HealthyPhase 1NCT04543383
A Study to Assess the Reversal of the Anticoagulant Effects of Milvexian by 4-Factor Prothrombin Complex Concentrate (4F-PCC) (Part 1) and Recombinant Human Factor VIIa (rFVIIa) (Part 2) in Healthy Participants
A Phase 1 study testing Milvexian, 4-Factor Prothrombin Complex Concentrate (4F-PCC) and Recombinant Human Factor VIIa (rFVIIa) in people with Healthy, run by Janssen Research & Development, LLC at 1 site in Netherlands.
Trial summary
The primary purpose of this study is to evaluate the reversal of the anticoagulant effects of milvexian by 4-Factor Prothrombin Complex Concentrate (4F-PCC) and Recombinant Human Factor VIIa (rFVIIa) in healthy participants as measured by changes from baselines of the coagulation testing parameters (activated partial… Read more about this study
- Who is it for?
- Ages 18 to 54 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Milvexian, 4-Factor Prothrombin Complex Concentrate (4F-PCC) and Recombinant Human Factor VIIa (rFVIIa)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 1 siteNetherlands
- Study dates
- 27 Jul 2020to 9 Jun 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 54 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participants must be healthy on the basis of medical history, physical examination, vital signs, electrocardiogram (ECG), and laboratory test results, including serum chemistry, lipid profiles (low-density lipoprotein [LDL], high-density lipoprotein [HDL], apolipoprotein B and lipoprotein a), levels of protein C, protein S and antithrombin, fibrinogen, factors VIIIc, IXc, Xc, XIc and blood coagulation (activated partial thromboplastin time [aPTT], prothrombin time [PT]) measured at local laboratory, hematology and urinalysis performed at screening. If abnormalities or deviations from normal are observed, they must be of no clinical significance in the opinion of the investigator
- Before randomization, a woman must either be: Not of childbearing potential defined as: Postmenopausal-A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level greater than (>) 40 International Units Per Liter (IU/L) or milli-international units per milliliter (mIU/mL) in the postmenopausal range may be used to confirm a postmenopausal state in women, however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient; Permanently sterile- Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Of childbearing potential, a woman must have an intrauterine device without estrogen- and or progestogen-containing system, or have vasectomized partner or practice sexual abstinence, agrees to remain on the above highly effective contraceptive method throughout the study and for at least 90 days after the last dose of study intervention
- A male participant must wear a condom when engaging in any activity with a woman of childbearing potential during the study and for the duration of treatment with milvexian plus 5 half-lives of the study intervention for a total of 94 days after the completion of treatment. Male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception because condom may break or leak
- If a woman, must have a negative highly sensitive serum (Beta-human chorionic gonadotropin [Beta-hCG]) pregnancy test at screening and urine (Beta-hCG) pregnancy test on Day -1 of each study period (Part 1) or on Day -1 of Period 1 (Part 2)
- Women must have no history of excessive menstrual bleeding or hemorrhage following pregnancy delivery
- A male participant must agree not to donate sperm for the purpose of reproduction during the study and for 94 days after receiving the last dose of study intervention
- Body mass index (weight [kilogram {kg}/height^2 [meter {m^2}]) more than equal to 18.0 and less than equal to 29.9 kg/m^2 body weight not less than 50 kg and not more than 100 kg.
Who cannot join
- History or family history of any known illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study intervention to the participant or that could prevent, limit or confound the protocol specified assessments. This may include but is not limited to any known bleeding or clotting disorder, cardiolipin antibody and anti-beta2-glycoprotein I, abnormal levels of fibrinogen, factors VIIIc, IXc, Xc, XIc, inherited or acquired thrombophilia, bleeding diathesis or coagulopathy, excessive bruising, bleeding from nose or gums or known disorders with increased bleeding risk, serious bleeding including gastrointestinal bleeding requiring hospitalization, intracranial bleeding of any type, or uncontrollable postoperative bleeding, a history of arterial or venous thrombosis, phlebitis, inherited or acquired thrombophilia, known family history of unexplained thrombotic disorders, known intracranial or intraabdominal tumor, hemorrhage, or aneurysm, liver or renal dysfunction, clinically significant cardiac, vascular disorders, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplastic abnormalities, or metabolic disturbances, or poor venous access
- History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders criteria within 1 year before screening or positive test result(s) for alcohol and/or drugs of abuse (such as hallucinogens (lysergic acid diethylamide [LSD]), barbiturates, opiates, opioids, cocaine, cannabinoids, amphetamines, and benzodiazepines) at screening and/or on Day -1 of Period 1
- Have laboratory values at screening or Day -1 of Period 1 above or below limits of normal that in the investigator's judgment may affect the safety of the participants
- Any of the following laboratory results outside of the ranges specified below at screening or on Day -1 of Period 1, confirmed by repeat: Hemoglobin or hematocrit < lower limit of normal, Platelet count less than (<) lower limit of normal, aPTT, or PT > upper limit of normal (ULN), LDL, HDL, apolipoprotein B, or lipoprotein a, outside the normal reference ranges, Factor II gene mutation or Factor V Leiden mutation assessed by polymerase chain reaction (PCR) tests, positive for Lupus Anticoagulants (LA screen, confirm and Silica Clotting Time [SCT]), cardiolipin antibody and anti-beta2-glycoprotein I, abnormal levels of protein C, protein S, antithrombin, fibrinogen, factors VIIIc, IXc, Xc, XIc
- Any of the following on 12-lead ECG based on an average of triplicate measurements at screening or Day -1 of Period 1: PR greater than or equal to (>=) 210 millisecond (msec), QRS >=120 msec, QTcF>=450 msec for male and >=470 msec for female, Heart Rate (HR) >= 100 beats per minute (bpm)
- History of any significant drug allergy (such as anaphylaxis or hepatotoxicity) and known allergy to the study interventions or any of the excipients of the formulations. History of allergy to or unwillingness to consume any component of high-fat breakfast menu to be provided in this study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Two-Part, Open-Label, Randomized, Placebo-Controlled Crossover Study to Assess the Reversal of the Anticoagulant Effects of Milvexian by 4-Factor Prothrombin Complex Concentrate (4F-PCC) (Part 1) and Recombinant Human Factor VIIa (rFVIIa) (Part 2) in Healthy Subjects
The primary purpose of this study is to evaluate the reversal of the anticoagulant effects of milvexian by 4-Factor Prothrombin Complex Concentrate (4F-PCC) and Recombinant Human Factor VIIa (rFVIIa) in healthy participants as measured by changes from baselines of the coagulation testing parameters (activated partial thromboplastin time [aPTT] and thrombin generation assay [TGA]).
- Conditions
- Healthy
- Being tested
- Milvexian, 4-Factor Prothrombin Complex Concentrate (4F-PCC), Recombinant Human Factor VIIa (rFVIIa), Placebo matching to 4F-PCC, Placebo matching to rFVIIa
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MilvexianDrug
Also called BMS-986177, JNJ-70033093
Milvexian will be administered orally.
4-Factor Prothrombin Complex Concentrate (4F-PCC)Biological
4F-PCC will be administered intravenously.
Recombinant Human Factor VIIa (rFVIIa)Biological
rFVIIa will be administered intravenously.
Placebo matching to 4F-PCCBiological
Placebo matching to 4F-PCC will be administered intravenously.
Placebo matching to rFVIIaBiological
Placebo matching to rFVIIa will be administered intravenously.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 | Experimental | Participants will receive two oral doses of milvexian (on Days 1 to 3), one in the morning and one in the evening. On Day 4, participants will only receive the morning dose of milvexian. On Day 4, four hours after the morning dosing of milvexian, each participant will receive an intravenous (IV) infusion of 4-Factor Prothrombin Complex Concentrate (4F-PCC) or matching placebo as per the treatment sequence AB and BA; in treatment period 1 and treatment period 2 where Treatment A=Dose 2 of milvexian + Dose 1 of 4F-PCC; Treatment B=Dose 2 milvexian + Placebo. A washout period of 14 days to 21 days will be maintained between each treatment period 1 and 2. Receives: Drug: Milvexian; Biological: 4-Factor Prothrombin Complex Concentrate (4F-PCC); Biological: Placebo matching to 4F-PCC |
| Part 2 (Group 1) | Experimental | Participants will receive an oral dose of milvexian in morning in fed state on Day 1 and IV injection of Recombinant Human Factor VIIa (rFVIIa) or placebo matching to rFVIIa on Day 1 after 4 hours post morning milvexian dose in the following treatment sequence: DEF1, EF1D, F1DE, EDF1, F1ED and DF1E; in treatment period 1, treatment period 2 and treatment period 3 respectively where Treatment D=Dose 1 of milvexian +Dose 1 of rFVIIa; Treatment E=Dose 3 of milvexian+Dose 1 of rFVIIa; Treatment F1=Dose 3 of milvexian+Placebo; Treatment F2=Dose 1 of milvexian+Placebo. A washout period of 4 days will be maintained between each treatment period 1, 2 and 3. Receives: Drug: Milvexian; Biological: Recombinant Human Factor VIIa (rFVIIa); Biological: Placebo matching to rFVIIa |
| Part 2 (Group 2) | Experimental | Participants will receive an oral dose of milvexian in morning in fed state on Day 1 and IV injection of rFVIIa or placebo matching to rFVIIa on Day 1 after 4 hours post morning milvexian dose in the following treatment sequence: DEF2, EF2D, F2DE, EDF2, F2ED and DF2E; in treatment period 1, treatment period 2 and treatment period 3 respectively where Treatment D=Dose 1 of milvexian+Dose 1 of rFVIIa; Treatment E=Dose 3 of milvexian+Dose 1 of rFVIIa; Treatment F1=Dose 3 of milvexian+Placebo; Treatment F2=Dose 1 of milvexian+Placebo. A washout period of 4 days will be maintained between each treatment period 1, 2 and 3. Receives: Drug: Milvexian; Biological: Recombinant Human Factor VIIa (rFVIIa); Biological: Placebo matching to rFVIIa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Change from Baseline in Activated Partial Thromboplastin Time (aPTT)
The aPTT measures the time it takes plasma to clot when exposed to substances that activate the contact factors, which assesses the intrinsic and common pathways of coagulation.
Measured: Baseline, Day 4
Part 2: Change from Baseline in aPTT
The aPTT measures the time it takes plasma to clot when exposed to substances that activate the contact factors, which assesses the intrinsic and common pathways of coagulation.
Measured: Baseline, Day 1
Part 1: Change from Baseline in Endogenous Thrombin Potential (ETP) (Thrombin Generation Assay [TGA] Parameter)
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the ETP (TGA parameter). The ETP assesses the amount of thrombin which can be generated after the in vitro activation of coagulation and represents the balance between pro and anti-coagulant forces in plasma.
Measured: Baseline, Day 4
Part 1: Change from Baseline in Lag Time (TGA Parameter)
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the lag time (TGA parameter). The lag time is defined as the time needed until thrombin is generated.
Measured: Baseline, Day 4
Part 1: Change from Baseline in Peak Thrombin (TGA Parameter)
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the peak thrombin (TGA parameter). The peak thrombin is defined as the maximal effect on thrombin generation.
Measured: Baseline, Day 4
Part 1: Change from Baseline in Time to Peak Thrombin (TGA Parameter)
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the time to peak thrombin (TGA parameter). The time to peak thrombin is defined as the time required to reach maximal effect on thrombin generation.
Measured: Baseline, Day 4
Part 2: Change from Baseline in ETP (TGA Parameter)
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the ETP (TGA parameter). The ETP assesses the amount of thrombin which can be generated after the in vitro activation of coagulation and represents the balance between pro and anti-coagulant forces in plasma.
Measured: Baseline, Day 1
Part 2: Change from Baseline in Lag Time (TGA Parameter)
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the lag time (TGA parameter). The lag time is defined as the time needed until thrombin is generated.
Measured: Baseline, Day 1
Part 2: Change from Baseline in Peak Thrombin (TGA Parameter)
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the peak thrombin (TGA parameter). The peak thrombin is defined as the maximal effect on thrombin generation.
Measured: Baseline, Day 1
Part 2: Change from Baseline in Time to Peak Thrombin (TGA Parameter)
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the time to peak thrombin (TGA parameter). The time to peak thrombin is defined as the time required to reach maximal effect on thrombin generation.
Measured: Baseline, Day 1
Secondary outcomes (46)
Number of Participants with Treatment-Emergent Adverse Events (TEAE) as a Measure of Safety and Tolerability
Treatment-emergent adverse events (TEAEs) are defined as adverse events (AEs) with onset or worsening on or after date of first dose of study treatment.
Measured: Part 1: Up to 74 Days; Part 2: Up to 25 Days
Number of Participants with TEAEs of interest
Number of participants with TEAEs of interest will be reported. TEAEs associated with the following situations are considered as TEAEs of interest: bleeding, thromboembolic events (TEs) and liver injury.
Measured: Part 1: Up to 74 Days; Part 2: Up to 25 Days
Parts 1 and 2: Change From Baseline in Pulse Rate
Changes from baseline in pulse rate will be assessed.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Changes from baseline in SBP and DBP will be assessed.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in QTc Interval
Change from baseline in QT interval corrected for heart rate (QTc interval) using Fridericia method will be measured by ECG.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change from Baseline in Heart Rate (HR)
Change from baseline in HR will be measured by ECG.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change from Baseline in QRS Interval
Change from baseline in QRS interval will be measured by ECG
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change from Baseline in PR Interval
Change from baseline in PR interval will be measured by ECG.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in QT Interval
Change from baseline in QT interval will be measured by ECG.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Hematology Parameter: Platelet Count
Change from baseline in hematology parameter (platelet count) will be assessed.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Hematology Parameter: Red Blood Cell (RBC) count
Change from baseline in hematology parameter (RBC count [Unit: Cells per liter]) will be assessed.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Hematology Parameter: Hemoglobin (Hb)
Change from baseline in hematology parameter (Hb [Grams per deciliter]) will be assessed.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Hematology Parameter: Hematocrit
Change from baseline in hematology parameter (Hematocrit) will be assessed.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV)
Change from baseline in hematology parameter (MCV [Femtoliter]) will be assessed.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH)
Change from baseline in hematology parameter (MCH [Picogram]) will be assessed.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Hematology Parameter: Percentage of Reticulocytes
Change from baseline in hematology parameter (Percentage of reticulocytes) will be assessed.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Hematology Parameters: Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils
Change from baseline in hematology parameters (Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils [Unit: Giga cells per liter]) will be assessed.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Coagulation Parameter: Activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT)
Change from baseline in coagulation parameter (aPTT and PT [Unit: Seconds]) will be assessed.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change from Baseline in Serum Chemistry Parameters: Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides
Change from baseline in serum chemistry parameters (Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Sodium, Blood urea nitrogen [BUN], Cholesterol, High density Lipoprotein [HDL], Low density lipoprotein [LDL], Triglycerides [Unit: Millimole per Liter]) will be assessed.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change from Baseline in Serum Chemistry Parameters: ALT, AST, GGT, LDH, Alkaline phosphatase, CPK
Change from baseline in serum chemistry parameters (Alanine Aminotransferase [ALT], Aspartate Aminotransferase [AST], Gamma-glutamyl transferase [GGT], Lactic acid dehydrogenase [LDH], Alkaline phosphatase, Creatine phosphokinase [CPK] [Unit: International units per Liter]) will be assessed.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change from Baseline in Serum Chemistry Parameters: Amylase
Change from baseline in serum chemistry parameters (Amylase [Unit: Units per liter]) will be assessed.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change from Baseline in Serum Chemistry Parameters: Lipase
Change from baseline in serum chemistry parameters (Lipase [Unit: Units per liter]) will be assessed.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change from Baseline in Serum Chemistry Parameters: Total Bilirubin, Creatinine and Uric Acid
Change from baseline in serum chemistry parameters (Total bilirubin, Creatinine and Uric acid [Unit: Micromoles per Liter]) will be assessed.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change from Baseline in Serum Chemistry Parameters: Total Protein and Albumin
Change from baseline in serum chemistry parameters (Total protein and Albumin [Unit: Gram per Liter]) will be assessed.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Urinalysis Parameter: Specific Gravity
Change from baseline in urinalysis parameter (Specific gravity) tests will be assessed.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Urinalysis Parameter: pH
Change from baseline in urinalysis parameter (pH) tests will be assessed.
Measured: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Part 1: Mean Trough Plasma Concentration of Milvexian at Steady State (Ctrough)
Mean trough plasma concentration of milvexian at steady state will be reported.
Measured: Part 1: Predose, 2, 4, 4.75, 5, 6, 8, 12, 24, 48, and 72 hours Postdose
Part 1 and Part 2: Maximum Observed Analyte Concentration (Cmax) of Milvexian
Cmax is the maximum observed analyte concentration.
Measured: Part 1: Predose, 2, 4, 4.75, 5, 6, 8, 12, 24, 48, and 72 hours Postdose; Part 2: 0.25, 2, 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 1 and Part 2: Time to Reach Maximum Plasma Concentration (Tmax) of milvexian
Tmax is defined as actual sampling time to reach the maximum observed analyte concentration.
Measured: Part 1: Predose, 2, 4, 4.75, 5, 6, 8, 12, 24, 48, and 72 hours Postdose; Part 2: 0.25, 2, 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Parts 1 and Part 2: Elimination Half-Life (t1/2) of Milvexian
t1/2 elimination half-life means time measured for the plasma concentration to decrease by 1 half to its original concentration of milvexian.
Measured: Part 1: Predose, 2, 4, 4.75, 5, 6, 8, 12, 24, 48, and 72 hours Postdose; Part 2: 0.25, 2, 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Dosing Interval (AUC [0-t]) of Milvexian
Area under the plasma concentration versus time curve from time zero to dosing interval of milvexian.
Measured: Part 1: Predose, 2, 4, 4.75, 5, 6, 8, 12, 24, 48, and 72 hours Postdose
Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of Milvexian
Area under the plasma concentration versus time curve from time zero to infinity with extrapolation of the terminal phase of milvexian.
Measured: Part 2: 0.25, 2, 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 1 and Part 2: Area Under Plasma Concentration From Time Zero to the Last Quantifiable Concentration (AUC [0-last]) of Milvexian
Area under the plasma concentration versus time curve from time zero to the time corresponding to the last quantifiable concentration of milvexian will be assessed.
Measured: Part 1: Predose, 2, 4, 4.75, 5, 6, 8, 12, 24, 48, and 72 hours Postdose; Part 2: 0.25, 2, 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 2: Maximum Observed Analyte Concentration (Cmax) of rFVIIa
Cmax is the maximum observed analyte concentration.
Measured: Part 2: 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 2: Time to Reach Maximum Plasma Concentration (Tmax) of rFVIIa
Tmax is defined as actual sampling time to reach the maximum observed analyte concentration.
Measured: Part 2: 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 2: Elimination Half-Life (t1/2) of rFVIIa
t1/2 elimination half-life means time measured for the plasma concentration to decrease by 1 half to its original concentration of rFVIIa.
Measured: Part 2: 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of rFVIIa
Area under the plasma concentration versus time curve from time zero to infinity with extrapolation of the terminal phase of rFVIIa.
Measured: Part 2: 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 2: Area Under Plasma Concentration From Time Zero to the Last Quantifiable Concentration (AUC [0-last]) of rFVIIa
Area under the plasma concentration versus time curve from time zero to the time corresponding to the last quantifiable concentration of rFVIIa will be assessed.
Measured: Part 2: 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 2: Systemic Clearance (CL) of rFVIIa
CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose will be estimated by dividing the total administered dose by the area under the plasma concentration-time curve from time zero to infinite time (AUC [0-infinity]).
Measured: Part 2: 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 2: Volume of distribution (Vz) of rFVIIa
The Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Measured: Part 2: 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 1 and Part 2: Change from Baseline in aPTT
Change from baseline in aPTT will be reported.
Measured: Part 1: Baseline, Day 1, Day 4, Day 5, Day 6 and Day 7; Part 2: Baseline, Day 1 and Day 2
Part 1 and Part 2: Change from Baseline in ETP (TGA Parameter)
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the ETP (TGA parameter). The ETP assesses the amount of thrombin which can be generated after the in vitro activation of coagulation and represents the balance between pro and anti-coagulant forces in plasma.
Measured: Part 1: Baseline, Day 1, Day 4, Day 5, Day 6 and Day 7; Part 2: Baseline, Day 1 and Day 2
Part 1 and Part 2: Change from Baseline in Lag Time (TGA Parameter)
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the lag time (TGA parameter). The lag time is defined as the time needed until thrombin is generated.
Measured: Part 1: Baseline, Day 1, Day 4, Day 5, Day 6 and Day 7; Part 2: Baseline, Day 1 and Day 2
Part 1 and Part 2: Change from Baseline in Peak Thrombin (TGA Parameter)
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the peak thrombin (TGA parameter). The peak thrombin is defined as the maximal effect on thrombin generation.
Measured: Part 1: Baseline, Day 1, Day 4, Day 5, Day 6 and Day 7; Part 2: Baseline, Day 1 and Day 2
Part 1 and Part 2: Change from Baseline in Time to Peak Thrombin (TGA Parameter)
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the time to peak thrombin (TGA parameter). The time to peak thrombin is defined as the time required to reach maximal effect on thrombin generation.
Measured: Part 1: Baseline, Day 1, Day 4, Day 5, Day 6 and Day 7; Part 2: Baseline, Day 1 and Day 2
Percent Change from Baselines in aPTT
Percent change from baseline in aPTT will be reported.
Measured: Part 1: Baseline, Day 1, Day 4, Day 5, Day 6 and Day 7; Part 2: Baseline, Day 1 and Day 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2020
- Study start27 Jul 2020
- Primary completion7 Jun 2023
- Study completion9 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04543383
- Sponsor's protocol ID
- CR108769
- Other IDs
- 2020-000180-24, 70033093EDI1001
- Status last verified
- Aug 2025
- First submitted
- 28 Jul 2020
- Last updated
- 15 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/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
Publications
Dishy V, Sha S, Koshkina A, Tesfaye F, Plotnikov AN, Makimura H, Chintala M. Reversal of the Anticoagulant Effect of Milvexian by 4-Factor PCC and rFVIIa in Healthy Participants: A Two-Part, Randomized, Crossover Study. J Cardiovasc Pharmacol. 2026 Sep 1;88(3):179-189. doi: 10.1097/FJC.0000000000001859.
PubMed 42440100
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two-Part, Open-Label, Randomized, Placebo-Controlled Crossover Study to Assess the Reversal of the Anticoagulant Effects of Milvexian by 4-Factor Prothrombin Complex Concentrate (4F-PCC) (Part 1) and Recombinant Human Factor VIIa (rFVIIa) (Part 2) in Healthy Subjects
- ClinicalTrials.gov ID
- NCT04543383
- Acronym / sponsor ID
- CR108769
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 27 Jul 2020 (actual)
- Primary completion
- 7 Jun 2023 (actual)
- Study completion
- 9 Jun 2023 (actual)
- First posted
- 10 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to evaluate the reversal of the anticoagulant effects of milvexian by 4-Factor Prothrombin Complex Concentrate (4F-PCC) and Recombinant Human Factor VIIa (rFVIIa) in healthy participants as measured by changes from baselines of the coagulation testing parameters (activated partial thromboplastin time [aPTT] and thrombin generation assay [TGA]).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1 | Experimental | Drug: Milvexian, Biological: 4-Factor Prothrombin Complex Concentrate (4F-PCC), Biological: Placebo matching to 4F-PCCParticipants will receive two oral doses of milvexian (on Days 1 to 3), one in the morning and one in the evening. On Day 4, participants will only receive the morning dose of milvexian. On Day 4, four hours after the morning dosing of milvexian, each participant will receive an intravenous (IV) infusion of 4-Factor Prothrombin Complex Concentrate (4F-PCC) or matching placebo as per the treatment sequence AB and BA; in treatment period 1 and treatment period 2 where Treatment A=Dose 2 of milvexian + Dose 1 of 4F-PCC; Treatment B=Dose 2 milvexian + Placebo. A washout period of 14 days to 21 days will be maintained between each treatment period 1 and 2. |
| Part 2 (Group 1) | Experimental | Drug: Milvexian, Biological: Recombinant Human Factor VIIa (rFVIIa), Biological: Placebo matching to rFVIIaParticipants will receive an oral dose of milvexian in morning in fed state on Day 1 and IV injection of Recombinant Human Factor VIIa (rFVIIa) or placebo matching to rFVIIa on Day 1 after 4 hours post morning milvexian dose in the following treatment sequence: DEF1, EF1D, F1DE, EDF1, F1ED and DF1E; in treatment period 1, treatment period 2 and treatment period 3 respectively where Treatment D=Dose 1 of milvexian +Dose 1 of rFVIIa; Treatment E=Dose 3 of milvexian+Dose 1 of rFVIIa; Treatment F1=Dose 3 of milvexian+Placebo; Treatment F2=Dose 1 of milvexian+Placebo. A washout period of 4 days will be maintained between each treatment period 1, 2 and 3. |
| Part 2 (Group 2) | Experimental | Drug: Milvexian, Biological: Recombinant Human Factor VIIa (rFVIIa), Biological: Placebo matching to rFVIIaParticipants will receive an oral dose of milvexian in morning in fed state on Day 1 and IV injection of rFVIIa or placebo matching to rFVIIa on Day 1 after 4 hours post morning milvexian dose in the following treatment sequence: DEF2, EF2D, F2DE, EDF2, F2ED and DF2E; in treatment period 1, treatment period 2 and treatment period 3 respectively where Treatment D=Dose 1 of milvexian+Dose 1 of rFVIIa; Treatment E=Dose 3 of milvexian+Dose 1 of rFVIIa; Treatment F1=Dose 3 of milvexian+Placebo; Treatment F2=Dose 1 of milvexian+Placebo. A washout period of 4 days will be maintained between each treatment period 1, 2 and 3. |
Who may qualify
- Ages
- 18 to 54 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Participants must be healthy on the basis of medical history, physical examination, vital signs, electrocardiogram (ECG), and laboratory test results, including serum chemistry, lipid profiles (low-density lipoprotein [LDL], high-density lipoprotein [HDL], apolipoprotein B and lipoprotein a), levels of protein C, protein S and antithrombin, fibrinogen, factors VIIIc, IXc, Xc, XIc and blood coagulation (activated partial thromboplastin time [aPTT], prothrombin time [PT]) measured at local laboratory, hematology and urinalysis performed at screening. If abnormalities or deviations from normal are observed, they must be of no clinical significance in the opinion of the investigator
- Before randomization, a woman must either be: Not of childbearing potential defined as: Postmenopausal-A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level greater than (>) 40 International Units Per Liter (IU/L) or milli-international units per milliliter (mIU/mL) in the postmenopausal range may be used to confirm a postmenopausal state in women, however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient; Permanently sterile- Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Of childbearing potential, a woman must have an intrauterine device without estrogen- and or progestogen-containing system, or have vasectomized partner or practice sexual abstinence, agrees to remain on the above highly effective contraceptive method throughout the study and for at least 90 days after the last dose of study intervention
- A male participant must wear a condom when engaging in any activity with a woman of childbearing potential during the study and for the duration of treatment with milvexian plus 5 half-lives of the study intervention for a total of 94 days after the completion of treatment. Male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception because condom may break or leak
- If a woman, must have a negative highly sensitive serum (Beta-human chorionic gonadotropin [Beta-hCG]) pregnancy test at screening and urine (Beta-hCG) pregnancy test on Day -1 of each study period (Part 1) or on Day -1 of Period 1 (Part 2)
- Women must have no history of excessive menstrual bleeding or hemorrhage following pregnancy delivery
Key exclusion criteria (6 listed)
- History or family history of any known illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study intervention to the participant or that could prevent, limit or confound the protocol specified assessments. This may include but is not limited to any known bleeding or clotting disorder, cardiolipin antibody and anti-beta2-glycoprotein I, abnormal levels of fibrinogen, factors VIIIc, IXc, Xc, XIc, inherited or acquired thrombophilia, bleeding diathesis or coagulopathy, excessive bruising, bleeding from nose or gums or known disorders with increased bleeding risk, serious bleeding including gastrointestinal bleeding requiring hospitalization, intracranial bleeding of any type, or uncontrollable postoperative bleeding, a history of arterial or venous thrombosis, phlebitis, inherited or acquired thrombophilia, known family history of unexplained thrombotic disorders, known intracranial or intraabdominal tumor, hemorrhage, or aneurysm, liver or renal dysfunction, clinically significant cardiac, vascular disorders, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplastic abnormalities, or metabolic disturbances, or poor venous access
- History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders criteria within 1 year before screening or positive test result(s) for alcohol and/or drugs of abuse (such as hallucinogens (lysergic acid diethylamide [LSD]), barbiturates, opiates, opioids, cocaine, cannabinoids, amphetamines, and benzodiazepines) at screening and/or on Day -1 of Period 1
- Have laboratory values at screening or Day -1 of Period 1 above or below limits of normal that in the investigator's judgment may affect the safety of the participants
- Any of the following laboratory results outside of the ranges specified below at screening or on Day -1 of Period 1, confirmed by repeat: Hemoglobin or hematocrit < lower limit of normal, Platelet count less than (<) lower limit of normal, aPTT, or PT > upper limit of normal (ULN), LDL, HDL, apolipoprotein B, or lipoprotein a, outside the normal reference ranges, Factor II gene mutation or Factor V Leiden mutation assessed by polymerase chain reaction (PCR) tests, positive for Lupus Anticoagulants (LA screen, confirm and Silica Clotting Time [SCT]), cardiolipin antibody and anti-beta2-glycoprotein I, abnormal levels of protein C, protein S, antithrombin, fibrinogen, factors VIIIc, IXc, Xc, XIc
- Any of the following on 12-lead ECG based on an average of triplicate measurements at screening or Day -1 of Period 1: PR greater than or equal to (>=) 210 millisecond (msec), QRS >=120 msec, QTcF>=450 msec for male and >=470 msec for female, Heart Rate (HR) >= 100 beats per minute (bpm)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MilvexianAlso: BMS-986177, JNJ-70033093Milvexian will be administered orally. | Drug | Part 1, Part 2 (Group 1), Part 2 (Group 2) |
| 4-Factor Prothrombin Complex Concentrate (4F-PCC)4F-PCC will be administered intravenously. | Biological | Part 1 |
| Recombinant Human Factor VIIa (rFVIIa)rFVIIa will be administered intravenously. | Biological | Part 2 (Group 1), Part 2 (Group 2) |
| Placebo matching to 4F-PCCPlacebo matching to 4F-PCC will be administered intravenously. | Biological | Part 1 |
| Placebo matching to rFVIIaPlacebo matching to rFVIIa will be administered intravenously. | Biological | Part 2 (Group 1), Part 2 (Group 2) |
Primary outcome
Part 1: Change from Baseline in Activated Partial Thromboplastin Time (aPTT)
Time frame: Baseline, Day 4
The aPTT measures the time it takes plasma to clot when exposed to substances that activate the contact factors, which assesses the intrinsic and common pathways of coagulation.
Part 2: Change from Baseline in aPTT
Time frame: Baseline, Day 1
The aPTT measures the time it takes plasma to clot when exposed to substances that activate the contact factors, which assesses the intrinsic and common pathways of coagulation.
Part 1: Change from Baseline in Endogenous Thrombin Potential (ETP) (Thrombin Generation Assay [TGA] Parameter)
Time frame: Baseline, Day 4
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the ETP (TGA parameter). The ETP assesses the amount of thrombin which can be generated after the in vitro activation of coagulation and represents the balance between pro and anti-coagulant forces in plasma.
Part 1: Change from Baseline in Lag Time (TGA Parameter)
Time frame: Baseline, Day 4
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the lag time (TGA parameter). The lag time is defined as the time needed until thrombin is generated.
Part 1: Change from Baseline in Peak Thrombin (TGA Parameter)
Time frame: Baseline, Day 4
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the peak thrombin (TGA parameter). The peak thrombin is defined as the maximal effect on thrombin generation.
Part 1: Change from Baseline in Time to Peak Thrombin (TGA Parameter)
Time frame: Baseline, Day 4
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the time to peak thrombin (TGA parameter). The time to peak thrombin is defined as the time required to reach maximal effect on thrombin generation.
Part 2: Change from Baseline in ETP (TGA Parameter)
Time frame: Baseline, Day 1
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the ETP (TGA parameter). The ETP assesses the amount of thrombin which can be generated after the in vitro activation of coagulation and represents the balance between pro and anti-coagulant forces in plasma.
Part 2: Change from Baseline in Lag Time (TGA Parameter)
Time frame: Baseline, Day 1
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the lag time (TGA parameter). The lag time is defined as the time needed until thrombin is generated.
Part 2: Change from Baseline in Peak Thrombin (TGA Parameter)
Time frame: Baseline, Day 1
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the peak thrombin (TGA parameter). The peak thrombin is defined as the maximal effect on thrombin generation.
Part 2: Change from Baseline in Time to Peak Thrombin (TGA Parameter)
Time frame: Baseline, Day 1
The TGA measures the thrombin generation that is indicative of an overall coagulating capacity. A calibrated automated thrombography is used to monitor the concentration of thrombin in clotting plasma with a fluorogenic substrate. The data derived from the thrombography can be used to determine the time to peak thrombin (TGA parameter). The time to peak thrombin is defined as the time required to reach maximal effect on thrombin generation.
46 secondary outcomes
Number of Participants with Treatment-Emergent Adverse Events (TEAE) as a Measure of Safety and Tolerability
Time frame: Part 1: Up to 74 Days; Part 2: Up to 25 Days
Number of Participants with TEAEs of interest
Time frame: Part 1: Up to 74 Days; Part 2: Up to 25 Days
Parts 1 and 2: Change From Baseline in Pulse Rate
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in QTc Interval
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change from Baseline in Heart Rate (HR)
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change from Baseline in QRS Interval
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change from Baseline in PR Interval
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in QT Interval
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Hematology Parameter: Platelet Count
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Hematology Parameter: Red Blood Cell (RBC) count
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Hematology Parameter: Hemoglobin (Hb)
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Hematology Parameter: Hematocrit
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV)
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH)
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Hematology Parameter: Percentage of Reticulocytes
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Hematology Parameters: Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Coagulation Parameter: Activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT)
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change from Baseline in Serum Chemistry Parameters: Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change from Baseline in Serum Chemistry Parameters: ALT, AST, GGT, LDH, Alkaline phosphatase, CPK
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change from Baseline in Serum Chemistry Parameters: Amylase
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change from Baseline in Serum Chemistry Parameters: Lipase
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change from Baseline in Serum Chemistry Parameters: Total Bilirubin, Creatinine and Uric Acid
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change from Baseline in Serum Chemistry Parameters: Total Protein and Albumin
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Urinalysis Parameter: Specific Gravity
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Parts 1 and 2: Change From Baseline in Urinalysis Parameter: pH
Time frame: Part 1: Up to 77 Days; Part 2: Up to 59 Days
Part 1: Mean Trough Plasma Concentration of Milvexian at Steady State (Ctrough)
Time frame: Part 1: Predose, 2, 4, 4.75, 5, 6, 8, 12, 24, 48, and 72 hours Postdose
Part 1 and Part 2: Maximum Observed Analyte Concentration (Cmax) of Milvexian
Time frame: Part 1: Predose, 2, 4, 4.75, 5, 6, 8, 12, 24, 48, and 72 hours Postdose; Part 2: 0.25, 2, 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 1 and Part 2: Time to Reach Maximum Plasma Concentration (Tmax) of milvexian
Time frame: Part 1: Predose, 2, 4, 4.75, 5, 6, 8, 12, 24, 48, and 72 hours Postdose; Part 2: 0.25, 2, 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Parts 1 and Part 2: Elimination Half-Life (t1/2) of Milvexian
Time frame: Part 1: Predose, 2, 4, 4.75, 5, 6, 8, 12, 24, 48, and 72 hours Postdose; Part 2: 0.25, 2, 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Dosing Interval (AUC [0-t]) of Milvexian
Time frame: Part 1: Predose, 2, 4, 4.75, 5, 6, 8, 12, 24, 48, and 72 hours Postdose
Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of Milvexian
Time frame: Part 2: 0.25, 2, 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 1 and Part 2: Area Under Plasma Concentration From Time Zero to the Last Quantifiable Concentration (AUC [0-last]) of Milvexian
Time frame: Part 1: Predose, 2, 4, 4.75, 5, 6, 8, 12, 24, 48, and 72 hours Postdose; Part 2: 0.25, 2, 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 2: Maximum Observed Analyte Concentration (Cmax) of rFVIIa
Time frame: Part 2: 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 2: Time to Reach Maximum Plasma Concentration (Tmax) of rFVIIa
Time frame: Part 2: 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 2: Elimination Half-Life (t1/2) of rFVIIa
Time frame: Part 2: 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of rFVIIa
Time frame: Part 2: 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 2: Area Under Plasma Concentration From Time Zero to the Last Quantifiable Concentration (AUC [0-last]) of rFVIIa
Time frame: Part 2: 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 2: Systemic Clearance (CL) of rFVIIa
Time frame: Part 2: 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Part 2: Volume of distribution (Vz) of rFVIIa
Time frame: Part 2: 4, 4.25, 4.5, 5, 6, 8, 12, 24 hours Postdose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2025.
- Derived from this study: PubMed 42440100Dishy V, Sha S, Koshkina A, Tesfaye F, Plotnikov AN, Makimura H, Chintala M. Reversal of the Anticoagulant Effect of Milvexian by 4-Factor PCC and rFVIIa in Healthy Participants: A Two-Part, Randomized, Crossover Study. J Cardiovasc Pharmacol. 2026 Sep 1;88(3):179-189. doi: 10.1097/FJC.0000000000001859.
- Individual participant dataSharing planned: Yes. The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Milvexian, 4-Factor Prothrombin Complex Concentrate (4F-PCC) and Recombinant Human Factor VIIa (rFVIIa) in people with Healthy, run by Janssen Research & Development, LLC at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Change from Baseline in Activated Partial Thromboplastin Time (aPTT) (time frame: Baseline, Day 4). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04543383, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2025.