Evaluation of long-term safety and effectiveness of fostamatinib in the treatment of rheumatoid arthritis (RA) - OSKIRA-X

Study identifier:D4300C00005

ClinicalTrials.gov identifier:N/A

EudraCT identifier:2010-020892-22

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

(OSKIRA-X): A Long-term Extension Study to Assess the Safety and Efficacy of Fostamatinib Disodium in the Treatment of Rheumatoid Arthritis

Medical condition

Rheumatoid Arthritis

Phase

Phase 3

Healthy volunteers

Study drug

Fostamatinib

Sex

All

Actual Enrollment

1917

Study type

Interventional

Age

18 Years - 150 Years

Date

Study Start Date: 01 Jan 2011

Primary Completion Date: 01 Jun 2013

Study Completion Date: 01 Sept 2013

Study design

Allocation: Non-randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Apr 2014 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Buenos Aires, Argentina

Location

Research Site

Ciudad de Buenos Aires, Argentina

Location

Research Site

Ciudad Autónoma Bs As, Argentina

Location

Research Site

San Miguel de Tucuman, Argentina

Location

Research Site

Rosario, Argentina

Location

Research Site

Ciudad Autonoma Bs As, Argentina

Location

Research Site

San Juan, Argentina

Location

Research Site

Cordoba, Argentina

Arms	Assigned Interventions
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

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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 Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 5 patients did not receive treatment.

Reporting Groups

	Description
Fostamatinib 100 mg bid	Oral treatment
Fostamatinib 150 mg qd	Oral treatment
Fostamatinib 100 mg qd	Oral treatment

Participant Flow: Overall Study

	Fostamatinib 100 mg bid	Fostamatinib 150 mg qd	Fostamatinib 100 mg qd
STARTED	1343^[1]	357^[2]	212^[3]
Enrolled but did not receive treatment	3^[4]	0	2^[5]
COMPLETED	0^[6]	0^[7]	0^[8]
NOT COMPLETED	1343	357	212
e.g., project closure	1042	305	171
Subject decision	33	8	2
Severe non-compliance to protocol	5	2	1
Lack of therapeutic response	99	16	10
Dev. of study specific discont. criteria	21	3	5
Lost to Follow-up	14	5	4
Adverse Event	129	18	19

[1]	Patients who received treatment
[2]	Patients who received treatment
[3]	Patients who received treatment
[4]	Other
[5]	Adverse event/other
[6]	Due to project closure.
[7]	Due to project closure.
[8]	Due to project closure.

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Fostamatinib 100 mg bid	Oral treatment
Fostamatinib 150 mg qd	Oral treatment
Fostamatinib 100 mg qd	Oral treatment

Baseline Measures

	Fostamatinib 100 mg bid	Fostamatinib 150 mg qd	Fostamatinib 100 mg qd	Total
Number of Participants [units: Participants]	1343	357	212	1912
Age Continuous [units: years] Mean ± Standard Deviation	53 ± 12.0	53 ± 11.6	53 ± 11.3	53 ± 11.8
Gender, Male/Female [units: Participants]
Female	1086	297	193	1576
Male	257	60	19	336
Race/Ethnicity, Customized [units: Participants]
White	1092	278	141	1511
Black or African American	63	11	6	80
Asian	40	12	7	59
American Indian or Alaska Native	20	11	6	37
Indian or Pakistani	54	15	22	91
Other	74	30	30	134

Outcome Measures

1. Primary Outcome Measure: Percentage of patients who had at least 1 adverse event in any category [ Time Frame: Entry in extension to end of study (variable duration; maximum 109 weeks) ]

Measure Type	Primary
Measure Name	Percentage of patients who had at least 1 adverse event in any category
Measure 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)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups

	Description
Fostamatinib 100 mg bid	Oral treatment
Fostamatinib 150 mg qd	Oral treatment
Fostamatinib 100 mg qd	Oral treatment

Measured Values

	Fostamatinib 100 mg bid	Fostamatinib 150 mg qd	Fostamatinib 100 mg qd
Number of Participants Analyzed [units:participants]	1343	357	212
Percentage of patients who had at least 1 adverse event in any category [units: Percentage of patients]
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

No statistical analysis provided for Percentage of patients who had at least 1 adverse event in any category

2. Secondary Outcome Measure: Mean DAS28-CRP score [ Time Frame: Weeks 0, 12, 24, 36 and 52 ]

Measure Type	Secondary
Measure Name	Mean DAS28-CRP score
Measure 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
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups

	Description
Fostamatinib 100 mg bid	Oral treatment
Fostamatinib 150 mg qd	Oral treatment
Fostamatinib 100 mg qd	Oral treatment

Measured Values

	Fostamatinib 100 mg bid	Fostamatinib 150 mg qd	Fostamatinib 100 mg qd
Number of Participants Analyzed [units:participants]	1247	336	198
Mean DAS28-CRP score [units: Units on a scale] Mean (Standard Deviation)
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)

No statistical analysis provided for Mean DAS28-CRP score

3. Secondary Outcome Measure: Mean mTSS score [ Time Frame: Weeks 0 and 52 ]

Measure Type	Secondary
Measure Name	Mean mTSS score
Measure 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
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups

	Description
Fostamatinib 100 mg bid	Oral treatment
Fostamatinib 150 mg qd	Oral treatment
Fostamatinib 100 mg qd	Oral treatment

Measured Values

	Fostamatinib 100 mg bid	Fostamatinib 150 mg qd	Fostamatinib 100 mg qd
Number of Participants Analyzed [units:participants]	480	73	37
Mean mTSS score [units: Units on a scale] Mean (Standard Deviation)
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 (N/A)^[1]	37.3 (67.70)

No statistical analysis provided for Mean mTSS score

4. Secondary Outcome Measure: Mean HAQ-DI score [ Time Frame: Weeks 0, 12, 24, 36 and 52 ]

Measure Type	Secondary
Measure Name	Mean HAQ-DI score
Measure 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
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

Reporting Groups

	Description
Fostamatinib 100 mg bid	Oral treatment
Fostamatinib 150 mg qd	Oral treatment
Fostamatinib 100 mg qd	Oral treatment

Measured Values

	Fostamatinib 100 mg bid	Fostamatinib 150 mg qd	Fostamatinib 100 mg qd
Number of Participants Analyzed [units:participants]	1271	342	201
Mean HAQ-DI score [units: Units on a scale] Mean (Standard Deviation)
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)

No statistical analysis provided for Mean HAQ-DI score

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
FOSTA 100 MG BID	No text entered.
FOSTA 100 MG QD	No text entered.
FOSTA 150 MG QD	No text entered.

Serious Adverse Events

FOSTA 100 MG BID

FOSTA 100 MG QD

FOSTA 150 MG QD

Total, serious adverse events

# participants affected / at risk

153/1343 (11.39%)

12/212 (5.66%)

31/357 (8.68%)

BLOOD AND LYMPHATIC SYSTEM DISORDERS

SPLENIC INFARCTION¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

CARDIAC DISORDERS

ACUTE MYOCARDIAL INFARCTION¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

CARDIAC DISORDERS

ANGINA UNSTABLE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

CARDIAC DISORDERS

ATRIAL FIBRILLATION¹,^†

# participants affected / at risk

2/1343 (0.15%)

0/212 (0.00%)

0/357 (0.00%)

# events

CARDIAC DISORDERS

BRADYCARDIA¹,^†

# participants affected / at risk

0/1343 (0.00%)

1/212 (0.47%)

0/357 (0.00%)

# events

CARDIAC DISORDERS

CARDIAC FAILURE CHRONIC¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

CARDIAC DISORDERS

CARDIAC FAILURE CONGESTIVE¹,^†

# participants affected / at risk

2/1343 (0.15%)

0/212 (0.00%)

0/357 (0.00%)

# events

CARDIAC DISORDERS

CARDIO-RESPIRATORY ARREST¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

CARDIAC DISORDERS

CARDIOMYOPATHY¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

CARDIAC DISORDERS

MYOCARDIAL INFARCTION¹,^†

# participants affected / at risk

2/1343 (0.15%)

0/212 (0.00%)

0/357 (0.00%)

# events

CARDIAC DISORDERS

MYOCARDIAL ISCHAEMIA¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

ENDOCRINE DISORDERS

GOITRE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

EYE DISORDERS

RETINAL DETACHMENT¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

GASTROINTESTINAL DISORDERS

ABDOMINAL PAIN¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

GASTROINTESTINAL DISORDERS

ABDOMINAL PAIN UPPER¹,^†

# participants affected / at risk

0/1343 (0.00%)

1/212 (0.47%)

0/357 (0.00%)

# events

GASTROINTESTINAL DISORDERS

ACUTE ABDOMEN¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

GASTROINTESTINAL DISORDERS

BARRETT'S OESOPHAGUS¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

GASTROINTESTINAL DISORDERS

COLITIS¹,^†

# participants affected / at risk

2/1343 (0.15%)

0/212 (0.00%)

0/357 (0.00%)

# events

GASTROINTESTINAL DISORDERS

COLITIS MICROSCOPIC¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

GASTROINTESTINAL DISORDERS

COLONIC STENOSIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

GASTROINTESTINAL DISORDERS

DIARRHOEA¹,^†

# participants affected / at risk

4/1343 (0.30%)

1/212 (0.47%)

0/357 (0.00%)

# events

GASTROINTESTINAL DISORDERS

DYSPEPSIA¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

GASTROINTESTINAL DISORDERS

GASTRIC ULCER¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

GASTROINTESTINAL DISORDERS

GASTRITIS¹,^†

# participants affected / at risk

2/1343 (0.15%)

0/212 (0.00%)

1/357 (0.28%)

# events

GASTROINTESTINAL DISORDERS

GASTRITIS EROSIVE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

GASTROINTESTINAL DISORDERS

GASTROINTESTINAL HAEMORRHAGE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

GASTROINTESTINAL DISORDERS

HAEMATEMESIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

GASTROINTESTINAL DISORDERS

ILEITIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

GASTROINTESTINAL DISORDERS

ILEUS¹,^†

# participants affected / at risk

2/1343 (0.15%)

0/212 (0.00%)

0/357 (0.00%)

# events

GASTROINTESTINAL DISORDERS

INGUINAL HERNIA¹,^†

# participants affected / at risk

2/1343 (0.15%)

0/212 (0.00%)

1/357 (0.28%)

# events

GASTROINTESTINAL DISORDERS

INTESTINAL HAEMORRHAGE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

GASTROINTESTINAL DISORDERS

INTESTINAL ISCHAEMIA¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

GASTROINTESTINAL DISORDERS

INTESTINAL OBSTRUCTION¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

GASTROINTESTINAL DISORDERS

OESOPHAGEAL ACHALASIA¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

GASTROINTESTINAL DISORDERS

PANCREATIC PSEUDOCYST¹,^†

# participants affected / at risk

0/1343 (0.00%)

1/212 (0.47%)

0/357 (0.00%)

# events

GASTROINTESTINAL DISORDERS

PANCREATITIS¹,^†

# participants affected / at risk

3/1343 (0.22%)

0/212 (0.00%)

0/357 (0.00%)

# events

GASTROINTESTINAL DISORDERS

PANCREATITIS ACUTE¹,^†

# participants affected / at risk

3/1343 (0.22%)

1/212 (0.47%)

0/357 (0.00%)

# events

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

DEVICE DISLOCATION¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

GENERAL PHYSICAL HEALTH DETERIORATION¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

NON-CARDIAC CHEST PAIN¹,^†

# participants affected / at risk

3/1343 (0.22%)

1/212 (0.47%)

0/357 (0.00%)

# events

HEPATOBILIARY DISORDERS

BILE DUCT OBSTRUCTION¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

HEPATOBILIARY DISORDERS

BILIARY COLIC¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

HEPATOBILIARY DISORDERS

CHOLECYSTITIS¹,^†

# participants affected / at risk

2/1343 (0.15%)

0/212 (0.00%)

0/357 (0.00%)

# events

HEPATOBILIARY DISORDERS

CHOLECYSTITIS ACUTE¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

HEPATOBILIARY DISORDERS

CHOLECYSTITIS CHRONIC¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

HEPATOBILIARY DISORDERS

CHOLELITHIASIS¹,^†

# participants affected / at risk

4/1343 (0.30%)

0/212 (0.00%)

0/357 (0.00%)

# events

HEPATOBILIARY DISORDERS

GALLBLADDER POLYP¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

HEPATOBILIARY DISORDERS

POST CHOLECYSTECTOMY SYNDROME¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

IMMUNE SYSTEM DISORDERS

ANAPHYLACTIC SHOCK¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

IMMUNE SYSTEM DISORDERS

FOOD ALLERGY¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

IMMUNE SYSTEM DISORDERS

HYPERSENSITIVITY¹,^†

# participants affected / at risk

2/1343 (0.15%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

ABSCESS LIMB¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

APPENDICITIS¹,^†

# participants affected / at risk

4/1343 (0.30%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

ARTHRITIS BACTERIAL¹,^†

# participants affected / at risk

0/1343 (0.00%)

1/212 (0.47%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

BACTERAEMIA¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

BACTERIAL PYELONEPHRITIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

BACTERIAL SEPSIS¹,^†

# participants affected / at risk

2/1343 (0.15%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

BRONCHITIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

BRONCHOPNEUMONIA¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

INFECTIONS AND INFESTATIONS

CELLULITIS¹,^†

# participants affected / at risk

6/1343 (0.45%)

1/212 (0.47%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

CYTOMEGALOVIRUS INFECTION¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

DIVERTICULITIS¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

INFECTIONS AND INFESTATIONS

ENTEROCOLITIS BACTERIAL¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

ENTEROCOLITIS VIRAL¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

ERYSIPELAS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

ESCHERICHIA URINARY TRACT INFECTION¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

GANGRENE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

GASTROENTERITIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

1/212 (0.47%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

GASTROENTERITIS BACTERIAL¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

GASTROENTERITIS VIRAL¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

1/357 (0.28%)

# events

INFECTIONS AND INFESTATIONS

HERPES ZOSTER¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

INTERVERTEBRAL DISCITIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

LIVER ABSCESS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

LUNG ABSCESS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

OSTEOMYELITIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

OTITIS EXTERNA¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

PANCREATITIS VIRAL¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

PERITONITIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

PNEUMONIA¹,^†

# participants affected / at risk

5/1343 (0.37%)

1/212 (0.47%)

1/357 (0.28%)

# events

INFECTIONS AND INFESTATIONS

PNEUMONIA BACTERIAL¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

PNEUMONIA VIRAL¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

PULMONARY TUBERCULOSIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

STAPHYLOCOCCAL SEPSIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

SUBCUTANEOUS ABSCESS¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

INFECTIONS AND INFESTATIONS

URINARY TRACT INFECTION¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

URINARY TRACT INFECTION BACTERIAL¹,^†

# participants affected / at risk

2/1343 (0.15%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

UROSEPSIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

VIRAL UPPER RESPIRATORY TRACT INFECTION¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INFECTIONS AND INFESTATIONS

WOUND INFECTION BACTERIAL¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

INFECTIONS AND INFESTATIONS

WOUND SEPSIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

ACCIDENTAL OVERDOSE¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

2/357 (0.56%)

# events

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

FACIAL BONES FRACTURE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

FEMORAL NECK FRACTURE¹,^†

# participants affected / at risk

1/1343 (0.07%)

1/212 (0.47%)

0/357 (0.00%)

# events

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

FEMUR FRACTURE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

FIBULA FRACTURE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

HUMERUS FRACTURE¹,^†

# participants affected / at risk

2/1343 (0.15%)

0/212 (0.00%)

1/357 (0.28%)

# events

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

JOINT DISLOCATION¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

JOINT INJURY¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

PATELLA FRACTURE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

TENDON RUPTURE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

TIBIA FRACTURE¹,^†

# participants affected / at risk

0/1343 (0.00%)

1/212 (0.47%)

0/357 (0.00%)

# events

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

ULNA FRACTURE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

UPPER LIMB FRACTURE¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

WOUND DEHISCENCE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

WRIST FRACTURE¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

INVESTIGATIONS

LIVER FUNCTION TEST ABNORMAL¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

METABOLISM AND NUTRITION DISORDERS

DEHYDRATION¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

METABOLISM AND NUTRITION DISORDERS

HYPOKALAEMIA¹,^†

# participants affected / at risk

1/1343 (0.07%)

1/212 (0.47%)

1/357 (0.28%)

# events

METABOLISM AND NUTRITION DISORDERS

HYPONATRAEMIA¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

1/357 (0.28%)

# events

METABOLISM AND NUTRITION DISORDERS

TYPE 2 DIABETES MELLITUS¹,^†

# participants affected / at risk

0/1343 (0.00%)

1/212 (0.47%)

0/357 (0.00%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

ARTHRITIS¹,^†

# participants affected / at risk

2/1343 (0.15%)

0/212 (0.00%)

0/357 (0.00%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

BACK PAIN¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

HIP DEFORMITY¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

INTERVERTEBRAL DISC DISORDER¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

INTERVERTEBRAL DISC DISPLACEMENT¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

INTERVERTEBRAL DISC PROTRUSION¹,^†

# participants affected / at risk

4/1343 (0.30%)

1/212 (0.47%)

0/357 (0.00%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

LUMBAR SPINAL STENOSIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

MUSCULOSKELETAL CHEST PAIN¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

OSTEITIS¹,^†

# participants affected / at risk

0/1343 (0.00%)

1/212 (0.47%)

0/357 (0.00%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

OSTEOARTHRITIS¹,^†

# participants affected / at risk

6/1343 (0.45%)

0/212 (0.00%)

2/357 (0.56%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

OSTEONECROSIS¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

PATHOLOGICAL FRACTURE¹,^†

# participants affected / at risk

2/1343 (0.15%)

0/212 (0.00%)

0/357 (0.00%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

RHEUMATOID ARTHRITIS¹,^†

# participants affected / at risk

9/1343 (0.67%)

0/212 (0.00%)

0/357 (0.00%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

SJOGREN'S SYNDROME¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

SPONDYLOLISTHESIS¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

SYNOVITIS¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

BASAL CELL CARCINOMA¹,^†

# participants affected / at risk

2/1343 (0.15%)

0/212 (0.00%)

0/357 (0.00%)

# events

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

BENIGN NEOPLASM OF PROSTATE¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

BENIGN SOFT TISSUE NEOPLASM¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

BREAST CANCER¹,^†

# participants affected / at risk

2/1343 (0.15%)

0/212 (0.00%)

0/357 (0.00%)

# events

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

CERVIX CARCINOMA¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

COLORECTAL CANCER¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

GASTRIC CANCER¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

LIPOMA¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

LUNG SQUAMOUS CELL CARCINOMA STAGE UNSPECIFIED¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

MALIGNANT MELANOMA¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

PANCREATIC NEUROENDOCRINE TUMOUR¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

PROSTATE CANCER¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

RECTAL CANCER¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

RENAL CANCER METASTATIC¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

RENAL CELL CARCINOMA¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

UTERINE LEIOMYOMA¹,^†

# participants affected / at risk

2/1343 (0.15%)

0/212 (0.00%)

1/357 (0.28%)

# events

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

VAGINAL CANCER¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NERVOUS SYSTEM DISORDERS

APHASIA¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NERVOUS SYSTEM DISORDERS

CAROTID ARTERY STENOSIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NERVOUS SYSTEM DISORDERS

CONVULSION¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NERVOUS SYSTEM DISORDERS

DYSARTHRIA¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NERVOUS SYSTEM DISORDERS

HAEMORRHAGIC STROKE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NERVOUS SYSTEM DISORDERS

HYPERTENSIVE ENCEPHALOPATHY¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NERVOUS SYSTEM DISORDERS

HYPOGLYCAEMIC COMA¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NERVOUS SYSTEM DISORDERS

ISCHAEMIC STROKE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NERVOUS SYSTEM DISORDERS

LUMBAR RADICULOPATHY¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NERVOUS SYSTEM DISORDERS

POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NERVOUS SYSTEM DISORDERS

RADICULITIS LUMBOSACRAL¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NERVOUS SYSTEM DISORDERS

SCIATICA¹,^†

# participants affected / at risk

0/1343 (0.00%)

1/212 (0.47%)

0/357 (0.00%)

# events

NERVOUS SYSTEM DISORDERS

SYNCOPE¹,^†

# participants affected / at risk

3/1343 (0.22%)

0/212 (0.00%)

2/357 (0.56%)

# events

NERVOUS SYSTEM DISORDERS

TENSION HEADACHE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NERVOUS SYSTEM DISORDERS

TRANSIENT ISCHAEMIC ATTACK¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

NERVOUS SYSTEM DISORDERS

VITH NERVE PARALYSIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

PSYCHIATRIC DISORDERS

ADJUSTMENT DISORDER¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

PSYCHIATRIC DISORDERS

ALCOHOL ABUSE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

PSYCHIATRIC DISORDERS

DEPRESSION¹,^†

# participants affected / at risk

2/1343 (0.15%)

0/212 (0.00%)

0/357 (0.00%)

# events

RENAL AND URINARY DISORDERS

CALCULUS URETERIC¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

RENAL AND URINARY DISORDERS

CALCULUS URINARY¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

RENAL AND URINARY DISORDERS

NEPHROLITHIASIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

1/212 (0.47%)

0/357 (0.00%)

# events

RENAL AND URINARY DISORDERS

RENAL FAILURE ACUTE¹,^†

# participants affected / at risk

3/1343 (0.22%)

0/212 (0.00%)

0/357 (0.00%)

# events

RENAL AND URINARY DISORDERS

RENAL IMPAIRMENT¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

RENAL AND URINARY DISORDERS

URINARY BLADDER POLYP¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

REPRODUCTIVE SYSTEM AND BREAST DISORDERS

ADENOMYOSIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

REPRODUCTIVE SYSTEM AND BREAST DISORDERS

BENIGN PROSTATIC HYPERPLASIA¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

REPRODUCTIVE SYSTEM AND BREAST DISORDERS

OVARIAN CYST¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

REPRODUCTIVE SYSTEM AND BREAST DISORDERS

UTERINE POLYP¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

ACUTE RESPIRATORY FAILURE¹,^†

# participants affected / at risk

2/1343 (0.15%)

0/212 (0.00%)

0/357 (0.00%)

# events

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

CHRONIC OBSTRUCTIVE PULMONARY DISEASE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

1/357 (0.28%)

# events

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

HYPERVENTILATION¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

PNEUMONIA ASPIRATION¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

PULMONARY EMBOLISM¹,^†

# participants affected / at risk

4/1343 (0.30%)

0/212 (0.00%)

0/357 (0.00%)

# events

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

RESPIRATORY FAILURE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

SKIN AND SUBCUTANEOUS TISSUE DISORDERS

DIGITAL ULCER¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

SKIN AND SUBCUTANEOUS TISSUE DISORDERS

ERYTHEMA MULTIFORME¹,^†

# participants affected / at risk

0/1343 (0.00%)

0/212 (0.00%)

1/357 (0.28%)

# events

SKIN AND SUBCUTANEOUS TISSUE DISORDERS

TOXIC EPIDERMAL NECROLYSIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

VASCULAR DISORDERS

AORTIC ANEURYSM RUPTURE¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

VASCULAR DISORDERS

AORTIC STENOSIS¹,^†

# participants affected / at risk

0/1343 (0.00%)

1/212 (0.47%)

0/357 (0.00%)

# events

VASCULAR DISORDERS

AORTIC THROMBOSIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

VASCULAR DISORDERS

ARTERIAL THROMBOSIS¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

VASCULAR DISORDERS

FEMORAL ARTERY OCCLUSION¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

VASCULAR DISORDERS

PERIPHERAL ISCHAEMIA¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

VASCULAR DISORDERS

THROMBOPHLEBITIS SUPERFICIAL¹,^†

# participants affected / at risk

1/1343 (0.07%)

0/212 (0.00%)

0/357 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 15.1

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
FOSTA 100 MG BID	No text entered.
FOSTA 100 MG QD	No text entered.
FOSTA 150 MG QD	No text entered.

Other Adverse Events

FOSTA 100 MG BID

FOSTA 100 MG QD

FOSTA 150 MG QD

Total, other (not including serious) adverse events

# participants affected / at risk

466/1343 (34.70%)

68/212 (32.08%)

98/357 (27.45%)

GASTROINTESTINAL DISORDERS

DIARRHOEA¹,^†

# participants affected / at risk

202/1343 (15.04%)

28/212 (13.21%)

43/357 (12.04%)

# events

268

INFECTIONS AND INFESTATIONS

NASOPHARYNGITIS¹,^†

# participants affected / at risk

86/1343 (6.40%)

15/212 (7.08%)

28/357 (7.84%)

# events

102

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

RHEUMATOID ARTHRITIS¹,^†

# participants affected / at risk

116/1343 (8.64%)

19/212 (8.96%)

30/357 (8.40%)

# events

155

VASCULAR DISORDERS

HYPERTENSION¹,^†

# participants affected / at risk

166/1343 (12.36%)

14/212 (6.60%)

20/357 (5.60%)

# events

197

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 15.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Dave Goldstraw
Organization:	AstraZeneca Pharmaceuticals
Phone	+44 (0)1625 512415
E-mail:	[email protected]

Documents available

CSR Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information

800-236-9933

ClinicalTrialTransparency@astrazeneca.com

Investigators

Principal Investigator

Neil Mackillop

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

CSR Synopsis

Trial Results Summaries