OSKIRA-X: Evaluation of Long-term Safety and Effectiveness of Fostamatinib in the Treatment of Rheumatoid Arthritis (RA)

• Sponsor: AstraZeneca (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01242514
• Collaborator: (none)
• Enrollment: 1,917
• Locations: 310
• Arms: 3
• Duration (Months): 48
• Patients Per Site: 6.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the long term safety and tolerability of fostamatinib in patients with rheumatoid arthritis (RA).

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Fostamatinib; Drug: Fostamatinib; Drug: Fostamatinib	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1917 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: (OSKIRA-X): A Long-term Extension Study to Assess the Safety and Efficacy of Fostamatinib Disodium in the Treatment of Rheumatoid Arthritis
• Study Start Date: Jan 1, 2011
• Anticipated Primary Completion Date: Jan 1, 2015
• Anticipated Study Completion Date: Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A Oral treatment	Drug: Fostamatinib; Fostamatinib 100mg twice daily
Experimental: B Oral treatment	Drug: Fostamatinib; Fostamatinib 150mg once daily
Experimental: C Oral treatment	Drug: Fostamatinib; Fostamatinib 100mg once daily

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients Who Had at Least 1 Adverse Event in Any Category [Entry in extension to end of study (variable duration; maximum 109 weeks)]

   AE = adverse event, bid = twice daily, IP = investigational product, qd = once daily, SAE = serious adverse event

Secondary Outcome Measures

1. Mean DAS28-CRP Score [Weeks 0, 12, 24, 36 and 52]

   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 patient's own assessment. Scores can take any positive value with a lower value indicating a better clinical condition. Number of participants are those with data at entry to this study (Week 0). As no imputation was applied, the numbers at subsequent visits are lower. bid = twice daily, CRP = C-reactive protein, qd = once daily

2. Mean mTSS Score [Weeks 0 and 52]

   mTSS: modified total sharp score, a measure of structural progression based upon X-rays. Hand and foot joints are scored for erosions 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. Number of participants are those with data at entry to this study (Week 0). As no imputation was applied, the numbers at subsequent visits are lower. bid = twice daily, N/A = not applicable, qd = once daily

3. Mean HAQ-DI Score [Weeks 0, 12, 24, 36 and 52]

   HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is then calculated by summing the category scores from 8 sub-categories (ie, scores for patient ability in dressing and grooming, rising, eating, walking, hygiene, 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. Number of participants are those with data at entry to this study (Week 0). As no imputation was applied, the numbers at subsequent visits are lower. bid = twice daily, qd = once daily

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients who have successfully completed a qualifying study (D4300C00001, D4300C00002, D4300C00003 or D4300C00004) with fostamatinib

• Patients who have participated in a qualifying study and who have been classified as non-responders due to pre-defined lack of efficacy at Week 12 (D4300C00001, D4300C00002, D4300C00003).

Exclusion Criteria:

• Premature withdrawal from the qualifying study (D4300C00001, D4300C00002, D4300C00003 and D4300C00004)

• Females who are pregnant or breast feeding

• Poorly controlled hypertension

• Significant liver function test abnormalities or physical symptoms of hepatotoxicity

• Significant infection

• Gastrointestinal intolerance

• Cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Anniston	Alabama	United States
2	Research Site	Birmingham	Alabama	United States
3	Research Site	Huntsville	Alabama	United States
4	Research Site	Tuscaloosa	Alabama	United States
5	Research Site	Glendale	Arizona	United States
6	Research Site	Mesa	Arizona	United States
7	Research Site	Phoenix	Arizona	United States
8	Research Site	Scottsdale	Arizona	United States
9	Research Site	Tucson	Arizona	United States
10	Research Site	Hot Springs	Arkansas	United States
11	Research Site	Anaheim	California	United States
12	Research Site	Fountain Valley	California	United States
13	Research Site	Huntington Beach	California	United States
14	Research Site	La Jolla	California	United States
15	Research Site	Long Beach	California	United States
16	Research Site	Palo Alto	California	United States
17	Research Site	Roseville	California	United States
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19	Research Site	Santa Monica	California	United States
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22	Research Site	Colorado Springs	Colorado	United States
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26	Research Site	Lewes	Delaware	United States
27	Research Site	Boca Raton	Florida	United States
28	Research Site	Brandon	Florida	United States
29	Research Site	Daytona Beach	Florida	United States
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215	Research Site	Ashkelon		Israel
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217	Research Site	Kfar-saba		Israel
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240	Research Site	Arequipa		Peru
241	Research Site	Lima		Peru
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250	Research Site	Wroclaw		Poland
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252	Research Site	Aveiro		Portugal
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255	Research Site	Porto		Portugal
256	Research Site	Ploiesti	Prahova	Romania
257	Research Site	Braila		Romania
258	Research Site	Moscow		Russian Federation
259	Research Site	Nizhniy Novgorod		Russian Federation
260	Research Site	Petrozavodsk		Russian Federation
261	Research Site	Ryazan		Russian Federation
262	Research Site	Sankt-peterburg		Russian Federation
263	Research Site	Voronezh		Russian Federation
264	Research Site	Yaroslavl		Russian Federation
265	Research Site	Belgrade		Serbia
266	Research Site	Kragujevac		Serbia
267	Research Site	Niska Banja		Serbia
268	Research Site	Novi Sad		Serbia
269	Research Site	Bratislava		Slovakia
270	Research Site	Poprad		Slovakia
271	Research Site	Rimavska Sobota		Slovakia
272	Research Site	Ruzomberok		Slovakia
273	Research Site	Trnava		Slovakia
274	Research Site	Zilina		Slovakia
275	Research Site	Panorama	Cape Town	South Africa
276	Research Site	Port Elizabeth	E Cape	South Africa
277	Research Site	Kempron Park	Gauteng	South Africa
278	Research Site	Pretoria	Gauteng	South Africa
279	Research Site	Durban	Kwazulu Natal	South Africa
280	Research Site	Cape Town	Western Cape	South Africa
281	Research Site	Stellenbosch		South Africa
282	Research Site	Merida	Extremadura	Spain
283	Research Site	Barcelona		Spain
284	Research Site	Donetsk		Ukraine
285	Research Site	Ivano-frankivsk		Ukraine
286	Research Site	Kharkiv		Ukraine
287	Research Site	Kyiv		Ukraine
288	Research Site	Lugansk		Ukraine
289	Research Site	Lutsk		Ukraine
290	Research Site	Lviv		Ukraine
291	Research Site	Odessa		Ukraine
292	Research Site	Simferopol		Ukraine
293	Research Site	Vinnytsia		Ukraine
294	Research Site	Vinnytsya		Ukraine
295	Research Site	Zaporizhzhya		Ukraine
296	Research Site	Zaporyzhzhya		Ukraine
297	Research Site	Bracknell	Berkshire	United Kingdom
298	Research Site	Warrington	Cheshire	United Kingdom
299	Research Site	London	Greater London	United Kingdom
300	Research Site	Maidstone	Kent	United Kingdom
301	Research Site	Eastbourne	Sussex	United Kingdom
302	Research Site	Solihull	West Midlands	United Kingdom
303	Research Site	Basingstoke		United Kingdom
304	Research Site	Cambridge		United Kingdom
305	Research Site	Christchurch		United Kingdom
306	Research Site	Ipswich		United Kingdom
307	Research Site	Nottingham		United Kingdom
308	Research Site	Stoke on Trent		United Kingdom
309	Research Site	Westcliff-on-the Sea		United Kingdom
310	Research Site	Wirral		United Kingdom

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: NCT01242514
• Other Study ID Numbers: D4300C00005; 2010-020892-22
• First Posted: Nov 17, 2010
• Last Update Posted: Apr 4, 2014
• Last Verified: Feb 1, 2014

• Keywords provided by AstraZeneca: Rheumatoid Arthritis; OSKIRA; Fostamatinib
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid

Study Results

Participant Flow

Recruitment Details	Total of 1917 enrolled patients: 1346, 357 & 214 were allocated to the 100 mg twice daily (bid), 150 mg once daily (qd) and 100 mg qd groups, respectively (1343, 357 & 212 received at least 1 dose of investigational product). As this was a long-term extension study no specific end date was given. As such no patients were recorded as completers.
Pre-assignment Detail	A total of 5 patients did not receive treatment.

Arm/Group Title	Fostamatinib 100 mg Bid	Fostamatinib 150 mg qd	Fostamatinib 100 mg qd
Arm/Group Description	Oral treatment	Oral treatment	Oral treatment
Period Title: Overall Study
STARTED	1343	357	212
Enrolled But Did Not Receive Treatment	3	0	2
COMPLETED	0	0	0
NOT COMPLETED	1343	357	212

Baseline Characteristics

Arm/Group Title	Fostamatinib 100 mg Bid	Fostamatinib 150 mg qd	Fostamatinib 100 mg qd	Total
Arm/Group Description	Oral treatment	Oral treatment	Oral treatment	Total of all reporting groups
Overall Participants	1343	357	212	1912
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53 (12.0)	53 (11.6)	53 (11.3)	53 (11.8)
Sex: Female, Male (Count of Participants)
Female	1086 80.9%	297 83.2%	193 91%	1576 82.4%
Male	257 19.1%	60 16.8%	19 9%	336 17.6%
Race/Ethnicity, Customized (Number) [Number]
White	1092 81.3%	278 77.9%	141 66.5%	1511 79%
Black or African American	63 4.7%	11 3.1%	6 2.8%	80 4.2%
Asian	40 3%	12 3.4%	7 3.3%	59 3.1%
American Indian or Alaska Native	20 1.5%	11 3.1%	6 2.8%	37 1.9%
Indian or Pakistani	54 4%	15 4.2%	22 10.4%	91 4.8%
Other	74 5.5%	30 8.4%	30 14.2%	134 7%

Outcome Measures

1. Secondary Outcome

Title	Mean DAS28-CRP Score
Description	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 patient's own assessment. Scores can take any positive value with a lower value indicating a better clinical condition. Number of participants are those with data at entry to this study (Week 0). As no imputation was applied, the numbers at subsequent visits are lower. bid = twice daily, CRP = C-reactive protein, qd = once daily
Time Frame	Weeks 0, 12, 24, 36 and 52

Outcome Measure Data

Analysis Population Description

The full analysis set includes those patients who received at least 1 dose of investigational product, and were summarised according to treatment first received in this study (intention-to-treat principle).

Arm/Group Title	Fostamatinib 100 mg Bid	Fostamatinib 150 mg qd	Fostamatinib 100 mg qd
Arm/Group Description	Oral treatment	Oral treatment	Oral treatment
Measure Participants	1247	336	198
Week 0 (n=1247, 336, 198)	4.5 (1.58)	3.8 (1.24)	3.9 (1.27)
Week 12 (n=1018, 288, 160)	3.8 (1.34)	3.6 (1.19)	3.7 (1.21)
Week 24 (n=800, 230 126)	3.8 (1.30)	3.7 (1.24)	3.6 (1.19)
Week 36 (n=581, 148, 68)	3.9 (1.32)	3.7 (1.24)	3.9 (1.07)
Week 52 (n=290, 28, 14)	4.0 (1.25)	3.8 (1.37)	3.6 (1.22)

2. Primary Outcome

Title	Percentage of Patients Who Had at Least 1 Adverse Event in Any Category
Description	AE = adverse event, bid = twice daily, IP = investigational product, qd = once daily, SAE = serious adverse event
Time Frame	Entry in extension to end of study (variable duration; maximum 109 weeks)

Outcome Measure Data

Analysis Population Description

The full analysis set includes those patients who received at least 1 dose of investigational product, and were summarised according to treatment first received in this study (intention-to-treat principle).

Arm/Group Title	Fostamatinib 100 mg Bid	Fostamatinib 150 mg qd	Fostamatinib 100 mg qd
Arm/Group Description	Oral treatment	Oral treatment	Oral treatment
Measure Participants	1343	357	212
Any AE	74.4	70.3	69.8
Any AE with outcome of death	0.7	0.3	0.5
Any SAE (including events with outcome of death)	11.4	8.7	5.7
Any AE leading to discontinuation of IP	10.5	5.9	9.9

3. Secondary Outcome

Title	Mean mTSS Score
Description	mTSS: modified total sharp score, a measure of structural progression based upon X-rays. Hand and foot joints are scored for erosions 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. Number of participants are those with data at entry to this study (Week 0). As no imputation was applied, the numbers at subsequent visits are lower. bid = twice daily, N/A = not applicable, qd = once daily
Time Frame	Weeks 0 and 52

Outcome Measure Data

Analysis Population Description

The full analysis set includes those patients who received at least 1 dose of investigational product, and were summarised according to treatment first received in this study (intention-to-treat principle).

Arm/Group Title	Fostamatinib 100 mg Bid	Fostamatinib 150 mg qd	Fostamatinib 100 mg qd
Arm/Group Description	Oral treatment	Oral treatment	Oral treatment
Measure Participants	480	73	37
Week 0 (n=480, 73, 37)	30.5 (47.73)	22.2 (32.89)	20.8 (46.60)
Week 52 (n=223, 1, 6)	30.1 (46.83)	0.5 (NA)	37.3 (67.70)

4. Secondary Outcome

Title	Mean HAQ-DI Score
Description	HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is then calculated by summing the category scores from 8 sub-categories (ie, scores for patient ability in dressing and grooming, rising, eating, walking, hygiene, 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. Number of participants are those with data at entry to this study (Week 0). As no imputation was applied, the numbers at subsequent visits are lower. bid = twice daily, qd = once daily
Time Frame	Weeks 0, 12, 24, 36 and 52

Outcome Measure Data

Analysis Population Description

The full analysis set includes those patients who received at least 1 dose of investigational product, and were summarised according to treatment first received in this study (intention-to-treat principle).

Arm/Group Title	Fostamatinib 100 mg Bid	Fostamatinib 150 mg qd	Fostamatinib 100 mg qd
Arm/Group Description	Oral treatment	Oral treatment	Oral treatment
Measure Participants	1271	342	201
Week 0 (n=1271, 342, 201)	1.2 (0.69)	1.0 (0.64)	1.0 (0.62)
Week 12 (n=1061, 298, 166)	1.1 (0.68)	1.0 (0.63)	1.0 (0.63)
Week 24 (n=817, 238, 132)	1.1 (0.68)	1.0 (0.67)	0.9 (0.55)
Week 36 (n=587, 149, 71)	1.1 (0.67)	1.0 (0.65)	1.1 (0.62)
Week 52 (n=296, 28, 14)	1.2 (0.68)	1.1 (0.64)	1.0 (0.73)

Adverse Events

Arm/Group Title	FOSTA 100 MG BID		FOSTA 100 MG QD		FOSTA 150 MG QD
Arm/Group Description
All Cause Mortality
	FOSTA 100 MG BID		FOSTA 100 MG QD		FOSTA 150 MG QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	FOSTA 100 MG BID		FOSTA 100 MG QD		FOSTA 150 MG QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	153/1343 (11.4%)		12/212 (5.7%)		31/357 (8.7%)
Blood and lymphatic system disorders
SPLENIC INFARCTION	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
ANGINA UNSTABLE	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
ATRIAL FIBRILLATION	2/1343 (0.1%)	2	0/212 (0%)	0	0/357 (0%)	0
BRADYCARDIA	0/1343 (0%)	0	1/212 (0.5%)	1	0/357 (0%)	0
CARDIAC FAILURE CHRONIC	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
CARDIAC FAILURE CONGESTIVE	2/1343 (0.1%)	2	0/212 (0%)	0	0/357 (0%)	0
CARDIO-RESPIRATORY ARREST	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
CARDIOMYOPATHY	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
MYOCARDIAL INFARCTION	2/1343 (0.1%)	2	0/212 (0%)	0	0/357 (0%)	0
MYOCARDIAL ISCHAEMIA	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
Endocrine disorders
GOITRE	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
Eye disorders
RETINAL DETACHMENT	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
Gastrointestinal disorders
ABDOMINAL PAIN	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
ABDOMINAL PAIN UPPER	0/1343 (0%)	0	1/212 (0.5%)	1	0/357 (0%)	0
ACUTE ABDOMEN	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
BARRETT'S OESOPHAGUS	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
COLITIS	2/1343 (0.1%)	2	0/212 (0%)	0	0/357 (0%)	0
COLITIS MICROSCOPIC	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
COLONIC STENOSIS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
DIARRHOEA	4/1343 (0.3%)	4	1/212 (0.5%)	1	0/357 (0%)	0
DYSPEPSIA	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
GASTRIC ULCER	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
GASTRITIS	2/1343 (0.1%)	2	0/212 (0%)	0	1/357 (0.3%)	1
GASTRITIS EROSIVE	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
GASTROINTESTINAL HAEMORRHAGE	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
HAEMATEMESIS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
ILEITIS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
ILEUS	2/1343 (0.1%)	2	0/212 (0%)	0	0/357 (0%)	0
INGUINAL HERNIA	2/1343 (0.1%)	2	0/212 (0%)	0	1/357 (0.3%)	1
INTESTINAL HAEMORRHAGE	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
INTESTINAL ISCHAEMIA	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
INTESTINAL OBSTRUCTION	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
OESOPHAGEAL ACHALASIA	1/1343 (0.1%)	2	0/212 (0%)	0	0/357 (0%)	0
PANCREATIC PSEUDOCYST	0/1343 (0%)	0	1/212 (0.5%)	1	0/357 (0%)	0
PANCREATITIS	3/1343 (0.2%)	3	0/212 (0%)	0	0/357 (0%)	0
PANCREATITIS ACUTE	3/1343 (0.2%)	3	1/212 (0.5%)	1	0/357 (0%)	0
General disorders
DEVICE DISLOCATION	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
GENERAL PHYSICAL HEALTH DETERIORATION	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
NON-CARDIAC CHEST PAIN	3/1343 (0.2%)	3	1/212 (0.5%)	1	0/357 (0%)	0
Hepatobiliary disorders
BILE DUCT OBSTRUCTION	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
BILIARY COLIC	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
CHOLECYSTITIS	2/1343 (0.1%)	2	0/212 (0%)	0	0/357 (0%)	0
CHOLECYSTITIS ACUTE	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
CHOLECYSTITIS CHRONIC	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
CHOLELITHIASIS	4/1343 (0.3%)	4	0/212 (0%)	0	0/357 (0%)	0
GALLBLADDER POLYP	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
POST CHOLECYSTECTOMY SYNDROME	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
Immune system disorders
ANAPHYLACTIC SHOCK	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
FOOD ALLERGY	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
HYPERSENSITIVITY	2/1343 (0.1%)	2	0/212 (0%)	0	0/357 (0%)	0
Infections and infestations
ABSCESS LIMB	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
APPENDICITIS	4/1343 (0.3%)	4	0/212 (0%)	0	0/357 (0%)	0
ARTHRITIS BACTERIAL	0/1343 (0%)	0	1/212 (0.5%)	1	0/357 (0%)	0
BACTERAEMIA	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
BACTERIAL PYELONEPHRITIS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
BACTERIAL SEPSIS	2/1343 (0.1%)	2	0/212 (0%)	0	0/357 (0%)	0
BRONCHITIS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
BRONCHOPNEUMONIA	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
CELLULITIS	6/1343 (0.4%)	7	1/212 (0.5%)	1	0/357 (0%)	0
CYTOMEGALOVIRUS INFECTION	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
DIVERTICULITIS	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
ENTEROCOLITIS BACTERIAL	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
ENTEROCOLITIS VIRAL	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
ERYSIPELAS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
ESCHERICHIA URINARY TRACT INFECTION	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
GANGRENE	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
GASTROENTERITIS	1/1343 (0.1%)	1	1/212 (0.5%)	1	0/357 (0%)	0
GASTROENTERITIS BACTERIAL	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
GASTROENTERITIS VIRAL	1/1343 (0.1%)	1	0/212 (0%)	0	1/357 (0.3%)	1
HERPES ZOSTER	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
INTERVERTEBRAL DISCITIS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
LIVER ABSCESS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
LUNG ABSCESS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
OSTEOMYELITIS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
OTITIS EXTERNA	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
PANCREATITIS VIRAL	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
PERITONITIS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
PNEUMONIA	5/1343 (0.4%)	5	1/212 (0.5%)	1	1/357 (0.3%)	1
PNEUMONIA BACTERIAL	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
PNEUMONIA VIRAL	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
PULMONARY TUBERCULOSIS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
STAPHYLOCOCCAL SEPSIS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
SUBCUTANEOUS ABSCESS	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
URINARY TRACT INFECTION	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
URINARY TRACT INFECTION BACTERIAL	2/1343 (0.1%)	2	0/212 (0%)	0	0/357 (0%)	0
UROSEPSIS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
VIRAL UPPER RESPIRATORY TRACT INFECTION	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
WOUND INFECTION BACTERIAL	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
WOUND SEPSIS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
Injury, poisoning and procedural complications
ACCIDENTAL OVERDOSE	0/1343 (0%)	0	0/212 (0%)	0	2/357 (0.6%)	2
FACIAL BONES FRACTURE	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
FEMORAL NECK FRACTURE	1/1343 (0.1%)	1	1/212 (0.5%)	1	0/357 (0%)	0
FEMUR FRACTURE	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
FIBULA FRACTURE	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
HUMERUS FRACTURE	2/1343 (0.1%)	2	0/212 (0%)	0	1/357 (0.3%)	1
JOINT DISLOCATION	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
JOINT INJURY	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
PATELLA FRACTURE	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
TENDON RUPTURE	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
TIBIA FRACTURE	0/1343 (0%)	0	1/212 (0.5%)	1	0/357 (0%)	0
ULNA FRACTURE	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
UPPER LIMB FRACTURE	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
WOUND DEHISCENCE	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
WRIST FRACTURE	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
Investigations
LIVER FUNCTION TEST ABNORMAL	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
Metabolism and nutrition disorders
DEHYDRATION	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
HYPOKALAEMIA	1/1343 (0.1%)	1	1/212 (0.5%)	1	1/357 (0.3%)	1
HYPONATRAEMIA	1/1343 (0.1%)	1	0/212 (0%)	0	1/357 (0.3%)	1
TYPE 2 DIABETES MELLITUS	0/1343 (0%)	0	1/212 (0.5%)	1	0/357 (0%)	0
Musculoskeletal and connective tissue disorders
ARTHRITIS	2/1343 (0.1%)	2	0/212 (0%)	0	0/357 (0%)	0
BACK PAIN	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
HIP DEFORMITY	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
INTERVERTEBRAL DISC DISORDER	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
INTERVERTEBRAL DISC DISPLACEMENT	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
INTERVERTEBRAL DISC PROTRUSION	4/1343 (0.3%)	4	1/212 (0.5%)	1	0/357 (0%)	0
LUMBAR SPINAL STENOSIS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
MUSCULOSKELETAL CHEST PAIN	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
OSTEITIS	0/1343 (0%)	0	1/212 (0.5%)	1	0/357 (0%)	0
OSTEOARTHRITIS	6/1343 (0.4%)	8	0/212 (0%)	0	2/357 (0.6%)	2
OSTEONECROSIS	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
PATHOLOGICAL FRACTURE	2/1343 (0.1%)	2	0/212 (0%)	0	0/357 (0%)	0
RHEUMATOID ARTHRITIS	9/1343 (0.7%)	11	0/212 (0%)	0	0/357 (0%)	0
SJOGREN'S SYNDROME	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
SPONDYLOLISTHESIS	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
SYNOVITIS	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA	2/1343 (0.1%)	2	0/212 (0%)	0	0/357 (0%)	0
BENIGN NEOPLASM OF PROSTATE	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
BENIGN SOFT TISSUE NEOPLASM	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
BREAST CANCER	2/1343 (0.1%)	2	0/212 (0%)	0	0/357 (0%)	0
CERVIX CARCINOMA	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
COLORECTAL CANCER	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
GASTRIC CANCER	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
LIPOMA	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
LUNG SQUAMOUS CELL CARCINOMA STAGE UNSPECIFIED	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
MALIGNANT MELANOMA	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
PANCREATIC NEUROENDOCRINE TUMOUR	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
PROSTATE CANCER	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
RECTAL CANCER	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
RENAL CANCER METASTATIC	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
RENAL CELL CARCINOMA	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
UTERINE LEIOMYOMA	2/1343 (0.1%)	2	0/212 (0%)	0	1/357 (0.3%)	1
VAGINAL CANCER	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
Nervous system disorders
APHASIA	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
CAROTID ARTERY STENOSIS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
CONVULSION	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
DYSARTHRIA	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
HAEMORRHAGIC STROKE	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
HYPERTENSIVE ENCEPHALOPATHY	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
HYPOGLYCAEMIC COMA	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
ISCHAEMIC STROKE	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
LUMBAR RADICULOPATHY	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
RADICULITIS LUMBOSACRAL	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
SCIATICA	0/1343 (0%)	0	1/212 (0.5%)	1	0/357 (0%)	0
SYNCOPE	3/1343 (0.2%)	3	0/212 (0%)	0	2/357 (0.6%)	2
TENSION HEADACHE	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
TRANSIENT ISCHAEMIC ATTACK	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
VITH NERVE PARALYSIS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
Psychiatric disorders
ADJUSTMENT DISORDER	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
ALCOHOL ABUSE	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
DEPRESSION	2/1343 (0.1%)	2	0/212 (0%)	0	0/357 (0%)	0
Renal and urinary disorders
CALCULUS URETERIC	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
CALCULUS URINARY	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
NEPHROLITHIASIS	1/1343 (0.1%)	1	1/212 (0.5%)	1	0/357 (0%)	0
RENAL FAILURE ACUTE	3/1343 (0.2%)	3	0/212 (0%)	0	0/357 (0%)	0
RENAL IMPAIRMENT	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
URINARY BLADDER POLYP	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
Reproductive system and breast disorders
ADENOMYOSIS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
BENIGN PROSTATIC HYPERPLASIA	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
OVARIAN CYST	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
UTERINE POLYP	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE	2/1343 (0.1%)	2	0/212 (0%)	0	0/357 (0%)	0
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	1/1343 (0.1%)	1	0/212 (0%)	0	1/357 (0.3%)	1
HYPERVENTILATION	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
PNEUMONIA ASPIRATION	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
PULMONARY EMBOLISM	4/1343 (0.3%)	4	0/212 (0%)	0	0/357 (0%)	0
RESPIRATORY FAILURE	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
Skin and subcutaneous tissue disorders
DIGITAL ULCER	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
ERYTHEMA MULTIFORME	0/1343 (0%)	0	0/212 (0%)	0	1/357 (0.3%)	1
TOXIC EPIDERMAL NECROLYSIS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
Vascular disorders
AORTIC ANEURYSM RUPTURE	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
AORTIC STENOSIS	0/1343 (0%)	0	1/212 (0.5%)	1	0/357 (0%)	0
AORTIC THROMBOSIS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
ARTERIAL THROMBOSIS	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
FEMORAL ARTERY OCCLUSION	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
PERIPHERAL ISCHAEMIA	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
THROMBOPHLEBITIS SUPERFICIAL	1/1343 (0.1%)	1	0/212 (0%)	0	0/357 (0%)	0
Other (Not Including Serious) Adverse Events
	FOSTA 100 MG BID		FOSTA 100 MG QD		FOSTA 150 MG QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	466/1343 (34.7%)		68/212 (32.1%)		98/357 (27.5%)
Gastrointestinal disorders
DIARRHOEA	202/1343 (15%)	268	28/212 (13.2%)	40	43/357 (12%)	61
Infections and infestations
NASOPHARYNGITIS	86/1343 (6.4%)	102	15/212 (7.1%)	16	28/357 (7.8%)	31
Musculoskeletal and connective tissue disorders
RHEUMATOID ARTHRITIS	116/1343 (8.6%)	155	19/212 (9%)	22	30/357 (8.4%)	35
Vascular disorders
HYPERTENSION	166/1343 (12.4%)	197	14/212 (6.6%)	15	20/357 (5.6%)	23

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. Sponsor will be allowed a review period of at least 60 days from submission but can request that publication be delayed for a period up to 6 months. Any reasonable comments made by the sponsor will be incorporated by the PI into the publication.