Odiparcil For The Prevention Of Venous Thromboembolism

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00244725
• Collaborator: (none)
• Enrollment: 961
• Locations: 101
• Duration (Months): 12
• Patients Per Site: 9.5
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

Odiparcil is being studied to determine if it can prevent blood clots from forming after a total knee replacement and also to prove that odiparcil is safe.

Condition or Disease	Intervention/Treatment	Phase
Deep Vein Thrombosis; Fibrillation, Atrial; Venous Thromboembolism; Pulmonary Embolism	Drug: Odiparcil; Drug: Warfarin; Drug: Coumadin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 961 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Double
• Primary Purpose: Prevention
• Official Title: A Dose Ranging Trial for the Evaluation of the Safety, Tolerability and Efficacy of Odiparcil in the Prevention of Venous Thromboembolism Following Total Knee Replacement Surgery
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Sep 1, 2006
• Actual Study Completion Date: Sep 1, 2006

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Total VTE Event Over 10 ± 2 Days of Treatment [Up to Visit 7 (10 ± 2 days of treatment)]

   Participants were assessed for VTE at all study visits and at the end of study (Day 10±2) or at early withdrawal. Any participant who remained asymptomatic for VTE at the end of the study did not receive a mandatory bilateral venogram following at least 8 days on study medication. Participants who were withdrawn early and had been objectively confirmed to have a VTE event by a method other than venography were not required to undergo venography. A participant was included in the Independent Central Adjudication Committee (ICAC)-adjudicated incidence of total VTE if he/ she experienced any of adjudicated asymptomatic deep vein thrombosis (DVT) at early withdrawal or after 8-12 days of study treatment and no later than 1 day after end of study treatment, adjudicated symptomatic DVT or pulmonary embolism (PE) at any time during study treatment or death adjudicated to be related to VTE during study treatment.

Secondary Outcome Measures

1. Percentage of Participants With Proximal DVT Over 10 ± 2 Days of Treatment [Up to 12 days]

   Proximal DVT is defined as DVT in or above the popliteal vein. A participant was considered to have had an asymptomatic evaluable venogram if the ICAC answer to the DVT question was 'Yes' or 'No', and to have had an adjudicated asymptomatic DVT if the answer was 'Yes'. A participant who reported symptoms of DVT was considered to had an adjudicated objectively confirmed symptomatic DVT if the ICAC answer to the question 'Was a symptomatic DVT identified?' was 'Yes' and the event happened no more than 12 days after start of study treatment (unless exemption for extended treatment was granted by the medical monitor) and no more than 1 day after end of study treatment. In both asymptomatic and symptomatic DVT, the participant was considered to had a proximal DVT if either of the ICAC answers to the questions 'Left proximal' and 'Right proximal' was 'DVT'. Percentage of participants with proximal DVT over 10 ± 2 days of treatment were reported.

2. Percentage of Participants With Distal DVT Over 10 ± 2 Days of Treatment [Up to 12 days]

   A participant was considered to have had an asymptomatic evaluable venogram if the ICAC answer to the DVT question was 'Yes' or 'No', and to have had an adjudicated asymptomatic DVT if the answer was 'Yes'. A participant who reported symptoms of DVT was considered to had an adjudicated objectively confirmed symptomatic DVT if the ICAC answer to the question 'Was a symptomatic DVT identified?' was 'Yes' and the event happened no more than 12 days after start of study treatment (unless exemption for extended treatment was granted by the medical monitor) and no more than 1 day after end of study treatment. In both asymptomatic and symptomatic DVT, the participant was considered to had a distal DVT if either of the investigator's answers to the questions 'Left distal' and 'Right distal' is 'DVT'.

3. Percentage of Participants With PE Over 10 ± 2 Days of Treatment [Up to 12 days]

   Participant who reported symptoms of PE were considered to have had an adjudicated objectively confirmed symptomatic PE if the ICAC answer to the question 'Was a PE identified?' was 'Yes'. E was characterized as fatal PE non-fatal PE and total PE events. Data has been presented for fatal PE non-fatal PE and total PE events over 12 days.

4. Number of Death Due to VTE Over 10 ± 2 Days of Treatment [Up to 12 days]

   A participant was considered dead from an adjudicated VTE-related cause if the death classification was recorded as 'Fatal PE'. A participant was considered to have died from an investigator-assessed VTE-related cause if the investigator's death classification was recorded as 'Fatal PE'. Number of death due to VTE over 10 ± 2 days of treatment were reported.

5. Percentage of Participants With Total Asymptomatic VTE Over 10 ± 2 Days of Treatment [Up to 12 days]

   A participant was included in the Independent Central Adjudication Committee (ICAC)-adjudicated incidence of total VTE if experienced any of adjudicated asymptomatic deep vein thrombosis (DVT) at early withdrawal or after 8-12 days of study treatment and no later than 1 day after end of study treatment, adjudicated symptomatic DVT or PE at any time during study treatment or death adjudicated to be related to VTE during study treatment. A participant was considered to have had an asymptomatic evaluable venogram if the ICAC answer to the DVT question was 'Yes' or 'No', and to have had an adjudicated asymptomatic DVT if the answer was 'Yes'. The participant was considered to had a proximal DVT if either of the investigator's answers to the questions 'Left distal' and 'Right distal' is 'DVT'. The participant was considered to had a distal DVT if either of the investigator's answers to the questions 'Left distal' and 'Right distal' is 'DVT'.

6. Percentage of Total Symptomatic VTE Over 10 ± 2 Days of Treatment [Up to 12 days]

   A participant who reported symptoms of DVT was considered to had an adjudicated objectively confirmed symptomatic DVT if the ICAC answer to the question 'Was a symptomatic DVT identified?' was 'Yes' and the event happened no more than 12 days after start of study treatment (unless exemption for extended treatment was granted by the medical monitor) and no more than 1 day after end of study treatment. The participant was considered to had a proximal DVT if either of the investigator's answers to the questions 'Left distal' and 'Right distal' was 'DVT'. The participant was considered to had a distal DVT if either of the investigator's answers to the questions 'Left distal' and 'Right distal' was 'DVT'. Percentage of participants with total symptomatic (distal and proximal) VTE over 10 ± 2 days of treatment were reported.

7. Concentration of Trough Anti-IIa Activity Over the Duration of Treatment and Follow-up [Up to 68 days]

   In all participants, additional 3 milliliter of blood was collected at the time of other blood sampling as follow: Baseline, Day 3 (predose, 2, 4, 8, 10, and 12 hours post dose), Day 5 (predose), and Day 10 (predose) or early withdrawal from study medication for the assessment of anti-factor IIa activity. Samples were collected in 3.8% sodium citrate tubes and immediately chilled in ice. Plasma were centrifuged and frozen at approximately -20ºC until time of shipment to the regional central laboratory. Concentration of Trough Anti-IIa Activity over the duration of treatment and follow-up were reported.

8. Percentage of Participants With Major Bleeds Over 10 ± 2 Days of Treatment [Up to 12 days]

   A participant was included in the ICAC-adjudicated incidence of major bleeding if participant experienced an adjudicated major bleed up to 12 days after the start of study treatment and no later than 1 day after end of study treatment. Major bleed was defined as clinically overt bleeding, 1) Clinical overt bleeding: clinically apparent bleeding or signs and/or symptoms suggestive of bleeding with confirmatory imaging studies (e.g., ultrasound, computed tomography) 2. Critical Site Involvement: Intracranial, retroperitoneal, intra-ocular, intraspinal, pericardial. 3. Decrease in Hgb > 2 g/dL from baseline, 4. Transfusion of > 2 units of packed RBCs, 5. Medical or Surgical Intervention for the Reported Bleed, 6. Fatal Bleed. If the event satisfied one of the above criteria.

9. Percentage of Participants With VTE and/or Major Bleeding Over 10±2 Days of Treatment [Up to 12 days]

   A participant was included in the ICAC-adjudicated incidence of major bleeding if experienced an adjudicated major bleed up to 12 days after the start of study treatment and no later than 1 day after end of study treatment. Percentage of participants with VTE and/or major bleeding over 10±2 days of treatment were reported.

10. Percentage of Participants With Total VTE Any Time After Start of Treatment [Up to Visit 9 (Day 28 post treatment)]

    Participants were assessed for VTE at all study visits and at the end of the study (Day 10±2) or at early withdrawal. Any participant who remained asymptomatic for VTE at the end of the study were received a mandatory bilateral venogram. Participants who were withdrawn early and had been objectively confirmed to have a VTE event by a method other than venography were not required to undergo venography. A participant was included in the ICAC-adjudicated incidence of total VTE if experienced any of adjudicated asymptomatic DVT at early withdrawal or after 8-12 days of study treatment and no later than 1 day after end of study treatment, adjudicated symptomatic DVT or PE at any time during study treatment or death adjudicated to be related to VTE during study treatment. Percentage of participants with total VTE any time after start of treatment were reported.

11. Percentage of Participants With Elevated Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Direct Bilirubin (DB) and Total Bilirubin (TB) by 2 Fold and 3 Fold From Upper Normal Limits (ULN) Any Time On-treatment [Up to 12 days]

    The ranges (low concern value; high concern value) for AST (none; > 3 fold upper normal limit (ULN) ), ALT (none; >3 fold ULN), total bilirubin (none; >= 34.2 micromole per litre [umol/L]), Direct bilirubin (none; >= 34.2 umol/L). Percentage of participants with elevated values by 2 fold and 3 fold from ULN any time on-treatment were reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Women must be unable to have children.

• Will have a total knee replacement.

Exclusion Criteria:

• Allergic to any X-ray dye.

• Allergies or reactions to warfarin or coumadin.

• Previous VTE (venous thromboembolism) or deep vein thrombosis (DVT).

• On anticoagulation therapy.

• Renal impairment.

• Participated in any clinical trial in the past 30 days.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35209
2	GSK Investigational Site	Mobile	Alabama	United States	36608
3	GSK Investigational Site	Phoenix	Arizona	United States	85023
4	GSK Investigational Site	Little Rock	Arkansas	United States	72205
5	GSK Investigational Site	Banning	California	United States	92220
6	GSK Investigational Site	Sacramento	California	United States	95817
7	GSK Investigational Site	Torrance	California	United States	90509
8	GSK Investigational Site	Yuba City	California	United States	95991
9	GSK Investigational Site	Colorado Springs	Colorado	United States	80907
10	GSK Investigational Site	Lonetree	Colorado	United States	80124
11	GSK Investigational Site	Clearwater	Florida	United States	33756
12	GSK Investigational Site	Deland	Florida	United States	32720
13	GSK Investigational Site	Jacksonville	Florida	United States	32216
14	GSK Investigational Site	Sarasota	Florida	United States	34239
15	GSK Investigational Site	Sarsota	Florida	United States	34239
16	GSK Investigational Site	St. Petersburg	Florida	United States	33701
17	GSK Investigational Site	Decatur	Georgia	United States	30033
18	GSK Investigational Site	Boise	Idaho	United States	83702
19	GSK Investigational Site	Lexington	Kentucky	United States	40509
20	GSK Investigational Site	Baton Rouge	Louisiana	United States	70808
21	GSK Investigational Site	Baltimore	Maryland	United States	21209
22	GSK Investigational Site	Baltimore	Maryland	United States	21215-5271
23	GSK Investigational Site	Baltimore	Maryland	United States	21218
24	GSK Investigational Site	Warren	Michigan	United States	48089
25	GSK Investigational Site	Mineola	New York	United States	11501
26	GSK Investigational Site	Charlotte	North Carolina	United States	28207
27	GSK Investigational Site	Durham	North Carolina	United States	27704
28	GSK Investigational Site	Cincinnati	Ohio	United States	45242
29	GSK Investigational Site	Cleveland	Ohio	United States	44195
30	GSK Investigational Site	Toledo	Ohio	United States	43614
31	GSK Investigational Site	Allentown	Pennsylvania	United States	18103
32	GSK Investigational Site	Altoona	Pennsylvania	United States	16601
33	GSK Investigational Site	Camp Hill	Pennsylvania	United States	17011
34	GSK Investigational Site	Hershey	Pennsylvania	United States	17033
35	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19107
36	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19140
37	GSK Investigational Site	Dallas	Texas	United States	75231
38	GSK Investigational Site	Dallas	Texas	United States	75246
39	GSK Investigational Site	Lubbock	Texas	United States	79410
40	GSK Investigational Site	San Antonio	Texas	United States	78217
41	GSK Investigational Site	San Antonio	Texas	United States	78229
42	GSK Investigational Site	Norfolk	Virginia	United States	23507
43	GSK Investigational Site	Richmond	Virginia	United States	23229
44	GSK Investigational Site	Richmond	Virginia	United States	23249
45	GSK Investigational Site	Huntington	West Virginia	United States	25701
46	GSK Investigational Site	Marshfield	Wisconsin	United States	54449
47	GSK Investigational Site	Camperdown	New South Wales	Australia	2050
48	GSK Investigational Site	Southport	Queensland	Australia	4215
49	GSK Investigational Site	Box Hill	Victoria	Australia	3128
50	GSK Investigational Site	Clayton	Victoria	Australia	3168
51	GSK Investigational Site	Geelong	Victoria	Australia	3220
52	GSK Investigational Site	Ringwood East	Victoria	Australia	3135
53	GSK Investigational Site	Windsor	Victoria	Australia	3181
54	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul	Brazil	90020-090
55	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul	Brazil	90035-903
56	GSK Investigational Site	Winnipeg	Manitoba	Canada	R3J 3M7
57	GSK Investigational Site	Ajax	Ontario	Canada	L1S 2J5
58	GSK Investigational Site	Don Mills	Ontario	Canada	M3C 1W3
59	GSK Investigational Site	Newmarket	Ontario	Canada	L3Y 2P9
60	GSK Investigational Site	North York	Ontario	Canada	M3M 2G2
61	GSK Investigational Site	Oshawa	Ontario	Canada	L1G 2B9
62	GSK Investigational Site	Scarborough	Ontario	Canada	M1W 3W3
63	GSK Investigational Site	Waterloo	Ontario	Canada	N2J 1C4
64	GSK Investigational Site	Charlottetown	Prince Edward Island	Canada	C1A 1L2
65	GSK Investigational Site	Montreal	Quebec	Canada	H1T 2M4
66	GSK Investigational Site	Québec	Quebec	Canada	G1J 1Z4
67	GSK Investigational Site	Sainte Jerome	Quebec	Canada	J7Z 5T3
68	GSK Investigational Site	Chennai		India	600 040
69	GSK Investigational Site	Secunderabad		India	500 003
70	GSK Investigational Site	Haifa		Israel	31096
71	GSK Investigational Site	Kfar Saba		Israel	44281
72	GSK Investigational Site	Petach Tikva		Israel	49372
73	GSK Investigational Site	Tel-Aviv		Israel	64239
74	GSK Investigational Site	Riga		Latvia	LV1004
75	GSK Investigational Site	Riga		Latvia	LV1005
76	GSK Investigational Site	Kaunas		Lithuania	LT-50009
77	GSK Investigational Site	Klaipeda		Lithuania	LT-92288
78	GSK Investigational Site	Vilnius		Lithuania	LT-04128
79	GSK Investigational Site	Bialystok		Poland	15-276
80	GSK Investigational Site	Krakow		Poland	31-862
81	GSK Investigational Site	Sosnowiec		Poland	41-200
82	GSK Investigational Site	Wroclaw		Poland	50-043
83	GSK Investigational Site	Irkutsk		Russian Federation	664003
84	GSK Investigational Site	Kurgan		Russian Federation	640014
85	GSK Investigational Site	Moscow		Russian Federation	117415
86	GSK Investigational Site	Mosocow		Russian Federation	115516
87	GSK Investigational Site	Mosocow		Russian Federation	117593
88	GSK Investigational Site	Rostov- on- Don		Russian Federation	344718
89	GSK Investigational Site	Pretoria	Gauteng	South Africa	0084
90	GSK Investigational Site	Centurion		South Africa	157
91	GSK Investigational Site	Pretoria		South Africa
92	GSK Investigational Site	Cherkasy		Ukraine	18009
93	GSK Investigational Site	Dnepropetrovsk		Ukraine	49005
94	GSK Investigational Site	Kyiv		Ukraine	03103
95	GSK Investigational Site	Kyiv		Ukraine	04107
96	GSK Investigational Site	Vinnitsa		Ukraine	21032
97	GSK Investigational Site	Birmingham	West Midlands	United Kingdom	B18 7QH
98	GSK Investigational Site	Bournmouth		United Kingdom	BH7 7DW
99	GSK Investigational Site	Fife		United Kingdom	KY2 5AH
100	GSK Investigational Site	London		United Kingdom	SE5 9JP
101	GSK Investigational Site	Wigan		United Kingdom	WN6 9EP

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: NCT00244725
• Other Study ID Numbers: ITI101711
• First Posted: Oct 27, 2005
• Last Update Posted: May 2, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by GlaxoSmithKline: deep vein thrombosis; total knee replacement; PE; Venous thromboembolism; DVT; pulmonary embolism; VTE
• Additional relevant MeSH terms: Pulmonary Embolism; Thrombosis; Embolism; Thromboembolism; Venous Thromboembolism; Venous Thrombosis; Atrial Fibrillation; Warfarin

Study Results

Participant Flow

Recruitment Details	Male or female participants >=35 years of age with scheduled for primary elective unilateral total knee arthroplasty were recruited at 82 centers from 13 countries. The study was conducted between 28 September 2005 and 27 September 2006.
Pre-assignment Detail	A total of 958 participants were randomized into the study. Two participants each from the treatment arm Odiparcil 250 milligram (mg), and Odiparcil 375 mg did not receive the study medication. Therefore, the intent to treat (ITT) population was comprised of 954 participants.

Arm/Group Title	Odiparcil MR 250 mg Tablet	Odiparcil MR 375 mg Tablet	Odiparcil MR 500 mg Tablet	Warfarin INR 2.0 to 3.0
Arm/Group Description	Eligible participants received Odiparcil modified release (MR) 250 mg tablet at every 12 hours interval (Q12h)for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 375 mg tablet at Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 500 mg tablet at Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received overencapsulated warfarin 1 mg and 5 mg as guided by investigator to adjust warfarin to a target International Normalized Ratio (INR) of 2.0 to 3.0 according to the investigators practice or participant status for the duration of 10 ± 2 days of double-blind treatment period.
Period Title: Overall Study
STARTED	237	245	239	237
COMPLETED	214	226	215	216
NOT COMPLETED	23	19	24	21

Baseline Characteristics

Arm/Group Title	Odiparcil MR 250 mg Tablet	Odiparcil MR 375 mg Tablet	Odiparcil MR 500 mg Tablet	Warfarin INR 2.0 to 3.0	Total
Arm/Group Description	Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received overencapsulated warfarin 1 mg and 5 mg as guided by investigator to adjust warfarin to a target INR of 2.0 to 3.0 according to the investigators practice or participant status for the duration of 10 ± 2 days of double-blind treatment period.	Total of all reporting groups
Overall Participants	235	243	239	237	954
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	66.1 (9.53)	65.3 (8.93)	64.5 (8.68)	66.1 (9.30)	65.5 (9.12)
Sex: Female, Male (Count of Participants)
Female	150 63.8%	156 64.2%	155 64.9%	150 63.3%	611 64%
Male	85 36.2%	87 35.8%	84 35.1%	87 36.7%	343 36%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage	18 7.7%	17 7%	20 8.4%	12 5.1%	67 7%
American Indian or Alaska Native	0 0%	0 0%	1 0.4%	0 0%	1 0.1%
Asian - Central/South Asian Heritage	3 1.3%	1 0.4%	3 1.3%	3 1.3%	10 1%
Asian - East Asian Heritage	0 0%	1 0.4%	1 0.4%	0 0%	2 0.2%
Asian - South East Asian Heritage	0 0%	0 0%	0 0%	1 0.4%	1 0.1%
White - Arabic/North African Heritage	1 0.4%	0 0%	1 0.4%	0 0%	2 0.2%
White - White/Caucasian/European Heritage	212 90.2%	224 92.2%	210 87.9%	220 92.8%	866 90.8%
Mixed Race	1 0.4%	0 0%	0 0%	1 0.4%	2 0.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Total VTE Event Over 10 ± 2 Days of Treatment
Description	Participants were assessed for VTE at all study visits and at the end of study (Day 10±2) or at early withdrawal. Any participant who remained asymptomatic for VTE at the end of the study did not receive a mandatory bilateral venogram following at least 8 days on study medication. Participants who were withdrawn early and had been objectively confirmed to have a VTE event by a method other than venography were not required to undergo venography. A participant was included in the Independent Central Adjudication Committee (ICAC)-adjudicated incidence of total VTE if he/ she experienced any of adjudicated asymptomatic deep vein thrombosis (DVT) at early withdrawal or after 8-12 days of study treatment and no later than 1 day after end of study treatment, adjudicated symptomatic DVT or pulmonary embolism (PE) at any time during study treatment or death adjudicated to be related to VTE during study treatment.
Time Frame	Up to Visit 7 (10 ± 2 days of treatment)

Outcome Measure Data

Analysis Population Description

ITT population comprised of all participants who were randomized and received at least one dose of study treatment. Total number of participants with objectively confirmed symptomatic VTE, venographically detected VTE at early withdrawal or an evaluable venogram at study completion were used for analysis.

Arm/Group Title	Odiparcil MR 250 mg Tablet	Odiparcil MR 375 mg Tablet	Odiparcil MR 500 mg Tablet	Warfarin INR 2.0 to 3.0
Arm/Group Description	Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received overencapsulated warfarin 1 mg and 5 mg as guided by investigator to adjust warfarin to a target INR of 2.0 to 3.0 according to the investigators practice or participant status for the duration of 10 ± 2 days of double-blind treatment period.
Measure Participants	164	169	160	157
Number (95% Confidence Interval) [Percentage of participants]	45.1 19.2%	44.4 18.3%	41.3 17.3%	31.2 13.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Odiparcil MR 250 mg Tablet, Warfarin INR 2.0 to 3.0
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.45
	Confidence Interval	(2-Sided) 95%; 1.1 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Odiparcil MR 375 mg Tablet, Warfarin INR 2.0 to 3.0
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.017
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.42
	Confidence Interval	(2-Sided) 95%; 1.1 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Odiparcil MR 250 mg Tablet, Warfarin INR 2.0 to 3.0
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.080
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95%; 1.0 to 1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With Proximal DVT Over 10 ± 2 Days of Treatment
Description	Proximal DVT is defined as DVT in or above the popliteal vein. A participant was considered to have had an asymptomatic evaluable venogram if the ICAC answer to the DVT question was 'Yes' or 'No', and to have had an adjudicated asymptomatic DVT if the answer was 'Yes'. A participant who reported symptoms of DVT was considered to had an adjudicated objectively confirmed symptomatic DVT if the ICAC answer to the question 'Was a symptomatic DVT identified?' was 'Yes' and the event happened no more than 12 days after start of study treatment (unless exemption for extended treatment was granted by the medical monitor) and no more than 1 day after end of study treatment. In both asymptomatic and symptomatic DVT, the participant was considered to had a proximal DVT if either of the ICAC answers to the questions 'Left proximal' and 'Right proximal' was 'DVT'. Percentage of participants with proximal DVT over 10 ± 2 days of treatment were reported.
Time Frame	Up to 12 days

Outcome Measure Data

Analysis Population Description

ITT population. The participants from ITT population who were with objectively confirmed symptomatic VTE, venographically detected VTE at early withdrawal or an evaluable venogram at completion of study treatment were used for the analysis.

Arm/Group Title	Odiparcil MR 250 mg Tablet	Odiparcil MR 375 mg Tablet	Odiparcil MR 500 mg Tablet	Warfarin INR 2.0 to 3.0
Arm/Group Description	Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received overencapsulated warfarin 1 mg and 5 mg as guided by investigator to adjust warfarin to a target INR of 2.0 to 3.0 according to the investigators practice or participant status for the duration of 10 ± 2 days of double-blind treatment period.
Measure Participants	164	169	160	157
Asymptomatic, Proximal DVT	1.8 0.8%	1.8 0.7%	4.4 1.8%	0.6 0.3%
Symptomatic, Proximal DVT	0.0 0%	0.0 0%	0.6 0.3%	0.0 0%
Total, Proximal DVT	1.8 0.8%	1.8 0.7%	5.0 2.1%	0.6 0.3%

3. Secondary Outcome

Title	Percentage of Participants With Distal DVT Over 10 ± 2 Days of Treatment
Description	A participant was considered to have had an asymptomatic evaluable venogram if the ICAC answer to the DVT question was 'Yes' or 'No', and to have had an adjudicated asymptomatic DVT if the answer was 'Yes'. A participant who reported symptoms of DVT was considered to had an adjudicated objectively confirmed symptomatic DVT if the ICAC answer to the question 'Was a symptomatic DVT identified?' was 'Yes' and the event happened no more than 12 days after start of study treatment (unless exemption for extended treatment was granted by the medical monitor) and no more than 1 day after end of study treatment. In both asymptomatic and symptomatic DVT, the participant was considered to had a distal DVT if either of the investigator's answers to the questions 'Left distal' and 'Right distal' is 'DVT'.
Time Frame	Up to 12 days

Outcome Measure Data

Analysis Population Description

ITT population. The participants from ITT population who were with objectively confirmed symptomatic VTE, venographically detected VTE at early withdrawal or an evaluable venogram at completion of study treatment were used for the analysis.

Arm/Group Title	Odiparcil MR 250 mg Tablet	Odiparcil MR 375 mg Tablet	Odiparcil MR 500 mg Tablet	Warfarin INR 2.0 to 3.0
Arm/Group Description	Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received overencapsulated warfarin 1 mg and 5 mg as guided by investigator to adjust warfarin to a target INR of 2.0 to 3.0 according to the investigators practice or participant status for the duration of 10 ± 2 days of double-blind treatment period.
Measure Participants	164	169	160	157
Asymptomatic, Distal DVT	42.1	43.8	38.8	30.6
Symptomatic, Distal DVT	1.8	0.0	0.6	0.0
Total, Distal DVT	43.9	43.8	39.4	30.6

4. Secondary Outcome

Title	Percentage of Participants With PE Over 10 ± 2 Days of Treatment
Description	Participant who reported symptoms of PE were considered to have had an adjudicated objectively confirmed symptomatic PE if the ICAC answer to the question 'Was a PE identified?' was 'Yes'. E was characterized as fatal PE non-fatal PE and total PE events. Data has been presented for fatal PE non-fatal PE and total PE events over 12 days.
Time Frame	Up to 12 days

Outcome Measure Data

Analysis Population Description

ITT population. The participants from ITT population who were with objectively confirmed symptomatic VTE, venographically detected VTE at early withdrawal or an evaluable venogram at completion of study treatment were used for the analysis.

Arm/Group Title	Odiparcil MR 250 mg Tablet	Odiparcil MR 375 mg Tablet	Odiparcil MR 500 mg Tablet	Warfarin INR 2.0 to 3.0
Arm/Group Description	Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received overencapsulated warfarin 1 mg and 5 mg as guided by investigator to adjust warfarin to a target INR of 2.0 to 3.0 according to the investigators practice or participant status for the duration of 10 ± 2 days of double-blind treatment period.
Measure Participants	164	169	160	157
Fatal PE	0.0 0%	0.0 0%	0.0 0%	0.0 0%
Non-fatal PE	1.2 0.5%	0.6 0.2%	0.0 0%	0.6 0.3%
Total PE	1.2 0.5%	0.6 0.2%	0.0 0%	0.6 0.3%

5. Secondary Outcome

Title	Number of Death Due to VTE Over 10 ± 2 Days of Treatment
Description	A participant was considered dead from an adjudicated VTE-related cause if the death classification was recorded as 'Fatal PE'. A participant was considered to have died from an investigator-assessed VTE-related cause if the investigator's death classification was recorded as 'Fatal PE'. Number of death due to VTE over 10 ± 2 days of treatment were reported.
Time Frame	Up to 12 days

Outcome Measure Data

Analysis Population Description

ITT population. The participants from ITT population who were with objectively confirmed symptomatic VTE, venographically detected VTE at early withdrawal or an evaluable venogram at completion of study treatment were used for the analysis.

Arm/Group Title	Odiparcil MR 250 mg Tablet	Odiparcil MR 375 mg Tablet	Odiparcil MR 500 mg Tablet	Warfarin INR 2.0 to 3.0
Arm/Group Description	Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received overencapsulated warfarin 1 mg and 5 mg as guided by investigator to adjust warfarin to a target INR of 2.0 to 3.0 according to the investigators practice or participant status for the duration of 10 ± 2 days of double-blind treatment period.
Measure Participants	164	169	160	157
Number [Participants]	0 0%	0 0%	0 0%	0 0%

6. Secondary Outcome

Title	Percentage of Participants With Total Asymptomatic VTE Over 10 ± 2 Days of Treatment
Description	A participant was included in the Independent Central Adjudication Committee (ICAC)-adjudicated incidence of total VTE if experienced any of adjudicated asymptomatic deep vein thrombosis (DVT) at early withdrawal or after 8-12 days of study treatment and no later than 1 day after end of study treatment, adjudicated symptomatic DVT or PE at any time during study treatment or death adjudicated to be related to VTE during study treatment. A participant was considered to have had an asymptomatic evaluable venogram if the ICAC answer to the DVT question was 'Yes' or 'No', and to have had an adjudicated asymptomatic DVT if the answer was 'Yes'. The participant was considered to had a proximal DVT if either of the investigator's answers to the questions 'Left distal' and 'Right distal' is 'DVT'. The participant was considered to had a distal DVT if either of the investigator's answers to the questions 'Left distal' and 'Right distal' is 'DVT'.
Time Frame	Up to 12 days

Outcome Measure Data

Analysis Population Description

ITT population. The participants from ITT population who were with objectively confirmed symptomatic VTE, venographically detected VTE at early withdrawal or an evaluable venogram at completion of study treatment were used for the analysis.

Arm/Group Title	Odiparcil MR 250 mg Tablet	Odiparcil MR 375 mg Tablet	Odiparcil MR 500 mg Tablet	Warfarin INR 2.0 to 3.0
Arm/Group Description	Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received overencapsulated warfarin 1 mg and 5 mg as guided by investigator to adjust warfarin to a target INR of 2.0 to 3.0 according to the investigators practice or participant status for the duration of 10 ± 2 days of double-blind treatment period.
Measure Participants	164	169	160	157
Number (95% Confidence Interval) [Percentage of participants]	42.1 17.9%	43.8 18%	40.0 16.7%	30.6 12.9%

7. Secondary Outcome

Title	Percentage of Total Symptomatic VTE Over 10 ± 2 Days of Treatment
Description	A participant who reported symptoms of DVT was considered to had an adjudicated objectively confirmed symptomatic DVT if the ICAC answer to the question 'Was a symptomatic DVT identified?' was 'Yes' and the event happened no more than 12 days after start of study treatment (unless exemption for extended treatment was granted by the medical monitor) and no more than 1 day after end of study treatment. The participant was considered to had a proximal DVT if either of the investigator's answers to the questions 'Left distal' and 'Right distal' was 'DVT'. The participant was considered to had a distal DVT if either of the investigator's answers to the questions 'Left distal' and 'Right distal' was 'DVT'. Percentage of participants with total symptomatic (distal and proximal) VTE over 10 ± 2 days of treatment were reported.
Time Frame	Up to 12 days

Outcome Measure Data

Analysis Population Description

ITT population. The participants from ITT population who were with objectively confirmed symptomatic VTE, venographically detected VTE at early withdrawal or an evaluable venogram at completion of study treatment were used for the analysis.

Arm/Group Title	Odiparcil MR 250 mg Tablet	Odiparcil MR 375 mg Tablet	Odiparcil MR 500 mg Tablet	Warfarin INR 2.0 to 3.0
Arm/Group Description	Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received overencapsulated warfarin 1 mg and 5 mg as guided by investigator to adjust warfarin to a target INR of 2.0 to 3.0 according to the investigators practice or participant status for the duration of 10 ± 2 days of double-blind treatment period.
Measure Participants	164	169	160	157
Number (95% Confidence Interval) [Perentage of participants]	1.8 0.8%	0.0 0%	1.3 0.5%	0.0 0%

8. Secondary Outcome

Title	Concentration of Trough Anti-IIa Activity Over the Duration of Treatment and Follow-up
Description	In all participants, additional 3 milliliter of blood was collected at the time of other blood sampling as follow: Baseline, Day 3 (predose, 2, 4, 8, 10, and 12 hours post dose), Day 5 (predose), and Day 10 (predose) or early withdrawal from study medication for the assessment of anti-factor IIa activity. Samples were collected in 3.8% sodium citrate tubes and immediately chilled in ice. Plasma were centrifuged and frozen at approximately -20ºC until time of shipment to the regional central laboratory. Concentration of Trough Anti-IIa Activity over the duration of treatment and follow-up were reported.
Time Frame	Up to 68 days

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Odiparcil MR 250 mg Tablet	Odiparcil MR 375 mg Tablet	Odiparcil MR 500 mg Tablet	Warfarin INR 2.0 to 3.0
Arm/Group Description	Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received overencapsulated warfarin 1 mg and 5 mg as guided by investigator to adjust warfarin to a target INR of 2.0 to 3.0 according to the investigators practice or participant status for the duration of 10 ± 2 days of double-blind treatment period.
Measure Participants	235	243	239	237
Day 3, n= 224, 221, 223, 220	2.44 (1.944)	3.15 (2.667)	3.75 (2.702)	0.26 (0.041)
Day 5, n= 201, 207, 215, 203	1.73 (1.456)	2.43 (1.924)	3.07 (2.440)	0.27 (0.099)
Day 10, n= 179, 197, 199, 181	1.45 (1.298)	2.23 (1.830)	2.45 (2.042)	0.25 (0.020)
Early Withdraw On-therapy, n= 13, 8, 10, 17	1.73 (1.286)	3.73 (2.684)	2.49 (3.072)	0.29 (0.159)
14 Day FU, n= 16, 11, 5, 9	0.95 (1.086)	1.16 (1.431)	1.02 (1.652)	0.30 (0.109)
Early Withdraw 14 Day FU, n= 13, 15, 6, 13	0.46 (0.376)	0.74 (0.767)	0.60 (0.666)	0.25 (0.008)
28 Day FU, n= 0, 1, 0, 1	NA (NA)	0.25 (NA)	NA (NA)	0.25 (NA)
Early Withdraw 28 Day FU, n=0, 1, 0, 1	NA (NA)	0.25 (NA)	NA (NA)	0.25 (NA)

9. Secondary Outcome

Title	Percentage of Participants With Major Bleeds Over 10 ± 2 Days of Treatment
Description	A participant was included in the ICAC-adjudicated incidence of major bleeding if participant experienced an adjudicated major bleed up to 12 days after the start of study treatment and no later than 1 day after end of study treatment. Major bleed was defined as clinically overt bleeding, 1) Clinical overt bleeding: clinically apparent bleeding or signs and/or symptoms suggestive of bleeding with confirmatory imaging studies (e.g., ultrasound, computed tomography) 2. Critical Site Involvement: Intracranial, retroperitoneal, intra-ocular, intraspinal, pericardial. 3. Decrease in Hgb > 2 g/dL from baseline, 4. Transfusion of > 2 units of packed RBCs, 5. Medical or Surgical Intervention for the Reported Bleed, 6. Fatal Bleed. If the event satisfied one of the above criteria.
Time Frame	Up to 12 days

Outcome Measure Data

Analysis Population Description

ITT Population. The participants from ITT population who completed study treatment (Day-10 visit) or reported a major bleed by the time of early withdrawal were used for the analysis

Arm/Group Title	Odiparcil MR 250 mg Tablet	Odiparcil MR 375 mg Tablet	Odiparcil MR 500 mg Tablet	Warfarin INR 2.0 to 3.0
Arm/Group Description	Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received overencapsulated warfarin 1 mg and 5 mg as guided by investigator to adjust warfarin to a target INR of 2.0 to 3.0 according to the investigators practice or participant status for the duration of 10 ± 2 days of double-blind treatment period.
Measure Participants	205	217	222	203
Number (95% Confidence Interval) [Percentage of participants]	0.0 0%	0.0 0%	0.9 0.4%	1.0 0.4%

10. Secondary Outcome

Title	Percentage of Participants With VTE and/or Major Bleeding Over 10±2 Days of Treatment
Description	A participant was included in the ICAC-adjudicated incidence of major bleeding if experienced an adjudicated major bleed up to 12 days after the start of study treatment and no later than 1 day after end of study treatment. Percentage of participants with VTE and/or major bleeding over 10±2 days of treatment were reported.
Time Frame	Up to 12 days

Outcome Measure Data

Analysis Population Description

ITT population. The participants from ITT population who were efficacy evaluable or reported a major bleed or VTE by the time of early withdrawal were used for the analysis

Arm/Group Title	Odiparcil MR 250 mg Tablet	Odiparcil MR 375 mg Tablet	Odiparcil MR 500 mg Tablet	Warfarin INR 2.0 to 3.0
Arm/Group Description	Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received overencapsulated warfarin 1 mg and 5 mg as guided by investigator to adjust warfarin to a target INR of 2.0 to 3.0 according to the investigators practice or participant status for the duration of 10 ± 2 days of double-blind treatment period.
Measure Participants	164	169	160	157
VTE and/or major bleed	45.1 19.2%	44.4 18.3%	42.5 17.8%	32.5 13.7%
VTE and major bleed	0.0 0%	0.0 0%	0.0 0%	0.0 0%
VTE with no major bleed	45.1 19.2%	44.4 18.3%	41.3 17.3%	31.2 13.2%
Major bleed with no VTE	0.0 0%	0.0 0%	1.3 0.5%	1.3 0.5%
No VTE and no major bleed	54.9 23.4%	55.6 22.9%	58.1 24.3%	68.2 28.8%

11. Secondary Outcome

Title	Percentage of Participants With Total VTE Any Time After Start of Treatment
Description	Participants were assessed for VTE at all study visits and at the end of the study (Day 10±2) or at early withdrawal. Any participant who remained asymptomatic for VTE at the end of the study were received a mandatory bilateral venogram. Participants who were withdrawn early and had been objectively confirmed to have a VTE event by a method other than venography were not required to undergo venography. A participant was included in the ICAC-adjudicated incidence of total VTE if experienced any of adjudicated asymptomatic DVT at early withdrawal or after 8-12 days of study treatment and no later than 1 day after end of study treatment, adjudicated symptomatic DVT or PE at any time during study treatment or death adjudicated to be related to VTE during study treatment. Percentage of participants with total VTE any time after start of treatment were reported.
Time Frame	Up to Visit 9 (Day 28 post treatment)

Outcome Measure Data

Analysis Population Description

ITT population. The participants from ITT population who were with objectively confirmed symptomatic VTE, venographically detected VTE at early withdrawal or an evaluable venogram at completion of study treatment were used for the analysis

Arm/Group Title	Odiparcil MR 250 mg Tablet	Odiparcil MR 375 mg Tablet	Odiparcil MR 500 mg Tablet	Warfarin INR 2.0 to 3.0
Arm/Group Description	Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received overencapsulated warfarin 1 mg and 5 mg as guided by investigator to adjust warfarin to a target INR of 2.0 to 3.0 according to the investigators practice or participant status for the duration of 10 ± 2 days of double-blind treatment period.
Measure Participants	170	179	171	168
Number (95% Confidence Interval) [Percenatge of participants]	46.5 19.8%	45.8 18.8%	43.3 18.1%	30.4 12.8%

12. Secondary Outcome

Title	Percentage of Participants With Elevated Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Direct Bilirubin (DB) and Total Bilirubin (TB) by 2 Fold and 3 Fold From Upper Normal Limits (ULN) Any Time On-treatment
Description	The ranges (low concern value; high concern value) for AST (none; > 3 fold upper normal limit (ULN) ), ALT (none; >3 fold ULN), total bilirubin (none; >= 34.2 micromole per litre [umol/L]), Direct bilirubin (none; >= 34.2 umol/L). Percentage of participants with elevated values by 2 fold and 3 fold from ULN any time on-treatment were reported.
Time Frame	Up to 12 days

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants were available at the time of analysis were included.

Arm/Group Title	Odiparcil MR 250 mg Tablet	Odiparcil MR 375 mg Tablet	Odiparcil MR 500 mg Tablet	Warfarin INR 2.0 to 3.0
Arm/Group Description	Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Eligible participants received overencapsulated warfarin 1 mg and 5 mg as guided by investigator to adjust warfarin to a target INR of 2.0 to 3.0 according to the investigators practice or participant status for the duration of 10 ± 2 days of double-blind treatment period.
Measure Participants	231	235	236	234
ALT, >=2xULN	4.8 2%	3.8 1.6%	3.8 1.6%	5.6 2.4%
ALT, >=3xULN	0.9 0.4%	2.6 1.1%	0.4 0.2%	2.1 0.9%
AST, >=2xULN	2.6 1.1%	3.4 1.4%	3.8 1.6%	4.7 2%
AST, >=3xULN	0.0 0%	0.9 0.4%	0.4 0.2%	1.7 0.7%
Total Billirubin, >=2xULN	0.0 0%	0.4 0.2%	0.4 0.2%	0.0 0%
Total Billirubin, >=3xULN	0.0 0%	0.0 0%	0.0 0%	0.0 0%
Direct Billirubin, >=2xULN	0.4 0.2%	0.4 0.2%	0.4 0.2%	0.9 0.4%
Direct Billirubin, >=3xULN	0.4 0.2%	0.4 0.2%	0.0 0%	0.0 0%

Adverse Events

Time Frame	Serious adverse events (SAE) and non-serious adverse events (nSAEs) were collected up to follow-up visit (Visit 9, Day 28±2 days after study medication discontinuation). On-treatment nSAEs were reported.
Adverse Event Reporting Description	ITT population was used for analysis.
Arm/Group Title	ODIPARCIL MR 250 mg Tablet		ODIPARCIL MR 375 MG TABLET		ODIPARCIL MR 500 MG TABLET		WARFARIN INR 2.0 TO 3.0
Arm/Group Description	Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.		Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.		Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.		Eligible participants received overencapsulated warfarin 1 mg and 5 mg as guided by investigator to adjust warfarin to a target INR of 2.0 to 3.0 according to the investigators practice or participant status for the duration of 10 ± 2 days of double-blind treatment period.
All Cause Mortality
	ODIPARCIL MR 250 mg Tablet		ODIPARCIL MR 375 MG TABLET		ODIPARCIL MR 500 MG TABLET		WARFARIN INR 2.0 TO 3.0
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	ODIPARCIL MR 250 mg Tablet		ODIPARCIL MR 375 MG TABLET		ODIPARCIL MR 500 MG TABLET		WARFARIN INR 2.0 TO 3.0
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/235 (6%)		11/243 (4.5%)		16/239 (6.7%)		9/237 (3.8%)
Blood and lymphatic system disorders
Coagulopathy	0/235 (0%)		1/243 (0.4%)		0/239 (0%)		0/237 (0%)
Cardiac disorders
Atrial fibrillation	1/235 (0.4%)		0/243 (0%)		2/239 (0.8%)		0/237 (0%)
Cardiac failure congestive	1/235 (0.4%)		0/243 (0%)		1/239 (0.4%)		0/237 (0%)
Acute myocardial infarction	0/235 (0%)		0/243 (0%)		0/239 (0%)		1/237 (0.4%)
Atrial flutter	1/235 (0.4%)		0/243 (0%)		0/239 (0%)		0/237 (0%)
Atrial thrombosis	1/235 (0.4%)		0/243 (0%)		0/239 (0%)		0/237 (0%)
Myocardial ischaemia	1/235 (0.4%)		0/243 (0%)		0/239 (0%)		0/237 (0%)
Gastrointestinal disorders
Ileus paralytic	1/235 (0.4%)		0/243 (0%)		0/239 (0%)		1/237 (0.4%)
Gastric ulcer haemorrhage	0/235 (0%)		0/243 (0%)		1/239 (0.4%)		0/237 (0%)
Intestinal obstruction	0/235 (0%)		1/243 (0.4%)		0/239 (0%)		0/237 (0%)
General disorders
Chest pain	1/235 (0.4%)		0/243 (0%)		0/239 (0%)		0/237 (0%)
Oedema peripheral	0/235 (0%)		1/243 (0.4%)		0/239 (0%)		0/237 (0%)
Infections and infestations
Pneumonia	1/235 (0.4%)		1/243 (0.4%)		1/239 (0.4%)		0/237 (0%)
Postoperative wound infection	1/235 (0.4%)		1/243 (0.4%)		0/239 (0%)		0/237 (0%)
Arthritis infective	0/235 (0%)		0/243 (0%)		1/239 (0.4%)		0/237 (0%)
Bronchitis acute	1/235 (0.4%)		0/243 (0%)		0/239 (0%)		0/237 (0%)
Device related infection	0/235 (0%)		0/243 (0%)		1/239 (0.4%)		0/237 (0%)
Diverticulitis	0/235 (0%)		0/243 (0%)		0/239 (0%)		1/237 (0.4%)
Gastroenteritis	0/235 (0%)		0/243 (0%)		0/239 (0%)		1/237 (0.4%)
Infection	0/235 (0%)		0/243 (0%)		1/239 (0.4%)		0/237 (0%)
Influenza	0/235 (0%)		1/243 (0.4%)		0/239 (0%)		0/237 (0%)
Postoperative infection	0/235 (0%)		1/243 (0.4%)		0/239 (0%)		0/237 (0%)
Viral upper respiratory tract infection	1/235 (0.4%)		0/243 (0%)		0/239 (0%)		0/237 (0%)
Injury, poisoning and procedural complications
Wound dehiscence	1/235 (0.4%)		0/243 (0%)		2/239 (0.8%)		0/237 (0%)
Fall	1/235 (0.4%)		0/243 (0%)		0/239 (0%)		0/237 (0%)
Joint injury	1/235 (0.4%)		0/243 (0%)		0/239 (0%)		0/237 (0%)
Overdose	1/235 (0.4%)		0/243 (0%)		0/239 (0%)		0/237 (0%)
Patella fracture	0/235 (0%)		1/243 (0.4%)		0/239 (0%)		0/237 (0%)
Post procedural complication	0/235 (0%)		1/243 (0.4%)		0/239 (0%)		0/237 (0%)
Postoperative ileus	0/235 (0%)		0/243 (0%)		0/239 (0%)		1/237 (0.4%)
Traumatic haematoma	0/235 (0%)		0/243 (0%)		0/239 (0%)		1/237 (0.4%)
Investigations
Bleeding time abnormal	1/235 (0.4%)		0/243 (0%)		0/239 (0%)		0/237 (0%)
Body temperature increased	0/235 (0%)		0/243 (0%)		0/239 (0%)		1/237 (0.4%)
Hepatic enzyme increased	0/235 (0%)		1/243 (0.4%)		0/239 (0%)		0/237 (0%)
Metabolism and nutrition disorders
Dehydration	0/235 (0%)		0/243 (0%)		0/239 (0%)		1/237 (0.4%)
Hyponatraemia	0/235 (0%)		0/243 (0%)		0/239 (0%)		1/237 (0.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/235 (0.4%)		0/243 (0%)		1/239 (0.4%)		0/237 (0%)
Joint swelling	1/235 (0.4%)		0/243 (0%)		0/239 (0%)		0/237 (0%)
Nervous system disorders
Headache	1/235 (0.4%)		0/243 (0%)		0/239 (0%)		0/237 (0%)
Ischaemic stroke	1/235 (0.4%)		0/243 (0%)		0/239 (0%)		0/237 (0%)
Syncope	0/235 (0%)		0/243 (0%)		1/239 (0.4%)		0/237 (0%)
Transient ischaemic attack	0/235 (0%)		0/243 (0%)		1/239 (0.4%)		0/237 (0%)
Psychiatric disorders
Confusional state	0/235 (0%)		1/243 (0.4%)		0/239 (0%)		0/237 (0%)
Renal and urinary disorders
Calculus ureteric	0/235 (0%)		0/243 (0%)		1/239 (0.4%)		0/237 (0%)
Renal failure	0/235 (0%)		0/243 (0%)		1/239 (0.4%)		0/237 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/235 (0%)		0/243 (0%)		1/239 (0.4%)		0/237 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/235 (0.4%)		0/243 (0%)		0/239 (0%)		1/237 (0.4%)
Dyspnoea	0/235 (0%)		0/243 (0%)		0/239 (0%)		1/237 (0.4%)
Vascular disorders
Haematoma	0/235 (0%)		0/243 (0%)		1/239 (0.4%)		0/237 (0%)
Haemorrhage	0/235 (0%)		1/243 (0.4%)		0/239 (0%)		0/237 (0%)
Other (Not Including Serious) Adverse Events
	ODIPARCIL MR 250 mg Tablet		ODIPARCIL MR 375 MG TABLET		ODIPARCIL MR 500 MG TABLET		WARFARIN INR 2.0 TO 3.0
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	124/235 (52.8%)		120/243 (49.4%)		122/239 (51%)		104/237 (43.9%)
Cardiac disorders
Tachycardia	11/235 (4.7%)	12	12/243 (4.9%)	12	19/239 (7.9%)	19	12/237 (5.1%)	12
Gastrointestinal disorders
Nausea	27/235 (11.5%)	28	35/243 (14.4%)	36	40/239 (16.7%)	41	33/237 (13.9%)	36
Constipation	29/235 (12.3%)	30	25/243 (10.3%)	25	26/239 (10.9%)	26	29/237 (12.2%)	31
Vomiting	19/235 (8.1%)	19	15/243 (6.2%)	15	21/239 (8.8%)	21	13/237 (5.5%)	14
General disorders
Pyrexia	40/235 (17%)	42	28/243 (11.5%)	30	29/239 (12.1%)	29	34/237 (14.3%)	34
Oedema peripheral	27/235 (11.5%)	30	23/243 (9.5%)	27	28/239 (11.7%)	36	25/237 (10.5%)	35
Injury, poisoning and procedural complications
Anaemia postoperative	20/235 (8.5%)	20	21/243 (8.6%)	21	24/239 (10%)	24	19/237 (8%)	19
Contusion	7/235 (3%)	8	13/243 (5.3%)	14	8/239 (3.3%)	10	9/237 (3.8%)	10
Investigations
Body temperature increased	18/235 (7.7%)	20	21/243 (8.6%)	21	13/239 (5.4%)	13	13/237 (5.5%)	13
Musculoskeletal and connective tissue disorders
Pain in extremity	8/235 (3.4%)	9	10/243 (4.1%)	10	13/239 (5.4%)	14	9/237 (3.8%)	11
Nervous system disorders
Dizziness	8/235 (3.4%)	8	9/243 (3.7%)	9	14/239 (5.9%)	16	11/237 (4.6%)	14
Psychiatric disorders
Insomnia	17/235 (7.2%)	18	11/243 (4.5%)	11	16/239 (6.7%)	17	13/237 (5.5%)	13
Skin and subcutaneous tissue disorders
Pruritus	11/235 (4.7%)	11	14/243 (5.8%)	14	10/239 (4.2%)	10	9/237 (3.8%)	9

Limitations/Caveats

[Not Specified]

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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.