Trial Outcomes & Findings for Evaluation of Fondaparinux in Patients With a Heart Rhythm Disturbance Who Undergo Restoration of Normal Heart Rhythm (NCT NCT00911300)

NCT ID: NCT00911300

Last Updated: 2012-10-01

Results Overview

Cerebral neurologic events are defined as any new neurologic disorders caused by cerebrovascular embolization, e.g., Transient Ischemic Attack (TIA), cerebral infarction. The cerebrovascular origin of the event has to be confirmed by objective procedures. Systemic thromboembolism comprises any arterial thromboembolic event (e.g., peripheral vascular embolism, mesenteric infarct, or myocardial infarction). All cerebral neurologic events were adjudicated by a Central Adjudication Committee (CAC), members of which were unaware of the participants' treatment assignment.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 349 participants
• Primary outcome timeframe: Baseline (Day 1) until Day 64 (4 days after the EOT [i.e., last administration of study drug]) for CP participants; Baseline until Day 36 (4 days after the EOT) for CN participants
• Results posted on: 2012-10-01

Participant Flow

Participants (par.) were required to undergo transesophageal echocardiography (TEE) to guide cardioversion (CV). TEEs were recorded and archived to allow for later central adjudication and possible evaluation of details. At randomization (Day 1, immediately after TEE), par. were stratified to thrombus (clot)-positive and thrombus (clot)-negative.

Participant milestones

Measure	Fondaparinux For clot-negative (CN) participants (par.), 7.5 milligrams (mg) fondaparinux was injected once daily (OD) subcutaneously (for par. with body weight \[BW\] 50-100 kilograms \[kg\]); for par. with BW \>100 kg, 10 mg fondaparinux was administered using a disposable prefilled syringe for the first 7-10 days after randomization, followed by 3 weeks of 2.5 mg fondaparinux OD (until Day 28+/-4). For clot-positive (CP) par. with creatinine clearance (CrCl) \>= 50 milliliters (mL)/minute (min), 7.5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 10 mg fondaparinux was administered OD. For CP par. with CrCl 30 to \<50 mL/min, 5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 7.5 mg fondaparinux was injected for 28+/-4 days. If the second TEE showed thrombus disappearance, treatment continued until 7-10 days after the second TEE followed by 3 weeks of 2.5 mg fondaparinux OD (total treatment duration: 56+/-4 days).	Unfractioned Heparin (UFH)/Vitamin K Antagonist (VKA) Both CN and CP participants received an initial intravenous (i.v.) bolus injection of 70 international units (IU)/kg (at least 5000 IU) UFH, followed by continuous infusion at an initial rate of 15 IU/kg/hour (h) (at least 1250 IU per hour). The infusion dose was adjusted to maintain an activated partial thromboplastin time (aPTT) at 1.5 to 2 times the reference control value. Infusion continued for at least 72 h. In parallel to UFH, treatment with VKA was started as soon as possible (preferably on Day 1). The dose of VKA was adjusted to reach a target international normalized ratio (INR) of 2.0-3.0. UFH was continued until INR \>2.0. Total treatment duration: 28+/-4 days. For CP participants for whom the second TEE showed thrombus disappearance, VKA was continued during cardioversion and up to a total treatment duration of 56+/-4 days.
Overall Study STARTED	175	174
Overall Study COMPLETED	140	131
Overall Study NOT COMPLETED	35	43

Reasons for withdrawal

Measure	Fondaparinux For clot-negative (CN) participants (par.), 7.5 milligrams (mg) fondaparinux was injected once daily (OD) subcutaneously (for par. with body weight \[BW\] 50-100 kilograms \[kg\]); for par. with BW \>100 kg, 10 mg fondaparinux was administered using a disposable prefilled syringe for the first 7-10 days after randomization, followed by 3 weeks of 2.5 mg fondaparinux OD (until Day 28+/-4). For clot-positive (CP) par. with creatinine clearance (CrCl) \>= 50 milliliters (mL)/minute (min), 7.5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 10 mg fondaparinux was administered OD. For CP par. with CrCl 30 to \<50 mL/min, 5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 7.5 mg fondaparinux was injected for 28+/-4 days. If the second TEE showed thrombus disappearance, treatment continued until 7-10 days after the second TEE followed by 3 weeks of 2.5 mg fondaparinux OD (total treatment duration: 56+/-4 days).	Unfractioned Heparin (UFH)/Vitamin K Antagonist (VKA) Both CN and CP participants received an initial intravenous (i.v.) bolus injection of 70 international units (IU)/kg (at least 5000 IU) UFH, followed by continuous infusion at an initial rate of 15 IU/kg/hour (h) (at least 1250 IU per hour). The infusion dose was adjusted to maintain an activated partial thromboplastin time (aPTT) at 1.5 to 2 times the reference control value. Infusion continued for at least 72 h. In parallel to UFH, treatment with VKA was started as soon as possible (preferably on Day 1). The dose of VKA was adjusted to reach a target international normalized ratio (INR) of 2.0-3.0. UFH was continued until INR \>2.0. Total treatment duration: 28+/-4 days. For CP participants for whom the second TEE showed thrombus disappearance, VKA was continued during cardioversion and up to a total treatment duration of 56+/-4 days.
Overall Study Primary Endpoint Component Occurred	1	2
Overall Study Death	1	0
Overall Study Thrombus Persistant in Second TEE	3	7
Overall Study Adverse Event	14	6
Overall Study Protocol Violation	3	2
Overall Study Consent Withdrawn	4	12
Overall Study Coronary Angiography Performed	1	0
Overall Study Atrial Fibrillation (AF) Recurrence	3	3
Overall Study Received Commercial Treatment	1	0
Overall Study Recurrent Tachyarrhythmia	1	1
Overall Study Recurrent Tachy-Arrhythmia Absoluta	1	1
Overall Study Nurse Unavailable in Participant's City	1	0
Overall Study CV Unsuccessful; Phenprocoumon Received	1	0
Overall Study Participant Could Not Stay in Hospital	0	1
Overall Study Investigator's Decision; New AF Episode	0	1
Overall Study International Normalized Ratio Too High	0	1
Overall Study Participant Refused Hospital Consulation	0	1
Overall Study Underlying Disease (Myocarditis)	0	1
Overall Study Physician Decision	0	1
Overall Study Treatment Stopped by Mistake	0	1
Overall Study Randomized; No Study Medication Received	0	2

Baseline Characteristics

Evaluation of Fondaparinux in Patients With a Heart Rhythm Disturbance Who Undergo Restoration of Normal Heart Rhythm

Baseline characteristics by cohort

Measure	Fondaparinux n=174 Participants For CN par., 7.5 mg fondaparinux was injected OD subcutaneously (for par. with BW 50-100 kg; for par. with BW \>100 kg, 10 mg fondaparinux was administered using a disposable prefilled syringe for the first 7-10 days after randomization, followed by 3 weeks of 2.5 mg fondaparinux OD (until Day 28+/-4). For CP par. with CrCl \>= 50 mL/min, 7.5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 10 mg fondaparinux was administered OD. For CP par. with CrCl 30 to \<50 mL/min, 5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 7.5 mg fondaparinux was injected for 28+/-4 days. If the second TEE showed thrombus disappearance, treatment continued until 7-10 days after the second TEE followed by 3 weeks of 2.5 mg fondaparinux OD (total treatment duration: 56+/-4 days).	UFH/VKA n=170 Participants Both CN and CP participants received an initial i.v. bolus injection of 70 IU/kg (at least 5000 IU) UFH, followed by continuous infusion at an initial rate of 15 IU/kg/h (at least 1250 IU per h). The infusion dose was adjusted to maintain an activated partial thromboplastin aPTT at 1.5 to 2 times the reference control value. Infusion continued for at least 72 h. In parallel to UFH, treatment with VKA was started as soon as possible (preferably on Day 1). The dose of VKA was adjusted to reach a target INR of 2.0-3.0. UFH was continued until INR \>2.0. Total treatment duration: 28+/-4 days. For CP participants for whom the second TEE showed thrombus disappearance, VKA was continued during cardioversion and up to a total treatment duration of 56+/-4 days.	Total n=344 Participants Total of all reporting groups
Age Continuous	68.24 Years STANDARD_DEVIATION 11.09 • n=5 Participants	66.78 Years STANDARD_DEVIATION 11.93 • n=7 Participants	67.52 Years STANDARD_DEVIATION 11.52 • n=5 Participants
Sex: Female, Male Female	69 Participants n=5 Participants	60 Participants n=7 Participants	129 Participants n=5 Participants
Sex: Female, Male Male	105 Participants n=5 Participants	110 Participants n=7 Participants	215 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) until Day 64 (4 days after the EOT [i.e., last administration of study drug]) for CP participants; Baseline until Day 36 (4 days after the EOT) for CN participants

Population: Modified Intent-to-Treat (mITT) Population: all randomized participants receiving at least one dose of study medication and for whom any post-baseline value was available

Cerebral neurologic events are defined as any new neurologic disorders caused by cerebrovascular embolization, e.g., Transient Ischemic Attack (TIA), cerebral infarction. The cerebrovascular origin of the event has to be confirmed by objective procedures. Systemic thromboembolism comprises any arterial thromboembolic event (e.g., peripheral vascular embolism, mesenteric infarct, or myocardial infarction). All cerebral neurologic events were adjudicated by a Central Adjudication Committee (CAC), members of which were unaware of the participants' treatment assignment.

Outcome measures

Measure	Fondaparinux n=174 Participants For CN par., 7.5 mg fondaparinux was injected OD subcutaneously (for par. with BW 50-100 kg; for par. with BW \>100 kg, 10 mg fondaparinux was administered using a disposable prefilled syringe for the first 7-10 days after randomization, followed by 3 weeks of 2.5 mg fondaparinux OD (until Day 28+/-4). For CP par. with CrCl \>= 50 mL/min, 7.5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 10 mg fondaparinux was administered OD. For CP par. with CrCl 30 to \<50 mL/min, 5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 7.5 mg fondaparinux was injected for 28+/-4 days. If the second TEE showed thrombus disappearance, treatment continued until 7-10 days after the second TEE followed by 3 weeks of 2.5 mg fondaparinux OD (total treatment duration: 56+/-4 days).	UFH/VKA n=170 Participants Both CN and CP participants received an initial i.v. bolus injection of 70 IU/kg (at least 5000 IU) UFH, followed by continuous infusion at an initial rate of 15 IU/kg/h (at least 1250 IU per h). The infusion dose was adjusted to maintain an activated partial thromboplastin aPTT at 1.5 to 2 times the reference control value. Infusion continued for at least 72 h. In parallel to UFH, treatment with VKA was started as soon as possible (preferably on Day 1). The dose of VKA was adjusted to reach a target INR of 2.0-3.0. UFH was continued until INR \&amp;gt;2.0. Total treatment duration: 28+/-4 days. For CP participants for whom the second TEE showed thrombus disappearance, VKA was continued during cardioversion and up to a total treatment duration of 56+/-4 days.
Number of Participants With at Least One Event of Cerebral Neurologic Event, Systemic Thromboembolism, Death From Any Cause, and/or Major Bleeding Until the End of Treatment (EOT) Plus 4 Days	3 participants	2 participants

SECONDARY outcome

Timeframe: Baseline (Day 1) until Day 64 (4 days after the EOT [i.e., last administration of study drug]) for CP participants; Baseline until Day 36 (4 days after the EOT) for CN participants; and from Baseline until the follow-up visit (FU) (Day 90+/-7)

Population: mITT Population

Cerebral neurologic events are defined as any new neurologic disorders caused by cerebrovascular embolisation, e.g., TIA, cerebral infarction. All cerebral neurologic events were adjudicated by a CAC, members of which were unaware of the participants' treatment assignment.The cerebrovascular origin of the event was confirmed by objective procedures. A thrombus or blood clot is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system (i.e., clotting factors).

Outcome measures

Measure	Fondaparinux n=174 Participants For CN par., 7.5 mg fondaparinux was injected OD subcutaneously (for par. with BW 50-100 kg; for par. with BW \>100 kg, 10 mg fondaparinux was administered using a disposable prefilled syringe for the first 7-10 days after randomization, followed by 3 weeks of 2.5 mg fondaparinux OD (until Day 28+/-4). For CP par. with CrCl \>= 50 mL/min, 7.5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 10 mg fondaparinux was administered OD. For CP par. with CrCl 30 to \<50 mL/min, 5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 7.5 mg fondaparinux was injected for 28+/-4 days. If the second TEE showed thrombus disappearance, treatment continued until 7-10 days after the second TEE followed by 3 weeks of 2.5 mg fondaparinux OD (total treatment duration: 56+/-4 days).	UFH/VKA n=170 Participants Both CN and CP participants received an initial i.v. bolus injection of 70 IU/kg (at least 5000 IU) UFH, followed by continuous infusion at an initial rate of 15 IU/kg/h (at least 1250 IU per h). The infusion dose was adjusted to maintain an activated partial thromboplastin aPTT at 1.5 to 2 times the reference control value. Infusion continued for at least 72 h. In parallel to UFH, treatment with VKA was started as soon as possible (preferably on Day 1). The dose of VKA was adjusted to reach a target INR of 2.0-3.0. UFH was continued until INR \&amp;gt;2.0. Total treatment duration: 28+/-4 days. For CP participants for whom the second TEE showed thrombus disappearance, VKA was continued during cardioversion and up to a total treatment duration of 56+/-4 days.
Number of Thrombus-negative and Thrombus-positive Participants (Par.) With at Least One Cerebral Neurologic Event Thrombus-negative par. until 4 days after EOT	0 participants	1 participants
Number of Thrombus-negative and Thrombus-positive Participants (Par.) With at Least One Cerebral Neurologic Event Thrombus-positive par. until 4 days after EOT	0 participants	0 participants
Number of Thrombus-negative and Thrombus-positive Participants (Par.) With at Least One Cerebral Neurologic Event Thrombus-negative participants until the FU	1 participants	1 participants
Number of Thrombus-negative and Thrombus-positive Participants (Par.) With at Least One Cerebral Neurologic Event Thrombus-positive participants until the FU	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline (Day 1) until Day 64 (4 days after the EOT [i.e., last administration of study drug]) for CP participants; Baseline until Day 36 (4 days after the EOT) for CN participants; and from Baseline until the follow-up visit (FU) (Day 90+/-7)

Population: mITT Population

Systemic thromboembolism comprises any arterial thromboembolic event (e.g., peripheral vascular embolism, mesenteric infarct, or myocardial infarction). All systemic thromboembolic events were adjudicated by a CAC, the members of which were unaware of the participants' treatment assignment. A thrombus or blood clot is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system (i.e., clotting factors).

Outcome measures

Measure	Fondaparinux n=174 Participants For CN par., 7.5 mg fondaparinux was injected OD subcutaneously (for par. with BW 50-100 kg; for par. with BW \>100 kg, 10 mg fondaparinux was administered using a disposable prefilled syringe for the first 7-10 days after randomization, followed by 3 weeks of 2.5 mg fondaparinux OD (until Day 28+/-4). For CP par. with CrCl \>= 50 mL/min, 7.5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 10 mg fondaparinux was administered OD. For CP par. with CrCl 30 to \<50 mL/min, 5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 7.5 mg fondaparinux was injected for 28+/-4 days. If the second TEE showed thrombus disappearance, treatment continued until 7-10 days after the second TEE followed by 3 weeks of 2.5 mg fondaparinux OD (total treatment duration: 56+/-4 days).	UFH/VKA n=170 Participants Both CN and CP participants received an initial i.v. bolus injection of 70 IU/kg (at least 5000 IU) UFH, followed by continuous infusion at an initial rate of 15 IU/kg/h (at least 1250 IU per h). The infusion dose was adjusted to maintain an activated partial thromboplastin aPTT at 1.5 to 2 times the reference control value. Infusion continued for at least 72 h. In parallel to UFH, treatment with VKA was started as soon as possible (preferably on Day 1). The dose of VKA was adjusted to reach a target INR of 2.0-3.0. UFH was continued until INR \&amp;gt;2.0. Total treatment duration: 28+/-4 days. For CP participants for whom the second TEE showed thrombus disappearance, VKA was continued during cardioversion and up to a total treatment duration of 56+/-4 days.
Number of Thrombus-negative and Thrombus-positive Participants With at Least One Systemic Thromboembolism Thrombus-negative par. until 4 days after EOT	0 participants	0 participants
Number of Thrombus-negative and Thrombus-positive Participants With at Least One Systemic Thromboembolism Thrombus-positive par. until 4 days after EOT	0 participants	0 participants
Number of Thrombus-negative and Thrombus-positive Participants With at Least One Systemic Thromboembolism Thrombus-negative participants until the FU	0 participants	0 participants
Number of Thrombus-negative and Thrombus-positive Participants With at Least One Systemic Thromboembolism Thrombus-positive participants until the FU	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline (Day 1) until Day 64 (4 days after the EOT [i.e., last administration of study drug]) for CP participants; Baseline until Day 36 (4 days after the EOT) for CN participants; and from Baseline until the follow-up visit (FU) (Day 90+/-7)

Population: mITT Population

The cause of death was classified as due to a thromboembolic event (like cerebral infarction), bleeding, or other established diagnosis, or as unexplained. All deaths were adjudicated by an independent CAC, the members of which were unaware of the participants' treatment assignment. A thrombus or blood clot is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system (i.e., clotting factors).

Outcome measures

Measure	Fondaparinux n=174 Participants For CN par., 7.5 mg fondaparinux was injected OD subcutaneously (for par. with BW 50-100 kg; for par. with BW \>100 kg, 10 mg fondaparinux was administered using a disposable prefilled syringe for the first 7-10 days after randomization, followed by 3 weeks of 2.5 mg fondaparinux OD (until Day 28+/-4). For CP par. with CrCl \>= 50 mL/min, 7.5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 10 mg fondaparinux was administered OD. For CP par. with CrCl 30 to \<50 mL/min, 5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 7.5 mg fondaparinux was injected for 28+/-4 days. If the second TEE showed thrombus disappearance, treatment continued until 7-10 days after the second TEE followed by 3 weeks of 2.5 mg fondaparinux OD (total treatment duration: 56+/-4 days).	UFH/VKA n=170 Participants Both CN and CP participants received an initial i.v. bolus injection of 70 IU/kg (at least 5000 IU) UFH, followed by continuous infusion at an initial rate of 15 IU/kg/h (at least 1250 IU per h). The infusion dose was adjusted to maintain an activated partial thromboplastin aPTT at 1.5 to 2 times the reference control value. Infusion continued for at least 72 h. In parallel to UFH, treatment with VKA was started as soon as possible (preferably on Day 1). The dose of VKA was adjusted to reach a target INR of 2.0-3.0. UFH was continued until INR \&amp;gt;2.0. Total treatment duration: 28+/-4 days. For CP participants for whom the second TEE showed thrombus disappearance, VKA was continued during cardioversion and up to a total treatment duration of 56+/-4 days.
Number of Thrombus-negative and Thrombus-positive Participants Who Died From Any Cause Thrombus-negative par. until 4 days after EOT	1 participants	0 participants
Number of Thrombus-negative and Thrombus-positive Participants Who Died From Any Cause Thrombus-positive par. until 4 days after EOT	0 participants	0 participants
Number of Thrombus-negative and Thrombus-positive Participants Who Died From Any Cause Thrombus-negative participants until the FU	3 participants	0 participants
Number of Thrombus-negative and Thrombus-positive Participants Who Died From Any Cause Thrombus-positive participants until the FU	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline (Day 1) until Day 64 (4 days after the EOT [i.e., last administration of study drug]) for CP participants; Baseline until Day 36 (4 days after the EOT) for CN participants; and from Baseline until the follow-up visit (FU) (Day 90+/-7)

Population: mITT Population

Major bleeding: fatal, and/or symptomatic in a critical area/ organ, causes a fall in hemoglobin of >=3 grams/deciliter compared with the pre-randomization level, or leads to the transfusion of >=2 units of whole blood/red blood cells. All bleeding events were adjudicated by a CAC, the members of which were unaware of the participants' treatment assignment. A thrombus/ blood clot is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets, and the activation of the humoral coagulation system (i.e., clotting factors).

Outcome measures

Measure	Fondaparinux n=174 Participants For CN par., 7.5 mg fondaparinux was injected OD subcutaneously (for par. with BW 50-100 kg; for par. with BW \>100 kg, 10 mg fondaparinux was administered using a disposable prefilled syringe for the first 7-10 days after randomization, followed by 3 weeks of 2.5 mg fondaparinux OD (until Day 28+/-4). For CP par. with CrCl \>= 50 mL/min, 7.5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 10 mg fondaparinux was administered OD. For CP par. with CrCl 30 to \<50 mL/min, 5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 7.5 mg fondaparinux was injected for 28+/-4 days. If the second TEE showed thrombus disappearance, treatment continued until 7-10 days after the second TEE followed by 3 weeks of 2.5 mg fondaparinux OD (total treatment duration: 56+/-4 days).	UFH/VKA n=170 Participants Both CN and CP participants received an initial i.v. bolus injection of 70 IU/kg (at least 5000 IU) UFH, followed by continuous infusion at an initial rate of 15 IU/kg/h (at least 1250 IU per h). The infusion dose was adjusted to maintain an activated partial thromboplastin aPTT at 1.5 to 2 times the reference control value. Infusion continued for at least 72 h. In parallel to UFH, treatment with VKA was started as soon as possible (preferably on Day 1). The dose of VKA was adjusted to reach a target INR of 2.0-3.0. UFH was continued until INR \&amp;gt;2.0. Total treatment duration: 28+/-4 days. For CP participants for whom the second TEE showed thrombus disappearance, VKA was continued during cardioversion and up to a total treatment duration of 56+/-4 days.
Number of Thrombus-negative and Thrombus-positive Participants With at Least One Major Bleeding Event Thrombus-negative par. until 4 days after EOT	3 participants	1 participants
Number of Thrombus-negative and Thrombus-positive Participants With at Least One Major Bleeding Event Thrombus-positive par. until 4 days after EOT	0 participants	0 participants
Number of Thrombus-negative and Thrombus-positive Participants With at Least One Major Bleeding Event Thrombus-negative participants until the FU	4 participants	1 participants
Number of Thrombus-negative and Thrombus-positive Participants With at Least One Major Bleeding Event Thrombus-positive participants until the FU	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline (Day 1) until Day 64 (4 days after the EOT [i.e., last administration of study drug]) for CP participants; Baseline until Day 36 (4 days after the EOT) for CN participants; and from Baseline until the follow-up visit (FU) (Day 90+/-7)

Population: mITT Population

Minor bleeding is defined as clinically overt bleeding events that do not meet the criteria for major or clinically relevant non-major bleeding. All episodes of bleeding were adjudicated by an independent CAC, the members of which were unaware of the participants' treatment assignment.

Outcome measures

Measure	Fondaparinux n=174 Participants For CN par., 7.5 mg fondaparinux was injected OD subcutaneously (for par. with BW 50-100 kg; for par. with BW \>100 kg, 10 mg fondaparinux was administered using a disposable prefilled syringe for the first 7-10 days after randomization, followed by 3 weeks of 2.5 mg fondaparinux OD (until Day 28+/-4). For CP par. with CrCl \>= 50 mL/min, 7.5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 10 mg fondaparinux was administered OD. For CP par. with CrCl 30 to \<50 mL/min, 5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 7.5 mg fondaparinux was injected for 28+/-4 days. If the second TEE showed thrombus disappearance, treatment continued until 7-10 days after the second TEE followed by 3 weeks of 2.5 mg fondaparinux OD (total treatment duration: 56+/-4 days).	UFH/VKA n=170 Participants Both CN and CP participants received an initial i.v. bolus injection of 70 IU/kg (at least 5000 IU) UFH, followed by continuous infusion at an initial rate of 15 IU/kg/h (at least 1250 IU per h). The infusion dose was adjusted to maintain an activated partial thromboplastin aPTT at 1.5 to 2 times the reference control value. Infusion continued for at least 72 h. In parallel to UFH, treatment with VKA was started as soon as possible (preferably on Day 1). The dose of VKA was adjusted to reach a target INR of 2.0-3.0. UFH was continued until INR \&amp;gt;2.0. Total treatment duration: 28+/-4 days. For CP participants for whom the second TEE showed thrombus disappearance, VKA was continued during cardioversion and up to a total treatment duration of 56+/-4 days.
Number of Thrombus-negative and Thrombus-positive Participants With at Least One Minor Bleeding Event Thrombus-negative par. until 4 days after EOT	3 participants	4 participants
Number of Thrombus-negative and Thrombus-positive Participants With at Least One Minor Bleeding Event Thrombus-positive par. until 4 days after EOT	0 participants	0 participants
Number of Thrombus-negative and Thrombus-positive Participants With at Least One Minor Bleeding Event Thrombus-negative participants until the FU	3 participants	5 participants
Number of Thrombus-negative and Thrombus-positive Participants With at Least One Minor Bleeding Event Thrombus-positive participants until the FU	1 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 until Day 3

Population: mITT Population. Only participants with data for primary successful electric cardioversion at the indicated timepoint were analyzed.

CV may be performed electively to restore sinus rhythm in patients with persistent AF. The primary successful electric CV was assessed by a 12- lead electrocardiogram (ECG) directly after the CV. Results of the last cardioversion were used in cases for which more than one CV was performed.

Outcome measures

Measure	Fondaparinux n=151 Participants For CN par., 7.5 mg fondaparinux was injected OD subcutaneously (for par. with BW 50-100 kg; for par. with BW \>100 kg, 10 mg fondaparinux was administered using a disposable prefilled syringe for the first 7-10 days after randomization, followed by 3 weeks of 2.5 mg fondaparinux OD (until Day 28+/-4). For CP par. with CrCl \>= 50 mL/min, 7.5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 10 mg fondaparinux was administered OD. For CP par. with CrCl 30 to \<50 mL/min, 5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 7.5 mg fondaparinux was injected for 28+/-4 days. If the second TEE showed thrombus disappearance, treatment continued until 7-10 days after the second TEE followed by 3 weeks of 2.5 mg fondaparinux OD (total treatment duration: 56+/-4 days).	UFH/VKA n=148 Participants Both CN and CP participants received an initial i.v. bolus injection of 70 IU/kg (at least 5000 IU) UFH, followed by continuous infusion at an initial rate of 15 IU/kg/h (at least 1250 IU per h). The infusion dose was adjusted to maintain an activated partial thromboplastin aPTT at 1.5 to 2 times the reference control value. Infusion continued for at least 72 h. In parallel to UFH, treatment with VKA was started as soon as possible (preferably on Day 1). The dose of VKA was adjusted to reach a target INR of 2.0-3.0. UFH was continued until INR \&amp;gt;2.0. Total treatment duration: 28+/-4 days. For CP participants for whom the second TEE showed thrombus disappearance, VKA was continued during cardioversion and up to a total treatment duration of 56+/-4 days.
Number of Participants With Primary Successful Electrical Cardioversion (CV) in Sinus Rhythm	137 participants	133 participants

SECONDARY outcome

Timeframe: At second TEE (at Day 28+/-4)

Population: mITT Population. Only clot-positive participants at the time of the first TEE were analyzed.

Atrial fibrillation (AF) causes stagnant blood in the LA or LAA and can lead to a thromboembolism. Stasis in the LAA represents the principal mechanism of thrombus formation in AF.

Outcome measures

Measure	Fondaparinux n=14 Participants For CN par., 7.5 mg fondaparinux was injected OD subcutaneously (for par. with BW 50-100 kg; for par. with BW \>100 kg, 10 mg fondaparinux was administered using a disposable prefilled syringe for the first 7-10 days after randomization, followed by 3 weeks of 2.5 mg fondaparinux OD (until Day 28+/-4). For CP par. with CrCl \>= 50 mL/min, 7.5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 10 mg fondaparinux was administered OD. For CP par. with CrCl 30 to \<50 mL/min, 5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 7.5 mg fondaparinux was injected for 28+/-4 days. If the second TEE showed thrombus disappearance, treatment continued until 7-10 days after the second TEE followed by 3 weeks of 2.5 mg fondaparinux OD (total treatment duration: 56+/-4 days).	UFH/VKA n=14 Participants Both CN and CP participants received an initial i.v. bolus injection of 70 IU/kg (at least 5000 IU) UFH, followed by continuous infusion at an initial rate of 15 IU/kg/h (at least 1250 IU per h). The infusion dose was adjusted to maintain an activated partial thromboplastin aPTT at 1.5 to 2 times the reference control value. Infusion continued for at least 72 h. In parallel to UFH, treatment with VKA was started as soon as possible (preferably on Day 1). The dose of VKA was adjusted to reach a target INR of 2.0-3.0. UFH was continued until INR \&amp;gt;2.0. Total treatment duration: 28+/-4 days. For CP participants for whom the second TEE showed thrombus disappearance, VKA was continued during cardioversion and up to a total treatment duration of 56+/-4 days.
Number of Participants With a Thrombus in the Left Atrium (LA) or in the Left Atrial Appendage (LAA) at the Time of the Second TEE	3 participants	7 participants

SECONDARY outcome

Timeframe: Baseline (Day 1) until Day 64 (4 days after the EOT [i.e., last administration of study drug]) for CP participants; Baseline until Day 36 (4 days after the EOT) for CN participants; and from Day 64 until the follow-up visit (FU) (Day 90+/-7)

Population: mITT Population

Sinus rhythm is the normal beating of the heart, as measured by an ECG. Normal sinus rhythm not only indicates that the rhythm is normally generated by the sinus node and is traveling in a normal fashion in the heart, but it also indicates that the heart rate (the rate at which the sinus node is generating impulses) is within normal limits.

Outcome measures

Measure	Fondaparinux n=174 Participants For CN par., 7.5 mg fondaparinux was injected OD subcutaneously (for par. with BW 50-100 kg; for par. with BW \>100 kg, 10 mg fondaparinux was administered using a disposable prefilled syringe for the first 7-10 days after randomization, followed by 3 weeks of 2.5 mg fondaparinux OD (until Day 28+/-4). For CP par. with CrCl \>= 50 mL/min, 7.5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 10 mg fondaparinux was administered OD. For CP par. with CrCl 30 to \<50 mL/min, 5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 7.5 mg fondaparinux was injected for 28+/-4 days. If the second TEE showed thrombus disappearance, treatment continued until 7-10 days after the second TEE followed by 3 weeks of 2.5 mg fondaparinux OD (total treatment duration: 56+/-4 days).	UFH/VKA n=170 Participants Both CN and CP participants received an initial i.v. bolus injection of 70 IU/kg (at least 5000 IU) UFH, followed by continuous infusion at an initial rate of 15 IU/kg/h (at least 1250 IU per h). The infusion dose was adjusted to maintain an activated partial thromboplastin aPTT at 1.5 to 2 times the reference control value. Infusion continued for at least 72 h. In parallel to UFH, treatment with VKA was started as soon as possible (preferably on Day 1). The dose of VKA was adjusted to reach a target INR of 2.0-3.0. UFH was continued until INR \&amp;gt;2.0. Total treatment duration: 28+/-4 days. For CP participants for whom the second TEE showed thrombus disappearance, VKA was continued during cardioversion and up to a total treatment duration of 56+/-4 days.
Number of Thrombus-negative and Thrombus-positive Participants With Conversion to Sinus Rhythm Clot-negative par. until 4 days after EOT	109 participants	115 participants
Number of Thrombus-negative and Thrombus-positive Participants With Conversion to Sinus Rhythm Clot-positive par. until 4 days after EOT	5 participants	4 participants
Number of Thrombus-negative and Thrombus-positive Participants With Conversion to Sinus Rhythm Clot-negative participants until the FU	105 participants	106 participants
Number of Thrombus-negative and Thrombus-positive Participants With Conversion to Sinus Rhythm Clot-positive participants until the FU	4 participants	5 participants

SECONDARY outcome

Timeframe: Baseline (Day 1) until Day 64 (4 days after the EOT [i.e., last administration of study drug]) for CP participants; Baseline until Day 36 (4 days after the EOT) for CN participants; and from Baseline until the follow-up visit (FU) (Day 90+/-7)

Population: mITT Population

Hospitalization signifies that the participant has been detained (usually involving at least an overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have been appropriate in the physician's office or out-patient setting. Re-hospitalization refers to an event of hospitalization after discharge for the initial hospitilization for the cardioversion.

Outcome measures

Measure	Fondaparinux n=174 Participants For CN par., 7.5 mg fondaparinux was injected OD subcutaneously (for par. with BW 50-100 kg; for par. with BW \>100 kg, 10 mg fondaparinux was administered using a disposable prefilled syringe for the first 7-10 days after randomization, followed by 3 weeks of 2.5 mg fondaparinux OD (until Day 28+/-4). For CP par. with CrCl \>= 50 mL/min, 7.5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 10 mg fondaparinux was administered OD. For CP par. with CrCl 30 to \<50 mL/min, 5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 7.5 mg fondaparinux was injected for 28+/-4 days. If the second TEE showed thrombus disappearance, treatment continued until 7-10 days after the second TEE followed by 3 weeks of 2.5 mg fondaparinux OD (total treatment duration: 56+/-4 days).	UFH/VKA n=170 Participants Both CN and CP participants received an initial i.v. bolus injection of 70 IU/kg (at least 5000 IU) UFH, followed by continuous infusion at an initial rate of 15 IU/kg/h (at least 1250 IU per h). The infusion dose was adjusted to maintain an activated partial thromboplastin aPTT at 1.5 to 2 times the reference control value. Infusion continued for at least 72 h. In parallel to UFH, treatment with VKA was started as soon as possible (preferably on Day 1). The dose of VKA was adjusted to reach a target INR of 2.0-3.0. UFH was continued until INR \&amp;gt;2.0. Total treatment duration: 28+/-4 days. For CP participants for whom the second TEE showed thrombus disappearance, VKA was continued during cardioversion and up to a total treatment duration of 56+/-4 days.
Number of Participants Who Were Re-hospitalized until 4 days after EOT	14 participants	7 participants
Number of Participants Who Were Re-hospitalized until the FU	18 participants	11 participants

Adverse Events

Fondaparinux

Serious events: 30 serious events

Other events: 68 other events

Deaths: 0 deaths

UFH/VKA

Serious events: 26 serious events

Other events: 70 other events

Deaths: 0 deaths

Serious adverse events

Measure	Fondaparinux n=174 participants at risk For CN par., 7.5 mg fondaparinux was injected OD subcutaneously (for par. with BW 50-100 kg; for par. with BW \>100 kg, 10 mg fondaparinux was administered using a disposable prefilled syringe for the first 7-10 days after randomization, followed by 3 weeks of 2.5 mg fondaparinux OD (until Day 28+/-4). For CP par. with CrCl \>= 50 mL/min, 7.5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 10 mg fondaparinux was administered OD. For CP par. with CrCl 30 to \<50 mL/min, 5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 7.5 mg fondaparinux was injected for 28+/-4 days. If the second TEE showed thrombus disappearance, treatment continued until 7-10 days after the second TEE followed by 3 weeks of 2.5 mg fondaparinux OD (total treatment duration: 56+/-4 days).	UFH/VKA n=170 participants at risk Both CN and CP participants received an initial i.v. bolus injection of 70 IU/kg (at least 5000 IU) UFH, followed by continuous infusion at an initial rate of 15 IU/kg/h (at least 1250 IU per h). The infusion dose was adjusted to maintain an activated partial thromboplastin aPTT at 1.5 to 2 times the reference control value. Infusion continued for at least 72 h. In parallel to UFH, treatment with VKA was started as soon as possible (preferably on Day 1). The dose of VKA was adjusted to reach a target INR of 2.0-3.0. UFH was continued until INR \>2.0. Total treatment duration: 28+/-4 days. For CP participants for whom the second TEE showed thrombus disappearance, VKA was continued during cardioversion and up to a total treatment duration of 56+/-4 days.
Cardiac disorders Atrial fibrillation	6.9% 12/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	2.9% 5/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Cardiac failure	2.3% 4/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.8% 3/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Angina pectoris	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Atrial flutter	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Cardiac failure congestive	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Tachyarrhythmia	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Arrhythmia supraventricular	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Atrioventricular block complete	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Cardiac valve disease	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Coronary artery disease	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Ischemic cardiomyopathy	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Mitral valve incompetence	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Sinoatrial block	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Gastrointestinal disorders Gastrointestinal hemorrhage	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Gastrointestinal disorders Colonic polyp	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Gastrointestinal disorders Diarrhea	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Gastrointestinal disorders Erosive esophagitis	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Gastrointestinal disorders Vomiting	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bronchial carcinoma	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm skin	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Nervous system disorders Cerebrovascular accident	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Nervous system disorders Syncope	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Nervous system disorders Cerebral infarction	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Vascular disorders Hematoma	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Vascular disorders Hypertensive crisis	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Infections and infestations Gastroenteritis	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Infections and infestations Staphylococcal sepsis	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Renal and urinary disorders Renal failure acute	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
General disorders Death	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Injury, poisoning and procedural complications Fall	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Metabolism and nutrition disorders Hypokalemia	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Skin necrosis	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.

Other adverse events

Measure	Fondaparinux n=174 participants at risk For CN par., 7.5 mg fondaparinux was injected OD subcutaneously (for par. with BW 50-100 kg; for par. with BW \>100 kg, 10 mg fondaparinux was administered using a disposable prefilled syringe for the first 7-10 days after randomization, followed by 3 weeks of 2.5 mg fondaparinux OD (until Day 28+/-4). For CP par. with CrCl \>= 50 mL/min, 7.5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 10 mg fondaparinux was administered OD. For CP par. with CrCl 30 to \<50 mL/min, 5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 7.5 mg fondaparinux was injected for 28+/-4 days. If the second TEE showed thrombus disappearance, treatment continued until 7-10 days after the second TEE followed by 3 weeks of 2.5 mg fondaparinux OD (total treatment duration: 56+/-4 days).	UFH/VKA n=170 participants at risk Both CN and CP participants received an initial i.v. bolus injection of 70 IU/kg (at least 5000 IU) UFH, followed by continuous infusion at an initial rate of 15 IU/kg/h (at least 1250 IU per h). The infusion dose was adjusted to maintain an activated partial thromboplastin aPTT at 1.5 to 2 times the reference control value. Infusion continued for at least 72 h. In parallel to UFH, treatment with VKA was started as soon as possible (preferably on Day 1). The dose of VKA was adjusted to reach a target INR of 2.0-3.0. UFH was continued until INR \>2.0. Total treatment duration: 28+/-4 days. For CP participants for whom the second TEE showed thrombus disappearance, VKA was continued during cardioversion and up to a total treatment duration of 56+/-4 days.
Cardiac disorders Bradycardia	1.1% 2/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Atrial fibrillation	7.5% 13/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	6.5% 11/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Angina pectoris	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Atrial flutter	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Atrioventricular block first degree	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Cardiac failure	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Mitral valve incompetence	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Palpitations	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Sinus bradycardia	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Supraventricular extrasystoles	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Tricuspid valve incompetence	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Cardiac disorders Ventricular tachycardia	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Gastrointestinal disorders Diarrhea	1.7% 3/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	2.9% 5/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Gastrointestinal disorders Vomiting	3.4% 6/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Gastrointestinal disorders Constipation	1.7% 3/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.8% 3/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Gastrointestinal disorders Nausea	2.3% 4/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Gastrointestinal disorders Abdominal pain	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Gastrointestinal disorders Dry mouth	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Gastrointestinal disorders Dysphagia	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Gastrointestinal disorders Gastric disorder	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Gastrointestinal disorders Gastrointestinal pain	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Gastrointestinal disorders Intestinal hemorrhage	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Gastrointestinal disorders Toothache	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
General disorders Edema	2.3% 4/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.8% 3/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
General disorders Chest pain	2.3% 4/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
General disorders Edema peripheral	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.8% 3/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
General disorders Chest discomfort	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.8% 3/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
General disorders Asthenia	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
General disorders Fatigue	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
General disorders Vessel puncture site hematoma	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Vascular disorders Hypertension	2.3% 4/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.8% 3/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Vascular disorders Hematoma	1.7% 3/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Vascular disorders Hypotension	2.3% 4/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Vascular disorders Hypertensive crisis	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Vascular disorders Phlebitis	1.1% 2/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Vascular disorders Circulatory collapse	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Vascular disorders Thrombophlebitis	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	2.4% 4/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	1.7% 3/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.1% 2/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Hemoptysis	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.1% 2/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Bronchial disorder	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Rhinalgia	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Infections and infestations Urinary tract infection	1.7% 3/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.8% 3/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Infections and infestations Nasopharyngitis	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Infections and infestations Lung infection	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Infections and infestations Bronchitis	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Infections and infestations Cystitis	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Infections and infestations Gastroenteritis norovirus	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Infections and infestations Infection	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Infections and infestations Onychomycosis	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Infections and infestations Paronychia	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Infections and infestations Sebaceous gland infection	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Infections and infestations Varicella	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Rash	1.1% 2/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Pruritus	1.7% 3/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Alopecia	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Drug eruption	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Hyperkeratosis	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Psoriasis	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Skin hemorrhage	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Metabolism and nutrition disorders Hypokalemia	2.3% 4/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Metabolism and nutrition disorders Gout	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Metabolism and nutrition disorders Hyperkalemia	1.1% 2/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Metabolism and nutrition disorders Appetite disorder	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Metabolism and nutrition disorders Hypercholesterolaemia	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Metabolism and nutrition disorders Magnesium deficiency	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Nervous system disorders Headache	4.0% 7/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Nervous system disorders Dizziness	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Nervous system disorders Syncope	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Nervous system disorders Paraesthesia	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Nervous system disorders Restless legs syndrome	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Psychiatric disorders Sleep disorder	1.1% 2/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	2.4% 4/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Psychiatric disorders Insomnia	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Psychiatric disorders Disorientation	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Psychiatric disorders Nightmare	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Psychiatric disorders Transient psychosis	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Myalgia	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Pain in extremity	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Sensation of heaviness	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Spinal disorder	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Ear and labyrinth disorders Vertigo	2.9% 5/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.8% 3/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Ear and labyrinth disorders Tinnitus	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Investigations C-reactive protein increased	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	1.2% 2/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Investigations Blood creatinine increased	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Investigations Blood potassium decreased	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Investigations International normalised ratio decreased	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Investigations International normalized ratio increased	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Investigations Weight decreased	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Injury, poisoning and procedural complications Contusion	1.1% 2/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Injury, poisoning and procedural complications Ankle fracture	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Injury, poisoning and procedural complications Joint sprain	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Injury, poisoning and procedural complications Wound	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Renal and urinary disorders Renal cyst	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Renal and urinary disorders Renal failure	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Renal and urinary disorders Renal impairment	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Endocrine disorders Hyperthyroidism	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Endocrine disorders Hypothyroidism	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Surgical and medical procedures Skin operation	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Surgical and medical procedures Tooth extraction	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Blood and lymphatic system disorders Anemia	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Eye disorders Vision blurred	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostatic adenoma	0.00% 0/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.59% 1/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Reproductive system and breast disorders Menstruation irregular	0.57% 1/174 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.	0.00% 0/170 • Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days). Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER