Trial Outcomes & Findings for Study of the Effect of Fostamatinib Twice Daily on Blood Pressure in Patients With Rheumatoid Arthritis (NCT NCT01563978)

NCT ID: NCT01563978

Last Updated: 2014-05-08

Results Overview

ANCOVA=analysis of covariance, BID=twice daily, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 266 participants
• Primary outcome timeframe: 4 weeks
• Results posted on: 2014-05-08

Participant Flow

A total of 266 patients were enrolled.

A total of 131 patients failed screening.

Participant milestones

Measure	FOSTA 100 MG BID Fostamatinib 100 mg bid, oral treatment	PLACEBO Oral treatment
Overall Study STARTED	68	67
Overall Study Randomised But Did Not Receive Treatment	0	0
Overall Study COMPLETED	64	65
Overall Study NOT COMPLETED	4	2

Reasons for withdrawal

Measure	FOSTA 100 MG BID Fostamatinib 100 mg bid, oral treatment	PLACEBO Oral treatment
Overall Study Physician Decision	1	0
Overall Study Lost to Follow-up	1	0
Overall Study Dev. of study specific discont. criteria	1	0
Overall Study Adverse Event	1	2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	FOSTA 100 MG BID n=68 Participants Fostamatinib 100 mg bid, oral treatment	PLACEBO n=67 Participants Oral treatment	Total n=135 Participants Total of all reporting groups
Age, Continuous	54 Years STANDARD_DEVIATION 12.0 • n=5 Participants	54 Years STANDARD_DEVIATION 13.0 • n=7 Participants	54 Years STANDARD_DEVIATION 12.5 • n=5 Participants
Sex: Female, Male Female	57 Participants n=5 Participants	57 Participants n=7 Participants	114 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Race/Ethnicity, Customized White	63 Participants n=5 Participants	58 Participants n=7 Participants	121 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Indian or Pakistani	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

ANCOVA=analysis of covariance, BID=twice daily, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure.

Outcome measures

Measure	FOSTA 100 MG BID n=64 Participants Fostamatinib 100 mg bid, oral treatment	PLACEBO n=62 Participants Oral treatment
Change From Baseline in 24-hour Mean Ambulatory SBP	4.3 mmHg Standard Deviation 7.34	1.3 mmHg Standard Deviation 7.87

SECONDARY outcome

Timeframe: 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.

ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product.

Outcome measures

Measure	FOSTA 100 MG BID n=64 Participants Fostamatinib 100 mg bid, oral treatment	PLACEBO n=62 Participants Oral treatment
Change From Baseline in 24-hour Mean Ambulatory DBP	4.4 mmHg Standard Deviation 4.67	0.7 mmHg Standard Deviation 4.41

SECONDARY outcome

Timeframe: 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.

ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure.

Outcome measures

Measure	FOSTA 100 MG BID n=64 Participants Fostamatinib 100 mg bid, oral treatment	PLACEBO n=62 Participants Oral treatment
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	1.6 mmHg Standard Deviation 8.45
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 5.20	0.8 mmHg Standard Deviation 4.89
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	0.9 mmHg Standard Deviation 9.75
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	0.8 mmHg Standard Deviation 6.46

SECONDARY outcome

Timeframe: 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.

ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure.

Outcome measures

Measure	FOSTA 100 MG BID n=63 Participants Fostamatinib 100 mg bid, oral treatment	PLACEBO n=62 Participants Oral treatment
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	1.4 mmHg Standard Deviation 8.37
Change From Baseline in Mean Awake SBP and DBP by Ambulatory Blood Pressure Monitoring Day 28 awake DBP	4.8 mmHg Standard Deviation 4.80	0.8 mmHg Standard Deviation 4.69

SECONDARY outcome

Timeframe: 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.

ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure.

Outcome measures

Measure	FOSTA 100 MG BID n=58 Participants Fostamatinib 100 mg bid, oral treatment	PLACEBO n=60 Participants Oral treatment
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	0.7 mmHg Standard Deviation 10.12
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	0.5 mmHg Standard Deviation 6.72

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	FOSTA 100 MG BID n=64 Participants Fostamatinib 100 mg bid, oral treatment	PLACEBO n=64 Participants Oral treatment
Mean Change From Baseline in Clinic SBP and DBP Day 29 SBP	3.8 mmHg Standard Deviation 11.53	2.9 mmHg Standard Deviation 9.61
Mean Change From Baseline in Clinic SBP and DBP Day 29 DBP	2.7 mmHg Standard Deviation 7.88	0.7 mmHg Standard Deviation 6.72

SECONDARY outcome

Timeframe: 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.

ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure.

Outcome measures

Measure	FOSTA 100 MG BID n=62 Participants Fostamatinib 100 mg bid, oral treatment	PLACEBO n=59 Participants Oral treatment
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	-1.3 mmHg Standard Deviation 6.50
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	-0.4 mmHg Standard Deviation 3.78

SECONDARY outcome

Timeframe: 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.

ANCOVA=analysis of covariance, BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure.

Outcome measures

Measure	FOSTA 100 MG BID n=61 Participants Fostamatinib 100 mg bid, oral treatment	PLACEBO n=59 Participants Oral treatment
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	-1.0 mmHg Standard Deviation 4.95
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	-1.6 mmHg Standard Deviation 7.71

SECONDARY outcome

Timeframe: 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.

BID=twice daily, DBP=diastolic blood pressure, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure.

Outcome measures

Measure	FOSTA 100 MG BID n=64 Participants Fostamatinib 100 mg bid, oral treatment	PLACEBO n=64 Participants Oral treatment
Mean Change From Completion/Discontinuation to Follow-up in Clinical Measurement of SBP and DBP SBP	-3.3 mmHg Standard Deviation 12.32	-0.5 mmHg Standard Deviation 9.25
Mean Change From Completion/Discontinuation to Follow-up in Clinical Measurement of SBP and DBP DBP	-1.8 mmHg Standard Deviation 9.56	-0.6 mmHg Standard Deviation 6.38

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	FOSTA 100 MG BID n=67 Participants Fostamatinib 100 mg bid, oral treatment	PLACEBO n=67 Participants Oral treatment
DAS28-CRP Improvement Day 15	1.0 Units on a scale Standard Deviation 1.06	0.3 Units on a scale Standard Deviation 0.77
DAS28-CRP Improvement Day 8	0.8 Units on a scale Standard Deviation 0.77	0.3 Units on a scale Standard Deviation 0.61
DAS28-CRP Improvement Day 29	1.2 Units on a scale Standard Deviation 1.06	0.5 Units on a scale Standard Deviation 1.00

Adverse Events

FOSTA 100 MG BID

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

PLACEBO

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	FOSTA 100 MG BID n=68 participants at risk	PLACEBO n=67 participants at risk
Gastrointestinal disorders DIARRHOEA	2.9% 2/68 • Number of events 3	6.0% 4/67 • Number of events 4

Additional Information

Dave Goldstraw

AstraZeneca Pharmaceuticals

Phone: +44-1625-512415

Email: dave.goldstraw@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER