Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis
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.
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
Interventions
DRUGfostamatinib
fostamatinib 100 mg twice daily
DRUGplacebo
placebo
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Bulgaria, Czechia, Germany, Poland, South Africa, Ukraine, United States
Participant flow
Recruitment details
A total of 266 patients were enrolled.
Pre-assignment details
A total of 131 patients failed screening.
Participants by arm
| Arm | Count |
|---|---|
| FOSTA 100 MG BID Fostamatinib 100 mg bid, oral treatment | 68 |
| PLACEBO Oral treatment | 67 |
| Total | 135 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Dev. of study specific discont. criteria | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | PLACEBO | Total | FOSTA 100 MG BID |
|---|---|---|---|
| Age, Continuous | 54 Years STANDARD_DEVIATION 13 | 54 Years STANDARD_DEVIATION 12.5 | 54 Years STANDARD_DEVIATION 12 |
| Race/Ethnicity, Customized Black or African American | 8 Participants | 11 Participants | 3 Participants |
| Race/Ethnicity, Customized Indian or Pakistani | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 58 Participants | 121 Participants | 63 Participants |
| Sex: Female, Male Female | 57 Participants | 114 Participants | 57 Participants |
| Sex: Female, Male Male | 10 Participants | 21 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 68 | 4 / 67 |
| serious Total, serious adverse events | 0 / 68 | 0 / 67 |
Outcome results
Primary
Change From Baseline in 24-hour Mean Ambulatory SBP
ANCOVA=analysis of covariance, BID=twice daily, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure.
Time frame: 4 weeks
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FOSTA 100 MG BID | Change From Baseline in 24-hour Mean Ambulatory SBP | 4.3 mmHg | Standard Deviation 7.34 |
| PLACEBO | Change From Baseline in 24-hour Mean Ambulatory SBP | 1.3 mmHg | Standard Deviation 7.87 |
p-value: 0.02395% CI: [0.4, 5.45]ANCOVA
Secondary
Change From Baseline in 24-hour Mean Ambulatory DBP
ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product.
Time frame: 4 weeks
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FOSTA 100 MG BID | Change From Baseline in 24-hour Mean Ambulatory DBP | 4.4 mmHg | Standard Deviation 4.67 |
| PLACEBO | Change From Baseline in 24-hour Mean Ambulatory DBP | 0.7 mmHg | Standard Deviation 4.41 |
p-value: <0.00195% CI: [2.04, 5.03]ANCOVA
Secondary
Change From Baseline in Mean Awake SBP and DBP by Ambulatory Blood Pressure Monitoring
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FOSTA 100 MG BID | Change From Baseline in Mean Awake SBP and DBP by Ambulatory Blood Pressure Monitoring | Day 28 awake SBP | 4.8 mmHg | Standard Deviation 8.24 |
| FOSTA 100 MG BID | Change From Baseline in Mean Awake SBP and DBP by Ambulatory Blood Pressure Monitoring | Day 28 awake DBP | 4.8 mmHg | Standard Deviation 4.8 |
| PLACEBO | Change From Baseline in Mean Awake SBP and DBP by Ambulatory Blood Pressure Monitoring | Day 28 awake SBP | 1.4 mmHg | Standard Deviation 8.37 |
| PLACEBO | Change From Baseline in Mean Awake SBP and DBP by Ambulatory Blood Pressure Monitoring | Day 28 awake DBP | 0.8 mmHg | Standard Deviation 4.69 |
Comparison: Change from baseline in mean awake SBP (Day 28)p-value: 0.02495% CI: [0.41, 5.81]ANCOVA
Comparison: Change from baseline in mean awake DBP (Day 28)p-value: <0.00195% CI: [2.1, 5.22]ANCOVA
Secondary
Change From Baseline in Mean Daytime and Night-time SBP and DBP by Ambulatory Blood Pressure Monitoring
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FOSTA 100 MG BID | Change From Baseline in Mean Daytime and Night-time SBP and DBP by Ambulatory Blood Pressure Monitoring | Day 28 daytime SBP | 4.9 mmHg | Standard Deviation 8.44 |
| FOSTA 100 MG BID | Change From Baseline in Mean Daytime and Night-time SBP and DBP by Ambulatory Blood Pressure Monitoring | Day 28 daytime DBP | 4.7 mmHg | Standard Deviation 5.2 |
| FOSTA 100 MG BID | Change From Baseline in Mean Daytime and Night-time SBP and DBP by Ambulatory Blood Pressure Monitoring | Day 28 night-time SBP | 3.0 mmHg | Standard Deviation 8.59 |
| FOSTA 100 MG BID | Change From Baseline in Mean Daytime and Night-time SBP and DBP by Ambulatory Blood Pressure Monitoring | Day 28 night-time DBP | 3.7 mmHg | Standard Deviation 6.04 |
| PLACEBO | Change From Baseline in Mean Daytime and Night-time SBP and DBP by Ambulatory Blood Pressure Monitoring | Day 28 night-time DBP | 0.8 mmHg | Standard Deviation 6.46 |
| PLACEBO | Change From Baseline in Mean Daytime and Night-time SBP and DBP by Ambulatory Blood Pressure Monitoring | Day 28 daytime SBP | 1.6 mmHg | Standard Deviation 8.45 |
| PLACEBO | Change From Baseline in Mean Daytime and Night-time SBP and DBP by Ambulatory Blood Pressure Monitoring | Day 28 night-time SBP | 0.9 mmHg | Standard Deviation 9.75 |
| PLACEBO | Change From Baseline in Mean Daytime and Night-time SBP and DBP by Ambulatory Blood Pressure Monitoring | Day 28 daytime DBP | 0.8 mmHg | Standard Deviation 4.89 |
Comparison: Change from baseline in mean daytime SBP (Day 28)p-value: 0.0295% CI: [0.53, 6.08]ANCOVA
Comparison: Change from baseline in mean daytime DBP (Day 28)p-value: <0.00195% CI: [2.08, 5.42]ANCOVA
Comparison: Change from baseline in mean night-time SBP (Day 28)p-value: 0.17995% CI: [-0.96, 5.11]ANCOVA
Comparison: Change from baseline in mean night-time DBP (Day 28)p-value: 0.00295% CI: [1.13, 5.14]ANCOVA
Secondary
Change From Baseline in Mean Sleeping SBP and DBP by Ambulatory Blood Pressure Monitoring
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FOSTA 100 MG BID | Change From Baseline in Mean Sleeping SBP and DBP by Ambulatory Blood Pressure Monitoring | Day 28 sleeping SBP | 2.4 mmHg | Standard Deviation 8.86 |
| FOSTA 100 MG BID | Change From Baseline in Mean Sleeping SBP and DBP by Ambulatory Blood Pressure Monitoring | Day 28 sleeping DBP | 2.8 mmHg | Standard Deviation 6.28 |
| PLACEBO | Change From Baseline in Mean Sleeping SBP and DBP by Ambulatory Blood Pressure Monitoring | Day 28 sleeping SBP | 0.7 mmHg | Standard Deviation 10.12 |
| PLACEBO | Change From Baseline in Mean Sleeping SBP and DBP by Ambulatory Blood Pressure Monitoring | Day 28 sleeping DBP | 0.5 mmHg | Standard Deviation 6.72 |
Comparison: Change from baseline in mean sleeping SBPp-value: 0.22395% CI: [-1.22, 5.2]ANCOVA
Comparison: Change from baseline in mean sleeping DBPp-value: 0.00795% CI: [0.81, 4.93]ANCOVA
Secondary
DAS28-CRP Improvement
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FOSTA 100 MG BID | DAS28-CRP Improvement | Day 8 | 0.8 Units on a scale | Standard Deviation 0.77 |
| FOSTA 100 MG BID | DAS28-CRP Improvement | Day 15 | 1.0 Units on a scale | Standard Deviation 1.06 |
| FOSTA 100 MG BID | DAS28-CRP Improvement | Day 29 | 1.2 Units on a scale | Standard Deviation 1.06 |
| PLACEBO | DAS28-CRP Improvement | Day 8 | 0.3 Units on a scale | Standard Deviation 0.61 |
| PLACEBO | DAS28-CRP Improvement | Day 15 | 0.3 Units on a scale | Standard Deviation 0.77 |
| PLACEBO | DAS28-CRP Improvement | Day 29 | 0.5 Units on a scale | Standard Deviation 1 |
Comparison: 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.p-value: <0.00195% CI: [0.4, 1.08]ANCOVA
Secondary
Mean Change From Baseline in Clinic SBP and DBP
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FOSTA 100 MG BID | Mean Change From Baseline in Clinic SBP and DBP | Day 29 DBP | 2.7 mmHg | Standard Deviation 7.88 |
| FOSTA 100 MG BID | Mean Change From Baseline in Clinic SBP and DBP | Day 29 SBP | 3.8 mmHg | Standard Deviation 11.53 |
| PLACEBO | Mean Change From Baseline in Clinic SBP and DBP | Day 29 SBP | 2.9 mmHg | Standard Deviation 9.61 |
| PLACEBO | Mean Change From Baseline in Clinic SBP and DBP | Day 29 DBP | 0.7 mmHg | Standard Deviation 6.72 |
Comparison: Change from baseline in clinic SBP (Day 29)p-value: 0.295% CI: [-1.2, 5.69]ANCOVA
Comparison: Change from baseline in clinic DBP (Day 29)p-value: 0.04695% CI: [0.05, 4.68]ANCOVA
Secondary
Mean Change From Baseline in Evening Post-dose Home SBP and DBP
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FOSTA 100 MG BID | Mean Change From Baseline in Evening Post-dose Home SBP and DBP | Weekly average post-dose SBP (Week 4) | 5.3 mmHg | Standard Deviation 9.11 |
| FOSTA 100 MG BID | Mean Change From Baseline in Evening Post-dose Home SBP and DBP | Weekly average post-dose DBP (Week 4) | 3.7 mmHg | Standard Deviation 5.69 |
| PLACEBO | Mean Change From Baseline in Evening Post-dose Home SBP and DBP | Weekly average post-dose SBP (Week 4) | -1.6 mmHg | Standard Deviation 7.71 |
| PLACEBO | Mean Change From Baseline in Evening Post-dose Home SBP and DBP | Weekly average post-dose DBP (Week 4) | -1.0 mmHg | Standard Deviation 4.95 |
Comparison: Change from baseline in weekly average post-dose home SBP (Week 4)p-value: <0.00195% CI: [4.29, 10.16]ANCOVA
Comparison: Change from baseline in weekly average post-dose home DBP (Week 4)p-value: <0.00195% CI: [2.9, 6.59]ANCOVA
Secondary
Mean Change From Baseline in Morning Pre-dose Home SBP and DBP
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FOSTA 100 MG BID | Mean Change From Baseline in Morning Pre-dose Home SBP and DBP | Weekly average pre-dose SBP (Week 4) | 5.1 mmHg | Standard Deviation 8.53 |
| FOSTA 100 MG BID | Mean Change From Baseline in Morning Pre-dose Home SBP and DBP | Weekly average pre-dose DBP (Week 4) | 4.0 mmHg | Standard Deviation 5.82 |
| PLACEBO | Mean Change From Baseline in Morning Pre-dose Home SBP and DBP | Weekly average pre-dose SBP (Week 4) | -1.3 mmHg | Standard Deviation 6.5 |
| PLACEBO | Mean Change From Baseline in Morning Pre-dose Home SBP and DBP | Weekly average pre-dose DBP (Week 4) | -0.4 mmHg | Standard Deviation 3.78 |
Comparison: Change from baseline in weekly average pre-dose home SBP (Week 4)p-value: <0.00195% CI: [3.6, 9.03]ANCOVA
Comparison: Change from baseline in weekly average pre-dose home DBP (Week 4)p-value: <0.00195% CI: [2.91, 6.25]ANCOVA
Secondary
Mean Change From Completion/Discontinuation to Follow-up in Clinical Measurement of SBP and DBP
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FOSTA 100 MG BID | Mean Change From Completion/Discontinuation to Follow-up in Clinical Measurement of SBP and DBP | SBP | -3.3 mmHg | Standard Deviation 12.32 |
| FOSTA 100 MG BID | Mean Change From Completion/Discontinuation to Follow-up in Clinical Measurement of SBP and DBP | DBP | -1.8 mmHg | Standard Deviation 9.56 |
| PLACEBO | Mean Change From Completion/Discontinuation to Follow-up in Clinical Measurement of SBP and DBP | SBP | -0.5 mmHg | Standard Deviation 9.25 |
| PLACEBO | Mean Change From Completion/Discontinuation to Follow-up in Clinical Measurement of SBP and DBP | DBP | -0.6 mmHg | Standard Deviation 6.38 |