A Study of Milvexian in Healthy Adult Females

An Open-label, Non-randomized Study to Investigate the Effects of Twice-Daily Milvexian Administration on the Pharmacokinetics of Single Doses of Midazolam, Ethinylestradiol and Drospirenone in Healthy Adult Females

The purpose of this study is to measure the effect of milvexian given for approximately 2 weeks on (a) how the liver metabolizes other drugs (in this case one called midazolam), and (b) the pharmacokinetics (the way the body absorbs, distributes, and gets rid of a drug) of an oral contraceptive pill in healthy adult females.

Study Overview

• Status: Completed
• Conditions: Healthy Female
• Intervention / Treatment: Drug: Milvexian; Drug: Midazolam; Drug: Ethinylestradiol; Drug: Drospirenone

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • SGS Belgium NV

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy on the basis of physical examination, medical history, and vital signs, and 12-lead electrocardiography (ECG) performed at screening and on 1 day prior midazolam intervention (Day -1)
• Healthy on the basis of clinical laboratory tests performed at screening and on Day -1 (screening) of the treatment phase. If the results of the serum chemistry panel, coagulation (activated partial thromboplastin time [aPTT] and prothrombin time [PT]), hematology, or urinalysis
• Body weight not less than 50.0 kilograms (kg) and body mass index (BMI; weight (kg) per height metered square (kg/m^2) within the range 18.5-30.0 kg/m^2 (inclusive) at screening and Day -1
• All women must have a negative highly sensitive serum human chorionic gonadotropin (beta-hCG) test at screening and urine pregnancy test on Day -1
• A woman must be: a. Not of childbearing potential or b. Of childbearing potential and practicing a highly effective method of contraception and agrees to remain on a highly effective method (failure rate of less than [<]1 percentage [%] per year when used consistently and correctly) until 4 days (5 half-lives) after last dose of milvexian-the end of relevant exposure

Exclusion Criteria:

• 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
• History of any clinically significant drug or food allergies (such as anaphylaxis or hepatotoxicity) and known allergy to the study intervention or any of the excipients of milvexian, midazolam, or Drospifem 20 (ethinylestradiol + drospirenone)
• Clinically significant abnormal values for hematology, coagulation, clinical chemistry or urinalysis at screening or on Day -1 as determined by the investigator or appropriate designee. If any of the following laboratory rules are met at screening or Day -1, the participant should be excluded. A retest is allowed once: hemoglobin or hematocrit < lower limit of normal, platelet count < lower limit of normal, aPTT or PT greater than (>) 1.2 x upper limit of normal (ULN)
• Received an investigational intervention or used an invasive investigational medical device within 60 days or received a biological product within 3 months, or within a period less than 6 times the drug's half-life, if known, whichever is longer, before the first dose of study intervention or is currently enrolled in an investigational study
• Has used hormonal contraception injections or implants within 6 months of the first study intervention administration or has used any other hormonal contraception within 30 days of the first study intervention administration on Day 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Milvexian + Midazolam + Ethinylestradiol/Drospirenone; Participants will receive midazolam on Day 1 and Day 19; ethinylestradiol and drospirenone on Day 2 and Day 20; and milvexian from Day 7 to Day 24.	Drug: Milvexian; Milvexian will be administered orally.; Other Names: BMS-986177; JNJ-70033093; Drug: Midazolam; Midazolam will be administered orally.; Drug: Ethinylestradiol; Ethinylestradiol will be administered orally.; Drug: Drospirenone; Drospirenone will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Midazolam and 1-hydroxymidzolam	Cmax is defined as the maximum observed plasma concentration of midazolam and 1-hydroxymidzolam.	Up to Day 19
Area Under the Plasma Concentration-time Curve from Time 0 to Time of the Last Observed Quantifiable Concentration (AUC[0-last]) of Midazolam and 1-hydroxymidzolam	AUC(0-last) is defined as area under the plasma concentration-time curve from time 0 to time of the last observed quantifiable concentration of midazolam and 1-hydroxymidzolam.	Up to Day 19
Area Under the Plasma Concentration-time Curve from Time 0 to Infinite time (AUC[0-infinity]) of Midazolam and 1-hydroxymidzolam	AUC(0-infinity) is defined as the area under the plasma concentration-time curve from time 0 to infinite time of midazolam and 1-hydroxymidzolam.	Up to Day 19
Maximum Observed Plasma Concentration (Cmax) of Ethinylestradiol and Drospirenone	Cmax is defined as the maximum observed plasma concentration of ethinylestradiol and drospirenone.	Up to Day 25
Area Under the Plasma Concentration-time Curve from Time 0 to Time of the Last Observed Quantifiable Concentration (AUC[0-last]) of Ethinylestradiol and Drospirenone	AUC(0-last) is defined as area under the plasma concentration-time curve from time 0 to time of the last observed quantifiable concentration of ethinylestradiol and drospirenone.	Up to Day 25
Area Under the Plasma Concentration-time Curve from Time 0 to Infinite Time (AUC[0-infinity]) of Ethinylestradiol and Drospirenone	AUC(0-infinity) is defined as the area under the plasma concentration-time curve of from time 0 to infinite time ethinylestradiol and drospirenone.	Up to Day 25

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Milvexian	Cmax is defined as the maximum observed plasma concentration of milvexian.	Up to Day 19
Maximum Observed Plasma Concentration of Milvexian at Steady-state (Cmax,ss)	Cmax,ss is defined as the maximum observed plasma concentration of milvexian at steady-state.	Up to Day 19
Area Under the Plasma Concentration-time Curve from Time 0 to Time of the Last Observed Quantifiable Concentration (AUC[0-last]) of Milvexian	AUC(0-last) is defined as area under the plasma concentration-time curve from time 0 to time of the last observed quantifiable concentration of milvexian.	Up to Day 19
Area Under the Plasma Concentration-time Curve of Milvexian over the Dosing Interval (tau) at Steady-state (AUCtau,ss)	AUCtau,ss is defined as the area under the plasma concentration-time curve of milvexian over the dosing interval (tau) at steady-state (AUCtau,ss).	Up to Day 19
Number of Participants with Adverse Events (AEs)	An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention.	Up to 16 weeks
Number of Participants with Adverse Events (AEs) of Interest	AEs of Interest includes bleeding events, liver enzyme elevation and clinical liver events, and cutaneous events.	Up to 16 weeks
Number of Participants with Abnormalities in Vital Signs	Number of participants with abnormalities in vital signs (including blood pressure, pulse/heart rate, respiratory rate, body temperature) will be reported.	Up to 16 weeks
Number of Participants with Abnormalities in Electrocardiograms (ECGs)	Number of participants with abnormalities in ECGs will be reported.	Up to 16 weeks
Number of Participants with Abnormalities in Clinical Laboratory Tests	Number of participants with abnormalities in clinical laboratory tests will be reported.	Up to 16 weeks

Collaborators and Investigators

• Sponsor: Janssen Pharmaceutica N.V., Belgium
• Collaborators: Bristol Myers Squibb Company (BMS)
• Investigators: Study Director: Janssen Pharmaceutica N.V., Belgium ClinicalTrial, Janssen Pharmaceutica N.V., Belgium

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2023
• Primary Completion (Actual): July 20, 2023
• Study Completion (Actual): July 20, 2023

Study Registration Dates

• First Submitted: January 23, 2023
• First Submitted That Met QC Criteria: January 23, 2023
• First Posted (Actual): January 31, 2023

Study Record Updates

• Last Update Posted (Actual): March 30, 2025
• Last Update Submitted That Met QC Criteria: March 28, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Contraceptive Agents, Hormonal; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Reproductive Control Agents; Anesthetics; Central Nervous System Depressants; Neurotransmitter Agents; Adjuvants, Anesthesia; Hypnotics and Sedatives; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; GABA Modulators; GABA Agents; Hormone Antagonists; Diuretics; Natriuretic Agents; Contraceptive Agents, Female; Contraceptive Agents; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Estrogens; Contraceptives, Oral; Contraceptives, Oral, Hormonal; Midazolam; Ethinyl Estradiol; Drospirenone
• Other Study ID Numbers: CR109284; 2022-002828-12 (EudraCT Number); 70033093THR1009 (Other Identifier: Janssen Pharmaceutica N.V., Belgium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No