Trial Outcomes & Findings for Odiparcil For The Prevention Of Venous Thromboembolism (NCT NCT00244725)

Last Updated: 2017-05-02

Results Overview

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 Participants who were withdrawn early and had been objectively confirmed to have a VTE event by a method other than venography were not required to undergo venography.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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

961 participants

Primary outcome timeframe

Up to Visit 7 (10 ± 2 days of treatment)

Results posted on

2017-05-02

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Odiparcil MR 250 mg Tablet 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.	Odiparcil MR 375 mg Tablet Eligible participants received Odiparcil MR 375 mg tablet at Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 500 mg Tablet Eligible participants received Odiparcil MR 500 mg tablet at Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Warfarin INR 2.0 to 3.0 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.
Overall Study STARTED	237	245	239	237
Overall Study COMPLETED	214	226	215	216
Overall Study NOT COMPLETED	23	19	24	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Odiparcil MR 250 mg Tablet 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.	Odiparcil MR 375 mg Tablet Eligible participants received Odiparcil MR 375 mg tablet at Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 500 mg Tablet Eligible participants received Odiparcil MR 500 mg tablet at Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Warfarin INR 2.0 to 3.0 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.
Overall Study Lost to Follow-up	3	4	9	2
Overall Study Withdrawal by Subject	9	7	7	8
Overall Study Not meet treatment eligibility criteria	1	2	0	0
Overall Study Physician Decision	3	0	1	2
Overall Study Adverse Events	3	1	4	4
Overall Study Withdrwal by participant	1	0	0	1
Overall Study Liver function test abnormality	2	0	0	1
Overall Study Sponsor withdrew the participant	1	0	0	1
Overall Study Mediciation Error	0	1	0	0
Overall Study Rehab Refused to allow participantion	0	1	0	0
Overall Study Headache	0	1	0	0
Overall Study Received prohibited medication	0	1	0	1
Overall Study Confirmed venous thromboembolism (VTE)	0	1	0	0
Overall Study Administrative reason	0	0	1	0
Overall Study Vomit	0	0	1	0
Overall Study Failed to follow-up	0	0	1	1

Baseline Characteristics

Odiparcil For The Prevention Of Venous Thromboembolism

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Odiparcil MR 250 mg Tablet n=235 Participants Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 375 mg Tablet n=243 Participants Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 500 mg Tablet n=239 Participants Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Warfarin INR 2.0 to 3.0 n=237 Participants 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 n=954 Participants Total of all reporting groups
Age, Continuous	66.1 Years STANDARD_DEVIATION 9.53 • n=5 Participants	65.3 Years STANDARD_DEVIATION 8.93 • n=7 Participants	64.5 Years STANDARD_DEVIATION 8.68 • n=5 Participants	66.1 Years STANDARD_DEVIATION 9.30 • n=4 Participants	65.5 Years STANDARD_DEVIATION 9.12 • n=21 Participants
Sex: Female, Male Female	150 Participants n=5 Participants	156 Participants n=7 Participants	155 Participants n=5 Participants	150 Participants n=4 Participants	611 Participants n=21 Participants
Sex: Female, Male Male	85 Participants n=5 Participants	87 Participants n=7 Participants	84 Participants n=5 Participants	87 Participants n=4 Participants	343 Participants n=21 Participants
Race/Ethnicity, Customized African American/African Heritage	18 Participants n=5 Participants	17 Participants n=7 Participants	20 Participants n=5 Participants	12 Participants n=4 Participants	67 Participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	3 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	10 Participants n=21 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	212 Participants n=5 Participants	224 Participants n=7 Participants	210 Participants n=5 Participants	220 Participants n=4 Participants	866 Participants n=21 Participants
Race/Ethnicity, Customized Mixed Race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to Visit 7 (10 ± 2 days of treatment)

Population: 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.

Outcome measures

Outcome measures
Measure	Odiparcil MR 250 mg Tablet n=164 Participants Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 375 mg Tablet n=169 Participants Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 500 mg Tablet n=160 Participants Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Warfarin INR 2.0 to 3.0 n=157 Participants 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.
Percentage of Participants With Total VTE Event Over 10 ± 2 Days of Treatment	45.1 Percentage of participants Interval 37.4 to 53.1	44.4 Percentage of participants Interval 36.8 to 52.2	41.3 Percentage of participants Interval 33.5 to 49.3	31.2 Percentage of participants Interval 24.1 to 39.1

SECONDARY outcome

Timeframe: Up to 12 days

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Odiparcil MR 250 mg Tablet n=164 Participants Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 375 mg Tablet n=169 Participants Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 500 mg Tablet n=160 Participants Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Warfarin INR 2.0 to 3.0 n=157 Participants 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.
Percentage of Participants With Proximal DVT Over 10 ± 2 Days of Treatment Asymptomatic, Proximal DVT	1.8 Percentage of participants Interval 0.4 to 5.3	1.8 Percentage of participants Interval 0.4 to 5.1	4.4 Percentage of participants Interval 1.8 to 8.8	0.6 Percentage of participants Interval 0.0 to 3.5
Percentage of Participants With Proximal DVT Over 10 ± 2 Days of Treatment Symptomatic, Proximal DVT	0.0 Percentage of participants Interval 0.0 to 2.2	0.0 Percentage of participants Interval 0.0 to 2.2	0.6 Percentage of participants Interval 0.0 to 3.4	0.0 Percentage of participants Interval 0.0 to 2.3
Percentage of Participants With Proximal DVT Over 10 ± 2 Days of Treatment Total, Proximal DVT	1.8 Percentage of participants Interval 0.4 to 5.3	1.8 Percentage of participants Interval 0.4 to 5.1	5.0 Percentage of participants Interval 2.2 to 9.6	0.6 Percentage of participants Interval 0.0 to 3.5

SECONDARY outcome

Timeframe: 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'.

Outcome measures

Outcome measures
Measure	Odiparcil MR 250 mg Tablet n=164 Participants Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 375 mg Tablet n=169 Participants Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 500 mg Tablet n=160 Participants Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Warfarin INR 2.0 to 3.0 n=157 Participants 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.
Percentage of Participants With Distal DVT Over 10 ± 2 Days of Treatment Asymptomatic, Distal DVT	42.1 Percentage of paticipants Interval 34.4 to 50.0	43.8 Percentage of paticipants Interval 36.2 to 51.6	38.8 Percentage of paticipants Interval 31.2 to 46.8	30.6 Percentage of paticipants Interval 23.5 to 38.4
Percentage of Participants With Distal DVT Over 10 ± 2 Days of Treatment Symptomatic, Distal DVT	1.8 Percentage of paticipants Interval 0.4 to 5.3	0.0 Percentage of paticipants Interval 0.0 to 2.2	0.6 Percentage of paticipants Interval 0.0 to 3.4	0.0 Percentage of paticipants Interval 0.0 to 2.3
Percentage of Participants With Distal DVT Over 10 ± 2 Days of Treatment Total, Distal DVT	43.9 Percentage of paticipants Interval 36.2 to 51.9	43.8 Percentage of paticipants Interval 36.2 to 51.6	39.4 Percentage of paticipants Interval 31.8 to 47.4	30.6 Percentage of paticipants Interval 23.5 to 38.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Odiparcil MR 250 mg Tablet n=164 Participants Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 375 mg Tablet n=169 Participants Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 500 mg Tablet n=160 Participants Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Warfarin INR 2.0 to 3.0 n=157 Participants 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.
Percentage of Participants With PE Over 10 ± 2 Days of Treatment Total PE	1.2 Percentage of participants Interval 0.1 to 4.3	0.6 Percentage of participants Interval 0.0 to 3.3	0.0 Percentage of participants Interval 0.0 to 2.3	0.6 Percentage of participants Interval 0.0 to 3.5
Percentage of Participants With PE Over 10 ± 2 Days of Treatment Fatal PE	0.0 Percentage of participants Interval 0.0 to 2.2	0.0 Percentage of participants Interval 0.0 to 2.2	0.0 Percentage of participants Interval 0.0 to 2.3	0.0 Percentage of participants Interval 0.0 to 2.3
Percentage of Participants With PE Over 10 ± 2 Days of Treatment Non-fatal PE	1.2 Percentage of participants Interval 0.1 to 4.3	0.6 Percentage of participants Interval 0.0 to 3.3	0.0 Percentage of participants Interval 0.0 to 2.3	0.6 Percentage of participants Interval 0.0 to 3.5

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Odiparcil MR 250 mg Tablet n=164 Participants Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 375 mg Tablet n=169 Participants Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 500 mg Tablet n=160 Participants Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Warfarin INR 2.0 to 3.0 n=157 Participants 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.
Number of Death Due to VTE Over 10 ± 2 Days of Treatment	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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'.

Outcome measures

Outcome measures
Measure	Odiparcil MR 250 mg Tablet n=164 Participants Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 375 mg Tablet n=169 Participants Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 500 mg Tablet n=160 Participants Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Warfarin INR 2.0 to 3.0 n=157 Participants 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.
Percentage of Participants With Total Asymptomatic VTE Over 10 ± 2 Days of Treatment	42.1 Percentage of participants Interval 34.4 to 50.0	43.8 Percentage of participants Interval 36.2 to 51.6	40.0 Percentage of participants Interval 32.3 to 48.0	30.6 Percentage of participants Interval 23.5 to 38.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Odiparcil MR 250 mg Tablet n=164 Participants Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 375 mg Tablet n=169 Participants Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 500 mg Tablet n=160 Participants Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Warfarin INR 2.0 to 3.0 n=157 Participants 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.
Percentage of Total Symptomatic VTE Over 10 ± 2 Days of Treatment	1.8 Perentage of participants Interval 0.4 to 5.3	0.0 Perentage of participants Interval 0.0 to 2.2	1.3 Perentage of participants Interval 0.2 to 4.4	0.0 Perentage of participants Interval 0.0 to 2.3

SECONDARY outcome

Timeframe: Up to 68 days

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	Odiparcil MR 250 mg Tablet n=235 Participants Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 375 mg Tablet n=243 Participants Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 500 mg Tablet n=239 Participants Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Warfarin INR 2.0 to 3.0 n=237 Participants 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.
Concentration of Trough Anti-IIa Activity Over the Duration of Treatment and Follow-up Day 3, n= 224, 221, 223, 220	2.44 Microgram per millilitre (mcg/ml) Standard Deviation 1.944	3.15 Microgram per millilitre (mcg/ml) Standard Deviation 2.667	3.75 Microgram per millilitre (mcg/ml) Standard Deviation 2.702	0.26 Microgram per millilitre (mcg/ml) Standard Deviation 0.041
Concentration of Trough Anti-IIa Activity Over the Duration of Treatment and Follow-up Day 10, n= 179, 197, 199, 181	1.45 Microgram per millilitre (mcg/ml) Standard Deviation 1.298	2.23 Microgram per millilitre (mcg/ml) Standard Deviation 1.830	2.45 Microgram per millilitre (mcg/ml) Standard Deviation 2.042	0.25 Microgram per millilitre (mcg/ml) Standard Deviation 0.020
Concentration of Trough Anti-IIa Activity Over the Duration of Treatment and Follow-up Early Withdraw On-therapy, n= 13, 8, 10, 17	1.73 Microgram per millilitre (mcg/ml) Standard Deviation 1.286	3.73 Microgram per millilitre (mcg/ml) Standard Deviation 2.684	2.49 Microgram per millilitre (mcg/ml) Standard Deviation 3.072	0.29 Microgram per millilitre (mcg/ml) Standard Deviation 0.159
Concentration of Trough Anti-IIa Activity Over the Duration of Treatment and Follow-up 14 Day FU, n= 16, 11, 5, 9	0.95 Microgram per millilitre (mcg/ml) Standard Deviation 1.086	1.16 Microgram per millilitre (mcg/ml) Standard Deviation 1.431	1.02 Microgram per millilitre (mcg/ml) Standard Deviation 1.652	0.30 Microgram per millilitre (mcg/ml) Standard Deviation 0.109
Concentration of Trough Anti-IIa Activity Over the Duration of Treatment and Follow-up Early Withdraw 14 Day FU, n= 13, 15, 6, 13	0.46 Microgram per millilitre (mcg/ml) Standard Deviation 0.376	0.74 Microgram per millilitre (mcg/ml) Standard Deviation 0.767	0.60 Microgram per millilitre (mcg/ml) Standard Deviation 0.666	0.25 Microgram per millilitre (mcg/ml) Standard Deviation 0.008
Concentration of Trough Anti-IIa Activity Over the Duration of Treatment and Follow-up Early Withdraw 28 Day FU, n=0, 1, 0, 1	NA Microgram per millilitre (mcg/ml) Standard Deviation NA Participants were not analyzed at this time point.	0.25 Microgram per millilitre (mcg/ml) Standard Deviation NA Standard deviation was not derived as only one participant was available at the time of analysis analyzed.	NA Microgram per millilitre (mcg/ml) Standard Deviation NA Participants were not analyzed at this time point.	0.25 Microgram per millilitre (mcg/ml) Standard Deviation NA Standard deviation was not derived as only one participant was available at the time of analysis analyzed.
Concentration of Trough Anti-IIa Activity Over the Duration of Treatment and Follow-up Day 5, n= 201, 207, 215, 203	1.73 Microgram per millilitre (mcg/ml) Standard Deviation 1.456	2.43 Microgram per millilitre (mcg/ml) Standard Deviation 1.924	3.07 Microgram per millilitre (mcg/ml) Standard Deviation 2.440	0.27 Microgram per millilitre (mcg/ml) Standard Deviation 0.099
Concentration of Trough Anti-IIa Activity Over the Duration of Treatment and Follow-up 28 Day FU, n= 0, 1, 0, 1	NA Microgram per millilitre (mcg/ml) Standard Deviation NA Participants were not analyzed at this time point.	0.25 Microgram per millilitre (mcg/ml) Standard Deviation NA Standard deviation was not derived as only one participant was available at the time of analysis analyzed.	NA Microgram per millilitre (mcg/ml) Standard Deviation NA Participants were not analyzed at this time point.	0.25 Microgram per millilitre (mcg/ml) Standard Deviation NA Standard deviation was not derived as only one participant was available at the time of analysis analyzed.

SECONDARY outcome

Timeframe: Up to 12 days

Population: 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

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.

Outcome measures

Outcome measures
Measure	Odiparcil MR 250 mg Tablet n=205 Participants Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 375 mg Tablet n=217 Participants Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 500 mg Tablet n=222 Participants Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Warfarin INR 2.0 to 3.0 n=203 Participants 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.
Percentage of Participants With Major Bleeds Over 10 ± 2 Days of Treatment	0.0 Percentage of participants Interval 0.0 to 1.8	0.0 Percentage of participants Interval 0.0 to 1.7	0.9 Percentage of participants Interval 0.1 to 3.2	1.0 Percentage of participants Interval 0.1 to 3.5

SECONDARY outcome

Timeframe: Up to 12 days

Population: 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

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.

Outcome measures

Outcome measures
Measure	Odiparcil MR 250 mg Tablet n=164 Participants Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 375 mg Tablet n=169 Participants Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 500 mg Tablet n=160 Participants Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Warfarin INR 2.0 to 3.0 n=157 Participants 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.
Percentage of Participants With VTE and/or Major Bleeding Over 10±2 Days of Treatment VTE and/or major bleed	45.1 Percentage of participants Interval 37.4 to 53.1	44.4 Percentage of participants Interval 36.8 to 52.2	42.5 Percentage of participants Interval 34.7 to 50.6	32.5 Percentage of participants Interval 25.2 to 40.4
Percentage of Participants With VTE and/or Major Bleeding Over 10±2 Days of Treatment VTE with no major bleed	45.1 Percentage of participants Interval 37.4 to 53.1	44.4 Percentage of participants Interval 36.8 to 52.2	41.3 Percentage of participants Interval 33.5 to 49.3	31.2 Percentage of participants Interval 24.1 to 39.1
Percentage of Participants With VTE and/or Major Bleeding Over 10±2 Days of Treatment Major bleed with no VTE	0.0 Percentage of participants Interval 0.0 to 2.2	0.0 Percentage of participants Interval 0.0 to 2.2	1.3 Percentage of participants Interval 0.2 to 4.4	1.3 Percentage of participants Interval 0.2 to 4.5
Percentage of Participants With VTE and/or Major Bleeding Over 10±2 Days of Treatment No VTE and no major bleed	54.9 Percentage of participants Interval 46.9 to 62.6	55.6 Percentage of participants Interval 47.8 to 63.2	58.1 Percentage of participants Interval 50.1 to 65.9	68.2 Percentage of participants Interval 60.3 to 75.4
Percentage of Participants With VTE and/or Major Bleeding Over 10±2 Days of Treatment VTE and major bleed	0.0 Percentage of participants Interval 0.0 to 2.2	0.0 Percentage of participants Interval 0.0 to 2.2	0.0 Percentage of participants Interval 0.0 to 2.3	0.0 Percentage of participants Interval 0.0 to 2.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Odiparcil MR 250 mg Tablet n=170 Participants Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 375 mg Tablet n=179 Participants Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 500 mg Tablet n=171 Participants Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Warfarin INR 2.0 to 3.0 n=168 Participants 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.
Percentage of Participants With Total VTE Any Time After Start of Treatment	46.5 Percenatge of participants Interval 38.8 to 54.3	45.8 Percenatge of participants Interval 38.4 to 53.4	43.3 Percenatge of participants Interval 35.7 to 51.1	30.4 Percenatge of participants Interval 23.5 to 37.9

SECONDARY outcome

Timeframe: Up to 12 days

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

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.

Outcome measures

Outcome measures
Measure	Odiparcil MR 250 mg Tablet n=231 Participants Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 375 mg Tablet n=235 Participants Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Odiparcil MR 500 mg Tablet n=236 Participants Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	Warfarin INR 2.0 to 3.0 n=234 Participants 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.
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 ALT, >=2xULN	4.8 Percentage of participants Interval 2.4 to 8.4	3.8 Percentage of participants Interval 1.8 to 7.1	3.8 Percentage of participants Interval 1.8 to 7.1	5.6 Percentage of participants Interval 3.0 to 9.3
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 ALT, >=3xULN	0.9 Percentage of participants Interval 0.1 to 3.1	2.6 Percentage of participants Interval 0.9 to 5.5	0.4 Percentage of participants Interval 0.0 to 2.3	2.1 Percentage of participants Interval 0.7 to 4.9
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 AST, >=2xULN	2.6 Percentage of participants Interval 1.0 to 5.6	3.4 Percentage of participants Interval 1.5 to 6.6	3.8 Percentage of participants Interval 1.8 to 7.1	4.7 Percentage of participants Interval 2.4 to 8.3
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 AST, >=3xULN	0.0 Percentage of participants Interval 0.0 to 1.6	0.9 Percentage of participants Interval 0.1 to 3.1	0.4 Percentage of participants Interval 0.0 to 2.3	1.7 Percentage of participants Interval 0.5 to 4.3
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 Total Billirubin, >=2xULN	0.0 Percentage of participants Interval 0.0 to 1.6	0.4 Percentage of participants Interval 0.0 to 2.3	0.4 Percentage of participants Interval 0.0 to 2.3	0.0 Percentage of participants Interval 0.0 to 1.6
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 Total Billirubin, >=3xULN	0.0 Percentage of participants Interval 0.0 to 1.6	0.0 Percentage of participants Interval 0.0 to 1.6	0.0 Percentage of participants Interval 0.0 to 1.6	0.0 Percentage of participants Interval 0.0 to 1.6
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 Direct Billirubin, >=2xULN	0.4 Percentage of participants Interval 0.0 to 2.4	0.4 Percentage of participants Interval 0.0 to 2.3	0.4 Percentage of participants Interval 0.0 to 2.3	0.9 Percentage of participants Interval 0.1 to 3.1
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 Direct Billirubin, >=3xULN	0.4 Percentage of participants Interval 0.0 to 2.4	0.4 Percentage of participants Interval 0.0 to 2.3	0.0 Percentage of participants Interval 0.0 to 1.6	0.0 Percentage of participants Interval 0.0 to 1.6

Adverse Events

ODIPARCIL MR 250 mg Tablet

Serious events: 14 serious events

Other events: 124 other events

Deaths: 0 deaths

ODIPARCIL MR 375 MG TABLET

Serious events: 11 serious events

Other events: 120 other events

Deaths: 0 deaths

ODIPARCIL MR 500 MG TABLET

Serious events: 16 serious events

Other events: 122 other events

Deaths: 0 deaths

WARFARIN INR 2.0 TO 3.0

Serious events: 9 serious events

Other events: 104 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	ODIPARCIL MR 250 mg Tablet n=235 participants at risk Eligible participants received Odiparcil MR 250 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	ODIPARCIL MR 375 MG TABLET n=243 participants at risk Eligible participants received Odiparcil MR 375 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	ODIPARCIL MR 500 MG TABLET n=239 participants at risk Eligible participants received Odiparcil MR 500 mg tablet, Q12h for the duration of 10 ± 2 days of double-blind treatment period.	WARFARIN INR 2.0 TO 3.0 n=237 participants at risk 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.
Gastrointestinal disorders Nausea	11.5% 27/235 • Number of events 28 • 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. ITT population was used for analysis.	14.4% 35/243 • Number of events 36 • 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. ITT population was used for analysis.	16.7% 40/239 • Number of events 41 • 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. ITT population was used for analysis.	13.9% 33/237 • Number of events 36 • 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. ITT population was used for analysis.
General disorders Pyrexia	17.0% 40/235 • Number of events 42 • 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. ITT population was used for analysis.	11.5% 28/243 • Number of events 30 • 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. ITT population was used for analysis.	12.1% 29/239 • Number of events 29 • 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. ITT population was used for analysis.	14.3% 34/237 • Number of events 34 • 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. ITT population was used for analysis.
Gastrointestinal disorders Constipation	12.3% 29/235 • Number of events 30 • 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. ITT population was used for analysis.	10.3% 25/243 • Number of events 25 • 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. ITT population was used for analysis.	10.9% 26/239 • Number of events 26 • 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. ITT population was used for analysis.	12.2% 29/237 • Number of events 31 • 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. ITT population was used for analysis.
General disorders Oedema peripheral	11.5% 27/235 • Number of events 30 • 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. ITT population was used for analysis.	9.5% 23/243 • Number of events 27 • 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. ITT population was used for analysis.	11.7% 28/239 • Number of events 36 • 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. ITT population was used for analysis.	10.5% 25/237 • Number of events 35 • 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. ITT population was used for analysis.
Injury, poisoning and procedural complications Anaemia postoperative	8.5% 20/235 • Number of events 20 • 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. ITT population was used for analysis.	8.6% 21/243 • Number of events 21 • 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. ITT population was used for analysis.	10.0% 24/239 • Number of events 24 • 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. ITT population was used for analysis.	8.0% 19/237 • Number of events 19 • 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. ITT population was used for analysis.
Gastrointestinal disorders Vomiting	8.1% 19/235 • Number of events 19 • 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. ITT population was used for analysis.	6.2% 15/243 • Number of events 15 • 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. ITT population was used for analysis.	8.8% 21/239 • Number of events 21 • 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. ITT population was used for analysis.	5.5% 13/237 • Number of events 14 • 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. ITT population was used for analysis.
Investigations Body temperature increased	7.7% 18/235 • Number of events 20 • 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. ITT population was used for analysis.	8.6% 21/243 • Number of events 21 • 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. ITT population was used for analysis.	5.4% 13/239 • Number of events 13 • 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. ITT population was used for analysis.	5.5% 13/237 • Number of events 13 • 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. ITT population was used for analysis.
Psychiatric disorders Insomnia	7.2% 17/235 • Number of events 18 • 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. ITT population was used for analysis.	4.5% 11/243 • Number of events 11 • 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. ITT population was used for analysis.	6.7% 16/239 • Number of events 17 • 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. ITT population was used for analysis.	5.5% 13/237 • Number of events 13 • 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. ITT population was used for analysis.
Cardiac disorders Tachycardia	4.7% 11/235 • Number of events 12 • 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. ITT population was used for analysis.	4.9% 12/243 • Number of events 12 • 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. ITT population was used for analysis.	7.9% 19/239 • Number of events 19 • 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. ITT population was used for analysis.	5.1% 12/237 • Number of events 12 • 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. ITT population was used for analysis.
Skin and subcutaneous tissue disorders Pruritus	4.7% 11/235 • Number of events 11 • 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. ITT population was used for analysis.	5.8% 14/243 • Number of events 14 • 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. ITT population was used for analysis.	4.2% 10/239 • Number of events 10 • 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. ITT population was used for analysis.	3.8% 9/237 • Number of events 9 • 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. ITT population was used for analysis.
Nervous system disorders Dizziness	3.4% 8/235 • Number of events 8 • 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. ITT population was used for analysis.	3.7% 9/243 • Number of events 9 • 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. ITT population was used for analysis.	5.9% 14/239 • Number of events 16 • 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. ITT population was used for analysis.	4.6% 11/237 • Number of events 14 • 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. ITT population was used for analysis.
Musculoskeletal and connective tissue disorders Pain in extremity	3.4% 8/235 • Number of events 9 • 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. ITT population was used for analysis.	4.1% 10/243 • Number of events 10 • 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. ITT population was used for analysis.	5.4% 13/239 • Number of events 14 • 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. ITT population was used for analysis.	3.8% 9/237 • Number of events 11 • 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. ITT population was used for analysis.
Injury, poisoning and procedural complications Contusion	3.0% 7/235 • Number of events 8 • 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. ITT population was used for analysis.	5.3% 13/243 • Number of events 14 • 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. ITT population was used for analysis.	3.3% 8/239 • Number of events 10 • 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. ITT population was used for analysis.	3.8% 9/237 • Number of events 10 • 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. ITT population was used for analysis.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

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