Arthroplasty, Replacement, Knee
Conditions
Brief summary
The purpose of this study is to determine the efficacy of JNJ-70033093 in preventing total venous thromboembolism (VTE) events (proximal and/or distal deep vein thrombosis \[DVT\] \[asymptomatic confirmed by venography assessment or objectively confirmed symptomatic\], nonfatal pulmonary embolism \[PE\], or any death) during the treatment period.
Detailed description
JNJ-70033093 is an oral anticoagulant for prevention and treatment of thromboembolic events (for example, VTE) that binds and inhibits activated form of human coagulation Factor XI (FXIa) with high affinity and selectivity. The study will consist of 3 phases: up to 30-day screening phase before total knee replacement (TKR) surgery, 10 to14 day postoperative dosing phase, and 4-week follow-up phase. The hypothesis of this study is JNJ-70033093 reduces risk of total VTE during treatment period. The total duration of participation following randomization will be approximately 6 weeks. Efficacy evaluations include unilateral venography assessment of operated leg and assessments of symptomatic DVT, PE, or death. Safety evaluation includes adverse events, clinical laboratory tests, and physical examinations. The safety and efficacy will be monitored throughout the study.
Interventions
DRUGJNJ-70033093 25 mg
Participants will receive JNJ-70033093 25 mg (1\*25 mg capsule) BID (in Group A) or once daily (in Group E), orally for 10 to 14 postoperative days.
DRUGJNJ-70033093 50 mg
Participants will receive JNJ-70033093 50 mg (2\*25 mg capsules) BID orally for 10 to 14 postoperative days.
DRUGJNJ-70033093 100 mg
Participants will receive JNJ-70033093 100 mg (1\*100 mg capsule) BID, orally for 10 to 14 postoperative days.
DRUGJNJ-70033093 200 mg
Participants will receive JNJ-70033093 200 mg (2\*100 mg capsules) BID (in Group D) or once daily (in Group F), orally for 10 to 14 postoperative days.
DRUGPlacebo
Participants will receive placebo matching to JNJ-70033093, orally.
DRUGEnoxaparin 40 mg
Participants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days.
Sponsors
Bristol-Myers Squibb
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Masking description
Treatment arms and study drug dose regimens will be blinded.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Medically stable and appropriate for anticoagulant prophylaxis as determined by the investigator on the basis of physical examination, medical history, and vital signs performed as part of screening for elective total knee replacement (TKR) surgery * Medically stable and appropriate for anticoagulant prophylaxis on the basis of clinical laboratory tests performed as part of local standard-of-care as part of screening for elective TKR surgery * Has plans to undergo an elective primary unilateral TKR surgery * A woman must be- a) Not of childbearing potential; b) Of childbearing potential and practicing a highly effective method of contraception (failure rate of less than \[\<\]1 percent \[%\] per year when used consistently and correctly) and agrees to remain on a highly effective method for the duration of study drug with JNJ-70033093 plus 5 half-lives of study drug plus 30 days (duration of ovulatory cycle) for a total of 34 days after the completion of treatment, pregnancy testing (serum or urine) prior to the first dose of study drug * Willing and able to adhere to the lifestyle restrictions specified in this protocol
Exclusion criteria
* History of any condition for which the use of low molecular-weight heparin (LMWH) is not recommended in the opinion of the investigator (for example, previous allergic reaction, creatinine clearance \<30 milliliter per minute \[mL/minute\]) * History of severe hepatic impairment * Planned bilateral revision or unicompartmental procedure * Unable to undergo venography (for example, due to contrast agent allergy, poor venous access, or impaired renal function that would increase the risk of contrast-induced nephropathy * Known previous pulmonary embolism (PE) or deep vein thrombosis (DVT) in either lower extremity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) | Up to Day 14 | Total VTE was defined as the composite of clinical events committee (CEC)-adjudicated proximal and/or distal Deep Vein Thrombosis (DVT) (asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic), nonfatal pulmonary embolism (PE), or any death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Total VTE (CEC-adjudicated) | Up to Day 52 | Total VTE was defined as the composite of (CEC-adjudicated) proximal and/or DVT (asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic), nonfatal PE, or any death. |
| Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated) | Up to Day 14, Up to Day 52 | Composite of Major bleeding event (BE): Fatal bleeding; bleeding that is symptomatic and occurs in critical area/organ and/or; extrasurgical site bleeding causing fall in Hemoglobin (Hb) level of 20 grams per liter (g/L) or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; surgical site bleeding that requires second intervention open, arthroscopic, endovascular,or hemarthrosis resulting in prolonged hospitalization, deep wound infection and/or either unexpected and prolonged and/or sufficiently large to cause hemodynamic instability. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE is still considered clinically relevant for example: Epistaxis, Gastrointestinal bleed,Hematuria,Bruising/ecchymosis,Hemoptysis,Hematoma. |
| Number of Participants With Major Bleeding Events (CEC-adjudicated) | Up to Day 14; Up to Day 52 | Number of participants with major BE (adjudicated by CEC) were reported. Major Bleeding events were defined as: fatal bleeding; bleeding that is symptomatic and occurs in critical area/organ and/or; extrasurgical site bleeding causing fall in Hb level of 20 g/L or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; either unexpected and prolonged and/or sufficiently large to cause hemodynamic instability. |
| Number of Participants With CRNM Bleeding Events (CEC-adjudicated) | Up to Day 14; Up to Day 52 | Number of participants with CRNM bleeding events (adjudicated by CEC) were reported. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE is still considered clinically relevant for example: epistaxis, gastrointestinal bleed, hematuria, bruising/ecchymosis, hemoptysis, hematoma. |
| Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | Up to Day 14; Up to Day 52 | Number of participants with minimal bleeding events (adjudicated by CEC) were reported. Minimal bleeding event was defined as any bleeding event not met major or CRNM criteria. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE is still considered clinically relevant for example: epistaxis, gastrointestinal bleed, hematuria, bruising/ecchymosis, hemoptysis, hematoma. |
| Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated) | Up to Day 14; Up to Day 52 | Major Bleeding events were defined as: fatal bleeding; bleeding that is symptomatic and occurs in critical area/organ and/or; extrasurgical site bleeding causing fall in Hb level of 20 g/L or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; either unexpected and prolonged and/or sufficiently large to cause hemodynamic instability. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE is still considered clinically relevant for example: epistaxis, gastrointestinal bleed, hematuria, bruising/ecchymosis, hemoptysis, hematoma. |
| Number of Participants With Major VTE (CEC-adjudicated) | Up to Day 52 | Number of participants with major VTE (adjudicated by CEC) were reported. Major VTE was defined as a composite of proximal DVT (asymptomatic confirmed by venography or objectively confirmed symptomatic), nonfatal PE, or any death. |
| Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Up to Day 14 | Number of participants with proximal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic. |
| Number of Participants With Proximal DVT (CEC-adjudicated) | Up to Day 52 | Number of participants with proximal DVT (CEC-adjudicated) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic. |
| Number of Participants With Distal DVT (CEC-adjudicated) | Up to Day 14 | Number of participants with distal DVT (CEC-adjudicated) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic. |
| Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | Up to Day 14 | Number of participants with nonfatal PE (adjudicated by CEC) were reported. |
| Number of Participants With Deaths (CEC-adjudicated) | Up to Day 14 | Number of participants with deaths (CEC-adjudicated) were reported. |
| Number of Participants With Any Bleeding Event (CEC-adjudicated) | Up to Day 14; Up to Day 52 | Any bleeding was defined as the composite of major bleeding according to the International Society on Thrombosis and Haemostasis (ISTH) criteria modified for the surgical setting, clinically relevant nonmajor bleeding events, or minimal bleeding events as assessed by the CEC. |
| Apparent Volume of Distribution (V/F) of JNJ-70033093 | Up to Day 14 | V/F was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. |
| Impact of Selected Demographics: Apparent Clearance (CL/F) Based on Sex | Up to Day 14 | Impact of demographic character (sex) on CL/F was assessed. |
| Impact of Selected Demographic: Age on CL/F | Up to Day 14 | Impact of age on CL/F was assessed. |
| Impact of Selected Demographic: Weight on CL/F | Up to Day 14 | Impact of weight on CL/F was assessed. |
| Impact of Selected Laboratory Values: Renal Function on CL/F | Up to Day 14 | Impact of renal function on CL/F was assessed. The outcome measure was reported based on CRCL. |
| Impact of Selected Demographics: Sex on Apparent Volume of Distribution (V/F) | Up to Day 14 | Impact of sex on V/F was assessed. |
| Impact of Selected Demographics : Age on V/F | Up to Day 14 | Impact of age on V/F was assessed. |
| Impact of Selected Demographics : Weight on V/F | Up to Day 14 | Impact of weight on V/F was assessed. |
| Impact of Selected Laboratory Values: Renal Function on V/F | Up to Day 14 | Impact of renal function on V/F was assessed. The outcome measure is reported based on CRCL. |
| Trend Test for Primary Efficacy Event Rate (CEC Adjudicated) by Multiple Comparison Procedure - Modelling (MCP-Mod) Approach | Up to 14 days | The dose-response trend test based on the MCP-Mod framework consisted of contrast tests defined by prespecified candidate models (4 Emax dose-response models with varying degrees of ED50). Each model was evaluated for significance of trend, based on its optimal contrast, resulting in four t-test statistics, one for each candidate model. The t-test statistics were adjusted for the fact that 4 candidate models were included in the trend testing. The dose response of the drug was then established if the maximum of the t-test statistics exceeded the 95th percentile critical value. Here 'number' signifies the estimated response rate. |
| Trend Test for the Composite of On-Treatment Major and Clinically Relevant Nonmajor Bleeding (CEC Adjudicated) by MCP-Mod Approach | Up to 14 days | The dose-response trend test based on the MCP-Mod framework consisted of contrast tests defined by prespecified candidate models (4 Emax dose-response models with varying degrees of ED50). Each model was evaluated for significance of trend, based on its optimal contrast, resulting in four t-test statistics, one for each candidate model. The t-test statistics were adjusted for the fact that 4 candidate models were included in the trend testing. The dose response of the drug was then established if the maximum of the t-test statistics exceeded the 95th percentile critical value. Here 'number' signifies the estimated response rate. |
| Apparent Clearance (CL/F) of JNJ-70033093 | Up to Day 14 | Apparent clearance of a drug was defined as a measure of the rate at which a drug got metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. |
Countries
Argentina, Belgium, Brazil, Bulgaria, Canada, Greece, Hungary, Israel, Italy, Japan, Poland, Portugal, Russia, South Africa, Spain, Turkey (Türkiye), Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo Participants received JNJ-70033093 25 milligrams (mg) (1\*25 mg capsule) once daily and 1 placebo capsule in the morning and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days. | 34 |
| JNJ-70033093 50 mg Once Daily + Placebo Participants received JNJ-70033093 50 mg (2\*25 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days. | 150 |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) Participants received JNJ-70033093 25 mg (1\*25 mg capsule) and 1 placebo capsule twice daily (BID), orally for 10 to 14 postoperative days. | 153 |
| JNJ-70033093 50 mg BID Participants received JNJ-70033093 50 mg (2\*25 mg capsules) BID orally for 10 to 14 postoperative days. | 150 |
| JNJ-70033093 200 mg Once Daily + Placebo Participants received JNJ-70033093 200 mg (2\*100 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days. | 149 |
| JNJ-70033093 100 mg + Placebo BID Participants received JNJ-70033093 100 mg (1\*100 mg capsule) and 1 placebo capsule BID orally for 10 to 14 postoperative days. | 152 |
| JNJ-70033093 200 mg BID Participants received JNJ-70033093 200 mg (2\*100 mg capsules) BID orally for 10 to 14 postoperative days. | 153 |
| Enoxaparin 40 mg Once Daily Participants received enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days. | 301 |
| Total | 1,242 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 2 | 1 | 2 | 2 | 2 | 1 |
Baseline characteristics
| Characteristic | JNJ-70033093 25 mg Once Daily + Placebo | JNJ-70033093 50 mg Once Daily + Placebo | JNJ-70033093 25 mg + Placebo Twice Daily (BID) | JNJ-70033093 50 mg BID | JNJ-70033093 200 mg Once Daily + Placebo | JNJ-70033093 100 mg + Placebo BID | JNJ-70033093 200 mg BID | Enoxaparin 40 mg Once Daily | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 68.1 years STANDARD_DEVIATION 5.74 | 67.9 years STANDARD_DEVIATION 8.03 | 68.4 years STANDARD_DEVIATION 8.49 | 68.8 years STANDARD_DEVIATION 8.17 | 68 years STANDARD_DEVIATION 8.25 | 67 years STANDARD_DEVIATION 8 | 68.6 years STANDARD_DEVIATION 7.76 | 67.8 years STANDARD_DEVIATION 7.97 | 68 years STANDARD_DEVIATION 8.02 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 21 Participants | 19 Participants | 20 Participants | 20 Participants | 14 Participants | 14 Participants | 42 Participants | 156 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 121 Participants | 126 Participants | 125 Participants | 125 Participants | 129 Participants | 133 Participants | 250 Participants | 1037 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 8 Participants | 8 Participants | 5 Participants | 4 Participants | 9 Participants | 6 Participants | 9 Participants | 49 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 22 Participants | 17 Participants | 16 Participants | 17 Participants | 16 Participants | 16 Participants | 32 Participants | 136 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 4 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) White | 34 Participants | 124 Participants | 134 Participants | 132 Participants | 129 Participants | 132 Participants | 136 Participants | 260 Participants | 1081 Participants |
| Region of Enrollment Asia | 0 Participants | 22 Participants | 16 Participants | 16 Participants | 16 Participants | 16 Participants | 16 Participants | 32 Participants | 134 Participants |
| Region of Enrollment Europe | 21 Participants | 55 Participants | 65 Participants | 65 Participants | 64 Participants | 64 Participants | 65 Participants | 129 Participants | 528 Participants |
| Region of Enrollment North America | 5 Participants | 19 Participants | 20 Participants | 19 Participants | 19 Participants | 19 Participants | 21 Participants | 38 Participants | 160 Participants |
| Region of Enrollment South America | 0 Participants | 9 Participants | 7 Participants | 6 Participants | 7 Participants | 7 Participants | 6 Participants | 13 Participants | 55 Participants |
| Region of Enrollment Western Europe | 8 Participants | 45 Participants | 45 Participants | 44 Participants | 43 Participants | 46 Participants | 45 Participants | 89 Participants | 365 Participants |
| Sex: Female, Male Female | 24 Participants | 107 Participants | 113 Participants | 108 Participants | 108 Participants | 102 Participants | 106 Participants | 208 Participants | 876 Participants |
| Sex: Female, Male Male | 10 Participants | 43 Participants | 40 Participants | 42 Participants | 41 Participants | 50 Participants | 47 Participants | 93 Participants | 366 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 150 | 0 / 148 | 0 / 148 | 0 / 147 | 0 / 149 | 0 / 148 | 1 / 296 |
| other Total, other adverse events | 0 / 33 | 6 / 150 | 9 / 148 | 8 / 148 | 3 / 147 | 4 / 149 | 3 / 148 | 17 / 296 |
| serious Total, serious adverse events | 1 / 33 | 2 / 150 | 5 / 148 | 5 / 148 | 2 / 147 | 5 / 149 | 2 / 148 | 11 / 296 |
Outcome results
Primary
Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated)
Total VTE was defined as the composite of clinical events committee (CEC)-adjudicated proximal and/or distal Deep Vein Thrombosis (DVT) (asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic), nonfatal pulmonary embolism (PE), or any death.
Time frame: Up to Day 14
Population: The modified Intent-to-treat (mITT) analysis set included all intent-to-treat (ITT) participants who received at least 1 dose of study drug with an evaluable venography assessment or a confirmed symptomatic proximal DVT, PE or death as adjudicated by the CEC.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) | 7 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) | 30 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) | 27 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) | 14 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) | 8 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) | 12 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) | 10 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) | 54 Participants |
Secondary
Apparent Clearance (CL/F) of JNJ-70033093
Apparent clearance of a drug was defined as a measure of the rate at which a drug got metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Time frame: Up to Day 14
Population: The pharmacokinetic (PK) analysis set consisted of participants who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure. This outcome measure was planned to be analyzed for overall participants and not group wise.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Apparent Clearance (CL/F) of JNJ-70033093 | 7.72 Liter per hour (L/h) | Geometric Coefficient of Variation 39.5 |
Secondary
Apparent Volume of Distribution (V/F) of JNJ-70033093
V/F was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug.
Time frame: Up to Day 14
Population: The PK analysis set consisted of participants who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure. This outcome measure was planned to be analyzed for overall participants and not group wise.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Apparent Volume of Distribution (V/F) of JNJ-70033093 | 125 Liter | Geometric Coefficient of Variation 60.5 |
Secondary
Impact of Selected Demographic: Age on CL/F
Impact of age on CL/F was assessed.
Time frame: Up to Day 14
Population: The PK analysis set consisted of participants who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure. Arms are created based on age to report the effect of age on CL/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Impact of Selected Demographic: Age on CL/F | 8.70 L/h | Geometric Coefficient of Variation 36.9 |
| JNJ-70033093 50 mg Once Daily + Placebo | Impact of Selected Demographic: Age on CL/F | 6.83 L/h | Geometric Coefficient of Variation 37.7 |
Secondary
Impact of Selected Demographics : Age on V/F
Impact of age on V/F was assessed.
Time frame: Up to Day 14
Population: The PK analysis set consisted of participants who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure. Arms are created based on age to report the effect of age on V/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Impact of Selected Demographics : Age on V/F | 135 Liters | Geometric Coefficient of Variation 59.5 |
| JNJ-70033093 50 mg Once Daily + Placebo | Impact of Selected Demographics : Age on V/F | 116 Liters | Geometric Coefficient of Variation 60.3 |
Secondary
Impact of Selected Demographics: Apparent Clearance (CL/F) Based on Sex
Impact of demographic character (sex) on CL/F was assessed.
Time frame: Up to Day 14
Population: The PK analysis set consisted of participants who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure. Arms are created based on sex (male and female) to report the effect of sex on CL/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Impact of Selected Demographics: Apparent Clearance (CL/F) Based on Sex | 7.14 Liter per hour (L/h) | Geometric Coefficient of Variation 38.5 |
| JNJ-70033093 50 mg Once Daily + Placebo | Impact of Selected Demographics: Apparent Clearance (CL/F) Based on Sex | 9.32 Liter per hour (L/h) | Geometric Coefficient of Variation 34.2 |
Secondary
Impact of Selected Demographics: Sex on Apparent Volume of Distribution (V/F)
Impact of sex on V/F was assessed.
Time frame: Up to Day 14
Population: The PK analysis set consisted of participants who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure. Arms are created based on sex (male and female) to report the effect of sex on V/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Impact of Selected Demographics: Sex on Apparent Volume of Distribution (V/F) | 118 Liters | Geometric Coefficient of Variation 61.2 |
| JNJ-70033093 50 mg Once Daily + Placebo | Impact of Selected Demographics: Sex on Apparent Volume of Distribution (V/F) | 143 Liters | Geometric Coefficient of Variation 56 |
Secondary
Impact of Selected Demographics : Weight on V/F
Impact of weight on V/F was assessed.
Time frame: Up to Day 14
Population: The PK analysis set consisted of participants who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure. Arms are created based on weight to report the effect of weight on V/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Impact of Selected Demographics : Weight on V/F | 109 Liters | Geometric Coefficient of Variation 58.8 |
| JNJ-70033093 50 mg Once Daily + Placebo | Impact of Selected Demographics : Weight on V/F | 145 Liters | Geometric Coefficient of Variation 57.5 |
Secondary
Impact of Selected Demographic: Weight on CL/F
Impact of weight on CL/F was assessed.
Time frame: Up to Day 14
Population: The PK analysis set consisted of participants who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure. Arms are created based on weight to report the effect of weight on CL/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Impact of Selected Demographic: Weight on CL/F | 7.04 L/h | Geometric Coefficient of Variation 37.9 |
| JNJ-70033093 50 mg Once Daily + Placebo | Impact of Selected Demographic: Weight on CL/F | 8.54 L/h | Geometric Coefficient of Variation 38.4 |
Secondary
Impact of Selected Laboratory Values: Renal Function on CL/F
Impact of renal function on CL/F was assessed. The outcome measure was reported based on CRCL.
Time frame: Up to Day 14
Population: The PK analysis set consisted of participants who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure. Arms are created based on CRCL to report the effect of renal function on CL/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Impact of Selected Laboratory Values: Renal Function on CL/F | 6.71 L/h | Geometric Coefficient of Variation 38.1 |
| JNJ-70033093 50 mg Once Daily + Placebo | Impact of Selected Laboratory Values: Renal Function on CL/F | 8.83 L/h | Geometric Coefficient of Variation 35.1 |
Secondary
Impact of Selected Laboratory Values: Renal Function on V/F
Impact of renal function on V/F was assessed. The outcome measure is reported based on CRCL.
Time frame: Up to Day 14
Population: The PK analysis set consisted of participants who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure. Arms are created based on CRCL to report the effect of renal function on V/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Impact of Selected Laboratory Values: Renal Function on V/F | 116 Liters | Geometric Coefficient of Variation 62.2 |
| JNJ-70033093 50 mg Once Daily + Placebo | Impact of Selected Laboratory Values: Renal Function on V/F | 135 Liters | Geometric Coefficient of Variation 58.5 |
Secondary
Number of Participants With Any Bleeding Event (CEC-adjudicated)
Any bleeding was defined as the composite of major bleeding according to the International Society on Thrombosis and Haemostasis (ISTH) criteria modified for the surgical setting, clinically relevant nonmajor bleeding events, or minimal bleeding events as assessed by the CEC.
Time frame: Up to Day 14; Up to Day 52
Population: The safety analysis set was a subset of the ITT analysis set, consisting of all ITT participants who received at least 1 dose (partial or complete) of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Any Bleeding Event (CEC-adjudicated) | Up to Day 14 | 0 Participants |
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Any Bleeding Event (CEC-adjudicated) | Up to Day 52 | 0 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Any Bleeding Event (CEC-adjudicated) | Up to Day 14 | 8 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Any Bleeding Event (CEC-adjudicated) | Up to Day 52 | 8 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Any Bleeding Event (CEC-adjudicated) | Up to Day 14 | 2 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Any Bleeding Event (CEC-adjudicated) | Up to Day 52 | 2 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Any Bleeding Event (CEC-adjudicated) | Up to Day 14 | 7 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Any Bleeding Event (CEC-adjudicated) | Up to Day 52 | 7 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Any Bleeding Event (CEC-adjudicated) | Up to Day 14 | 11 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Any Bleeding Event (CEC-adjudicated) | Up to Day 52 | 11 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Any Bleeding Event (CEC-adjudicated) | Up to Day 14 | 7 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Any Bleeding Event (CEC-adjudicated) | Up to Day 52 | 7 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Any Bleeding Event (CEC-adjudicated) | Up to Day 52 | 6 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Any Bleeding Event (CEC-adjudicated) | Up to Day 14 | 6 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Any Bleeding Event (CEC-adjudicated) | Up to Day 14 | 12 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Any Bleeding Event (CEC-adjudicated) | Up to Day 52 | 12 Participants |
Secondary
Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated)
Composite of Major bleeding event (BE): Fatal bleeding; bleeding that is symptomatic and occurs in critical area/organ and/or; extrasurgical site bleeding causing fall in Hemoglobin (Hb) level of 20 grams per liter (g/L) or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; surgical site bleeding that requires second intervention open, arthroscopic, endovascular,or hemarthrosis resulting in prolonged hospitalization, deep wound infection and/or either unexpected and prolonged and/or sufficiently large to cause hemodynamic instability. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE is still considered clinically relevant for example: Epistaxis, Gastrointestinal bleed,Hematuria,Bruising/ecchymosis,Hemoptysis,Hematoma.
Time frame: Up to Day 14, Up to Day 52
Population: The safety analysis set was a subset of the ITT analysis set, consisting of all ITT participants who received at least 1 dose (partial or complete) of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated) | Up to Day 14 | 0 Participants |
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated) | Up to Day 52 | 0 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated) | Up to Day 14 | 2 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated) | Up to Day 52 | 2 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated) | Up to Day 14 | 0 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated) | Up to Day 52 | 0 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated) | Up to Day 14 | 2 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated) | Up to Day 52 | 2 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated) | Up to Day 14 | 1 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated) | Up to Day 52 | 2 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated) | Up to Day 14 | 1 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated) | Up to Day 52 | 1 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated) | Up to Day 52 | 1 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated) | Up to Day 14 | 1 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated) | Up to Day 14 | 5 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated) | Up to Day 52 | 5 Participants |
Secondary
Number of Participants With CRNM Bleeding Events (CEC-adjudicated)
Number of participants with CRNM bleeding events (adjudicated by CEC) were reported. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE is still considered clinically relevant for example: epistaxis, gastrointestinal bleed, hematuria, bruising/ecchymosis, hemoptysis, hematoma.
Time frame: Up to Day 14; Up to Day 52
Population: The safety analysis set was a subset of the ITT analysis set, consisting of all ITT participants who received at least 1 dose (partial or complete) of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With CRNM Bleeding Events (CEC-adjudicated) | Up to Day 14 | 0 Participants |
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With CRNM Bleeding Events (CEC-adjudicated) | Up to Day 52 | 0 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With CRNM Bleeding Events (CEC-adjudicated) | Up to Day 14 | 2 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With CRNM Bleeding Events (CEC-adjudicated) | Up to Day 52 | 2 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With CRNM Bleeding Events (CEC-adjudicated) | Up to Day 14 | 0 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With CRNM Bleeding Events (CEC-adjudicated) | Up to Day 52 | 0 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With CRNM Bleeding Events (CEC-adjudicated) | Up to Day 14 | 2 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With CRNM Bleeding Events (CEC-adjudicated) | Up to Day 52 | 2 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With CRNM Bleeding Events (CEC-adjudicated) | Up to Day 14 | 1 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With CRNM Bleeding Events (CEC-adjudicated) | Up to Day 52 | 2 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With CRNM Bleeding Events (CEC-adjudicated) | Up to Day 14 | 1 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With CRNM Bleeding Events (CEC-adjudicated) | Up to Day 52 | 1 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With CRNM Bleeding Events (CEC-adjudicated) | Up to Day 52 | 1 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With CRNM Bleeding Events (CEC-adjudicated) | Up to Day 14 | 1 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With CRNM Bleeding Events (CEC-adjudicated) | Up to Day 14 | 4 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With CRNM Bleeding Events (CEC-adjudicated) | Up to Day 52 | 4 Participants |
Secondary
Number of Participants With Deaths (CEC-adjudicated)
Number of participants with deaths (CEC-adjudicated) were reported.
Time frame: Up to Day 14
Population: The mITT analysis set at Day 14 included all ITT participants who received at least 1 dose of study drug with an evaluable venography assessment or a confirmed symptomatic VTE event (DVT, non-fatal PE or any death).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Deaths (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Deaths (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Deaths (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Deaths (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Deaths (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Deaths (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Deaths (CEC-adjudicated) | 0 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Deaths (CEC-adjudicated) | 1 Participants |
Secondary
Number of Participants With Deaths (CEC-adjudicated)
Number of participants with deaths (CEC-adjudicated) were reported.
Time frame: Up to Day 52
Population: The mITT analysis set included all the participants in mITT at Day 14 plus the participants who had symptomatic/asymptomatic VTE events (DVT, non-fatal PE or any death) after day 17 through day 52.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Deaths (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Deaths (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Deaths (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Deaths (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Deaths (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Deaths (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Deaths (CEC-adjudicated) | 0 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Deaths (CEC-adjudicated) | 1 Participants |
Secondary
Number of Participants With Distal DVT (CEC-adjudicated)
Number of participants with distal DVT (CEC-adjudicated) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic.
Time frame: Up to Day 14
Population: The mITT analysis set at Day 14 included all ITT participants who received at least 1 dose of study drug with an evaluable venography assessment or a confirmed symptomatic VTE event (DVT, non-fatal PE or any death).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 7 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 2 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 27 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 26 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 13 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 8 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 10 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 1 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 10 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 50 Participants |
Secondary
Number of Participants With Distal DVT (CEC-adjudicated)
Number of participants with distal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic.
Time frame: Up to Day 52
Population: The mITT analysis set included all the participants in mITT at Day 14 plus the participants who had symptomatic/asymptomatic VTE events (DVT, non-fatal PE or any death) after day 17 through day 52.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 7 Participants |
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 27 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 2 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 26 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 2 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 13 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 8 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 10 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 1 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 10 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 50 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
Secondary
Number of Participants With Major Bleeding Events (CEC-adjudicated)
Number of participants with major BE (adjudicated by CEC) were reported. Major Bleeding events were defined as: fatal bleeding; bleeding that is symptomatic and occurs in critical area/organ and/or; extrasurgical site bleeding causing fall in Hb level of 20 g/L or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; either unexpected and prolonged and/or sufficiently large to cause hemodynamic instability.
Time frame: Up to Day 14; Up to Day 52
Population: The safety analysis set was a subset of the ITT analysis set, consisting of all ITT participants who received at least 1 dose (partial or complete) of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Major Bleeding Events (CEC-adjudicated) | Up to Day 14 | 0 Participants |
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Major Bleeding Events (CEC-adjudicated) | Up to Day 52 | 0 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Major Bleeding Events (CEC-adjudicated) | Up to Day 14 | 0 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Major Bleeding Events (CEC-adjudicated) | Up to Day 52 | 0 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Major Bleeding Events (CEC-adjudicated) | Up to Day 14 | 0 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Major Bleeding Events (CEC-adjudicated) | Up to Day 52 | 0 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Major Bleeding Events (CEC-adjudicated) | Up to Day 14 | 0 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Major Bleeding Events (CEC-adjudicated) | Up to Day 52 | 0 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Major Bleeding Events (CEC-adjudicated) | Up to Day 14 | 0 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Major Bleeding Events (CEC-adjudicated) | Up to Day 52 | 0 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Major Bleeding Events (CEC-adjudicated) | Up to Day 14 | 0 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Major Bleeding Events (CEC-adjudicated) | Up to Day 52 | 0 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Major Bleeding Events (CEC-adjudicated) | Up to Day 52 | 0 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Major Bleeding Events (CEC-adjudicated) | Up to Day 14 | 0 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Major Bleeding Events (CEC-adjudicated) | Up to Day 14 | 1 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Major Bleeding Events (CEC-adjudicated) | Up to Day 52 | 1 Participants |
Secondary
Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated)
Major Bleeding events were defined as: fatal bleeding; bleeding that is symptomatic and occurs in critical area/organ and/or; extrasurgical site bleeding causing fall in Hb level of 20 g/L or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; either unexpected and prolonged and/or sufficiently large to cause hemodynamic instability. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE is still considered clinically relevant for example: epistaxis, gastrointestinal bleed, hematuria, bruising/ecchymosis, hemoptysis, hematoma.
Time frame: Up to Day 14; Up to Day 52
Population: The safety analysis set was a subset of the ITT analysis set, consisting of all ITT participants who received at least 1 dose (partial or complete) of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated) | Up to Day 52 | 0 Participants |
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated) | Up to Day 14 | 0 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated) | Up to Day 52 | 2 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated) | Up to Day 14 | 2 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated) | Up to Day 14 | 0 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated) | Up to Day 52 | 0 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated) | Up to Day 14 | 2 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated) | Up to Day 52 | 2 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated) | Up to Day 14 | 1 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated) | Up to Day 52 | 2 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated) | Up to Day 52 | 1 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated) | Up to Day 14 | 1 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated) | Up to Day 14 | 1 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated) | Up to Day 52 | 1 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated) | Up to Day 52 | 5 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated) | Up to Day 14 | 5 Participants |
Secondary
Number of Participants With Major VTE (CEC-adjudicated)
Number of participants with major VTE (adjudicated by CEC) were reported. Major VTE was defined as a composite of proximal DVT (asymptomatic confirmed by venography or objectively confirmed symptomatic), nonfatal PE, or any death.
Time frame: Up to Day 52
Population: The mITT analysis set included all the participants in mITT at Day 14 plus the participants who had symptomatic/asymptomatic VTE events (DVT, non-fatal PE or any death) after day 17 through day 52.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Major VTE (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Major VTE (CEC-adjudicated) | 2 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Major VTE (CEC-adjudicated) | 1 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Major VTE (CEC-adjudicated) | 1 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Major VTE (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Major VTE (CEC-adjudicated) | 2 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Major VTE (CEC-adjudicated) | 0 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Major VTE (CEC-adjudicated) | 4 Participants |
Secondary
Number of Participants With Major VTE (CEC-adjudicated)
Number of participants with major VTE (adjudicated by CEC) were reported. Major VTE was defined as a composite of proximal DVT (asymptomatic confirmed by venography or objectively confirmed symptomatic), nonfatal PE, or any death.
Time frame: Up to Day 14
Population: The mITT analysis set at Day 14 included all ITT participants who received at least 1 dose of study drug with an evaluable venography assessment or a confirmed symptomatic VTE event (DVT, non-fatal PE or any death).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Major VTE (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Major VTE (CEC-adjudicated) | 2 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Major VTE (CEC-adjudicated) | 1 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Major VTE (CEC-adjudicated) | 1 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Major VTE (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Major VTE (CEC-adjudicated) | 2 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Major VTE (CEC-adjudicated) | 0 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Major VTE (CEC-adjudicated) | 4 Participants |
Secondary
Number of Participants With Minimal Bleeding Events (CEC-adjudicated)
Number of participants with minimal bleeding events (adjudicated by CEC) were reported. Minimal bleeding event was defined as any bleeding event not met major or CRNM criteria. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE is still considered clinically relevant for example: epistaxis, gastrointestinal bleed, hematuria, bruising/ecchymosis, hemoptysis, hematoma.
Time frame: Up to Day 14; Up to Day 52
Population: The safety analysis set was a subset of the ITT analysis set, consisting of all ITT participants who received at least 1 dose (partial or complete) of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | Up to Day 14 | 0 Participants |
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | Up to Day 52 | 0 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | Up to Day 14 | 6 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | Up to Day 52 | 6 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | Up to Day 14 | 2 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | Up to Day 52 | 2 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | Up to Day 14 | 5 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | Up to Day 52 | 5 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | Up to Day 14 | 8 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | Up to Day 52 | 9 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | Up to Day 14 | 7 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | Up to Day 52 | 7 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | Up to Day 52 | 5 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | Up to Day 14 | 4 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | Up to Day 14 | 8 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | Up to Day 52 | 8 Participants |
Secondary
Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated)
Number of participants with nonfatal PE (adjudicated by CEC) were reported.
Time frame: Up to Day 52
Population: The mITT analysis set included all the participants in mITT at Day 14 plus the participants who had symptomatic/asymptomatic VTE events (DVT, non-fatal PE or any death) after day 17 through day 52.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 1 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 1 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 0 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 1 Participants |
Secondary
Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated)
Number of participants with nonfatal PE (adjudicated by CEC) were reported.
Time frame: Up to Day 14
Population: The mITT analysis set at Day 14 included all ITT participants who received at least 1 dose of study drug with an evaluable venography assessment or a confirmed symptomatic VTE event (DVT, non-fatal PE or any death).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 1 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 0 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 1 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 0 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 1 Participants |
Secondary
Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated)
Number of participants with proximal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic.
Time frame: Up to Day 14
Population: The mITT analysis set at Day 14 includes all ITT participants who received at least 1 dose of study drug with an evaluable venography assessment or a confirmed symptomatic VTE event (DVT, non-fatal PE or any death). Also includes the subjects whose venography result is not evaluable distal but no proximal clot.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Asymptomatic | 0 Participants |
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Asymptomatic | 0 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Asymptomatic | 0 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Asymptomatic | 0 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Asymptomatic | 0 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Asymptomatic | 0 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Asymptomatic | 0 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Asymptomatic | 1 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Symptomatic | 0 Participants |
Secondary
Number of Participants With Proximal DVT (CEC-adjudicated)
Number of participants with proximal DVT (CEC-adjudicated) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic.
Time frame: Up to Day 52
Population: The mITT analysis set included all the participants in mITT at Day 14 plus the participants who had symptomatic/asymptomatic VTE events (DVT, non-fatal PE or any death) after day 17 through day 52 and also included the participants whose venography result was not evaluable distal but no proximal clot.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Proximal DVT (CEC-adjudicated) | Asymptomatic | 0 Participants |
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Proximal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Proximal DVT (CEC-adjudicated) | Asymptomatic | 0 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Proximal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Proximal DVT (CEC-adjudicated) | Asymptomatic | 0 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Proximal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Proximal DVT (CEC-adjudicated) | Asymptomatic | 0 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Proximal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Proximal DVT (CEC-adjudicated) | Asymptomatic | 0 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Proximal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Proximal DVT (CEC-adjudicated) | Asymptomatic | 0 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Proximal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Proximal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Proximal DVT (CEC-adjudicated) | Asymptomatic | 0 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Proximal DVT (CEC-adjudicated) | Asymptomatic | 1 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Proximal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
Secondary
Number of Participants With Total VTE (CEC-adjudicated)
Total VTE was defined as the composite of (CEC-adjudicated) proximal and/or DVT (asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic), nonfatal PE, or any death.
Time frame: Up to Day 52
Population: The mITT analysis set included all the participants in mITT at Day 14 plus the participants who had symptomatic/asymptomatic VTE events (DVT, non-fatal PE or any death) after day 17 through day 52. Also included the participants whose venography result was not evaluable distal but no proximal clot.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Number of Participants With Total VTE (CEC-adjudicated) | 7 Participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Number of Participants With Total VTE (CEC-adjudicated) | 30 Participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Number of Participants With Total VTE (CEC-adjudicated) | 27 Participants |
| JNJ-70033093 50 mg BID | Number of Participants With Total VTE (CEC-adjudicated) | 14 Participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Number of Participants With Total VTE (CEC-adjudicated) | 8 Participants |
| JNJ-70033093 100 mg + Placebo BID | Number of Participants With Total VTE (CEC-adjudicated) | 12 Participants |
| JNJ-70033093 200 mg BID | Number of Participants With Total VTE (CEC-adjudicated) | 10 Participants |
| Enoxaparin 40 mg Once Daily | Number of Participants With Total VTE (CEC-adjudicated) | 54 Participants |
Secondary
Trend Test for Primary Efficacy Event Rate (CEC Adjudicated) by Multiple Comparison Procedure - Modelling (MCP-Mod) Approach
The dose-response trend test based on the MCP-Mod framework consisted of contrast tests defined by prespecified candidate models (4 Emax dose-response models with varying degrees of ED50). Each model was evaluated for significance of trend, based on its optimal contrast, resulting in four t-test statistics, one for each candidate model. The t-test statistics were adjusted for the fact that 4 candidate models were included in the trend testing. The dose response of the drug was then established if the maximum of the t-test statistics exceeded the 95th percentile critical value. Here 'number' signifies the estimated response rate.
Time frame: Up to 14 days
Population: The mITT analysis set at Day 14 included all ITT participants who received at least 1 dose of study drug with an evaluable venography assessment or a confirmed symptomatic VTE event (DVT, non-fatal PE or any death).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Trend Test for Primary Efficacy Event Rate (CEC Adjudicated) by Multiple Comparison Procedure - Modelling (MCP-Mod) Approach | 0.35 proportion of participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Trend Test for Primary Efficacy Event Rate (CEC Adjudicated) by Multiple Comparison Procedure - Modelling (MCP-Mod) Approach | 0.21 proportion of participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Trend Test for Primary Efficacy Event Rate (CEC Adjudicated) by Multiple Comparison Procedure - Modelling (MCP-Mod) Approach | 0.20 proportion of participants |
| JNJ-70033093 50 mg BID | Trend Test for Primary Efficacy Event Rate (CEC Adjudicated) by Multiple Comparison Procedure - Modelling (MCP-Mod) Approach | 0.13 proportion of participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Trend Test for Primary Efficacy Event Rate (CEC Adjudicated) by Multiple Comparison Procedure - Modelling (MCP-Mod) Approach | 0.09 proportion of participants |
| JNJ-70033093 100 mg + Placebo BID | Trend Test for Primary Efficacy Event Rate (CEC Adjudicated) by Multiple Comparison Procedure - Modelling (MCP-Mod) Approach | 0.09 proportion of participants |
| JNJ-70033093 200 mg BID | Trend Test for Primary Efficacy Event Rate (CEC Adjudicated) by Multiple Comparison Procedure - Modelling (MCP-Mod) Approach | 0.07 proportion of participants |
p-value: 0.0004MCP-mod analysis
Secondary
Trend Test for the Composite of On-Treatment Major and Clinically Relevant Nonmajor Bleeding (CEC Adjudicated) by MCP-Mod Approach
The dose-response trend test based on the MCP-Mod framework consisted of contrast tests defined by prespecified candidate models (4 Emax dose-response models with varying degrees of ED50). Each model was evaluated for significance of trend, based on its optimal contrast, resulting in four t-test statistics, one for each candidate model. The t-test statistics were adjusted for the fact that 4 candidate models were included in the trend testing. The dose response of the drug was then established if the maximum of the t-test statistics exceeded the 95th percentile critical value. Here 'number' signifies the estimated response rate.
Time frame: Up to 14 days
Population: The safety analysis set was a subset of the ITT analysis set, consisting of all ITT participants who received at least 1 dose (partial or complete) of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| JNJ-70033093 25 mg Once Daily + Placebo | Trend Test for the Composite of On-Treatment Major and Clinically Relevant Nonmajor Bleeding (CEC Adjudicated) by MCP-Mod Approach | 0.02 proportion of participants |
| JNJ-70033093 50 mg Once Daily + Placebo | Trend Test for the Composite of On-Treatment Major and Clinically Relevant Nonmajor Bleeding (CEC Adjudicated) by MCP-Mod Approach | 0.01 proportion of participants |
| JNJ-70033093 25 mg + Placebo Twice Daily (BID) | Trend Test for the Composite of On-Treatment Major and Clinically Relevant Nonmajor Bleeding (CEC Adjudicated) by MCP-Mod Approach | 0.01 proportion of participants |
| JNJ-70033093 50 mg BID | Trend Test for the Composite of On-Treatment Major and Clinically Relevant Nonmajor Bleeding (CEC Adjudicated) by MCP-Mod Approach | 0.01 proportion of participants |
| JNJ-70033093 200 mg Once Daily + Placebo | Trend Test for the Composite of On-Treatment Major and Clinically Relevant Nonmajor Bleeding (CEC Adjudicated) by MCP-Mod Approach | 0.01 proportion of participants |
| JNJ-70033093 100 mg + Placebo BID | Trend Test for the Composite of On-Treatment Major and Clinically Relevant Nonmajor Bleeding (CEC Adjudicated) by MCP-Mod Approach | 0.01 proportion of participants |
| JNJ-70033093 200 mg BID | Trend Test for the Composite of On-Treatment Major and Clinically Relevant Nonmajor Bleeding (CEC Adjudicated) by MCP-Mod Approach | 0.01 proportion of participants |
p-value: 0.7188MCP-MOD analysis