VTE Prophylaxis With Anticoagulation After Total Knee Replacement Surgery
Conditions
Brief summary
The primary purpose of Part 1 in this study is to assess the safety and tolerability of JNJ-64179375 for each dose level for dose escalation and any bleeding events (the composite of major, clinically relevant non-major, and minimal bleeding events) for the selection of doses for Part 2. The primary purpose of Part 2 is to assess the efficacy dose response of JNJ-64179375 for the prevention of total venous thromboembolism (VTE) (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).
Detailed description
This study has 2 parts, dose escalation and dose-response evaluation, and will be conducted in participants undergoing primary unilateral elective Total Knee Replacement (TKR) surgery. Participants will participate in either Part 1 or Part 2 of study only. The study will be conducted in 3 phases: an up to 30-day screening phase before surgery, a 14-day double-blind dosing phase, and a 16-week follow-up phase. Safety evaluations will include monitoring of all nonserious and serious adverse events, clinical laboratory tests, vital signs measurements, and physical examinations. Pharmacokinetics (dense and sparse), pharmacodynamic (PD), health resource utilization, and immunogenicity samples will also be assessed. The total study duration of participant's participation in Part 1 or part 2 after randomization will be approximately 18 weeks.
Interventions
JNJ-64179375 0.3 milligram per kilogram (mg/kg) intravenous (IV) infusion as a single dose on Day 1.
DRUGJNJ-64179375 0.6 mg/kg
JNJ-64179375 0.6 mg/kg IV infusion as a single dose on Day 1.
DRUGJNJ-64179375 1.2 mg/kg
JNJ-64179375 1.2 mg/kg IV infusion as a single dose on Day 1.
JNJ-64179375 IV infusion (Dose to be determined) as a single dose on Day 1.
DRUGJNJ-64179375 A mg/kg
JNJ-64179375 Dose A mg/kg IV as a single dose on Day 1.
DRUGJNJ-64179375 B mg/kg
JNJ-64179375 Dose B mg/kg IV as a single dose on Day 1.
DRUGJNJ-64179375 C mg/kg
JNJ-64179375 Dose C mg/kg IV as a single dose on Day 1.
DRUGJNJ-64179375 D mg/kg
JNJ-64179375 Dose D mg/kg IV as a single dose on Day 1.
DRUGPlacebo JNJ-64179375
Matching JNJ-64179375 placebo (normal saline) administered as IV infusion as a single dose on Day 1.
DRUGApixaban placebo
Matching apixaban placebo administered orally twice a day for 10 to 14 days.
DRUGApixaban 2.5 mg
Apixaban 2.5 mg administered orally twice a day for 10 to 14 days.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Double Blinded
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Weight greater than or equal to (\>=) 40 kg to less than or equal to (\<=) 150 kilogram (kg) * Medically appropriate for postoperative anticoagulant prophylaxis as determined by the investigator * Has undergone an elective primary unilateral total knee replacement (TKR) * Before randomization, a woman must not be of childbearing potential defined as postmenopausal (defined as no menses for 12 months without an alternative medical cause) and/ or permanently sterile (include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy) * Contraceptive use by men should be consistent with local regulations regarding the use of contraceptive methods for participant participating in clinical studies
Exclusion criteria
* Any condition for which the use of apixaban is not recommended in the opinion of the investigator * Bilateral, revision or unicompartmental procedure * Known or suspected hypersensitivity or intolerance to any biologic medication or known allergies or clinically significant reactions to murine, chimeric, or human proteins, monoclonal antibodies or antibody fragments, or any of the excipients of JNJ-64179375 * Unable to undergo venography * Known previous deep vein thrombosis (DVT) in either lower extremity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Bleeding Events (Clinical Events Committee [CEC]- Adjudicated) | Up to Day 10 to 14 (visit observation period) | Number of participants with treatment-emergent bleeding events (BE) (adjudicated by CEC) were reported. Bleeding event was defined as the composite of major, clinically relevant nonmajor (CRNM), and minimal bleeding events assessed through the Day 10 to 14. |
| Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) | Up to Day 10 to 14 (visit observation period) | Number of participants with total VTE were reported. Total VTE was defined as the composite of 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 assessed through the Day 10 to 14 visit. 1 participant had an asymptomatic distal clot in the non-operated leg which is not counted in the Total VTE and 2 participants had symptomatic proximal clots at the Day 10 to 14 venography and are counted in both the asymptomatic proximal and symptomatic proximal groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Relevant Non-major (CRNM) Bleeding Events (CEC-adjudicated) | Up to Day 10 to 14 (visit observation period) | Number of participants with CRNM bleeding events (adjudicated by CEC) were reported. CRNM bleeding was defined as acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major bleeding event and meets at least 1 of following criteria: Epistaxis, Gastrointestinal bleed, Hematuria, Bruising/ecchymosis, Hemoptysis, Hematoma. |
| Number of Participants With Major Bleeding or CRNM Bleeding Events (CEC-adjudicated) | Up to Day 10 and 14 (visit observation period) | Number of participants with major bleeding or CRNM bleeding events (adjudicated by CEC) were reported. Major Bleeding: 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; Surgical site bleeding that requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; Surgical site bleeding that is 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 and meets at least 1 of following criteria: Epistaxis, Gastrointestinal bleed, Hematuria, Bruising/ecchymosis, Hemoptysis, Hematoma. |
| Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | Up to Day 10 to 14 (visit observation period) | 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. |
| Number of Participants With Major VTE (CEC-adjudicated) | Up to Day 10 to 14 (visit observation period) | 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. 2 participants had symptomatic proximal clots at the Day 10 to 14 venography and are counted in both the asymptomatic proximal and symptomatic proximal groups. |
| Number of Participants With Composite of Major and CRNM Bleeding Events (CEC-adjudicated) | Up to Day 10 to 14 (visit observation period) | Number of participants with composite of major and CRNM bleeding events (adjudicated by CEC) were reported. Major Bleeding: 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; Surgical site bleeding that requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; Surgical site bleeding that is 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 and meets at least 1 of following criteria: Epistaxis, Gastrointestinal bleed, Hematuria, Bruising/ecchymosis, Hemoptysis, Hematoma. |
| Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | Up to Day 10 to 14 (visit observation period) | Number of participants with nonfatal PE (adjudicated by CEC) were reported. |
| Number of Participants With Death (CEC-adjudicated) | Up to Day 10 to 14 (visit observation period) | Number of participants with death (adjudicated by CEC) were reported. |
| Number of Participants With Proximal and Distal DVT (CEC-adjudicated) | Up to Day 10 to 14 (visit observation period) | Number of participants with proximal and distal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic. 2 participants had symptomatic proximal clots at the Day 10 to 14 venography and are counted in both the asymptomatic proximal and symptomatic proximal groups. |
| Number of Participants With Distal DVT (CEC-adjudicated) | Up to Day 10 to 14 (visit observation period) | 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. |
| Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Up to Day 10 to 14 (visit observation period) | 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. 2 participants had symptomatic proximal clots at the Day 10 to 14 venography and are counted in both the asymptomatic proximal and symptomatic proximal groups. |
| Number of Participants With Major Bleeding Event (CEC-adjudicated) | Up to Day 10 to 14 (visit observation period) | Number of participants with major bleeding events (BE) (adjudicated by CEC) were reported. Major Bleeding: 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 or a deep wound infection and/or; Surgical site bleeding that is unexpected and prolonged and/or sufficiently large to cause hemodynamic instability. |
Countries
Argentina, Belgium, Brazil, Bulgaria, Canada, Italy, Japan, Latvia, Lithuania, Malaysia, Poland, Russia, Spain, Turkey (Türkiye), Ukraine, United States
Participant flow
Pre-assignment details
The study was planned to be conducted in 2 parts: Part 1 (Dose- Escalation) and Part 2 (Dose-Response). After completion of Part 1, the sponsor made the decision to not move forward with Part 2 as there was sufficient data to make a determination of efficacy in Part 1. Part 2 was not conducted, hence endpoints for Part 2 are not reported.
Participants by arm
| Arm | Count |
|---|---|
| JNJ-64179375 0.3 mg/kg and Apixaban Placebo Participants received a single intravenous (IV) infusion of JNJ-64179375 0.3 milligrams per kilogram (mg/kg) on Day 1 and matching apixaban placebo tablets orally twice daily (BID) for 10 to 14 days. | 38 |
| JNJ-64179375 0.6 mg/kg and Apixaban Placebo Participants received a single IV infusion of JNJ-64179375 0.6 mg/kg on Day 1 and matching apixaban placebo tablets orally BID for 10 to 14 days. | 40 |
| JNJ-64179375 1.2 mg/kg and Apixaban Placebo Participants received a single IV infusion of JNJ-64179375 1.2 mg/kg on Day 1 and matching apixaban placebo tablets orally BID for 10 to 14 days. | 42 |
| JNJ-64179375 1.8 mg/kg and Apixaban Placebo Participants received a single IV infusion of JNJ-64179375 1.8 mg/kg on Day 1 and matching apixaban placebo tablets orally BID for 10 to 14 days. | 122 |
| Apixaban 2.5 mg and JNJ-64179375 Placebo IV Participants received a single IV infusion of matching JNJ-64179375 placebo on Day 1 and apixaban 2.5 mg tablet orally BID for 10 to 14 days. | 63 |
| Total | 305 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | JNJ-64179375 0.3 mg/kg and Apixaban Placebo | JNJ-64179375 0.6 mg/kg and Apixaban Placebo | JNJ-64179375 1.2 mg/kg and Apixaban Placebo | JNJ-64179375 1.8 mg/kg and Apixaban Placebo | Apixaban 2.5 mg and JNJ-64179375 Placebo IV | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 66.2 years STANDARD_DEVIATION 7.53 | 65.8 years STANDARD_DEVIATION 8.14 | 66.9 years STANDARD_DEVIATION 6.41 | 67.2 years STANDARD_DEVIATION 8.84 | 65.1 years STANDARD_DEVIATION 7.01 | 66.4 years STANDARD_DEVIATION 7.92 |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 2 Participants | 9 Participants | 5 Participants | 16 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Unspecified | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 8 Participants |
| Race/Ethnicity, Customized White | 36 Participants | 39 Participants | 39 Participants | 110 Participants | 54 Participants | 278 Participants |
| Region of Enrollment Argentina | 2 Participants | 4 Participants | 3 Participants | 8 Participants | 10 Participants | 27 Participants |
| Region of Enrollment Belgium | 5 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 16 Participants |
| Region of Enrollment Bulgaria | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Canada | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Region of Enrollment Italy | 0 Participants | 1 Participants | 0 Participants | 5 Participants | 2 Participants | 8 Participants |
| Region of Enrollment Japan | 0 Participants | 0 Participants | 2 Participants | 5 Participants | 5 Participants | 12 Participants |
| Region of Enrollment Latvia | 0 Participants | 0 Participants | 0 Participants | 8 Participants | 4 Participants | 12 Participants |
| Region of Enrollment Lithuania | 0 Participants | 0 Participants | 3 Participants | 8 Participants | 1 Participants | 12 Participants |
| Region of Enrollment Malaysia | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 4 Participants |
| Region of Enrollment Poland | 17 Participants | 9 Participants | 4 Participants | 18 Participants | 12 Participants | 60 Participants |
| Region of Enrollment Russian Federation | 0 Participants | 0 Participants | 2 Participants | 9 Participants | 3 Participants | 14 Participants |
| Region of Enrollment Spain | 3 Participants | 3 Participants | 3 Participants | 7 Participants | 2 Participants | 18 Participants |
| Region of Enrollment Turkey | 1 Participants | 7 Participants | 5 Participants | 8 Participants | 2 Participants | 23 Participants |
| Region of Enrollment Ukraine | 0 Participants | 4 Participants | 7 Participants | 20 Participants | 7 Participants | 38 Participants |
| Region of Enrollment United States | 10 Participants | 9 Participants | 10 Participants | 15 Participants | 12 Participants | 56 Participants |
| Sex: Female, Male Female | 21 Participants | 25 Participants | 35 Participants | 99 Participants | 42 Participants | 222 Participants |
| Sex: Female, Male Male | 17 Participants | 15 Participants | 7 Participants | 23 Participants | 21 Participants | 83 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 40 | 0 / 42 | 0 / 122 | 0 / 63 |
| other Total, other adverse events | 19 / 38 | 17 / 40 | 26 / 42 | 37 / 122 | 20 / 63 |
| serious Total, serious adverse events | 2 / 38 | 2 / 40 | 4 / 42 | 13 / 122 | 5 / 63 |
Outcome results
Primary
Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated)
Number of participants with total VTE were reported. Total VTE was defined as the composite of 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 assessed through the Day 10 to 14 visit. 1 participant had an asymptomatic distal clot in the non-operated leg which is not counted in the Total VTE and 2 participants had symptomatic proximal clots at the Day 10 to 14 venography and are counted in both the asymptomatic proximal and symptomatic proximal groups.
Time frame: Up to Day 10 to 14 (visit observation period)
Population: Modified Intent-to-treat (mITT) analysis set included all randomized participants with an evaluable venography assessment or a confirmed symptomatic VTE event, or any death adjudicated by CEC.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-64179375 0.3 mg/kg and Apixaban Placebo | Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) | 10 Participants |
| JNJ-64179375 0.6 mg/kg and Apixaban Placebo | Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) | 9 Participants |
| JNJ-64179375 1.2 mg/kg and Apixaban Placebo | Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) | 9 Participants |
| JNJ-64179375 1.8 mg/kg and Apixaban Placebo | Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) | 31 Participants |
| Apixaban 2.5 mg and JNJ-64179375 Placebo IV | Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) | 6 Participants |
Primary
Number of Participants With Treatment-emergent Bleeding Events (Clinical Events Committee [CEC]- Adjudicated)
Number of participants with treatment-emergent bleeding events (BE) (adjudicated by CEC) were reported. Bleeding event was defined as the composite of major, clinically relevant nonmajor (CRNM), and minimal bleeding events assessed through the Day 10 to 14.
Time frame: Up to Day 10 to 14 (visit observation period)
Population: Safety Analysis set included all randomized participants who received at least 1 dose (partial or complete) of active study drug (JNJ-64179375 or apixaban).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-64179375 0.3 mg/kg and Apixaban Placebo | Number of Participants With Treatment-emergent Bleeding Events (Clinical Events Committee [CEC]- Adjudicated) | 2 Participants |
| JNJ-64179375 0.6 mg/kg and Apixaban Placebo | Number of Participants With Treatment-emergent Bleeding Events (Clinical Events Committee [CEC]- Adjudicated) | 0 Participants |
| JNJ-64179375 1.2 mg/kg and Apixaban Placebo | Number of Participants With Treatment-emergent Bleeding Events (Clinical Events Committee [CEC]- Adjudicated) | 5 Participants |
| JNJ-64179375 1.8 mg/kg and Apixaban Placebo | Number of Participants With Treatment-emergent Bleeding Events (Clinical Events Committee [CEC]- Adjudicated) | 1 Participants |
| Apixaban 2.5 mg and JNJ-64179375 Placebo IV | Number of Participants With Treatment-emergent Bleeding Events (Clinical Events Committee [CEC]- Adjudicated) | 4 Participants |
Secondary
Number of Participants With Clinically Relevant Non-major (CRNM) Bleeding Events (CEC-adjudicated)
Number of participants with CRNM bleeding events (adjudicated by CEC) were reported. CRNM bleeding was defined as acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major bleeding event and meets at least 1 of following criteria: Epistaxis, Gastrointestinal bleed, Hematuria, Bruising/ecchymosis, Hemoptysis, Hematoma.
Time frame: Up to Day 10 to 14 (visit observation period)
Population: Safety analysis set included all randomized participants who received at least 1 dose (partial or complete) of active study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-64179375 0.3 mg/kg and Apixaban Placebo | Number of Participants With Clinically Relevant Non-major (CRNM) Bleeding Events (CEC-adjudicated) | 1 Participants |
| JNJ-64179375 0.6 mg/kg and Apixaban Placebo | Number of Participants With Clinically Relevant Non-major (CRNM) Bleeding Events (CEC-adjudicated) | 0 Participants |
| JNJ-64179375 1.2 mg/kg and Apixaban Placebo | Number of Participants With Clinically Relevant Non-major (CRNM) Bleeding Events (CEC-adjudicated) | 2 Participants |
| JNJ-64179375 1.8 mg/kg and Apixaban Placebo | Number of Participants With Clinically Relevant Non-major (CRNM) Bleeding Events (CEC-adjudicated) | 1 Participants |
| Apixaban 2.5 mg and JNJ-64179375 Placebo IV | Number of Participants With Clinically Relevant Non-major (CRNM) Bleeding Events (CEC-adjudicated) | 0 Participants |
Secondary
Number of Participants With Composite of Major and CRNM Bleeding Events (CEC-adjudicated)
Number of participants with composite of major and CRNM bleeding events (adjudicated by CEC) were reported. Major Bleeding: 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; Surgical site bleeding that requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; Surgical site bleeding that is 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 and meets at least 1 of following criteria: Epistaxis, Gastrointestinal bleed, Hematuria, Bruising/ecchymosis, Hemoptysis, Hematoma.
Time frame: Up to Day 10 to 14 (visit observation period)
Population: Safety analysis set included all randomized participants who received at least 1 dose (partial or complete) of active study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-64179375 0.3 mg/kg and Apixaban Placebo | Number of Participants With Composite of Major and CRNM Bleeding Events (CEC-adjudicated) | 1 Participants |
| JNJ-64179375 0.6 mg/kg and Apixaban Placebo | Number of Participants With Composite of Major and CRNM Bleeding Events (CEC-adjudicated) | 0 Participants |
| JNJ-64179375 1.2 mg/kg and Apixaban Placebo | Number of Participants With Composite of Major and CRNM Bleeding Events (CEC-adjudicated) | 2 Participants |
| JNJ-64179375 1.8 mg/kg and Apixaban Placebo | Number of Participants With Composite of Major and CRNM Bleeding Events (CEC-adjudicated) | 1 Participants |
| Apixaban 2.5 mg and JNJ-64179375 Placebo IV | Number of Participants With Composite of Major and CRNM Bleeding Events (CEC-adjudicated) | 0 Participants |
Secondary
Number of Participants With Death (CEC-adjudicated)
Number of participants with death (adjudicated by CEC) were reported.
Time frame: Up to Day 10 to 14 (visit observation period)
Population: mITT analysis set included all randomized participants with an evaluable venography assessment or a confirmed symptomatic VTE event, or any death.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-64179375 0.3 mg/kg and Apixaban Placebo | Number of Participants With Death (CEC-adjudicated) | 0 Participants |
| JNJ-64179375 0.6 mg/kg and Apixaban Placebo | Number of Participants With Death (CEC-adjudicated) | 0 Participants |
| JNJ-64179375 1.2 mg/kg and Apixaban Placebo | Number of Participants With Death (CEC-adjudicated) | 0 Participants |
| JNJ-64179375 1.8 mg/kg and Apixaban Placebo | Number of Participants With Death (CEC-adjudicated) | 0 Participants |
| Apixaban 2.5 mg and JNJ-64179375 Placebo IV | Number of Participants With Death (CEC-adjudicated) | 0 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 10 to 14 (visit observation period)
Population: mITT analysis set included all randomized participants with an evaluable venography assessment or a confirmed symptomatic VTE event, or any death.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| JNJ-64179375 0.3 mg/kg and Apixaban Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 8 Participants |
| JNJ-64179375 0.3 mg/kg and Apixaban Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-64179375 0.6 mg/kg and Apixaban Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 7 Participants |
| JNJ-64179375 0.6 mg/kg and Apixaban Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-64179375 1.2 mg/kg and Apixaban Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 8 Participants |
| JNJ-64179375 1.2 mg/kg and Apixaban Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-64179375 1.8 mg/kg and Apixaban Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 1 Participants |
| JNJ-64179375 1.8 mg/kg and Apixaban Placebo | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 24 Participants |
| Apixaban 2.5 mg and JNJ-64179375 Placebo IV | Number of Participants With Distal DVT (CEC-adjudicated) | Asymptomatic | 6 Participants |
| Apixaban 2.5 mg and JNJ-64179375 Placebo IV | Number of Participants With Distal DVT (CEC-adjudicated) | Symptomatic | 1 Participants |
Secondary
Number of Participants With Major Bleeding Event (CEC-adjudicated)
Number of participants with major bleeding events (BE) (adjudicated by CEC) were reported. Major Bleeding: 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 or a deep wound infection and/or; Surgical site bleeding that is unexpected and prolonged and/or sufficiently large to cause hemodynamic instability.
Time frame: Up to Day 10 to 14 (visit observation period)
Population: Safety analysis set included all randomized participants who received at least 1 dose (partial or complete) of active study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-64179375 0.3 mg/kg and Apixaban Placebo | Number of Participants With Major Bleeding Event (CEC-adjudicated) | 0 Participants |
| JNJ-64179375 0.6 mg/kg and Apixaban Placebo | Number of Participants With Major Bleeding Event (CEC-adjudicated) | 0 Participants |
| JNJ-64179375 1.2 mg/kg and Apixaban Placebo | Number of Participants With Major Bleeding Event (CEC-adjudicated) | 0 Participants |
| JNJ-64179375 1.8 mg/kg and Apixaban Placebo | Number of Participants With Major Bleeding Event (CEC-adjudicated) | 0 Participants |
| Apixaban 2.5 mg and JNJ-64179375 Placebo IV | Number of Participants With Major Bleeding Event (CEC-adjudicated) | 0 Participants |
Secondary
Number of Participants With Major Bleeding or CRNM Bleeding Events (CEC-adjudicated)
Number of participants with major bleeding or CRNM bleeding events (adjudicated by CEC) were reported. Major Bleeding: 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; Surgical site bleeding that requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; Surgical site bleeding that is 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 and meets at least 1 of following criteria: Epistaxis, Gastrointestinal bleed, Hematuria, Bruising/ecchymosis, Hemoptysis, Hematoma.
Time frame: Up to Day 10 and 14 (visit observation period)
Population: Safety analysis set included all randomized participants who received at least 1 dose (partial or complete) of active study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-64179375 0.3 mg/kg and Apixaban Placebo | Number of Participants With Major Bleeding or CRNM Bleeding Events (CEC-adjudicated) | 1 Participants |
| JNJ-64179375 0.6 mg/kg and Apixaban Placebo | Number of Participants With Major Bleeding or CRNM Bleeding Events (CEC-adjudicated) | 0 Participants |
| JNJ-64179375 1.2 mg/kg and Apixaban Placebo | Number of Participants With Major Bleeding or CRNM Bleeding Events (CEC-adjudicated) | 2 Participants |
| JNJ-64179375 1.8 mg/kg and Apixaban Placebo | Number of Participants With Major Bleeding or CRNM Bleeding Events (CEC-adjudicated) | 1 Participants |
| Apixaban 2.5 mg and JNJ-64179375 Placebo IV | Number of Participants With Major Bleeding or CRNM Bleeding Events (CEC-adjudicated) | 0 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. 2 participants had symptomatic proximal clots at the Day 10 to 14 venography and are counted in both the asymptomatic proximal and symptomatic proximal groups.
Time frame: Up to Day 10 to 14 (visit observation period)
Population: mITT analysis set included all randomized participants with an evaluable venography assessment or a confirmed symptomatic VTE event or any death.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-64179375 0.3 mg/kg and Apixaban Placebo | Number of Participants With Major VTE (CEC-adjudicated) | 2 Participants |
| JNJ-64179375 0.6 mg/kg and Apixaban Placebo | Number of Participants With Major VTE (CEC-adjudicated) | 2 Participants |
| JNJ-64179375 1.2 mg/kg and Apixaban Placebo | Number of Participants With Major VTE (CEC-adjudicated) | 1 Participants |
| JNJ-64179375 1.8 mg/kg and Apixaban Placebo | Number of Participants With Major VTE (CEC-adjudicated) | 7 Participants |
| Apixaban 2.5 mg and JNJ-64179375 Placebo IV | Number of Participants With Major VTE (CEC-adjudicated) | 0 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.
Time frame: Up to Day 10 to 14 (visit observation period)
Population: Safety analysis set included all randomized participants who received at least 1 dose (partial or complete) of active study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-64179375 0.3 mg/kg and Apixaban Placebo | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | 2 Participants |
| JNJ-64179375 0.6 mg/kg and Apixaban Placebo | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | 0 Participants |
| JNJ-64179375 1.2 mg/kg and Apixaban Placebo | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | 4 Participants |
| JNJ-64179375 1.8 mg/kg and Apixaban Placebo | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | 0 Participants |
| Apixaban 2.5 mg and JNJ-64179375 Placebo IV | Number of Participants With Minimal Bleeding Events (CEC-adjudicated) | 4 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 10 to 14 (visit observation period)
Population: mITT analysis set included all randomized participants with an evaluable venography assessment or a confirmed symptomatic VTE event, or any death.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JNJ-64179375 0.3 mg/kg and Apixaban Placebo | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 0 Participants |
| JNJ-64179375 0.6 mg/kg and Apixaban Placebo | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 0 Participants |
| JNJ-64179375 1.2 mg/kg and Apixaban Placebo | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 0 Participants |
| JNJ-64179375 1.8 mg/kg and Apixaban Placebo | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 0 Participants |
| Apixaban 2.5 mg and JNJ-64179375 Placebo IV | Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated) | 0 Participants |
Secondary
Number of Participants With Proximal and Distal DVT (CEC-adjudicated)
Number of participants with proximal and distal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic. 2 participants had symptomatic proximal clots at the Day 10 to 14 venography and are counted in both the asymptomatic proximal and symptomatic proximal groups.
Time frame: Up to Day 10 to 14 (visit observation period)
Population: mITT analysis set included all randomized participants with an evaluable venography assessment or a confirmed symptomatic VTE event, or any death.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| JNJ-64179375 0.3 mg/kg and Apixaban Placebo | Number of Participants With Proximal and Distal DVT (CEC-adjudicated) | Asymptomatic | 1 Participants |
| JNJ-64179375 0.3 mg/kg and Apixaban Placebo | Number of Participants With Proximal and Distal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-64179375 0.6 mg/kg and Apixaban Placebo | Number of Participants With Proximal and Distal DVT (CEC-adjudicated) | Asymptomatic | 0 Participants |
| JNJ-64179375 0.6 mg/kg and Apixaban Placebo | Number of Participants With Proximal and Distal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-64179375 1.2 mg/kg and Apixaban Placebo | Number of Participants With Proximal and Distal DVT (CEC-adjudicated) | Asymptomatic | 1 Participants |
| JNJ-64179375 1.2 mg/kg and Apixaban Placebo | Number of Participants With Proximal and Distal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-64179375 1.8 mg/kg and Apixaban Placebo | Number of Participants With Proximal and Distal DVT (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-64179375 1.8 mg/kg and Apixaban Placebo | Number of Participants With Proximal and Distal DVT (CEC-adjudicated) | Asymptomatic | 4 Participants |
| Apixaban 2.5 mg and JNJ-64179375 Placebo IV | Number of Participants With Proximal and Distal DVT (CEC-adjudicated) | Asymptomatic | 0 Participants |
| Apixaban 2.5 mg and JNJ-64179375 Placebo IV | Number of Participants With Proximal and Distal DVT (CEC-adjudicated) | Symptomatic | 0 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. 2 participants had symptomatic proximal clots at the Day 10 to 14 venography and are counted in both the asymptomatic proximal and symptomatic proximal groups.
Time frame: Up to Day 10 to 14 (visit observation period)
Population: mITT analysis set included all randomized participants with an evaluable venography assessment or a confirmed symptomatic VTE event, or any death.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| JNJ-64179375 0.3 mg/kg and Apixaban Placebo | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Asymptomatic | 1 Participants |
| JNJ-64179375 0.3 mg/kg and Apixaban Placebo | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-64179375 0.6 mg/kg and Apixaban Placebo | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Asymptomatic | 2 Participants |
| JNJ-64179375 0.6 mg/kg and Apixaban Placebo | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-64179375 1.2 mg/kg and Apixaban Placebo | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Asymptomatic | 0 Participants |
| JNJ-64179375 1.2 mg/kg and Apixaban Placebo | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Symptomatic | 0 Participants |
| JNJ-64179375 1.8 mg/kg and Apixaban Placebo | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Symptomatic | 2 Participants |
| JNJ-64179375 1.8 mg/kg and Apixaban Placebo | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Asymptomatic | 3 Participants |
| Apixaban 2.5 mg and JNJ-64179375 Placebo IV | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Asymptomatic | 0 Participants |
| Apixaban 2.5 mg and JNJ-64179375 Placebo IV | Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated) | Symptomatic | 0 Participants |