Evaluation of Effectiveness of Two Dosing Regimens of Fos... | NCT01197755

NCT01197755

ID	Type	Description	Link
2010-020745-27	EudraCT Number

Status Module

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Dosing Regimen A	Experimental	Oral Treatment	Drug: fostamatinib
Dosing Regimen B	Experimental	Oral Treatment	Drug: fostamatinib
Dosing Regimen C	Placebo Comparator	Oral Treatment	Drug: placebo

Name	Type	Description	Arm Group Labels	Other Names
fostamatinib	Drug	fostamatinib 100 mg twice daily	Dosing Regimen A

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Proportion of Patients Achieving ACR20 at Week 24, Comparison Between Fostamatinib and Placebo	ACR20: American College of Rheumatology 20% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as C-Reactive Protein) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once daily.	24 weeks

Secondary Outcomes

Measure	Description	Time Frame
Proportion of Patients Achieving ACR20 at Week 1, Comparison Between Fostamatinib and Placebo	ACR20: American College of Rheumatology 20% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as C-Reactive Protein) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once daily.

Eligibility Module

Name	Affiliation	Role
Neil MacKillop, MD PhD	AstraZeneca	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Anniston	Alabama		United States
Research Site

Label	URL
Related Info	View source
Related Info	View source

Results Section

Participant Flow Module

ID	Title	Description
FG000	FOSTA 100 MG BID PO	Dosing Group A
FG001	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO	Dosing Group B

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	FOSTA 100 MG BID PO	Dosing Group A
BG001	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO	Dosing Group B
BG002	PLACEBO PO	Dosing Group C
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00054± 11.9 BG00151± 12.0 BG00253± 13.0 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00089 BG00187 BG002

Race/Ethnicity, Customized

Number

Participants

Title

Denominators

Categories

White

Title	Measurements
	BG00086 BG00192 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Proportion of Patients Achieving ACR20 at Week 24, Comparison Between Fostamatinib and Placebo

ACR20: American College of Rheumatology 20% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as C-Reactive Protein) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once daily.

The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.

Posted

Number

Percentage of responders

24 weeks

ID	Title	Description
OG000	FOSTA 100 MG BID PO	Dosing Group A
OG001	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO	Dosing Group B
OG002	PLACEBO PO	Dosing Group C

Units	Counts
Participants	OG000105 OG001108 OG002109

Title

Denominators

Categories

Title	Measurements
	OG00036.2 OG00127.8 OG00221.1

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002	Non-responder imputation has been applied following premature withdrawal, or increased dose of methotrexate or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.	Mantel Haenszel	Treatment difference in proportion of responders at Week 24 with a Mantel-Haenszel approach stratified by pooled country.	0.004	Week 24	Weighted difference in proportion	0.17			2-Sided	95	0.05	0.28				No	Superiority or Other

Secondary

Proportion of Patients Achieving ACR20 at Week 1, Comparison Between Fostamatinib and Placebo

Posted

Number

Percentage of responders

1 week

ID	Title	Description
OG000	PLACEBO PO	Dosing Group C
OG001	Dosing Group A and B Combined PO	Fostamatinib 100 mg BID (combined)

Units	Counts
Participants	OG000

Secondary

Proportion of Patients Achieving ACR50 at Week 24, Comparison Between Fostamatinib and Placebo

ACR50: American College of Rheumatology 50% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as C-Reactive Protein) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once daily.

Posted

Number

Percentage of responders

24 weeks

ID	Title	Description
OG000	FOSTA 100 MG BID PO	Dosing Group A
OG001	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO	Dosing Group B
OG002	PLACEBO PO	Dosing Group C

Units	Counts

Secondary

Proportion of Patients Achieving ACR70 at Week 24, Comparison Between Fostamatinib and Placebo

ACR70: American College of Rheumatology 70% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as C-Reactive Protein) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once daily.

Posted

Number

Percentage of responders

24 weeks

ID	Title	Description
OG000	FOSTA 100 MG BID PO	Dosing Group A
OG001	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO	Dosing Group B
OG002	PLACEBO PO	Dosing Group C

Units	Counts

Secondary

ACRn - Comparison Between Fostamatinib and Placebo at Week 24

ACRn: American College of Rheumatology index of RA improvement, based on smallest percentage improvement in the count of swollen joints (out of 28 joints), count of tender joints (out of 28 joints), or in blood test measures of inflammation (such as C-Reactive Protein) or the physician or patient's own assessments of disease activity, pain and physical function. Scores are reported as a percentage improvement on a scale of -100 to +100, with larger values representing a better clinical outcome. Mean refers to change at Week 24. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.

Posted

Mean

Standard Deviation

Percentage improvement from baseline

Baseline and 24 weeks

ID	Title	Description
OG000	FOSTA 100 MG BID PO	Dosing Group A
OG001	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO	Dosing Group B
OG002	PLACEBO PO	Dosing Group C

Secondary

Proportion of Patients Achieving DAS28-CRP <2.6 at Week 24, Comparison Between Fostamatinib and Placebo

DAS28-CRP: Disease Activity Score based on a count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (CRP) and the patients' own assessment. Scores can take any positive value with a lower value indicating a better clinical condition. A DAS28-CRP score of <2.6 is indicative of remission of RA symptoms. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once daily.

Posted

Number

Percentage of responders

24 weeks

ID	Title	Description
OG000	FOSTA 100 MG BID PO	Dosing Group A
OG001	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO	Dosing Group B
OG002	PLACEBO PO	Dosing Group C

Secondary

Proportion of Patients Achieving DAS28-CRP <=3.2 at Week 12, Comparison Between Fostamatinib and Placebo

DAS28-CRP: Disease Activity Score based on a count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (CRP) and the patients' own assessment. Scores can take any positive value with a lower value indicating a better clinical condition. A DAS28-CRP score of <=3.2 indicates low disease activity. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once daily.

Posted

Number

Percentage of responders

12 weeks

ID	Title	Description
OG000	FOSTA 100 MG BID PO	Dosing Group A
OG001	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO	Dosing Group B
OG002	PLACEBO PO	Dosing Group C

Secondary

Proportion of Patients Achieving DAS28-CRP EULAR Response at Week 24, Comparison Between Fostamatinib and Placebo

Change from baseline in DAS28-CRP at Week 24 was categorised using the European League Against Rheumatism (EULAR) response criteria. BID = twice daily, CRP = C-reactive protein, DAS28 = Disease Activity Score based on a 28-joint count, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once a day.

Posted

Number

Percentage of responders

24 weeks

ID	Title	Description
OG000	FOSTA 100 MG BID PO	Dosing Group A
OG001	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO	Dosing Group B
OG002	PLACEBO PO	Dosing Group C

Units	Counts

Secondary

Proportion of Patients With a HAQ-DI Response at Week 24 - Comparison Between Fostamatinib and Placebo

HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is calculated by summing the category scores from 8 sub-categories (ie, scores for patient ability in dressing and grooming, rising, eating, walking, hygeine, reach, grip and common daily activities) and dividing by the number of categories completed. The HAQ-DI score takes values between 0 and 3, with a higher score indicating greater disability. A HAQ-DI response is a reduction from baseline in HAQ-DI greater than or equal to the minimally important difference (0.22). BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once a day.

Posted

Number

Percentage of responders

24 weeks

ID	Title	Description
OG000	FOSTA 100 MG BID PO	Dosing Group A
OG001	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO	Dosing Group B
OG002	PLACEBO PO

Secondary

Change From Baseline to Week 24 in mTSS Score, Comparison Between Fostamatinib and Placebo

mTSS: modified total sharp score, a measure of structural progression based upon X-rays. Hand and foot joints are scored for eroisions and joint space narrowing and the results summed to give a value between 0 and 488. A higher value represents more serious progression of the disease. After disregarding ineligible records, patients with 2 or more non-missing values had missing data imputed via linear extrapolation/interpolation methods. Patients with only 1 result were excluded from the analysis. ANCOVA = Analysis of covariance, BID = twice daily, IP = investigational product, PO = orally, QD = once a day.

The full analysis set includes patients who received at least 1 dose of IP. Patients were analysed by randomised treatment in accordance with the intention to treat principle. Measurements at 2 timepoints are required for a patient to be included in the analysis; therefore patients with only 1 result have been excluded from the analysis population.

Posted

Mean

Standard Deviation

Units on a scale

Baseline and 24 weeks

ID	Title	Description
OG000	FOSTA 100 MG BID PO	Dosing Group A
OG001	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO	Dosing Group B
OG002	PLACEBO PO

Secondary

SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Placebo at Week 24

SF-36: 36 item short form health survey, as a measure of health-related quality of life. Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional and Mental Health) are derived and normalised to a scale of 0 to 100. The physical and mental component scores (PCS and MCS) are derived by multiplying each of these 8 scores by a constant, summing them and standardising against a population with a mean of 50, standard deviation of 10. A higher score represents a better quality of life. Mean changes from baseline score are presented as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. Mean refers to change in scores at Week 24. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease modifying antirheumatic drugs, PO = orally, QD = once daily

Posted

Mean

Standard Deviation

Units on a scale

Baseline and 24 weeks

ID	Title	Description
OG000	FOSTA 100 MG BID PO	Dosing Group A
OG001	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO	Dosing Group B

Secondary

SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Placebo at Week 24

SF-36: 36 item short form health survey, as a measure of health-related quality of life. The SF-36 scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional and Mental Health) are derived and normalised to a scale of 0 to 100. The physical and mental component scores (PCS and MCS) are derived by multiplying each of these 8 scores by a constant, summing them and standardising against a population with a mean of 50, standard deviation of 10. A higher score represents a better quality of life. Mean changes from baseline score are presented as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. Mean refers to change in score at Week 24. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease modifying antirheumatic drugs, PO = orally, QD = once daily.

Posted

Mean

Standard Deviation

Units on a scale

Baseline and 24 weeks

ID	Title	Description
OG000	FOSTA 100 MG BID PO	Dosing Group A
OG001	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO	Dosing Group B

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	FOSTA 100 MG BID PO	Dosing Group A	7	105	51	105
EG001	FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO	Dosing Group B	7	108	49	108
EG002	PLACEBO PO	Dosing Group C	6	109	46	109

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ANAEMIA	Blood and lymphatic system disorders	MedDRA 15.1	Systematic Assessment	EG0000 events0 affected105 at risk EG0010 events0 affected108 at risk EG0021 events1 affected109 at risk
ACUTE CORONARY SYNDROME	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0000 events0 affected105 at risk EG0010 events0 affected108 at risk EG0021 events1 affected109 at risk
ARTERIOSCLEROSIS CORONARY ARTERY	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected108 at risk EG0020 events0 affected109 at risk
CARDIAC FAILURE CONGESTIVE	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0000 events0 affected105 at risk EG0011 events1 affected108 at risk EG0020 events0 affected109 at risk
CARDIO-RESPIRATORY ARREST	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0000 events0 affected105 at risk EG0011 events1 affected108 at risk EG0020 events0 affected109 at risk
CORONARY ARTERY OCCLUSION	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0000 events0 affected105 at risk EG0011 events1 affected108 at risk EG0020 events0 affected109 at risk
CROHN'S DISEASE	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 events0 affected105 at risk EG0010 events0 affected108 at risk EG0021 events1 affected109 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 events0 affected105 at risk EG0010 events0 affected108 at risk EG0021 events1 affected109 at risk
GASTRIC ULCER	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected108 at risk EG0020 events0 affected109 at risk
GASTRITIS	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected108 at risk EG0020 events0 affected109 at risk
VOMITING	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 events0 affected105 at risk EG0010 events0 affected108 at risk EG0021 events1 affected109 at risk
NON-CARDIAC CHEST PAIN	General disorders	MedDRA 15.1	Systematic Assessment	EG0001 events1 affected105 at risk EG0011 events1 affected108 at risk EG0020 events0 affected109 at risk
CHOLECYSTITIS	Hepatobiliary disorders	MedDRA 15.1	Systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected108 at risk EG0020 events0 affected109 at risk
DIVERTICULITIS	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected108 at risk EG0020 events0 affected109 at risk
ESCHERICHIA URINARY TRACT INFECTION	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 events0 affected105 at risk EG0010 events0 affected108 at risk EG0021 events1 affected109 at risk
GASTROENTERITIS	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 events1 affected105 at risk EG0012 events2 affected108 at risk EG0020 events0 affected109 at risk
GASTROENTERITIS BACTERIAL	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected108 at risk EG0020 events0 affected109 at risk
HERPES PHARYNGITIS	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 events0 affected105 at risk EG0010 events0 affected108 at risk EG0022 events1 affected109 at risk
OROPHARYNGEAL CANDIDIASIS	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 events0 affected105 at risk EG0010 events0 affected108 at risk EG0021 events1 affected109 at risk
DIABETES MELLITUS	Metabolism and nutrition disorders	MedDRA 15.1	Systematic Assessment	EG0000 events0 affected105 at risk EG0010 events0 affected108 at risk EG0021 events1 affected109 at risk
HYPOKALAEMIA	Metabolism and nutrition disorders	MedDRA 15.1	Systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected108 at risk EG0020 events0 affected109 at risk
HYPONATRAEMIA	Metabolism and nutrition disorders	MedDRA 15.1	Systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected108 at risk EG0020 events0 affected109 at risk
RENAL CELL CARCINOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.1	Systematic Assessment	EG0000 events0 affected105 at risk EG0011 events1 affected108 at risk EG0020 events0 affected109 at risk
SYNCOPE	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0000 events0 affected105 at risk EG0011 events1 affected108 at risk EG0020 events0 affected109 at risk
TRANSIENT GLOBAL AMNESIA	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected108 at risk EG0020 events0 affected109 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
DIARRHOEA	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG00023 events21 affected105 at risk EG00131 events29 affected108 at risk EG0028 events7 affected109 at risk
FLATULENCE	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0007 events6 affected105 at risk EG0012 events2 affected108 at risk EG0024 events4 affected109 at risk
NAUSEA	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0005 events4 affected105 at risk EG0018 events7 affected108 at risk EG0029 events9 affected109 at risk
VOMITING	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 events1 affected105 at risk EG0016 events6 affected108 at risk EG0024 events4 affected109 at risk
FATIGUE	General disorders	MedDRA 15.1	Systematic Assessment	EG0000 events0 affected105 at risk EG0010 events0 affected108 at risk EG0026 events6 affected109 at risk
NASOPHARYNGITIS	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0006 events6 affected105 at risk EG0015 events4 affected108 at risk EG0024 events4 affected109 at risk
UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0007 events6 affected105 at risk EG0012 events2 affected108 at risk EG0021 events1 affected109 at risk
ARTHRALGIA	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG0006 events6 affected105 at risk EG0010 events0 affected108 at risk EG0025 events5 affected109 at risk
RHEUMATOID ARTHRITIS	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG0005 events4 affected105 at risk EG0019 events6 affected108 at risk EG00211 events11 affected109 at risk
DIZZINESS	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0009 events7 affected105 at risk EG0016 events6 affected108 at risk EG0022 events2 affected109 at risk
HEADACHE	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG0008 events8 affected105 at risk EG0019 events9 affected108 at risk EG00212 events11 affected109 at risk
HYPERTENSION	Vascular disorders	MedDRA 15.1	Systematic Assessment	EG00015 events14 affected105 at risk EG00115 events15 affected108 at risk EG00211 events9 affected109 at risk

ID	Term
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases