Clinical trial NCT05706753: A Study of Milvexian in Healthy Adult Females
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Female
Lead sponsor: Janssen Pharmaceutica N.V., Belgium
Sponsor class: INDUSTRY
Collaborators: name: Bristol Myers Squibb Company (BMS)
First posted: 2023-01-31
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Midazolam and 1-hydroxymidzolam
timeFrame: Up to Day 19
measure: 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
timeFrame: Up to Day 19
measure: Area Under the Plasma Concentration-time Curve from Time 0 to Infinite time (AUC[0-infinity]) of Midazolam and 1-hydroxymidzolam
timeFrame: Up to Day 19
measure: Maximum Observed Plasma Concentration (Cmax) of Ethinylestradiol and Drospirenone
timeFrame: Up to Day 25
measure: 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
timeFrame: Up to Day 25
measure: Area Under the Plasma Concentration-time Curve from Time 0 to Infinite Time (AUC[0-infinity]) of Ethinylestradiol and Drospirenone
timeFrame: Up to Day 25
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Milvexian
timeFrame: Up to Day 19
measure: Maximum Observed Plasma Concentration of Milvexian at Steady-state (Cmax,ss)
timeFrame: Up to Day 19
measure: Area Under the Plasma Concentration-time Curve from Time 0 to Time of the Last Observed Quantifiable Concentration (AUC[0-last]) of Milvexian
timeFrame: Up to Day 19
measure: Area Under the Plasma Concentration-time Curve of Milvexian over the Dosing Interval (tau) at Steady-state (AUCtau,ss)
timeFrame: Up to Day 19
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 16 weeks
measure: Number of Participants with Adverse Events (AEs) of Interest
timeFrame: Up to 16 weeks
measure: Number of Participants with Abnormalities in Vital Signs
timeFrame: Up to 16 weeks
measure: Number of Participants with Abnormalities in Electrocardiograms (ECGs)
timeFrame: Up to 16 weeks
measure: Number of Participants with Abnormalities in Clinical Laboratory Tests
timeFrame: Up to 16 weeks
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: SGS Belgium NV
Study officials:
affiliation: Janssen Pharmaceutica N.V., Belgium
name: Janssen Pharmaceutica N.V., Belgium ClinicalTrial
role: STUDY_DIRECTOR
References: