Hip Fracture Study of GSK576428 (Fondaparinux Sodium)

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00320424
• Collaborator: (none)
• Enrollment: 48
• Location: 1
• Actual Duration (Months): 8.3
• Patients Per Site Per Month: 5.8

Study Details

Study Description

Brief Summary

This study is requested by PMDA to confirm the efficacy and the safety for HFS.

Condition or Disease	Intervention/Treatment	Phase
Thromboembolism	Drug: Fondaparinux	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Clinical Evaluation of GSK576428 (Fondaparinux Sodium) in Prevention of Venous Thromboembolism After Hip Fracture Surgery
• Actual Study Start Date: Feb 16, 2006
• Actual Primary Completion Date: Oct 26, 2006
• Actual Study Completion Date: Oct 26, 2006

Outcome Measures

Primary Outcome Measures

1. Rate of Major Bleeding During Treatment Period [From the first study drug injection up to Day 17]

   Rate (%) was defined as number of events divided by the number of participants evaluated multiplied by 100. Signs and symptoms suggestive of venous thromboembolic events (VTE) included, but were not limited to lower extremity deep vein thrombosis (DVT): erythema, warmth, pain, swelling, tenderness and pulmonary embolism (PE): pleuritic chest pain, dyspnea, cough, hemoptysis, syncope, light-headedness/dizziness, tachypnea, and tachycardia. Intended treatment period started 24±2 hours after surgical closure. Venogram was obtained not later than 2 calendar days after the last study drug administration (between Day 11 and 17). These events were adjudicated by the Central Independent Adjudication Committee of Efficacy (CIACE).

Secondary Outcome Measures

1. Rate of PE During Treatment Period [Up to Day 17]

   Rate (%) was defined as number of events divided by the number of participants evaluated multiplied by 100. Signs and symptoms suggestive of VTE included, but were not limited to lower extremity PE: pleuritic chest pain, dyspnea, cough, hemoptysis, syncope, light-headedness/dizziness, tachypnea, and tachycardia. Intended treatment period started 24±2 hours after surgical closure. Venogram was obtained not later than 2 calendar days after the last study drug administration (between Day 11 and 17). These events were adjudicated by the CIACE. It was evaluated from the first study drug injection up to Day 17 or to first venogram, whichever occurred first.

2. Rate of DVT During Treatment Period [Up to Day 17]

   Rate (%) was defined as number of events divided by the number of patients evaluated multiplied by 100. Signs and symptoms suggestive of VTE included, but were not limited to lower extremity DVT: erythema, warmth, pain, swelling, tenderness. Intended treatment period started 24±2 hours after surgical closure. Venogram was obtained not later than 2 calendar days after the last study drug administration (between Day 11 and 17). These events were adjudicated by the CIACE. It was evaluated from the first study drug injection up to Day 17 or to first venogram, whichever occurred first.

3. Rate of Proximal DVT During Treatment Period [Up to Day 17]

   Rate (%) was defined as number of events divided by the number of participants evaluated multiplied by 100. Signs and symptoms suggestive of VTE included, but were not limited to lower extremity DVT: erythema, warmth, pain, swelling, tenderness. Intended treatment period started 24±2 hours after surgical closure. Venogram was obtained not later than 2 calendar days after the last study drug administration (between Day 11 and 17). These events were adjudicated by the CIACE. It was evaluated from the first study drug injection up to Day 17 or to first venogram, whichever occurred first.

4. Rate of Distal Only DVT During Treatment Period [Up to Day 17]

   Rate (%) was defined as number of events divided by the number of participants evaluated multiplied by 100. Signs and symptoms suggestive of VTE included, but were not limited to lower extremity DVT: erythema, warmth, pain, swelling, tenderness. Intended treatment period started 24±2 hours after surgical closure. Venogram was obtained not later than 2 calendar days after the last study drug administration (between Day 11 and 17). These events were adjudicated by the CIACE. It was evaluated from the first study drug injection up to Day 17 or to first venogram, whichever occurred first.

5. Number of Participants With Major Bleeding During Treatment Period [From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17)]

   Major bleeding events were defined as clinically unusual bleeding meeting any of the following criteria: fatal bleeding, bleeding including retroperitoneal and intracranial bleeding or bleeding into a critical organ (eye, adrenal gland, pericardium, spine), reoperation due to bleeding/hematoma at the operative site, bleeding leading to a hemoglobin (Hb) fall >=2 grams per deciliter (g/dL, 1.6 millimoles per liter [mmol/L]) within 48 hour of the bleed, bleeding that required a transfusion of red blood cell or whole blood derived from >=900 millilters (mL) of whole blood within 48 hours of the bleed (excluding the autologous transfusion except for the treatment of bleeding adverse event (AE) and bleeding leading to the bleeding index (BI) >=2. Major bleeding events were adjudicated by the Central Independent Adjudication Committee of Safety (CIACS).

6. Number of Participants With Minor Bleeding and Any Bleeding (Major and/or Minor Bleeding) [From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17)]

   Minor bleeding and any bleeding (major and/or minor bleeding) events were adjudicated by the CIACS. Minor bleeding was defined as clinically overt bleeding not meeting the criteria for major bleeding and considered more than expected in the clinical context. Any bleeding (major and/or minor bleeding) could be recorded may be major and/or minor.

7. Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death [From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17)]

   An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.

8. Number of Transfused Participants [From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17)]

   Blood product transfusions consisted of packed red blood cells or fresh frozen plasma or both. This was done between Day 2 and 2 calendar days after the last injection.

9. Summary of Units Transfused [From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17)]

   Blood product transfusions consisted of packed red blood cells or fresh frozen plasma or both. This was done between Day 2 and 2 calendar days after the last injection.

10. Rate of Symptomatic DVT [Up to Day 17]

    Rate (%) was defined as number of events divided by the number of participants evaluated multiplied by 100. Signs and symptoms suggestive of VTE included, but were not limited to lower extremity DVT: erythema, warmth, pain, swelling, tenderness. Intended treatment period started 24±2 hours after surgical closure. Venogram was obtained not later than 2 calendar days after the last study drug administration (between Day 11 and 17). These events were adjudicated by the CIACE. It was evaluated from the first study drug injection up to Day 17 or to first venogram, whichever occurred first.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients undergoing hip fracture surgery within 10 days following the time of fracture of the hip (proximal femur) (or following the time of fracture estimated from trauma).

Exclusion Criteria:

• Active, clinically significant bleeding (excluding drainage).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00320424
• Other Study ID Numbers: AR3106335
• First Posted: May 3, 2006
• Last Update Posted: Sep 4, 2018
• Last Verified: Aug 1, 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GlaxoSmithKline: Xa factor; VTE; MOSLL; pentasaccharide
• Additional relevant MeSH terms: Thromboembolism; Hip Fractures; PENTA; Fondaparinux

Study Results

Participant Flow

Recruitment Details	Total of 48 participants undergoing major orthopedic surgery of the lower limb such as hip fracture surgery, knee replacement surgery and hip replacement surgery were enrolled from 16 February 2006 to 26 October 2006 at 9 centers in Japan. The safety population consisted of 48 participants and full analysis set consisted of 37 participants.

Arm/Group Title	Fondaparinux Sodium 2.5 mg s.c.
Arm/Group Description	Participants received fondaparinux sodium 2.5 milligrams (mg) by subcutaneous (s.c.) injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
Period Title: Overall Study
STARTED	48
COMPLETED	42
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Fondaparinux Sodium 2.5 mg s.c.
Arm/Group Description	Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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 Participants	48
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	76.6 (14.4)
Sex: Female, Male (Count of Participants)
Female	40 83.3%
Male	8 16.7%
Region of Enrollment (Count of Participants)
Japan	48 100%

Outcome Measures

1. Primary Outcome

Title	Rate of Major Bleeding During Treatment Period
Description	Rate (%) was defined as number of events divided by the number of participants evaluated multiplied by 100. Signs and symptoms suggestive of venous thromboembolic events (VTE) included, but were not limited to lower extremity deep vein thrombosis (DVT): erythema, warmth, pain, swelling, tenderness and pulmonary embolism (PE): pleuritic chest pain, dyspnea, cough, hemoptysis, syncope, light-headedness/dizziness, tachypnea, and tachycardia. Intended treatment period started 24±2 hours after surgical closure. Venogram was obtained not later than 2 calendar days after the last study drug administration (between Day 11 and 17). These events were adjudicated by the Central Independent Adjudication Committee of Efficacy (CIACE).
Time Frame	From the first study drug injection up to Day 17

Outcome Measure Data

Analysis Population Description

Full analysis set used which consisted of all participants who were assigned to study drug with the exception of those who did not receive study drug at all and those with no valid efficacy data (example no evaluable venogram).

Arm/Group Title	Fondaparinux Sodium 2.5 mg s.c.
Arm/Group Description	Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
Measure Participants	37
Number (95% Confidence Interval) [% of normalized events per participant]	21.6

2. Secondary Outcome

Title	Rate of PE During Treatment Period
Description	Rate (%) was defined as number of events divided by the number of participants evaluated multiplied by 100. Signs and symptoms suggestive of VTE included, but were not limited to lower extremity PE: pleuritic chest pain, dyspnea, cough, hemoptysis, syncope, light-headedness/dizziness, tachypnea, and tachycardia. Intended treatment period started 24±2 hours after surgical closure. Venogram was obtained not later than 2 calendar days after the last study drug administration (between Day 11 and 17). These events were adjudicated by the CIACE. It was evaluated from the first study drug injection up to Day 17 or to first venogram, whichever occurred first.
Time Frame	Up to Day 17

Outcome Measure Data

Analysis Population Description

Safety population used which consisted of all participants who received at least one dose of study drug.

Arm/Group Title	Fondaparinux Sodium 2.5 mg s.c.
Arm/Group Description	Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
Measure Participants	48
Number (95% Confidence Interval) [% of normalized events per participant]	0

3. Secondary Outcome

Title	Rate of DVT During Treatment Period
Description	Rate (%) was defined as number of events divided by the number of patients evaluated multiplied by 100. Signs and symptoms suggestive of VTE included, but were not limited to lower extremity DVT: erythema, warmth, pain, swelling, tenderness. Intended treatment period started 24±2 hours after surgical closure. Venogram was obtained not later than 2 calendar days after the last study drug administration (between Day 11 and 17). These events were adjudicated by the CIACE. It was evaluated from the first study drug injection up to Day 17 or to first venogram, whichever occurred first.
Time Frame	Up to Day 17

Outcome Measure Data

Analysis Population Description

Efficacy evaluable participants used consisted of a subpopulation of safety population who were judged to be evaluable for all DVT and proximal DVT or distal only DVT by the 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.

Arm/Group Title	Fondaparinux Sodium 2.5 mg s.c.
Arm/Group Description	Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
Measure Participants	37
Number [% of normalized events per participant]	21.6

4. Secondary Outcome

Title	Rate of Proximal DVT During Treatment Period
Description	Rate (%) was defined as number of events divided by the number of participants evaluated multiplied by 100. Signs and symptoms suggestive of VTE included, but were not limited to lower extremity DVT: erythema, warmth, pain, swelling, tenderness. Intended treatment period started 24±2 hours after surgical closure. Venogram was obtained not later than 2 calendar days after the last study drug administration (between Day 11 and 17). These events were adjudicated by the CIACE. It was evaluated from the first study drug injection up to Day 17 or to first venogram, whichever occurred first.
Time Frame	Up to Day 17

Outcome Measure Data

Analysis Population Description

Efficacy evaluable participants used. Only those participants with data available at the indicated time points were analyzed.

Arm/Group Title	Fondaparinux Sodium 2.5 mg s.c.
Arm/Group Description	Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
Measure Participants	38
Number [% of normalized events per participant]	2.6

5. Secondary Outcome

Title	Rate of Distal Only DVT During Treatment Period
Description	Rate (%) was defined as number of events divided by the number of participants evaluated multiplied by 100. Signs and symptoms suggestive of VTE included, but were not limited to lower extremity DVT: erythema, warmth, pain, swelling, tenderness. Intended treatment period started 24±2 hours after surgical closure. Venogram was obtained not later than 2 calendar days after the last study drug administration (between Day 11 and 17). These events were adjudicated by the CIACE. It was evaluated from the first study drug injection up to Day 17 or to first venogram, whichever occurred first.
Time Frame	Up to Day 17

Outcome Measure Data

Analysis Population Description

Efficacy evaluable participants used. Only those participants with data available at the indicated time points were analyzed.

Arm/Group Title	Fondaparinux Sodium 2.5 mg s.c.
Arm/Group Description	Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
Measure Participants	37
Number [% of normalized events per participant]	21.6

6. Secondary Outcome

Title	Number of Participants With Major Bleeding During Treatment Period
Description	Major bleeding events were defined as clinically unusual bleeding meeting any of the following criteria: fatal bleeding, bleeding including retroperitoneal and intracranial bleeding or bleeding into a critical organ (eye, adrenal gland, pericardium, spine), reoperation due to bleeding/hematoma at the operative site, bleeding leading to a hemoglobin (Hb) fall >=2 grams per deciliter (g/dL, 1.6 millimoles per liter [mmol/L]) within 48 hour of the bleed, bleeding that required a transfusion of red blood cell or whole blood derived from >=900 millilters (mL) of whole blood within 48 hours of the bleed (excluding the autologous transfusion except for the treatment of bleeding adverse event (AE) and bleeding leading to the bleeding index (BI) >=2. Major bleeding events were adjudicated by the Central Independent Adjudication Committee of Safety (CIACS).
Time Frame	From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17)

Outcome Measure Data

Analysis Population Description

Safety population used.

Arm/Group Title	Fondaparinux Sodium 2.5 mg s.c.
Arm/Group Description	Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
Measure Participants	48
Count of Participants [Participants]	0 0%

7. Secondary Outcome

Title	Number of Participants With Minor Bleeding and Any Bleeding (Major and/or Minor Bleeding)
Description	Minor bleeding and any bleeding (major and/or minor bleeding) events were adjudicated by the CIACS. Minor bleeding was defined as clinically overt bleeding not meeting the criteria for major bleeding and considered more than expected in the clinical context. Any bleeding (major and/or minor bleeding) could be recorded may be major and/or minor.
Time Frame	From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17)

Outcome Measure Data

Analysis Population Description

Safety population used.

Arm/Group Title	Fondaparinux Sodium 2.5 mg s.c.
Arm/Group Description	Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
Measure Participants	48
Minor Bleeding	0 0%
Any Bleeding	0 0%

8. Secondary Outcome

Title	Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death
Description	An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.
Time Frame	From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17)

Outcome Measure Data

Analysis Population Description

Safety population used.

Arm/Group Title	Fondaparinux Sodium 2.5 mg s.c.
Arm/Group Description	Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
Measure Participants	48
Any AE	37 77.1%
Any SAE	2 4.2%
Death	0 0%

9. Secondary Outcome

Title	Number of Transfused Participants
Description	Blood product transfusions consisted of packed red blood cells or fresh frozen plasma or both. This was done between Day 2 and 2 calendar days after the last injection.
Time Frame	From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17)

Outcome Measure Data

Analysis Population Description

Safety population used.

Arm/Group Title	Fondaparinux Sodium 2.5 mg s.c.
Arm/Group Description	Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
Measure Participants	48
Count of Participants [Participants]	1 2.1%

10. Secondary Outcome

Title	Summary of Units Transfused
Description	Blood product transfusions consisted of packed red blood cells or fresh frozen plasma or both. This was done between Day 2 and 2 calendar days after the last injection.
Time Frame	From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17)

Outcome Measure Data

Analysis Population Description

Safety population used.

Arm/Group Title	Fondaparinux Sodium 2.5 mg s.c.
Arm/Group Description	Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
Measure Participants	48
Number [mL]	280

11. Secondary Outcome

Title	Rate of Symptomatic DVT
Description	Rate (%) was defined as number of events divided by the number of participants evaluated multiplied by 100. Signs and symptoms suggestive of VTE included, but were not limited to lower extremity DVT: erythema, warmth, pain, swelling, tenderness. Intended treatment period started 24±2 hours after surgical closure. Venogram was obtained not later than 2 calendar days after the last study drug administration (between Day 11 and 17). These events were adjudicated by the CIACE. It was evaluated from the first study drug injection up to Day 17 or to first venogram, whichever occurred first.
Time Frame	Up to Day 17

Outcome Measure Data

Analysis Population Description

Safety population used.

Arm/Group Title	Fondaparinux Sodium 2.5 mg s.c.
Arm/Group Description	Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
Measure Participants	48
Number [% of normalized events per participant]	0

Adverse Events

Time Frame	AE and SAE were reported throughout the study (from the first study drug injection up to 2 days after the last study drug injection [approximately up to Day 17]).
Adverse Event Reporting Description	Safety population was used for reporting AE and SAE.
Arm/Group Title	Fondaparinux Sodium 2.5 mg s.c.
Arm/Group Description	Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
All Cause Mortality
	Fondaparinux Sodium 2.5 mg s.c.
	Affected / at Risk (%)	# Events
Total	0/48 (0%)
Serious Adverse Events
	Fondaparinux Sodium 2.5 mg s.c.
	Affected / at Risk (%)	# Events
Total	2/48 (4.2%)
Gastrointestinal disorders
Ileus	1/48 (2.1%)
Injury, poisoning and procedural complications
Femur fracture	1/48 (2.1%)
Other (Not Including Serious) Adverse Events
	Fondaparinux Sodium 2.5 mg s.c.
	Affected / at Risk (%)	# Events
Total	37/48 (77.1%)
Gastrointestinal disorders
Constipation	8/48 (16.7%)
Abdominal pain upper	2/48 (4.2%)
Diarrhea	2/48 (4.2%)
General disorders
Oedema peripheral	4/48 (8.3%)
Pyrexia	3/48 (6.3%)
Infections and infestations
Nasopharyngitis	2/48 (4.2%)
Injury, poisoning and procedural complications
Excoriation	4/48 (8.3%)
Investigations
Blood alkaline phosphatase increased	3/48 (6.3%)
C reactive protein increased	2/48 (4.2%)
Platelet count increased	2/48 (4.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/48 (4.2%)
Pain in extremity	2/48 (4.2%)
Psychiatric disorders
Insomnia	8/48 (16.7%)
Restlessness	3/48 (6.3%)
Skin and subcutaneous tissue disorders
Dermatitis contact	4/48 (8.3%)
Erythema	2/48 (4.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.