012
Last Update Posted:
May 8, 2014
Last Verified:
Apr 1, 2014