Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Fondaparinux for the Prevention of Venous Blood Clots in Patients With a Plaster Cast or Other Type of Immobilization for a Below-knee Injury Not Needing Surgery (NCT NCT00843492)

Last Updated: 2016-03-16

Results Overview

VTE is defined as asymptomatic deep vein thrombosis (DVT: the formation of a blood clot in a deep vein) detected by systematic compression ultrasonography, symptomatic DVT, or symptomatic fatal or non-fatal pulmonary embolism (PE). An embolism is a clot in the blood that forms and blocks a blood vessel. A pulmonary embolism is a blood clot that has travelled from elsewhere in the body through the blood stream to block the main artery of the lung or one of its branches. All venous thromboembolic events and deaths were adjudicated by the independent Central Adjudication Committee (CAC).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1351 participants

Primary outcome timeframe

Day 1 to complete mobilization plus 2 days (average of 35.9 study days)

Results posted on

2016-03-16

Participant Flow

Participant milestones

Participant milestones
Measure	Nadroparin 2850 anti-Xa International Units (IU) nadroparin calcium (in 0.3 milliliters \[ml\] in disposable prefilled syringes) was injected once daily subcutaneously after randomization (Day 1) until the end of immobilization and treatment period Day 45 (Visit 3)	Fondaparinux 2.5 milligrams (mg) fondaparinux sodium (in 0.5 ml) or 1.5 mg fondaparinux (in 0.3 ml) (in participants with creatinine clearance between 30 and 50 ml per minute) was injected once daily subcutaneously from Day 1 until Day 45 (Visit 3)
Overall Study STARTED	622	621
Overall Study COMPLETED	614	607
Overall Study NOT COMPLETED	8	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Nadroparin 2850 anti-Xa International Units (IU) nadroparin calcium (in 0.3 milliliters \[ml\] in disposable prefilled syringes) was injected once daily subcutaneously after randomization (Day 1) until the end of immobilization and treatment period Day 45 (Visit 3)	Fondaparinux 2.5 milligrams (mg) fondaparinux sodium (in 0.5 ml) or 1.5 mg fondaparinux (in 0.3 ml) (in participants with creatinine clearance between 30 and 50 ml per minute) was injected once daily subcutaneously from Day 1 until Day 45 (Visit 3)
Overall Study Adverse Event	0	3
Overall Study Lost to Follow-up	4	4
Overall Study Withdrawal by Subject	0	4
Overall Study Immobilization Stopped	1	0
Overall Study Investigator/Orthopedic Surgeon Decision	1	1
Overall Study Orthopedic Surgery	0	2
Overall Study Visit Not Performed	1	0
Overall Study Deep-vein Thrombosis	1	0

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Fondaparinux for the Prevention of Venous Blood Clots in Patients With a Plaster Cast or Other Type of Immobilization for a Below-knee Injury Not Needing Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nadroparin n=622 Participants 2850 anti-Xa International Units (IU) nadroparin calcium (in 0.3 milliliters \[ml\] in disposable prefilled syringes) was injected once daily subcutaneously after randomization (Day 1) until the end of immobilization and treatment period Day 45 (Visit 3)	Fondaparinux n=621 Participants 2.5 milligrams (mg) fondaparinux sodium (in 0.5 ml) or 1.5 mg fondaparinux (in 0.3 ml) (in participants with creatinine clearance between 30 and 50 ml per minute) was injected once daily subcutaneously from Day 1 until Day 45 (Visit 3)	Total n=1243 Participants Total of all reporting groups
Age, Continuous Years	46.5 Years STANDARD_DEVIATION 15.7 • n=5 Participants	46.1 Years STANDARD_DEVIATION 16.0 • n=7 Participants	46.3 Years STANDARD_DEVIATION 15.8 • n=5 Participants
Sex: Female, Male Female	336 Participants n=5 Participants	328 Participants n=7 Participants	664 Participants n=5 Participants
Sex: Female, Male Male	286 Participants n=5 Participants	293 Participants n=7 Participants	579 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 to complete mobilization plus 2 days (average of 35.9 study days)

Population: Intent-to-Treat (ITT) Population: all randomized participants with a VTE status or experiencing death. Participants without evaluation of the primary endpoint in the timeframe requested by the protocol were considered as missing data and therefore not included in the primary efficacy analysis.

Outcome measures

Outcome measures
Measure	Nadroparin n=586 Participants 2850 anti-Xa International Units (IU) nadroparin calcium (in 0.3 milliliters \[ml\] in disposable prefilled syringes) was injected once daily subcutaneously after randomization (Day 1) until the end of immobilization and treatment period Day 45 (Visit 3)	Fondaparinux n=584 Participants 2.5 milligrams (mg) fondaparinux sodium (in 0.5 ml) or 1.5 mg fondaparinux (in 0.3 ml) (in participants with creatinine clearance between 30 and 50 ml per minute) was injected once daily subcutaneously from Day 1 until Day 45 (Visit 3)
Number of Participants With Venous Thromboembolism (VTE) or Death up to the Time of Complete Mobilization	48 participants	15 participants

SECONDARY outcome

Timeframe: Day 1 to complete mobilization plus 2 days (average of 35.7 study days)

Population: ITT Population. Only those participants contributing data at the indicated time points were analyzed.

All components of the primary endpoint were considered separately: any VTE; symptomatic (providing no evidence of disease existence) DVT (the formation of a blood clot in a deep vein) detected by systematic compression ultrasonography; symptomatic(providing evidence of disease existence) DVT; symptomatic PE (blood clot that has travelled from elsewhere in the body through the blood stream to block the main artery of the lung of one of its branches); and death.

Outcome measures

Outcome measures
Measure	Nadroparin n=622 Participants 2850 anti-Xa International Units (IU) nadroparin calcium (in 0.3 milliliters \[ml\] in disposable prefilled syringes) was injected once daily subcutaneously after randomization (Day 1) until the end of immobilization and treatment period Day 45 (Visit 3)	Fondaparinux n=621 Participants 2.5 milligrams (mg) fondaparinux sodium (in 0.5 ml) or 1.5 mg fondaparinux (in 0.3 ml) (in participants with creatinine clearance between 30 and 50 ml per minute) was injected once daily subcutaneously from Day 1 until Day 45 (Visit 3)
Number of Participants With Any Adjudicated Components of VTE, Asymptomatic DVT, Symptomatic DVT, Symptomatic PE, and Death Any VTE, n=586, 583	48 participants	14 participants
Number of Participants With Any Adjudicated Components of VTE, Asymptomatic DVT, Symptomatic DVT, Symptomatic PE, and Death Any asymptomatic DVT, n=585, 582	42 participants	11 participants
Number of Participants With Any Adjudicated Components of VTE, Asymptomatic DVT, Symptomatic DVT, Symptomatic PE, and Death Any symptomatic DVT, n=622, 621	7 participants	2 participants
Number of Participants With Any Adjudicated Components of VTE, Asymptomatic DVT, Symptomatic DVT, Symptomatic PE, and Death Any symptomatic PE, n=622, 621	0 participants	2 participants
Number of Participants With Any Adjudicated Components of VTE, Asymptomatic DVT, Symptomatic DVT, Symptomatic PE, and Death Death, n=622, 621	0 participants	1 participants

SECONDARY outcome

Timeframe: Day 1 to 5 weeks (plus or minus 1 week) after complete mobilization (average of 67.8 study days)

Population: ITT Population

The number of participants with VTE (defined as asymptomatic deep vein thrombosis \[DVT: the formation of a blood clot in a deep vein\] detected by systematic compression ultrasonography, symptomatic DVT, or symptomatic fatal or non-fatal pulmonary embolism \[PE\]) and death was assessed. An embolism is a clot in the blood that forms and blocks a blood vessel. A PE is a blood clot that has travelled from elsewhere in the body through the blood stream to block the main artery of the lung or one of its branches.

Outcome measures

Outcome measures
Measure	Nadroparin n=622 Participants 2850 anti-Xa International Units (IU) nadroparin calcium (in 0.3 milliliters \[ml\] in disposable prefilled syringes) was injected once daily subcutaneously after randomization (Day 1) until the end of immobilization and treatment period Day 45 (Visit 3)	Fondaparinux n=621 Participants 2.5 milligrams (mg) fondaparinux sodium (in 0.5 ml) or 1.5 mg fondaparinux (in 0.3 ml) (in participants with creatinine clearance between 30 and 50 ml per minute) was injected once daily subcutaneously from Day 1 until Day 45 (Visit 3)
Number of Participants With Confirmed VTE and Death up to the Final Visit or Contact	49 participants	15 participants

SECONDARY outcome

Timeframe: Day 1 to complete mobilization plus 4 days (average of 37.7 study days); Day 1 up to final visit or contact (average of 66.3 study days)

Population: As-Treated Population: all participants who received at least one dose of study treatment

Major bleeding is defined as bleeding that results in a fatality, symptomatic bleeding in a critical area or organ, bleeding causing a fall in hemoglobin level of 20 grams/liter (1.24 millimoles/liter) or more compared with the pre-randomization hemoglobin level, or bleeding that leads to a transfusion of two or more units of whole blood or red blood cells. All episodes of bleeding were adjudicated by an independent CAC. The committee members were unaware of the participants' treatment assignment.

Outcome measures

Outcome measures
Measure	Nadroparin n=670 Participants 2850 anti-Xa International Units (IU) nadroparin calcium (in 0.3 milliliters \[ml\] in disposable prefilled syringes) was injected once daily subcutaneously after randomization (Day 1) until the end of immobilization and treatment period Day 45 (Visit 3)	Fondaparinux n=674 Participants 2.5 milligrams (mg) fondaparinux sodium (in 0.5 ml) or 1.5 mg fondaparinux (in 0.3 ml) (in participants with creatinine clearance between 30 and 50 ml per minute) was injected once daily subcutaneously from Day 1 until Day 45 (Visit 3)
Number of Participants With Major Bleeding From Day 1 to Complete Mobilization and From Day 1 up to the Final Visit or Contact Up to complete mobilization plus 4 days	0 participants	1 participants
Number of Participants With Major Bleeding From Day 1 to Complete Mobilization and From Day 1 up to the Final Visit or Contact Up to the final visit or contact	0 participants	1 participants

SECONDARY outcome

Timeframe: Day 1 to complete mobilization plus 4 days (average of 37.7 study days); Day 1 up to final visit or contact (average of 66.3 study days)

Population: As-Treated Population

Clinically relevant non-major bleeding that does not qualify as major is defined as bleeding leading to treatment discontinuation, and/or epistaxis (bleeding through the nose) that lasts for more than 5 minutes or necessitates intervention (e.g., packing), spontaneous macroscopic haematuria (blood in urine), gastrointestinal haemorrhage, haemoptysis (coughing up blood), or subcutaneous haematoma (localized collection of blood) \> 100 centimeters squared. All episodes of bleeding were adjudicated by an independent CAC. The committee members were unaware of the participants' treatment assignment.

Outcome measures

Outcome measures
Measure	Nadroparin n=670 Participants 2850 anti-Xa International Units (IU) nadroparin calcium (in 0.3 milliliters \[ml\] in disposable prefilled syringes) was injected once daily subcutaneously after randomization (Day 1) until the end of immobilization and treatment period Day 45 (Visit 3)	Fondaparinux n=674 Participants 2.5 milligrams (mg) fondaparinux sodium (in 0.5 ml) or 1.5 mg fondaparinux (in 0.3 ml) (in participants with creatinine clearance between 30 and 50 ml per minute) was injected once daily subcutaneously from Day 1 until Day 45 (Visit 3)
Number of Participants With Clinically Relevant Non-major Bleeding From Day 1 to Complete Mobilization and From Day 1 up to the Final Visit or Contact Up to complete mobilization plus 4 days	3 participants	1 participants
Number of Participants With Clinically Relevant Non-major Bleeding From Day 1 to Complete Mobilization and From Day 1 up to the Final Visit or Contact Up to the final visit or contact	4 participants	1 participants

SECONDARY outcome

Timeframe: Day 1 to complete mobilization plus 4 days (average of 37.7 study days); Day 1 up to final visit or contact (average of 66.3 study days)

Population: As-Treated 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 committee members were unaware of the participants' treatment assignment.

Outcome measures

Outcome measures
Measure	Nadroparin n=670 Participants 2850 anti-Xa International Units (IU) nadroparin calcium (in 0.3 milliliters \[ml\] in disposable prefilled syringes) was injected once daily subcutaneously after randomization (Day 1) until the end of immobilization and treatment period Day 45 (Visit 3)	Fondaparinux n=674 Participants 2.5 milligrams (mg) fondaparinux sodium (in 0.5 ml) or 1.5 mg fondaparinux (in 0.3 ml) (in participants with creatinine clearance between 30 and 50 ml per minute) was injected once daily subcutaneously from Day 1 until Day 45 (Visit 3)
Number of Participants With Minor Bleeding From Day 1 to Complete Mobilization and From Day 1 up to the Final Visit or Contact Up to complete mobilization plus 4 days	3 participants	9 participants
Number of Participants With Minor Bleeding From Day 1 to Complete Mobilization and From Day 1 up to the Final Visit or Contact Up to the final visit or contact	3 participants	9 participants

SECONDARY outcome

Timeframe: Day 1 to complete mobilization plus 4 days (average of 37.7 study days); Day 1 up to final visit or contact (average of 66.3 study days)

Population: As-Treated Population

All episodes of bleeding, except minor bruising, skin hematomas not greater than 5 centimeters in diameter, self-limited epistaxis (bleeding through the nose), and self-limited gingival (gum) bleeding, were adjudicated by an independent CAC. The committee members were unaware of the participants' treatment assignment.

Outcome measures

Outcome measures
Measure	Nadroparin n=670 Participants 2850 anti-Xa International Units (IU) nadroparin calcium (in 0.3 milliliters \[ml\] in disposable prefilled syringes) was injected once daily subcutaneously after randomization (Day 1) until the end of immobilization and treatment period Day 45 (Visit 3)	Fondaparinux n=674 Participants 2.5 milligrams (mg) fondaparinux sodium (in 0.5 ml) or 1.5 mg fondaparinux (in 0.3 ml) (in participants with creatinine clearance between 30 and 50 ml per minute) was injected once daily subcutaneously from Day 1 until Day 45 (Visit 3)
Participants With Any Incidence of Any Bleeding Event as Adjudicated by a CAC) From Day 1 to Complete Mobilization and From Day 1 up to the Final Visit or Contact Up to complete mobilization plus 4 days	6 participants	11 participants
Participants With Any Incidence of Any Bleeding Event as Adjudicated by a CAC) From Day 1 to Complete Mobilization and From Day 1 up to the Final Visit or Contact Up to the final visit or contact	7 participants	11 participants

Adverse Events

Nadroparin

Serious events: 9 serious events

Other events: 95 other events

Deaths: 0 deaths

Fondaparinux

Serious events: 6 serious events

Other events: 93 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Nadroparin n=670 participants at risk 2850 anti-Xa International Units (IU) nadroparin calcium (in 0.3 milliliters \[ml\] in disposable prefilled syringes) was injected once daily subcutaneously after randomization (Day 1) until the end of immobilization and treatment period Day 45 (Visit 3)	Fondaparinux n=674 participants at risk 2.5 milligrams (mg) fondaparinux sodium (in 0.5 ml) or 1.5 mg fondaparinux (in 0.3 ml) (in participants with creatinine clearance between 30 and 50 ml per minute) was injected once daily subcutaneously from Day 1 until Day 45 (Visit 3)
Nervous system disorders Headache	4.9% 33/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	3.6% 24/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
General disorders Injection site haematoma	4.6% 31/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	1.5% 10/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	2.7% 18/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	3.1% 21/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Gastrointestinal disorders Nausea	1.5% 10/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	1.8% 12/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	1.2% 8/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	2.1% 14/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Blood and lymphatic system disorders Lymphadenopathy	1.9% 13/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	1.2% 8/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
General disorders Oedema peripheral	1.0% 7/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	1.6% 11/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Nervous system disorders Dizziness	0.90% 6/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	1.0% 7/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Vascular disorders Hypertension	1.2% 8/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	1.0% 7/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Pruritus	1.2% 8/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	0.89% 6/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Vascular disorders Haematoma	0.15% 1/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	1.3% 9/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.

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

Measure	Nadroparin n=670 participants at risk 2850 anti-Xa International Units (IU) nadroparin calcium (in 0.3 milliliters \[ml\] in disposable prefilled syringes) was injected once daily subcutaneously after randomization (Day 1) until the end of immobilization and treatment period Day 45 (Visit 3)	Fondaparinux n=674 participants at risk 2.5 milligrams (mg) fondaparinux sodium (in 0.5 ml) or 1.5 mg fondaparinux (in 0.3 ml) (in participants with creatinine clearance between 30 and 50 ml per minute) was injected once daily subcutaneously from Day 1 until Day 45 (Visit 3)
Infections and infestations Appendicitis	0.00% 0/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	0.15% 1/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Infections and infestations Haematoma infection	0.15% 1/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	0.00% 0/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Infections and infestations Subcutaneous abscess	0.15% 1/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	0.00% 0/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Injury, poisoning and procedural complications Joint dislocation	0.15% 1/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	0.15% 1/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Injury, poisoning and procedural complications Ankle fracture	0.15% 1/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	0.00% 0/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Gastrointestinal disorders Abdominal wall haematoma	0.00% 0/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	0.15% 1/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Gastrointestinal disorders Faecaloma	0.15% 1/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	0.00% 0/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Fracture malunion	0.15% 1/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	0.00% 0/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Haemarthrosis	0.15% 1/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	0.00% 0/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Nervous system disorders Presyncope	0.00% 0/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	0.15% 1/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Nervous system disorders Transient ischaemic attack	0.15% 1/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	0.00% 0/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	0.15% 1/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Blister	0.15% 1/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	0.00% 0/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Cardiac disorders Cardiac failure	0.00% 0/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	0.15% 1/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
General disorders Pyrexia	0.15% 1/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	0.00% 0/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.15% 1/670 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.	0.00% 0/674 Serious adverse events (SAEs) and non-serious AEs were collected in members of the As-Treated Population, comprised of all participants having received at least one dose of study treatment.