Trial Outcomes & Findings for Total Hip Replacement Study Of GSK576428 (Fondaparinux Sodium) (NCT NCT00320398)

NCT ID: NCT00320398

Last Updated: 2018-09-04

Results Overview

The percentage of participants with VTE, who underwent elective total hip replacement surgery, detected by routine venography, during the treatment period were reported. The percentage VTE was calculated by the number of events divided by the number of participants evaluated multiplied by 100. The Venogram was obtained post 2 calendar days after the administration of last study drug (between Day 11 and 17). Day 1 was the day of surgery and the participant was given study drug 24±2 hours after surgical closure. It was adjudicated by the Central Independent Adjudication Committee of Efficacy (CIACE).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

114 participants

Primary outcome timeframe

Up to Day 17

Results posted on

2018-09-04

Participant Flow

A total of 115 participants who had undergone total Hip replacement surgery were randomized to the study. The study was conducted from 30 January 2006 to 18 July 2006 at eight centers in Japan. A total of 114 and 94 participants were included in Safety and Full analysis set population respectively.

Participant milestones

Participant milestones
Measure	Fondaparinux 1.5 mg Eligible participants in this arm received fondaparinux at 1.5 milligram (mg) administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Fondaparinux 2.5 mg Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Overall Study STARTED	58	56
Overall Study COMPLETED	56	52
Overall Study NOT COMPLETED	2	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Fondaparinux 1.5 mg Eligible participants in this arm received fondaparinux at 1.5 milligram (mg) administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Fondaparinux 2.5 mg Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Overall Study Adverse Event	1	4
Overall Study Other	1	0

Baseline Characteristics

Total Hip Replacement Study Of GSK576428 (Fondaparinux Sodium)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fondaparinux 1.5 mg n=58 Participants Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Fondaparinux 2.5 mg n=56 Participants Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Total n=114 Participants Total of all reporting groups
Age, Customized >=20 years	58 Participants n=5 Participants	56 Participants n=7 Participants	114 Participants n=5 Participants
Sex: Female, Male Female	51 Participants n=5 Participants	51 Participants n=7 Participants	102 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment Japan	58 Participants n=5 Participants	56 Participants n=7 Participants	114 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Day 17

Population: The Full Analysis Set (FAS) population consisted of all participants who were randomized to either treatment with the exception of: those who did not receive study drug at all; and those with no valid post-randomization efficacy data (e.g., no evaluable venogram).

Outcome measures

Outcome measures
Measure	Fondaparinux 1.5 mg n=48 Participants Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Fondaparinux 2.5 mg n=46 Participants Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Percentage of Participants With Venous Thromboembolism (VTE) During Efficacy Period	8.3 percentage of participants Interval 2.3 to 20.0	2.2 percentage of participants Interval 0.1 to 11.5

PRIMARY outcome

Timeframe: Up to Day 17

Population: The safety population consisted of all participants who received at least one dose of randomized study drug.

Major bleeding defined as any clinically unusual bleeding meeting 1 of following criteria; a)Fatal bleeding; b) Including retroperitoneal and intracranial bleeding, or bleeding into critical organ (eye, adrenal gland, pericardium, spine); c) Reoperation due to bleeding or hematoma at operative site; d)Bleeding leading to hemoglobin (Hb) fall \> = 2 gram per deciliter (g/dL)(1.6 millimole per litre \[mmol/L\]) within 48 hour of the bleed; e)Bleeding that required transfusion of red blood cells (RBCs) or whole blood (WB) derived from \>= 900 milliliter (mL) of WB within 48 hours of the bleed (excluding autologous transfusion except for treatment of bleeding adverse event); f) Bleeding leading to bleeding index (BI) \>=2. The percentage was calculated by the number of events divided by the number of participants evaluated multiplied by 100. This was adjudicated by the CIACE.

Outcome measures

Outcome measures
Measure	Fondaparinux 1.5 mg n=58 Participants Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Fondaparinux 2.5 mg n=56 Participants Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Percentage of Participants With Major Bleeding	0 percentage of participants Interval 0.0 to 6.2	0 percentage of participants Interval 0.0 to 6.4

SECONDARY outcome

Timeframe: Up to Day 17

Population: Safety population.

Minor bleeding was defined as the clinically overt bleeding not meeting the criteria for major bleeding like: (Fatal bleed; Including retroperitoneal and intracranial bleeding, or bleed in critical organ \[eye, adrenal gland, pericardium, spine\]; c) Reoperation due to bleeding or hematoma at operative site; d) Bleeding leading to hemoglobin (Hb) fall \> = 2 g/dL(1.6 mmol/L) within 48 hour of the bleed; e)Bleeding that required transfusion of RBCs or WB derived from \>= 900 mL of WB within 48 hours of the bleed (excluding autologous transfusion except for treatment of bleeding adverse event); f) Bleeding leading to bleeding index (BI) \>=2), and which were considered more than expected in the clinical context. The percentage was calculated by the number of events divided by the number of participants evaluated multiplied by 100. This was adjudicated by the CIACE.

Outcome measures

Outcome measures
Measure	Fondaparinux 1.5 mg n=58 Participants Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Fondaparinux 2.5 mg n=56 Participants Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Percentage of Participants With Minor Bleeding	1.7 percentage of participants Interval 0.0 to 9.2	3.6 percentage of participants Interval 0.4 to 12.3

SECONDARY outcome

Timeframe: Up to Day 17

Population: Efficacy Evaluable Patients (EEP) included subpopulation of safety participants judged to be evaluable for all DVT, proximal DVT or distal only DVT by site of occurrence (total/ side of operation/ opposite side of operation/ both sides). Only those participants with data available at the indicated time points were analyzed.

The percentage of participants with All DVT were reported, where the analysis was done using a venogram. It was calculated by the number of events divided by the number of participants evaluated multiplied by 100. The Venogram was obtained post 2 calendar days after the administration of last study drug (between Day 11 and 17). Day 1 was the day of surgery and the participant was given study drug 24±2 hours after surgical closure. It was adjudicated by the CIACE.

Outcome measures

Outcome measures
Measure	Fondaparinux 1.5 mg n=48 Participants Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Fondaparinux 2.5 mg n=46 Participants Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Percentage of Participants With All Deep Vein Thrombosis (DVT)	8.3 percentage of participants	2.2 percentage of participants

SECONDARY outcome

Timeframe: Up to Day 17

Population: EEP population. Only those participants with data available at the indicated time points were analyzed.

The percentage of participants with DVT (proximal) were reported, by using a venogram. It was calculated by the number of events divided by the number of participants evaluated multiplied by 100. The Venogram was obtained post 2 calendar days after the administration of last study drug (between Day 11 and 17). Day 1 was the day of surgery and the participant was given study drug 24±2 hours after surgical closure. It was adjudicated by the CIACE.

Outcome measures

Outcome measures
Measure	Fondaparinux 1.5 mg n=53 Participants Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Fondaparinux 2.5 mg n=52 Participants Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Percentage of Participants With Proximal DVT	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Up to Day 17

Population: EEP population. Only those participants with data available at the indicated time points were analyzed.

The percentage of participants with distal only DVT were reported, by using a venogram. It was calculated by the number of events divided by the number of participants evaluated multiplied by 100. The Venogram was obtained post 2 calendar days after the administration of last study drug (between Day 11 and 17). Day 1 was the day of surgery and the participant was given study drug 24±2 hours after surgical closure. It was adjudicated by the CIACE.

Outcome measures

Outcome measures
Measure	Fondaparinux 1.5 mg n=48 Participants Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Fondaparinux 2.5 mg n=46 Participants Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Percentage of Participants With Distal Only DVT	4 percentage participants	1 percentage participants

SECONDARY outcome

Timeframe: Up to Day 17

Population: Safety population.

The percentage of participants with different symptoms of DVT (proximal) like pain or tenderness, swelling, warmth, redness or discoloration, and distention of surface veins, post the total hip replacement surgery were reported, where analysis was done using a venogram. It was calculated by the number of events divided by the number of participants evaluated multiplied by 100. The Venogram was obtained post 2 calendar days after the administration of last study drug (between Day 11 and 17). Day 1 was the day of surgery and the participant was given study drug 24±2 hours after surgical closure. It was adjudicated by the CIACE.

Outcome measures

Outcome measures
Measure	Fondaparinux 1.5 mg n=58 Participants Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Fondaparinux 2.5 mg n=56 Participants Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Percentage of Participants With Symptomatic DVT During Main Efficacy Period	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Up to Day 17

Population: Safety population.

The percentage of participants with pulmonary embolism (pleuritic chest pain, dyspnea, cough, hemoptysis, syncope, light-headedness/dizziness, tachypnea, and tachycardia ) were reported, by using a venogram. It was calculated by the number of events divided by the number of participants evaluated multiplied by 100. The Venogram was obtained post 2 calendar days after the administration of last study drug (between Day 11 and 17). Day 1 was the day of surgery and the participant was given study drug 24±2 hours after surgical closure. It was adjudicated by the CIACE.

Outcome measures

Outcome measures
Measure	Fondaparinux 1.5 mg n=58 Participants Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Fondaparinux 2.5 mg n=56 Participants Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Percentage of Participants With Pulmonary Embolism During Efficacy Period	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17.

Population: Safety population.

An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant.

Outcome measures

Outcome measures
Measure	Fondaparinux 1.5 mg n=58 Participants Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Fondaparinux 2.5 mg n=56 Participants Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths Deaths	0 participants	0 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths Any SAE	0 participants	0 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths Any AE	49 participants	45 participants

SECONDARY outcome

Timeframe: Up to Day 17.

Population: Safety population.

The number of participants who received RBCs or WB after the total hip replacement surgery within 48 hours of bleed were reported.

Outcome measures

Outcome measures
Measure	Fondaparinux 1.5 mg n=58 Participants Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Fondaparinux 2.5 mg n=56 Participants Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Number of Transfused Participants	5 participants	2 participants

SECONDARY outcome

Timeframe: Up to Day 17

Population: Safety population.

The total volume of transfusion (RBCs or WB) received by the participant was reported.

Outcome measures

Outcome measures
Measure	Fondaparinux 1.5 mg n=58 Participants Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Fondaparinux 2.5 mg n=56 Participants Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Volume of Transfusion	400.0 mL Standard Deviation 0.0	600.0 mL Standard Deviation 282.8

Adverse Events

Fondaparinux 1.5 mg

Serious events: 0 serious events

Other events: 49 other events

Deaths: 0 deaths

Fondaparinux 2.5 mg

Serious events: 0 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

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	Fondaparinux 1.5 mg n=58 participants at risk Eligible participants in this arm received Fondaparinux at 1.5 milligram (mg) administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Fondaparinux 2.5 mg n=56 participants at risk Eligible participants in this arm received Fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Musculoskeletal and connective tissue disorders Myalgia	20.7% 12/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	25.0% 14/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
Psychiatric disorders Insomnia	15.5% 9/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	23.2% 13/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
Gastrointestinal disorders Constipation	8.6% 5/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	17.9% 10/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
Skin and subcutaneous tissue disorders Pruritus	5.2% 3/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	16.1% 9/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
Investigations Platelet count increased	12.1% 7/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	8.9% 5/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
Musculoskeletal and connective tissue disorders Pain in extremity	1.7% 1/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	7.1% 4/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
Investigations Gamma glutamyl transferase increased	1.7% 1/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	5.4% 3/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
Nervous system disorders Headache	8.6% 5/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	3.6% 2/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
Nervous system disorders Dizziness	5.2% 3/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	3.6% 2/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
Skin and subcutaneous tissue disorders Dermatitis contact	3.4% 2/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	3.6% 2/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
Skin and subcutaneous tissue disorders Erythema	3.4% 2/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	3.6% 2/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
Investigations Blood alkaline phosphatase increased	3.4% 2/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	3.6% 2/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
Hepatobiliary disorders Hepatic function abnormal	3.4% 2/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	3.6% 2/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
Skin and subcutaneous tissue disorders Rash	1.7% 1/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	3.6% 2/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
Gastrointestinal disorders Haemorrhoids	1.7% 1/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	3.6% 2/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	3.6% 2/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
Gastrointestinal disorders Abdominal pain upper	8.6% 5/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	1.8% 1/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
Musculoskeletal and connective tissue disorders Back pain	10.3% 6/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	0.00% 0/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
Gastrointestinal disorders Diarrhoea	5.2% 3/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	0.00% 0/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
Gastrointestinal disorders Nausea	5.2% 3/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	0.00% 0/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.
General disorders Pyrexia	5.2% 3/58 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.	0.00% 0/56 • From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17. Safety population was used.