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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03891524




Registration number
NCT03891524
Ethics application status
Date submitted
25/03/2019
Date registered
27/03/2019

Titles & IDs
Public title
A Study of JNJ-70033093 (BMS-986177) Versus Subcutaneous Enoxaparin in Participants Undergoing Elective Total Knee Replacement Surgery
Scientific title
A Randomized, Open-Label, Study Drug-Dose Blind, Multicenter Study to Evaluate the Efficacy and Safety of JNJ-70033093 (BMS-986177), an Oral Factor XIa Inhibitor, Versus Subcutaneous Enoxaparin in Subjects Undergoing Elective Total Knee Replacement Surgery
Secondary ID [1] 0 0
70033093THR2001
Secondary ID [2] 0 0
CR108600
Universal Trial Number (UTN)
Trial acronym
AXIOMATIC-TKR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Arthroplasty, Replacement, Knee 0 0
Condition category
Condition code
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - JNJ-70033093 25 mg
Treatment: Drugs - JNJ-70033093 50 mg
Treatment: Drugs - JNJ-70033093 100 mg
Treatment: Drugs - JNJ-70033093 200 mg
Treatment: Drugs - Placebo
Treatment: Drugs - Enoxaparin 40 mg

Experimental: Group A: JNJ-70033093 25 mg + Placebo BID - Participants will receive JNJ-70033093 25 milligram (mg) (1\*25 mg capsule) and 1 placebo capsule twice daily (BID), orally for 10 to 14 postoperative days.

Experimental: Group B: JNJ-70033093 50 mg BID - Participants will receive JNJ-70033093 50 mg (2\*25 mg capsules) BID orally for 10 to 14 postoperative days.

Experimental: Group C: JNJ-70033093 100 mg + Placebo BID - Participants will receive JNJ-70033093 100 mg (1\*100 mg capsule) and 1 placebo capsule BID orally for 10 to 14 postoperative days.

Experimental: Group D: JNJ-70033093 200 mg BID - Participants will receive JNJ-70033093 200 mg (2\*100 mg capsules) BID orally for 10 to 14 postoperative days.

Experimental: Group E: JNJ-70033093 25 mg Once Daily + Placebo - Participants will receive JNJ-70033093 25 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.

Experimental: Group F: JNJ-70033093 200 mg Once Daily + Placebo - Participants will receive 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.

Experimental: Group G: JNJ-70033093 50 mg once daily + Placebo - Participants will receive 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.

Active comparator: Group I: Enoxaparin 40 mg Once Daily - Participants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days.


Treatment: Drugs: JNJ-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.

Treatment: Drugs: JNJ-70033093 50 mg
Participants will receive JNJ-70033093 50 mg (2\*25 mg capsules) BID orally for 10 to 14 postoperative days.

Treatment: Drugs: JNJ-70033093 100 mg
Participants will receive JNJ-70033093 100 mg (1\*100 mg capsule) BID, orally for 10 to 14 postoperative days.

Treatment: Drugs: JNJ-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.

Treatment: Drugs: Placebo
Participants will receive placebo matching to JNJ-70033093, orally.

Treatment: Drugs: Enoxaparin 40 mg
Participants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated)
Timepoint [1] 0 0
Up to Day 14
Primary outcome [2] 0 0
Number of Participants With Dose Limiting Toxicities (DLTs): Safety Lead-in (SLI) Phase
Timepoint [2] 0 0
Cycle 1 of SLI phase (up to 28 days)
Primary outcome [3] 0 0
Number of Participants With Treatment Emergent Adverse Events Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI _CTCAE) Version (v) 4.03: SLI Phase
Timepoint [3] 0 0
Day 1 of dosing up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
Primary outcome [4] 0 0
Number of Participants With Hepatology Laboratory Test Abnormalities: SLI Phase
Timepoint [4] 0 0
Baseline (Day 1) up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
Primary outcome [5] 0 0
Number of Participants With Shift From Baseline for Hematology and Coagulation Laboratory Test Abnormalities Based on NCI-CTCAE v4.03: SLI Phase
Timepoint [5] 0 0
Baseline (Day 1) up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
Primary outcome [6] 0 0
Number of Participants With Shift From Baseline for Biochemistry Laboratory Test Abnormalities Based on NCI-CTCAE v4.03: SLI Phase
Timepoint [6] 0 0
Baseline (Day 1) up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
Primary outcome [7] 0 0
Number of Participants With Notable Abnormal Vital Signs: SLI Phase
Timepoint [7] 0 0
Baseline (Day 1) up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
Primary outcome [8] 0 0
Number of Participants With Notable Abnormal Electrocardiogram (ECG) Values: SLI Phase
Timepoint [8] 0 0
Baseline (Day 1) up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
Primary outcome [9] 0 0
Number of Participants With Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to AEs: SLI Phase
Timepoint [9] 0 0
Baseline (Day 1) up to 30 days after last dose of study drug in SLI Phase, maximum duration up to 10.4 months
Primary outcome [10] 0 0
Brain Metastasis Response Rate (BMRR) Based on Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (mRECIST v1.1): Phase 2
Timepoint [10] 0 0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in Phase 2 (approximately up to 8.3 months)
Secondary outcome [1] 0 0
Number of Participants With Any Bleeding Event (CEC-adjudicated)
Timepoint [1] 0 0
Up to Day 14; Up to Day 52
Secondary outcome [2] 0 0
Number of Participants With Total VTE (CEC-adjudicated)
Timepoint [2] 0 0
Up to Day 52
Secondary outcome [3] 0 0
Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated)
Timepoint [3] 0 0
Up to Day 14, Up to Day 52
Secondary outcome [4] 0 0
Number of Participants With Major Bleeding Events (CEC-adjudicated)
Timepoint [4] 0 0
Up to Day 14; Up to Day 52
Secondary outcome [5] 0 0
Number of Participants With CRNM Bleeding Events (CEC-adjudicated)
Timepoint [5] 0 0
Up to Day 14; Up to Day 52
Secondary outcome [6] 0 0
Number of Participants With Minimal Bleeding Events (CEC-adjudicated)
Timepoint [6] 0 0
Up to Day 14; Up to Day 52
Secondary outcome [7] 0 0
Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated)
Timepoint [7] 0 0
Up to Day 14; Up to Day 52
Secondary outcome [8] 0 0
Number of Participants With Major VTE (CEC-adjudicated)
Timepoint [8] 0 0
Up to Day 52
Secondary outcome [9] 0 0
Number of Participants With Major VTE (CEC-adjudicated)
Timepoint [9] 0 0
Up to Day 14
Secondary outcome [10] 0 0
Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated)
Timepoint [10] 0 0
Up to Day 14
Secondary outcome [11] 0 0
Number of Participants With Proximal DVT (CEC-adjudicated)
Timepoint [11] 0 0
Up to Day 52
Secondary outcome [12] 0 0
Number of Participants With Distal DVT (CEC-adjudicated)
Timepoint [12] 0 0
Up to Day 14
Secondary outcome [13] 0 0
Number of Participants With Distal DVT (CEC-adjudicated)
Timepoint [13] 0 0
Up to Day 52
Secondary outcome [14] 0 0
Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated)
Timepoint [14] 0 0
Up to Day 14
Secondary outcome [15] 0 0
Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated)
Timepoint [15] 0 0
Up to Day 52
Secondary outcome [16] 0 0
Number of Participants With Deaths (CEC-adjudicated)
Timepoint [16] 0 0
Up to Day 14
Secondary outcome [17] 0 0
Number of Participants With Deaths (CEC-adjudicated)
Timepoint [17] 0 0
Up to Day 52
Secondary outcome [18] 0 0
Apparent Clearance (CL/F) of JNJ-70033093
Timepoint [18] 0 0
Up to Day 14
Secondary outcome [19] 0 0
Apparent Volume of Distribution (V/F) of JNJ-70033093
Timepoint [19] 0 0
Up to Day 14
Secondary outcome [20] 0 0
Impact of Selected Demographics: Apparent Clearance (CL/F) Based on Sex
Timepoint [20] 0 0
Up to Day 14
Secondary outcome [21] 0 0
Impact of Selected Demographic: Age on CL/F
Timepoint [21] 0 0
Up to Day 14
Secondary outcome [22] 0 0
Impact of Selected Demographic: Weight on CL/F
Timepoint [22] 0 0
Up to Day 14
Secondary outcome [23] 0 0
Impact of Selected Laboratory Values: Renal Function on CL/F
Timepoint [23] 0 0
Up to Day 14
Secondary outcome [24] 0 0
Impact of Selected Demographics: Sex on Apparent Volume of Distribution (V/F)
Timepoint [24] 0 0
Up to Day 14
Secondary outcome [25] 0 0
Impact of Selected Demographics : Age on V/F
Timepoint [25] 0 0
Up to Day 14
Secondary outcome [26] 0 0
Impact of Selected Demographics : Weight on V/F
Timepoint [26] 0 0
Up to Day 14
Secondary outcome [27] 0 0
Impact of Selected Laboratory Values: Renal Function on V/F
Timepoint [27] 0 0
Up to Day 14
Secondary outcome [28] 0 0
Trend Test for Primary Efficacy Event Rate (CEC Adjudicated) by Multiple Comparison Procedure - Modelling (MCP-Mod) Approach
Timepoint [28] 0 0
Up to 14 days
Secondary outcome [29] 0 0
Trend Test for the Composite of On-Treatment Major and Clinically Relevant Nonmajor Bleeding (CEC Adjudicated) by MCP-Mod Approach
Timepoint [29] 0 0
Up to 14 days
Secondary outcome [30] 0 0
Extracranial Response Rate Based on RECIST v1.1: SLI Phase and Phase 2
Timepoint [30] 0 0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Secondary outcome [31] 0 0
Global Response Rate: SLI Phase and Phase 2
Timepoint [31] 0 0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Secondary outcome [32] 0 0
Disease Control Rate (DCR) for Brain Metastasis Response Based on mRECIST v1.1: SLI Phase and Phase 2
Timepoint [32] 0 0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Secondary outcome [33] 0 0
DCR for Extracranial Response Based on RECIST v1.1: SLI Phase and Phase 2
Timepoint [33] 0 0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Secondary outcome [34] 0 0
DCR for Global Response: SLI Phase and Phase 2
Timepoint [34] 0 0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Secondary outcome [35] 0 0
Duration of Response (DOR) for Brain Metastasis Response Based on mRECIST v1.1: SLI Phase and Phase 2
Timepoint [35] 0 0
From date of first radiographic response (CR or PR) to earliest documented disease progression or death due to any cause in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Secondary outcome [36] 0 0
DOR for Global Response: SLI Phase and Phase 2
Timepoint [36] 0 0
From date of first radiographic response (CR or PR) to earliest documented disease progression or death due to any cause in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Secondary outcome [37] 0 0
DOR for Extracranial Response Based on RECIST v1.1: SLI Phase and Phase 2
Timepoint [37] 0 0
From date of first radiographic response (CR or PR) to earliest documented disease progression or death due to any cause in SLI Phase (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Secondary outcome [38] 0 0
Progression Free Survival (PFS) for Brain Metastasis Based on mRECIST v1.1: SLI Phase and Phase 2
Timepoint [38] 0 0
From date of first dose of study treatment to the earliest documented disease progression by investigator assessment, or death due to any cause, whichever occurs first in SLI (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Secondary outcome [39] 0 0
PFS for Global Tumor Assessment: SLI Phase and Phase 2
Timepoint [39] 0 0
From date of first dose of study treatment to the earliest documented disease progression by investigator assessment, or death due to any cause, whichever occurs first in SLI (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Secondary outcome [40] 0 0
BMRR Based on mRECIST v1.1: SLI Phase
Timepoint [40] 0 0
From date of first dose until disease progression, death due to any cause or subsequent therapy initiation, whichever occurred first in SLI Phase (approximately up to 10.4 months)
Secondary outcome [41] 0 0
Overall Survival: SLI Phase and Phase 2
Timepoint [41] 0 0
From date of first dose of study treatment to the earliest documented disease progression by investigator assessment, or death due to any cause, whichever occurs first in SLI (approximately up to 10.4 months) and Phase 2 (approximately up to 8.3 months)
Secondary outcome [42] 0 0
Number of Participants With Treatment Emergent AEs of Maximum Severity Grades Based on NCI CTCAE v4.03: Phase 2
Timepoint [42] 0 0
Day 1 of dosing up to 30 days after last dose of study drug in Phase 2, maximum duration up to 8.3 months
Secondary outcome [43] 0 0
Number of Participants With Hepatology Laboratory Test Abnormalities: Phase 2
Timepoint [43] 0 0
Baseline (Day 1) up to 30 days after last dose of study drug in Phase 2, maximum duration up to 8.3 months
Secondary outcome [44] 0 0
Number of Participants With Shift From Baseline for Hematology and Coagulation Laboratory Test Abnormalities Based on NCI-CTCAE v4.03: Phase 2
Timepoint [44] 0 0
Baseline (Day 1) up to 30 days after last dose of study drug in Phase 2, maximum duration up to 8.3 months
Secondary outcome [45] 0 0
Number of Participants With Shift From Baseline for Biochemistry Laboratory Test Abnormalities Based on NCI-CTCAE v4.03: Phase 2
Timepoint [45] 0 0
Baseline (Day 1) up to 30 days after last dose of study drug in Phase 2, maximum duration up to 8.3 months
Secondary outcome [46] 0 0
Number of Participants With Clinically Significant Change in Notable Abnormal Vital Signs: Phase 2
Timepoint [46] 0 0
Baseline (Day 1) up to 30 days after last dose of study drug in Phase 2, maximum duration up to 8.3 months
Secondary outcome [47] 0 0
Number of Participants With Notable Abnormal Electrocardiogram (ECG) Values: Phase 2
Timepoint [47] 0 0
Baseline (Day 1) up to 30 days after last dose of study drug in Phase 2, maximum duration up to 8.3 months
Secondary outcome [48] 0 0
Plasma Concentrations of Encorafenib and Its Metabolite LHY746: SLI Phase
Timepoint [48] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose; Pre-dose on Cycle 2 Day 1, Cycle 3 Day 1
Secondary outcome [49] 0 0
Plasma Concentrations of Binimetinib and Its Metabolite AR00426032: SLI Phase
Timepoint [49] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose; Pre-dose on Cycle 2 Day 1, Cycle 3 Day 1
Secondary outcome [50] 0 0
Area Under the Plasma Concentration-Time Curve From Time Zero to 6 Hours (AUC 0-6) of Encorafenib and Its Metabolite LHY746: SLI Phase
Timepoint [50] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Secondary outcome [51] 0 0
AUC0-6 of Binimetinib and Its Metabolite AR00426032: SLI Phase
Timepoint [51] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Secondary outcome [52] 0 0
Area Under the Plasma Concentration-time Curve From Time Zero to Last Time Point (AUClast) of Encorafenib and Its Metabolite LHY746: SLI Phase
Timepoint [52] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Secondary outcome [53] 0 0
AUClast of Binimetinib and Its Metabolite AR00426032: SLI Phase
Timepoint [53] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Secondary outcome [54] 0 0
Area Under the Plasma Concentration-time Curve From Time Zero to Tau (AUCtau) of Encorafenib and Its Metabolite LHY746: SLI Phase
Timepoint [54] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Secondary outcome [55] 0 0
AUCtau of Binimetinib and Its Metabolite AR00426032: SLI Phase
Timepoint [55] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Secondary outcome [56] 0 0
Maximum Observed Plasma Concentration (Cmax) After Drug Administration of Encorafenib and Its Metabolite LHY746: SLI Phase
Timepoint [56] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Secondary outcome [57] 0 0
Cmax of Binimetinib and Its Metabolite AR00426032: SLI Phase
Timepoint [57] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Secondary outcome [58] 0 0
Minimum Observed Plasma Concentration (Cmin) at the End of a Dosing Interval at Steady State of Encorafenib and Its Metabolite LHY746: SLI Phase
Timepoint [58] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Secondary outcome [59] 0 0
Cmin of Binimetinib and Its Metabolite AR00426032: SLI Phase
Timepoint [59] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Secondary outcome [60] 0 0
Ctrough of Encorafenib and Its Metabolite LHY746: SLI Phase
Timepoint [60] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose; Pre-dose on Cycle 2 Day 1, Cycle 3 Day 1
Secondary outcome [61] 0 0
Ctrough of Binimetinib and Its Metabolite AR00426032: SLI Phase
Timepoint [61] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose; Pre-dose on Cycle 2 Day 1, Cycle 3 Day 1
Secondary outcome [62] 0 0
Time to Reach Maximum Concentration (Tmax) of Encorafenib and Its Metabolite LHY746: SLI Phase
Timepoint [62] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Secondary outcome [63] 0 0
Tmax of Binimetinib and Its Metabolite AR00426032: SLI Phase
Timepoint [63] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hrs (+/- 20 minutes [min]) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs (+/- 20 min) post-dose
Secondary outcome [64] 0 0
Time of Last PK Sample (Tlast) of Encorafenib and Its Metabolite LHY746: SLI Phase
Timepoint [64] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6, 24 hrs post-dose
Secondary outcome [65] 0 0
Tlast of Binimetinib and Its Metabolite AR00426032: SLI Phase
Timepoint [65] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6, 12 hrs post-dose
Secondary outcome [66] 0 0
Accumulation Ratio Between AUClast,ss and AUClast (RAUC) of Encorafenib and Its Metabolite LHY746: SLI Phase
Timepoint [66] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Secondary outcome [67] 0 0
RAUC of Binimetinib and Its Metabolite AR00426032: SLI Phase
Timepoint [67] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Secondary outcome [68] 0 0
Accumulation Ratio Between Cmax,ss and Cmax (RCmax) of Encorafenib and Its Metabolite LHY746: SLI Phase
Timepoint [68] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Secondary outcome [69] 0 0
Rcmax of Binimetinib and Its Metabolite AR00426032: SLI Phase
Timepoint [69] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Secondary outcome [70] 0 0
Ratio of AUClast Values of the Metabolite Compared to Parent (MRAUClast) of LHY746: SLI Phase
Timepoint [70] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Secondary outcome [71] 0 0
MRAUClast of AR00426032: SLI Phase
Timepoint [71] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Secondary outcome [72] 0 0
Ratio of Cmax Values of the Metabolite Compared to Parent (MRCmax) of LHY746: SLI Phase
Timepoint [72] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose
Secondary outcome [73] 0 0
MRCmax of AR00426032: SLI Phase
Timepoint [73] 0 0
Cycle 1 Day 1: 0.5, 1.5, 3, 6 hours (hrs) post-dose; Cycle 1 Day 15: Pre-dose, 0.5, 1.5, 3, 6 hrs post-dose

Eligibility
Key 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
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/06/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/04/2021
Sample size
Target
Accrual to date
Final
1242
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Crows Nest Eye Surgery - Crows Nest
Recruitment hospital [2] 0 0
Melanoma Institute Australia - North Sydney
Recruitment hospital [3] 0 0
Royal north shore center hospital dermatology clinics - st Leonards
Recruitment hospital [4] 0 0
Mater Imaging - Wollstonecraft
Recruitment postcode(s) [1] 0 0
2065 - Crows Nest
Recruitment postcode(s) [2] 0 0
2060 - North Sydney
Recruitment postcode(s) [3] 0 0
2065 - st Leonards
Recruitment postcode(s) [4] 0 0
2065 - Wollstonecraft
Recruitment outside Australia
Country [1] 0 0
Germany
State/province [1] 0 0
Berlin
Country [2] 0 0
United States of America
State/province [2] 0 0
Alabama
Country [3] 0 0
United States of America
State/province [3] 0 0
Arizona
Country [4] 0 0
United States of America
State/province [4] 0 0
Arkansas
Country [5] 0 0
United States of America
State/province [5] 0 0
California
Country [6] 0 0
United States of America
State/province [6] 0 0
Colorado
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
Argentina
State/province [9] 0 0
Caba
Country [10] 0 0
Argentina
State/province [10] 0 0
Ciudad Autonoma de Buenos Aires
Country [11] 0 0
Argentina
State/province [11] 0 0
Córdoba
Country [12] 0 0
Argentina
State/province [12] 0 0
La Plata
Country [13] 0 0
Argentina
State/province [13] 0 0
Rosario
Country [14] 0 0
Argentina
State/province [14] 0 0
San Martín
Country [15] 0 0
Belgium
State/province [15] 0 0
Antwerpen
Country [16] 0 0
Belgium
State/province [16] 0 0
Genk
Country [17] 0 0
Belgium
State/province [17] 0 0
Hasselt
Country [18] 0 0
Belgium
State/province [18] 0 0
Merksem
Country [19] 0 0
Brazil
State/province [19] 0 0
Belo Horizonte
Country [20] 0 0
Brazil
State/province [20] 0 0
Santo André
Country [21] 0 0
Bulgaria
State/province [21] 0 0
Pleven
Country [22] 0 0
Bulgaria
State/province [22] 0 0
Sofa
Country [23] 0 0
Bulgaria
State/province [23] 0 0
Sofia
Country [24] 0 0
Bulgaria
State/province [24] 0 0
Stara Zagora
Country [25] 0 0
Canada
State/province [25] 0 0
Ontario
Country [26] 0 0
Greece
State/province [26] 0 0
Kifisia
Country [27] 0 0
Greece
State/province [27] 0 0
Nea Ionia
Country [28] 0 0
Greece
State/province [28] 0 0
Patra
Country [29] 0 0
Greece
State/province [29] 0 0
Thessaloniki
Country [30] 0 0
Hungary
State/province [30] 0 0
Budapest
Country [31] 0 0
Hungary
State/province [31] 0 0
Debrecen
Country [32] 0 0
Hungary
State/province [32] 0 0
Gyõr
Country [33] 0 0
Hungary
State/province [33] 0 0
Kaposvar
Country [34] 0 0
Hungary
State/province [34] 0 0
Kecskemét
Country [35] 0 0
Hungary
State/province [35] 0 0
Szeged
Country [36] 0 0
Hungary
State/province [36] 0 0
Szekesfehervar
Country [37] 0 0
Hungary
State/province [37] 0 0
Szolnok
Country [38] 0 0
Israel
State/province [38] 0 0
Haifa
Country [39] 0 0
Israel
State/province [39] 0 0
Kfar Saba
Country [40] 0 0
Israel
State/province [40] 0 0
Rehovot
Country [41] 0 0
Italy
State/province [41] 0 0
Bergamo
Country [42] 0 0
Italy
State/province [42] 0 0
Bologna
Country [43] 0 0
Italy
State/province [43] 0 0
Pavia
Country [44] 0 0
Italy
State/province [44] 0 0
Rozzano
Country [45] 0 0
Italy
State/province [45] 0 0
Torino
Country [46] 0 0
Japan
State/province [46] 0 0
Chiba
Country [47] 0 0
Japan
State/province [47] 0 0
Hakodate
Country [48] 0 0
Japan
State/province [48] 0 0
Hamamatsu
Country [49] 0 0
Japan
State/province [49] 0 0
Itami-shi
Country [50] 0 0
Japan
State/province [50] 0 0
Kagoshima-shi
Country [51] 0 0
Japan
State/province [51] 0 0
Kitakyushu-shi,
Country [52] 0 0
Japan
State/province [52] 0 0
Matsumoto
Country [53] 0 0
Japan
State/province [53] 0 0
Nagoya
Country [54] 0 0
Japan
State/province [54] 0 0
Nerima-Ku
Country [55] 0 0
Japan
State/province [55] 0 0
Okayama
Country [56] 0 0
Japan
State/province [56] 0 0
Okinawa, Tomigusuku-shi
Country [57] 0 0
Japan
State/province [57] 0 0
Saitama-shi
Country [58] 0 0
Japan
State/province [58] 0 0
Saitama
Country [59] 0 0
Japan
State/province [59] 0 0
Suzaka
Country [60] 0 0
Japan
State/province [60] 0 0
Tokyo
Country [61] 0 0
Poland
State/province [61] 0 0
Bielsk Podlaski
Country [62] 0 0
Poland
State/province [62] 0 0
Grajewo
Country [63] 0 0
Poland
State/province [63] 0 0
Kielce
Country [64] 0 0
Poland
State/province [64] 0 0
Krakow
Country [65] 0 0
Poland
State/province [65] 0 0
Lodz
Country [66] 0 0
Poland
State/province [66] 0 0
Lublin
Country [67] 0 0
Poland
State/province [67] 0 0
Tarnow
Country [68] 0 0
Poland
State/province [68] 0 0
Warszawa
Country [69] 0 0
Poland
State/province [69] 0 0
Wroclaw
Country [70] 0 0
Portugal
State/province [70] 0 0
Aveiro
Country [71] 0 0
Portugal
State/province [71] 0 0
Cascais
Country [72] 0 0
Portugal
State/province [72] 0 0
Porto
Country [73] 0 0
Portugal
State/province [73] 0 0
Setubal
Country [74] 0 0
Portugal
State/province [74] 0 0
Viana do Castelo
Country [75] 0 0
Russian Federation
State/province [75] 0 0
Kurgan
Country [76] 0 0
Russian Federation
State/province [76] 0 0
Moscow
Country [77] 0 0
Russian Federation
State/province [77] 0 0
Nizhniy Novgorod
Country [78] 0 0
Russian Federation
State/province [78] 0 0
Saint-Petersburg
Country [79] 0 0
Russian Federation
State/province [79] 0 0
Samara
Country [80] 0 0
Russian Federation
State/province [80] 0 0
Smolensk
Country [81] 0 0
Russian Federation
State/province [81] 0 0
Sochi
Country [82] 0 0
South Africa
State/province [82] 0 0
Pretoria
Country [83] 0 0
South Africa
State/province [83] 0 0
Worcester
Country [84] 0 0
Spain
State/province [84] 0 0
Alcorcón
Country [85] 0 0
Spain
State/province [85] 0 0
Badalona
Country [86] 0 0
Spain
State/province [86] 0 0
Barcelona
Country [87] 0 0
Spain
State/province [87] 0 0
Jaen
Country [88] 0 0
Spain
State/province [88] 0 0
Madrid
Country [89] 0 0
Spain
State/province [89] 0 0
Sabadell
Country [90] 0 0
Spain
State/province [90] 0 0
Valencia
Country [91] 0 0
Turkey
State/province [91] 0 0
Adana
Country [92] 0 0
Turkey
State/province [92] 0 0
Ankara
Country [93] 0 0
Turkey
State/province [93] 0 0
Antalya
Country [94] 0 0
Turkey
State/province [94] 0 0
Istanbul
Country [95] 0 0
Turkey
State/province [95] 0 0
Izmir
Country [96] 0 0
Ukraine
State/province [96] 0 0
Ivano-Frankivsk
Country [97] 0 0
Ukraine
State/province [97] 0 0
Kharkiv
Country [98] 0 0
Ukraine
State/province [98] 0 0
Kyiv
Country [99] 0 0
Ukraine
State/province [99] 0 0
Lviv-Vynnyky
Country [100] 0 0
Ukraine
State/province [100] 0 0
Odesa
Country [101] 0 0
Ukraine
State/province [101] 0 0
Vinnytsia
Country [102] 0 0
Germany
State/province [102] 0 0
Bielefeld
Country [103] 0 0
Germany
State/province [103] 0 0
Bonn
Country [104] 0 0
Germany
State/province [104] 0 0
Frankfurt
Country [105] 0 0
Germany
State/province [105] 0 0
Hamburg
Country [106] 0 0
Germany
State/province [106] 0 0
Mahlow
Country [107] 0 0
Germany
State/province [107] 0 0
Schwerin
Country [108] 0 0
Hungary
State/province [108] 0 0
Kecskemet
Country [109] 0 0
Hungary
State/province [109] 0 0
Miskolc
Country [110] 0 0
Japan
State/province [110] 0 0
Hokkaido
Country [111] 0 0
Japan
State/province [111] 0 0
Osaka
Country [112] 0 0
Latvia
State/province [112] 0 0
Riga
Country [113] 0 0
Latvia
State/province [113] 0 0
Ventspils
Country [114] 0 0
Poland
State/province [114] 0 0
Bialystok
Country [115] 0 0
Poland
State/province [115] 0 0
Torun
Country [116] 0 0
United States of America
State/province [116] 0 0
Oregon
Country [117] 0 0
Argentina
State/province [117] 0 0
Ciudad Autónoma DE Buenosaires
Country [118] 0 0
Argentina
State/province [118] 0 0
Santa FE
Country [119] 0 0
Italy
State/province [119] 0 0
Naples
Country [120] 0 0
Italy
State/province [120] 0 0
Napoli
Country [121] 0 0
United States of America
State/province [121] 0 0
Michigan
Country [122] 0 0
United States of America
State/province [122] 0 0
New York
Country [123] 0 0
Canada
State/province [123] 0 0
Alberta
Country [124] 0 0
Canada
State/province [124] 0 0
Quebec

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Janssen Research & Development, LLC
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Bristol-Myers Squibb
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinicaltrials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.janssen.com/clinical-trials/transparency


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03891524