Long-term safety in Atrial Fibrillation patients

Study identifier:D1250C00042

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

Long-term treatment with the oral direct thrombin inhibitor AZD0837, compared to Vitamin-K antagonists, as stroke prevention in patients with non-valvular atrial fibrillation and one or more risk factors for stroke and systemic embolic events. A 5-year follow-up study

Medical condition

Persistent or Permanent Nonvalvular Atrial Fibrillation

Phase

Phase 2

Healthy volunteers

Study drug

AZD0837, VKA INR 2-3

Sex

All

Actual Enrollment

523

Study type

Interventional

Age

18 Years +

Date

Study Start Date: 01 Oct 2007

Primary Completion Date: 01 May 2009

Study Completion Date: 01 May 2009

Study design

Allocation: Non-randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention

Verification:

Verified 01 Mar 2012 by AstraZeneca Pharmaceuticals

Collaborators

Inclusion and exclusion criteria

No locations available

Arms	Assigned Interventions
Experimental: 1	Drug: AZD0837 Treatment with AZD0837 starting with 4 different doses, 150 mg od, 300 mg od, 200 mg bid or 450 mg od and then switching to one general common dose, 300 mg od
Active Comparator: 2	Drug: VKA INR 2-3 Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5 Other Name: warfarin

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study population included male and female participants >18 years of age with chronic non-valvular Atrial Fibrillation. The participants were recruited during the time period from 25 October 2007 to 20 May 2008 at medical clinics in Europe.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
All participants had previously participated in the Prevention of Stroke and Systemic Embolic Events in Patients With Atrial Fibrillation (NCT00684307) study

Reporting Groups

	Description
AZD0837	Treatment with AZD0837 starting with 4 different doses, 150 mg od, 300 mg od, 200 mg bid or 450 mg od, then switching to one general common dose, 300 mg od.
VKA, INR 2-3	Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5

Participant Flow: Overall Study

	AZD0837	VKA, INR 2-3
STARTED	288	235
No of patients after Dose Switch	209^[1]	188^[2]
Discontinued patient No due to closure	196^[3]	178^[4]
AZ study closure in Hungary	60	40
COMPLETED	196	178
NOT COMPLETED	92	57
Adverse Event	18	7
AZ study closure in Hungary	60	40
Withdrawal by Subject	5	2
Protocol Violation	0	2
Discontinuation criteria	2	2
recall of ICF, planned operation, death	7	4

[1]	All patients in the AZD0837 arm switched from their initial doses, to a general dose of 300 mg od
[2]	No changes for VKA patients
[3]	No of patients discontinued due the study termination caused tablet formulation stability problems
[4]	No of patients discontinued due the study termination caused tablet formulation stability problems

Baseline Characteristics

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

Reporting Groups

	Description
AZD0837	Treatment with AZD0837 starting with 4 different doses, 150 mg od, 300 mg od, 200 mg bid or 450 mg od, then switching to one general common dose, 300 mg od.
VKA, INR 2-3	Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5

Baseline Measures

	AZD0837	VKA, INR 2-3	Total
Number of Participants [units: Participants]	288	235	523
Age Continuous [units: Years] Mean ( Full Range )	69.9 (34 to 93)	68.0 (33 to 86)	68.95 (33 to 93)
Gender, Male/Female [units: Participants]
Female	90	73	163
Male	198	162	360

Outcome Measures

1. Primary Outcome Measure: Bleeding: Number of patients with any bleeding event, during treatment period [ Time Frame: 154-711 days on treatment ]

Measure Type	Primary
Measure Name	Bleeding: Number of patients with any bleeding event, during treatment period
Measure Description	Participants
Time Frame	154-711 days on treatment
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.

Reporting Groups

	Description
AZD0837	Treatment with AZD0837 starting with 4 different doses, 150 mg od, 300 mg od, 200 mg bid or 450 mg od, then switching to one general common dose, 300 mg od.
VKA, INR 2-3	Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5

Measured Values

	AZD0837	VKA, INR 2-3
Number of Participants Analyzed [units:participants]	288	235
Bleeding: Number of patients with any bleeding event, during treatment period [units: Participants]	55	56

No statistical analysis provided for Bleeding: Number of patients with any bleeding event, during treatment period

2. Secondary Outcome Measure: Alanine Transaminase (ALAT): Number of Patients With ALAT>=3xULN, post baseline [ Time Frame: From baseline to Follow up ]

Measure Type	Secondary
Measure Name	Alanine Transaminase (ALAT): Number of Patients With ALAT>=3xULN, post baseline
Measure Description	ULN=Upper limit of Normal
Time Frame	From baseline to Follow up
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.

Reporting Groups

	Description
AZD0837	Treatment with AZD0837 starting with 4 different doses, 150 mg od, 300 mg od, 200 mg bid or 450 mg od, then switching to one general common dose, 300 mg od.
VKA, INR 2-3	Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5

Measured Values

	AZD0837	VKA, INR 2-3
Number of Participants Analyzed [units:participants]	288	235
Alanine Transaminase (ALAT): Number of Patients With ALAT>=3xULN, post baseline [units: Participants]	9	6

No statistical analysis provided for Alanine Transaminase (ALAT): Number of Patients With ALAT>=3xULN, post baseline

3. Secondary Outcome Measure: Bilirubin: Number of Patients With Bilirubin>=2xULN, post baseline [ Time Frame: From baseline to Follow up ]

Measure Type	Secondary
Measure Name	Bilirubin: Number of Patients With Bilirubin>=2xULN, post baseline
Measure Description
Time Frame	From baseline to Follow up
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.

Reporting Groups

	Description
AZD0837	Treatment with AZD0837 starting with 4 different doses, 150 mg od, 300 mg od, 200 mg bid or 450 mg od, then switching to one general common dose, 300 mg od.
VKA, INR 2-3	Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5

Measured Values

	AZD0837	VKA, INR 2-3
Number of Participants Analyzed [units:participants]	288	235
Bilirubin: Number of Patients With Bilirubin>=2xULN, post baseline [units: Participants]	3	3

No statistical analysis provided for Bilirubin: Number of Patients With Bilirubin>=2xULN, post baseline

4. Secondary Outcome Measure: Creatinine: Absolute change from baseline, at end of treatment [ Time Frame: Baseline and End of treatment ]

Measure Type	Secondary
Measure Name	Creatinine: Absolute change from baseline, at end of treatment
Measure Description
Time Frame	Baseline and End of treatment
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.

Reporting Groups

	Description
AZD0837	Treatment with AZD0837 starting with 4 different doses, 150 mg od, 300 mg od, 200 mg bid or 450 mg od, then switching to one general common dose, 300 mg od.
VKA, INR 2-3	Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5

Measured Values

	AZD0837	VKA, INR 2-3
Number of Participants Analyzed [units:participants]	288	235
Creatinine: Absolute change from baseline, at end of treatment [units: µmol/L] Mean (Full Range)	3.70 (-67.0 to 120.0)	-1.17 (-56.0 to 116)

No statistical analysis provided for Creatinine: Absolute change from baseline, at end of treatment

5. Secondary Outcome Measure: D-dimer:Median and Quartile Range at End of Treatment [ Time Frame: End of treatment ]

Measure Type	Secondary
Measure Name	D-dimer:Median and Quartile Range at End of Treatment
Measure Description	Median (Lower Quartile-Upper Quartile ), ng/mL
Time Frame	End of treatment
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.
Only patients who switched to one common dose, 300 mg od, are included in the AZD0837 analysis

Reporting Groups

	Description
AZD0837	Treatment with AZD0837 starting with 4 different doses, 150 mg od, 300 mg od, 200 mg bid or 450 mg od, then switching to one general common dose, 300 mg od.
VKA, INR 2-3	Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5

Measured Values

	AZD0837	VKA, INR 2-3
Number of Participants Analyzed [units:participants]	193	232
D-dimer:Median and Quartile Range at End of Treatment [units: ng/mL] Median (Inter-Quartile Range)	68.9 (43.3 to 128.4)	54.9 (31.9 to 99.0)

No statistical analysis provided for D-dimer:Median and Quartile Range at End of Treatment

6. Secondary Outcome Measure: Activated partial thromboplastin time (APTT): Absolute change from baseline to end of treatment [ Time Frame: Baseline and End of treatment ]

Measure Type	Secondary
Measure Name	Activated partial thromboplastin time (APTT): Absolute change from baseline to end of treatment
Measure Description	Median Full range, Seconds
Time Frame	Baseline and End of treatment
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.
Only patients who switched to one common dose, 300 mg od, are included in the AZD0837 analysis

Reporting Groups

	Description
AZD0837	Treatment with AZD0837 starting with 4 different doses, 150 mg od, 300 mg od, 200 mg bid or 450 mg od, then switching to one general common dose, 300 mg od.

Measured Values

	AZD0837
Number of Participants Analyzed [units:participants]	173
Activated partial thromboplastin time (APTT): Absolute change from baseline to end of treatment [units: sec] Median (Full Range)	12.9 (-62 to 43)

No statistical analysis provided for Activated partial thromboplastin time (APTT): Absolute change from baseline to end of treatment

7. Secondary Outcome Measure: Electroconvulsive therapy (ECT): Absolute change from baseline to end of treatment [ Time Frame: Baseline and End of Treatment ]

Measure Type	Secondary
Measure Name	Electroconvulsive therapy (ECT): Absolute change from baseline to end of treatment
Measure Description
Time Frame	Baseline and End of Treatment
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.
Only patients who switched to one dose, 300 mg od, are included in the AZD0837 analysis

Reporting Groups

	Description
AZD0837	Treatment with AZD0837 starting with 4 different doses, 150 mg od, 300 mg od, 200 mg bid or 450 mg od, then switching to one general common dose, 300 mg od.

Measured Values

	AZD0837
Number of Participants Analyzed [units:participants]	129
Electroconvulsive therapy (ECT): Absolute change from baseline to end of treatment [units: sec] Median (Full Range)	49.0 (-5 to 96)

No statistical analysis provided for Electroconvulsive therapy (ECT): Absolute change from baseline to end of treatment

8. Secondary Outcome Measure: AZD0837: Plasma Concentration of AZD0837 at End of Treatment [ Time Frame: End of treatment ]

Measure Type	Secondary
Measure Name	AZD0837: Plasma Concentration of AZD0837 at End of Treatment
Measure Description
Time Frame	End of treatment
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.
Only patients who switched to one dose, 300 mg od, are included in the AZD0837 analysis

Reporting Groups

	Description
AZD0837	Treatment with AZD0837 starting with 4 different doses, 150 mg od, 300 mg od, 200 mg bid or 450 mg od, then switching to one general common dose, 300 mg od.

Measured Values

	AZD0837
Number of Participants Analyzed [units:participants]	195
AZD0837: Plasma Concentration of AZD0837 at End of Treatment [units: nmol/L] Median (Full Range)	675 (10 to 4090)

No statistical analysis provided for AZD0837: Plasma Concentration of AZD0837 at End of Treatment

9. Secondary Outcome Measure: AR-H067637XX, the active major metabolite of AD0837: Plasma Concentration of AR-H067637XX, at End of Treatment [ Time Frame: 154-711 days on treatment ]

Measure Type	Secondary
Measure Name	AR-H067637XX, the active major metabolite of AD0837: Plasma Concentration of AR-H067637XX, at End of Treatment
Measure Description
Time Frame	154-711 days on treatment
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.
Only patients who switched to one dose, 300 mg od, are included in the AZD0837 analysis

Reporting Groups

	Description
AZD0837	Treatment with AZD0837 starting with 4 different doses, 150 mg od, 300 mg od, 200 mg bid or 450 mg od, then switching to one general common dose, 300 mg od.

Measured Values

	AZD0837
Number of Participants Analyzed [units:participants]	195
AR-H067637XX, the active major metabolite of AD0837: Plasma Concentration of AR-H067637XX, at End of Treatment [units: nmol/L] Median (Full Range)	341 (10 to 929)

No statistical analysis provided for AR-H067637XX, the active major metabolite of AD0837: Plasma Concentration of AR-H067637XX, at End of Treatment

Serious Adverse Events

Time Frame	154-711 days on treatment
Additional Description	No text entered.

Reporting Groups

	Description
AZD0837	Treatment with AZD0837 starting with 4 different doses, 150 mg od, 300 mg od, 200 mg bid or 450 mg od and then switching to one general common dose, 300 mg od
VKA INR 2-3	Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5

Serious Adverse Events

AZD0837

VKA INR 2-3

Total, serious adverse events

# participants affected / at risk

73/288 (25.35%)

61/235 (25.96%)

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Cardiac disorders

Cardiac Failure¹,^†

# participants affected / at risk

7/288 (2.43%)

6/235 (2.55%)

Cardiac disorders

Atrial Fibrillation¹,^†

# participants affected / at risk

4/288 (1.39%)

4/235 (1.70%)

Cardiac disorders

Angina Unstable¹,^†

# participants affected / at risk

0/288 (0.00%)

3/235 (1.28%)

Cardiac disorders

Bradycardia¹,^†

# participants affected / at risk

3/288 (1.04%)

2/235 (0.85%)

Cardiac disorders

Angina Pectoris¹,^†

# participants affected / at risk

2/288 (0.69%)

1/235 (0.43%)

Cardiac disorders

Sick Sinus Syndrome¹,^†

# participants affected / at risk

2/288 (0.69%)

1/235 (0.43%)

Cardiac disorders

Acute Coronary Syndrome¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Cardiac disorders

Atrial Flutter¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Cardiac disorders

Bradyarrhythmia¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Cardiac disorders

Cardiac Failure Congestive¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Cardiac disorders

Chordae Tendinae Rupture¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Cardiac disorders

Coronary Artery Stenosis¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Cardiac disorders

Heart Valve Incompetence¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Cardiac disorders

Myocardial Ischaemia¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Cardiac disorders

Palpitations¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Cardiac disorders

Tachyarrhythmia¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Cardiac disorders

Tachycardia¹,^†

# participants affected / at risk

1/288 (0.35%)

1/235 (0.43%)

Cardiac disorders

Ventricular Tachycardia¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Endocrine disorders

Hyperthyroidism¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Eye disorders

Cataract¹,^†

# participants affected / at risk

1/288 (0.35%)

2/235 (0.85%)

Eye disorders

Eye Haemorrhage¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Eye disorders

Glaucoma¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Eye disorders

Retinal Artery Embolism¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Gastrointestinal disorders

Gastrointestinal Haemorrhage¹,^†

# participants affected / at risk

0/288 (0.00%)

3/235 (1.28%)

Gastrointestinal disorders

Gastric Ulcer¹,^†

# participants affected / at risk

0/288 (0.00%)

2/235 (0.85%)

Gastrointestinal disorders

Abdominal Hernia¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Gastrointestinal disorders

Abdominal Pain¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Gastrointestinal disorders

Abdominal Pain Lower¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Gastrointestinal disorders

Anal Haemorrhage¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Gastrointestinal disorders

Anal Ulcer¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Gastrointestinal disorders

Gastritis¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Gastrointestinal disorders

Haematemesis¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Gastrointestinal disorders

Inguinal Hernia¹,^†

# participants affected / at risk

1/288 (0.35%)

1/235 (0.43%)

Gastrointestinal disorders

Melaena¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Gastrointestinal disorders

Periodontal Disease¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

General disorders

Death¹,^†

# participants affected / at risk

2/288 (0.69%)

0/235 (0.00%)

General disorders

Non-Cardiac Chest Pain¹,^†

# participants affected / at risk

0/288 (0.00%)

2/235 (0.85%)

General disorders

Asthenia¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Hepatobiliary disorders

Cholecystitis Chronic¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Hepatobiliary disorders

Cholelithiasis¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Hepatobiliary disorders

Jaundice Cholestatic¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Immune system disorders

Corneal Graft Rejection¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

2/288 (0.69%)

3/235 (1.28%)

Infections and infestations

Erysipelas¹,^†

# participants affected / at risk

3/288 (1.04%)

1/235 (0.43%)

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

3/288 (1.04%)

3/235 (1.28%)

Infections and infestations

Abscess Limb¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Infections and infestations

Endocarditis¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Infections and infestations

Gastroenteritis¹,^†

# participants affected / at risk

1/288 (0.35%)

1/235 (0.43%)

Infections and infestations

Intervertebral Discitis¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Infections and infestations

Laryngitis¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Infections and infestations

Pyelonephritis¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Infections and infestations

Respiratory Tract Infection¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Infections and infestations

Sinusitis¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Infections and infestations

Urinary Tract Infection¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Infections and infestations

Urosepsis¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Injury, poisoning and procedural complications

Concussion¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Injury, poisoning and procedural complications

Contusion¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Injury, poisoning and procedural complications

Foreign Body Trauma¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Injury, poisoning and procedural complications

Head Injury¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Injury, poisoning and procedural complications

Joint Dislocation¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Injury, poisoning and procedural complications

Post Procedural Haemorrhage¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Injury, poisoning and procedural complications

Subdural Haematoma¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Injury, poisoning and procedural complications

Tibia Fracture¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Investigations

Alanine Aminotransferase Increased¹,^†

# participants affected / at risk

2/288 (0.69%)

1/235 (0.43%)

Investigations

Haemoglobin Decreased¹,^†

# participants affected / at risk

1/288 (0.35%)

2/235 (0.85%)

Investigations

Blood Alkaline Phosphatase Increased¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Investigations

Blood Glucose Increased¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Investigations

International Normalised Ratio Increased¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Metabolism and nutrition disorders

Diabetes Mellitus¹,^†

# participants affected / at risk

2/288 (0.69%)

1/235 (0.43%)

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

1/288 (0.35%)

1/235 (0.43%)

Metabolism and nutrition disorders

Hyperkalaemia¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Metabolism and nutrition disorders

Hypoglycaemia¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Musculoskeletal and connective tissue disorders

Arthritis¹,^†

# participants affected / at risk

0/288 (0.00%)

2/235 (0.85%)

Musculoskeletal and connective tissue disorders

Osteoarthritis¹,^†

# participants affected / at risk

2/288 (0.69%)

0/235 (0.00%)

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Musculoskeletal and connective tissue disorders

Back Pain¹,^†

# participants affected / at risk

1/288 (0.35%)

1/235 (0.43%)

Musculoskeletal and connective tissue disorders

Bursitis¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Musculoskeletal and connective tissue disorders

Inguinal Mass¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Musculoskeletal and connective tissue disorders

Muscle Atrophy¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Musculoskeletal and connective tissue disorders

Muscular Weakness¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Musculoskeletal and connective tissue disorders

Osteitis¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Musculoskeletal and connective tissue disorders

Rheumatoid Arthritis¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Musculoskeletal and connective tissue disorders

Scleroderma¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colon Cancer¹,^†

# participants affected / at risk

3/288 (1.04%)

0/235 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Basal Cell Carcinoma¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colon Adenoma¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colon Cancer Metastatic¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases To Central Nervous System¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Nervous system disorders

Syncope¹,^†

# participants affected / at risk

3/288 (1.04%)

1/235 (0.43%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

0/288 (0.00%)

2/235 (0.85%)

Nervous system disorders

Transient Ischaemic Attack¹,^†

# participants affected / at risk

1/288 (0.35%)

2/235 (0.85%)

Nervous system disorders

Cerebral Artery Embolism¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Nervous system disorders

Cerebrovascular Accident¹,^†

# participants affected / at risk

1/288 (0.35%)

1/235 (0.43%)

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

1/288 (0.35%)

1/235 (0.43%)

Nervous system disorders

Encephalitis¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Nervous system disorders

Epilepsy¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Nervous system disorders

Ischaemic Stroke¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Nervous system disorders

Status Epilepticus¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Nervous system disorders

Vascular Encephalopathy¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Nervous system disorders

Vertebrobasilar Insufficiency¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Psychiatric disorders

Delusional Disorder, Persecutory Type¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Psychiatric disorders

Dysthymic Disorder¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Renal and urinary disorders

Haematuria¹,^†

# participants affected / at risk

2/288 (0.69%)

1/235 (0.43%)

Renal and urinary disorders

Dysuria¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Renal and urinary disorders

Renal Failure¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Renal and urinary disorders

Urinary Bladder Haemorrhage¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Reproductive system and breast disorders

Postmenopausal Haemorrhage¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

2/288 (0.69%)

1/235 (0.43%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea Exertional¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Respiratory, thoracic and mediastinal disorders

Haemoptysis¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Respiratory, thoracic and mediastinal disorders

Pleural Effusion¹,^†

# participants affected / at risk

1/288 (0.35%)

1/235 (0.43%)

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

0/288 (0.00%)

1/235 (0.43%)

Vascular disorders

Arterial Occlusive Disease¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Vascular disorders

Arterial Stenosis Limb¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Vascular disorders

Orthostatic Hypotension¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Vascular disorders

Peripheral Artery Aneurysm¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Vascular disorders

Peripheral Embolism¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Vascular disorders

Subclavian Vein Thrombosis¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

Vascular disorders

800003Varicose Vein¹,^†

# participants affected / at risk

1/288 (0.35%)

0/235 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 10.0
2	Term from vocabulary,

Other Adverse Events

Time Frame	154-711 days on treatment
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
AZD0837	Treatment with AZD0837 starting with 4 different doses, 150 mg od, 300 mg od, 200 mg bid or 450 mg od and then switching to one general common dose, 300 mg od
VKA INR 2-3	Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5

Other Adverse Events

AZD0837

VKA INR 2-3

Total, other (not including serious) adverse events

# participants affected / at risk

125/288 (43.40%)

106/235 (45.11%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

37/288 (12.85%)

18/235 (7.66%)

Gastrointestinal disorders

Flatulence¹,^†

# participants affected / at risk

20/288 (6.94%)

1/235 (0.43%)

General disorders

Oedema Peripheral¹,^†

# participants affected / at risk

25/288 (8.68%)

20/235 (8.51%)

General disorders

Fatigue¹,^†

# participants affected / at risk

19/288 (6.60%)

9/235 (3.83%)

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

35/288 (12.15%)

30/235 (12.77%)

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

14/288 (4.86%)

18/235 (7.66%)

Infections and infestations

Urinary Tract Infection¹,^†

# participants affected / at risk

13/288 (4.51%)

15/235 (6.38%)

Injury, poisoning and procedural complications

Fall¹,^†

# participants affected / at risk

4/288 (1.39%)

12/235 (5.11%)

Musculoskeletal and connective tissue disorders

Back Pain¹,^†

# participants affected / at risk

15/288 (5.21%)

12/235 (5.11%)

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

9/288 (3.13%)

13/235 (5.53%)

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

24/288 (8.33%)

17/235 (7.23%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 10.0
2	Term from vocabulary,

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:

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:	Gerard Lynch
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=254&filename=CSR-D1250C00042.pdf
Download
CSR-D1250C00042.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information

800-236-9933

information.center@astrazeneca.com

Investigators

Principal Investigator

Lars Hvilstedt Rasmussen

Head of Cardiology at Heart Centre Aalborg Aarhus University Hospital DK 9100 Aalborg Denmark

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=254&filename=CSR-D1250C00042.pdf

CSR-D1250C00042.pdf

Trial Results Summaries