Trial Outcomes & Findings for The Treatment of Acute Deep Vein Thrombosis (DVT) of GSK576428 (Fondaparinux Sodium) in Japanese Patients (NCT NCT00911157)

Last Updated: 2016-11-23

Results Overview

VTE (pulmonary thromboembolism \[PE\] and/or deep vein thrombosis \[DVT\]) was adjudicated blindly by the Central Independent Adjudication Committee of Efficacy (CIACE).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

39 participants

Primary outcome timeframe

From Day 1 to Day 90 (±7 days)

Results posted on

2016-11-23

Participant Flow

Participant milestones

Participant milestones
Measure	Fondaparinux Sodium (FPX) The dose of FPX was determined based on a participant's body weight (\<50 kg, 5 mg; 50 to 100 kg, 7.5 mg; \>100 kg, 10 mg) and was administered once daily by subcutaneous (SC) injection for 5-10 days as a general rule. Concomitant warfarin therapy (administered no later than 72 hours after the first dose of FPX) was continued up to Day 90 (±7) at a dose adjusted to maintain the prothrombin time international normalized ratio (PT-INR) between 1.5 and 3.0.	Unfractionated Heparin (UFH) The dose of UFH was adjusted to maintain activated partial thromboplastin time (APTT) at 1.5-2.5 times control and was administered by intravenous (IV) drip bolus injection followed by IV infusion for 5-10 days as a general rule. Concomitant warfarin therapy (administered no later than 72 hours after the first dose of UFH) was continued up to Day 90 (±7) at a dose adjusted to maintain the PT-INR between 1.5 and 3.0.
Overall Study STARTED	29	10
Overall Study COMPLETED	22	8
Overall Study NOT COMPLETED	7	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Fondaparinux Sodium (FPX) The dose of FPX was determined based on a participant's body weight (\<50 kg, 5 mg; 50 to 100 kg, 7.5 mg; \>100 kg, 10 mg) and was administered once daily by subcutaneous (SC) injection for 5-10 days as a general rule. Concomitant warfarin therapy (administered no later than 72 hours after the first dose of FPX) was continued up to Day 90 (±7) at a dose adjusted to maintain the prothrombin time international normalized ratio (PT-INR) between 1.5 and 3.0.	Unfractionated Heparin (UFH) The dose of UFH was adjusted to maintain activated partial thromboplastin time (APTT) at 1.5-2.5 times control and was administered by intravenous (IV) drip bolus injection followed by IV infusion for 5-10 days as a general rule. Concomitant warfarin therapy (administered no later than 72 hours after the first dose of UFH) was continued up to Day 90 (±7) at a dose adjusted to maintain the PT-INR between 1.5 and 3.0.
Overall Study Adverse Event	4	1
Overall Study Withdrawal by Subject	1	1
Overall Study Need for prohibited drug (heparin)	1	0
Overall Study Need to treat for lung cancer	1	0

Baseline Characteristics

The Treatment of Acute Deep Vein Thrombosis (DVT) of GSK576428 (Fondaparinux Sodium) in Japanese Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fondaparinux Sodium (FPX) n=28 Participants The dose of FPX was determined based on a participant's body weight (\<50 kg, 5 mg; 50 to 100 kg, 7.5 mg; \>100 kg, 10 mg) and was administered once daily by subcutaneous (SC) injection for 5-10 days as a general rule. Concomitant warfarin therapy (administered no later than 72 hours after the first dose of FPX) was continued up to Day 90 (±7) at a dose adjusted to maintain the prothrombin time international normalized ratio (PT-INR) between 1.5 and 3.0.	Unfractionated Heparin (UFH) n=9 Participants The dose of UFH was adjusted to maintain activated partial thromboplastin time (APTT) at 1.5-2.5 times control and was administered by intravenous (IV) drip bolus injection followed by IV infusion for 5-10 days as a general rule. Concomitant warfarin therapy (administered no later than 72 hours after the first dose of UFH) was continued up to Day 90 (±7) at a dose adjusted to maintain the PT-INR between 1.5 and 3.0.	Total n=37 Participants Total of all reporting groups
Age, Continuous	64.5 years STANDARD_DEVIATION 19.7 • n=5 Participants	76.1 years STANDARD_DEVIATION 12.2 • n=7 Participants	67.3 years STANDARD_DEVIATION 18.7 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	9 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	0 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized Asian-Japanese	28 participants n=5 Participants	9 participants n=7 Participants	37 participants n=5 Participants
Number of Participants with the Indicated Body Weight <50 kg	8 participants n=5 Participants	3 participants n=7 Participants	11 participants n=5 Participants
Number of Participants with the Indicated Body Weight 50-100 kg	20 participants n=5 Participants	6 participants n=7 Participants	26 participants n=5 Participants
Number of Participants with the Indicated Body Weight >100 kg	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants

PRIMARY outcome

Timeframe: From Day 1 to Day 90 (±7 days)

Population: Full Analysis Set (FAS): all participants receiving at least one dose of medication (FPX or UFH) who had efficacy data and had a confirmed diagnosis of acute symptomatic deep vein thrombosis (DVT)

VTE (pulmonary thromboembolism \[PE\] and/or deep vein thrombosis \[DVT\]) was adjudicated blindly by the Central Independent Adjudication Committee of Efficacy (CIACE).

Outcome measures

Outcome measures
Measure	Unfractionated Heparin (UFH) n=9 Participants The dose of UFH was adjusted to maintain activated partial thromboplastin time (APTT) at 1.5-2.5 times control and was administered by intravenous (IV) drip bolus injection followed by IV infusion for 5-10 days as a general rule. Concomitant warfarin therapy (administered no later than 72 hours after the first dose of UFH) was continued up to Day 90 (±7) at a dose adjusted to maintain the PT-INR between 1.5 and 3.0.	Fondaparinux Sodium (FPX) n=28 Participants The dose of FPX was determined based on a participant's body weight (\<50 kg, 5 mg; 50 to 100 kg, 7.5 mg; \>100 kg, 10 mg) and was administered once daily by subcutaneous (SC) injection for 5-10 days as a general rule. Concomitant warfarin therapy (administered no later than 72 hours after the first dose of FPX) was continued up to Day 90 (±7) at a dose adjusted to maintain the prothrombin time international normalized ratio (PT-INR) between 1.5 and 3.0.
Percentage of Participants With Recurrent or New Symptomatic Venous Thromboembolism (VTE)	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: From Day 1 to Day 90 (±7 days)

Population: FAS

VTE (pulmonary thromboembolism \[PE\] and/or deep vein thrombosis \[DVT\]) was adjudicated blindly by the CIACE.

Outcome measures

Outcome measures
Measure	Unfractionated Heparin (UFH) n=9 Participants The dose of UFH was adjusted to maintain activated partial thromboplastin time (APTT) at 1.5-2.5 times control and was administered by intravenous (IV) drip bolus injection followed by IV infusion for 5-10 days as a general rule. Concomitant warfarin therapy (administered no later than 72 hours after the first dose of UFH) was continued up to Day 90 (±7) at a dose adjusted to maintain the PT-INR between 1.5 and 3.0.	Fondaparinux Sodium (FPX) n=28 Participants The dose of FPX was determined based on a participant's body weight (\<50 kg, 5 mg; 50 to 100 kg, 7.5 mg; \>100 kg, 10 mg) and was administered once daily by subcutaneous (SC) injection for 5-10 days as a general rule. Concomitant warfarin therapy (administered no later than 72 hours after the first dose of FPX) was continued up to Day 90 (±7) at a dose adjusted to maintain the prothrombin time international normalized ratio (PT-INR) between 1.5 and 3.0.
Percentage of Participants With Recurrent or New Symptomatic/Asymptomatic VTE (by Type) Symptomatic DVT only	0 percentage of participants	0 percentage of participants
Percentage of Participants With Recurrent or New Symptomatic/Asymptomatic VTE (by Type) (Symptomatic) Non-fatal PE	0 percentage of participants	0 percentage of participants
Percentage of Participants With Recurrent or New Symptomatic/Asymptomatic VTE (by Type) (Symptomatic) Fatal PE	0 percentage of participants	0 percentage of participants
Percentage of Participants With Recurrent or New Symptomatic/Asymptomatic VTE (by Type) Asymptomatic DVT only	0 percentage of participants	3.6 percentage of participants
Percentage of Participants With Recurrent or New Symptomatic/Asymptomatic VTE (by Type) Asymptomatic PE	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, single day between Day 5 and Day 10 (the day when the medication [FPX or UFH] was finished /discontinued) (±1 day)

Population: FAS

Classifications of "Improved," "No change," or "Worse" were adjudicated blindly by the CIACE.

Outcome measures

Outcome measures
Measure	Unfractionated Heparin (UFH) n=9 Participants The dose of UFH was adjusted to maintain activated partial thromboplastin time (APTT) at 1.5-2.5 times control and was administered by intravenous (IV) drip bolus injection followed by IV infusion for 5-10 days as a general rule. Concomitant warfarin therapy (administered no later than 72 hours after the first dose of UFH) was continued up to Day 90 (±7) at a dose adjusted to maintain the PT-INR between 1.5 and 3.0.	Fondaparinux Sodium (FPX) n=28 Participants The dose of FPX was determined based on a participant's body weight (\<50 kg, 5 mg; 50 to 100 kg, 7.5 mg; \>100 kg, 10 mg) and was administered once daily by subcutaneous (SC) injection for 5-10 days as a general rule. Concomitant warfarin therapy (administered no later than 72 hours after the first dose of FPX) was continued up to Day 90 (±7) at a dose adjusted to maintain the prothrombin time international normalized ratio (PT-INR) between 1.5 and 3.0.
Percentage of Participants With Perfusion Lung Scan Results Scored as Improved, no Change, or Worse Compared to Baseline Improved	11.1 percentage of participants	18.5 percentage of participants
Percentage of Participants With Perfusion Lung Scan Results Scored as Improved, no Change, or Worse Compared to Baseline No Change	88.9 percentage of participants	81.5 percentage of participants
Percentage of Participants With Perfusion Lung Scan Results Scored as Improved, no Change, or Worse Compared to Baseline Worse	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, single day between Day 5 and Day 10 (the day when the medication [FPX or UFH] was finished /discontinued) (±1 day)

Population: FAS

Change from baseline was calculated as the score on the day medication was finished/discontinued (anywhere from Day 5 to Day 10) minus the baseline score. The perfusion score (0: no perfusion; 0.25, 0.5, 0.75, 1: normal) in each of the six lobes of the lung was adjudicated blindly by the CIACE. Total perfusion score (r) was calculated as: r = (0.25 x right lower lobe) + (0.12 x right middle lobe) + (0.18 x right upper lobe) + (0.20 x left lower lobe) + (0.12 x lingula) + (0.13 x left upper lobe).

Outcome measures

Outcome measures
Measure	Unfractionated Heparin (UFH) n=9 Participants The dose of UFH was adjusted to maintain activated partial thromboplastin time (APTT) at 1.5-2.5 times control and was administered by intravenous (IV) drip bolus injection followed by IV infusion for 5-10 days as a general rule. Concomitant warfarin therapy (administered no later than 72 hours after the first dose of UFH) was continued up to Day 90 (±7) at a dose adjusted to maintain the PT-INR between 1.5 and 3.0.	Fondaparinux Sodium (FPX) n=28 Participants The dose of FPX was determined based on a participant's body weight (\<50 kg, 5 mg; 50 to 100 kg, 7.5 mg; \>100 kg, 10 mg) and was administered once daily by subcutaneous (SC) injection for 5-10 days as a general rule. Concomitant warfarin therapy (administered no later than 72 hours after the first dose of FPX) was continued up to Day 90 (±7) at a dose adjusted to maintain the prothrombin time international normalized ratio (PT-INR) between 1.5 and 3.0.
Total Perfusion Score at Baseline and Mean Change From Baseline at Day 5-10 Baseline	0.959 points on a scale Standard Deviation 0.048	0.944 points on a scale Standard Deviation 0.087
Total Perfusion Score at Baseline and Mean Change From Baseline at Day 5-10 Change from Baseline	0.004 points on a scale Standard Deviation 0.011	0.015 points on a scale Standard Deviation 0.034

SECONDARY outcome

Timeframe: Initial treatment period (from the first dose of FPX/UFH to N days after the last dose of FPX/UFH; specified based on creatinine clearance [CLcr]; N=3, CLcr >=50 mL/min; N=4, 30 =< CLcr < 50 mL/min; N=9, CLcr < 30 mL/min).

Population: Safety Population: all participants who received at least one dose of medication (FPX or UFH).

Bleeding events (major bleeding \[clinically overt bleeding with fatality, location in a critical organ, a fall in hemoglobin \>=2 grams (g)/deciliter (dL), or a transfusion \>=2 units\]; minor bleeding \[clinically overt bleeding and not adjudicated as major bleeding\], and no bleeding) were adjudicated blindly by the Central Independent Adjudication Committee of Safety (CIACS).

Outcome measures

Outcome measures
Measure	Unfractionated Heparin (UFH) n=10 Participants The dose of UFH was adjusted to maintain activated partial thromboplastin time (APTT) at 1.5-2.5 times control and was administered by intravenous (IV) drip bolus injection followed by IV infusion for 5-10 days as a general rule. Concomitant warfarin therapy (administered no later than 72 hours after the first dose of UFH) was continued up to Day 90 (±7) at a dose adjusted to maintain the PT-INR between 1.5 and 3.0.	Fondaparinux Sodium (FPX) n=29 Participants The dose of FPX was determined based on a participant's body weight (\<50 kg, 5 mg; 50 to 100 kg, 7.5 mg; \>100 kg, 10 mg) and was administered once daily by subcutaneous (SC) injection for 5-10 days as a general rule. Concomitant warfarin therapy (administered no later than 72 hours after the first dose of FPX) was continued up to Day 90 (±7) at a dose adjusted to maintain the prothrombin time international normalized ratio (PT-INR) between 1.5 and 3.0.
Percentage of Participants With a Bleeding Event Any bleeding (major and/or minor bleedings)	0 percentage of participants	6.9 percentage of participants
Percentage of Participants With a Bleeding Event Major bleeding	0 percentage of participants	3.4 percentage of participants
Percentage of Participants With a Bleeding Event Minor bleeding only	0 percentage of participants	3.4 percentage of participants

Adverse Events

Fondaparinux Sodium (FPX)

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Unfractionated Heparin (UFH)

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Fondaparinux Sodium (FPX) n=29 participants at risk The dose of FPX was determined based on a participant's body weight (\<50 kg, 5 mg; 50 to 100 kg, 7.5 mg; \>100 kg, 10 mg) and was administered once daily by subcutaneous (SC) injection for 5-10 days as a general rule. Concomitant warfarin therapy (administered no later than 72 hours after the first dose of FPX) was continued up to Day 90 (±7) at a dose adjusted to maintain the prothrombin time international normalized ratio (PT-INR) between 1.5 and 3.0.	Unfractionated Heparin (UFH) n=10 participants at risk The dose of UFH was adjusted to maintain activated partial thromboplastin time (APTT) at 1.5-2.5 times control and was administered by intravenous (IV) drip bolus injection followed by IV infusion for 5-10 days as a general rule. Concomitant warfarin therapy (administered no later than 72 hours after the first dose of UFH) was continued up to Day 90 (±7) at a dose adjusted to maintain the PT-INR between 1.5 and 3.0.
Gastrointestinal disorders Gastrointestinal haemorrhage	3.4% 1/29 • SAEs and AEs were evaluated during the initial treatment period (from the first dose of FPX/UFH to N days after the last dose of FPX/UFH; specified based on creatinine clearance [CLcr]. SAEs, serious adverse events; AEs, adverse events. CLcr was determined at the last dose of FPX/UFH; N=3, CLcr \>=50 mL/min; N=4, 30 =\< CLcr \< 50 mL/min; N=9, CLcr \< 30 mL/min). CLcr was calculated according to the Cockcroft and Gault formula: CLcr = (140 - age) × weight (kilograms)/(72 × serum creatinine \[mg/dL\]) × 0.85 (in case of women).	0.00% 0/10 • SAEs and AEs were evaluated during the initial treatment period (from the first dose of FPX/UFH to N days after the last dose of FPX/UFH; specified based on creatinine clearance [CLcr]. SAEs, serious adverse events; AEs, adverse events. CLcr was determined at the last dose of FPX/UFH; N=3, CLcr \>=50 mL/min; N=4, 30 =\< CLcr \< 50 mL/min; N=9, CLcr \< 30 mL/min). CLcr was calculated according to the Cockcroft and Gault formula: CLcr = (140 - age) × weight (kilograms)/(72 × serum creatinine \[mg/dL\]) × 0.85 (in case of women).
Psychiatric disorders Delirium	0.00% 0/29 • SAEs and AEs were evaluated during the initial treatment period (from the first dose of FPX/UFH to N days after the last dose of FPX/UFH; specified based on creatinine clearance [CLcr]. SAEs, serious adverse events; AEs, adverse events. CLcr was determined at the last dose of FPX/UFH; N=3, CLcr \>=50 mL/min; N=4, 30 =\< CLcr \< 50 mL/min; N=9, CLcr \< 30 mL/min). CLcr was calculated according to the Cockcroft and Gault formula: CLcr = (140 - age) × weight (kilograms)/(72 × serum creatinine \[mg/dL\]) × 0.85 (in case of women).	10.0% 1/10 • SAEs and AEs were evaluated during the initial treatment period (from the first dose of FPX/UFH to N days after the last dose of FPX/UFH; specified based on creatinine clearance [CLcr]. SAEs, serious adverse events; AEs, adverse events. CLcr was determined at the last dose of FPX/UFH; N=3, CLcr \>=50 mL/min; N=4, 30 =\< CLcr \< 50 mL/min; N=9, CLcr \< 30 mL/min). CLcr was calculated according to the Cockcroft and Gault formula: CLcr = (140 - age) × weight (kilograms)/(72 × serum creatinine \[mg/dL\]) × 0.85 (in case of women).

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.
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