MedPath

A Study of Milvexian in Healthy Adult Females

Phase 1
Completed
Conditions
Healthy Female
Interventions
Registration Number
NCT05706753
Lead Sponsor
Janssen Pharmaceutica N.V., Belgium
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
20
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Milvexian + Midazolam + Ethinylestradiol/DrospirenoneDrospirenoneParticipants 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.
Milvexian + Midazolam + Ethinylestradiol/DrospirenoneMidazolamParticipants 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.
Milvexian + Midazolam + Ethinylestradiol/DrospirenoneEthinylestradiolParticipants 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.
Milvexian + Midazolam + Ethinylestradiol/DrospirenoneMilvexianParticipants 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.
Primary Outcome Measures
NameTimeMethod
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-hydroxymidzolamUp to Day 19

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.

Area Under the Plasma Concentration-time Curve from Time 0 to Infinite time (AUC[0-infinity]) of Midazolam and 1-hydroxymidzolamUp to Day 19

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.

Maximum Observed Plasma Concentration (Cmax) of Ethinylestradiol and DrospirenoneUp to Day 25

Cmax is defined as the maximum observed plasma concentration of ethinylestradiol and drospirenone.

Area Under the Plasma Concentration-time Curve from Time 0 to Time of the Last Observed Quantifiable Concentration (AUC[0-last]) of Ethinylestradiol and DrospirenoneUp to Day 25

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.

Maximum Observed Plasma Concentration (Cmax) of Midazolam and 1-hydroxymidzolamUp to Day 19

Cmax is defined as the maximum observed plasma concentration of midazolam and 1-hydroxymidzolam.

Area Under the Plasma Concentration-time Curve from Time 0 to Infinite Time (AUC[0-infinity]) of Ethinylestradiol and DrospirenoneUp to Day 25

AUC(0-infinity) is defined as the area under the plasma concentration-time curve of from time 0 to infinite time ethinylestradiol and drospirenone.

Secondary Outcome Measures
NameTimeMethod
Number of Participants with Abnormalities in Vital SignsUp to 16 weeks

Number of participants with abnormalities in vital signs (including blood pressure, pulse/heart rate, respiratory rate, body temperature) will be reported.

Number of Participants with Adverse Events (AEs) of InterestUp to 16 weeks

AEs of Interest includes bleeding events, liver enzyme elevation and clinical liver events, and cutaneous events.

Area Under the Plasma Concentration-time Curve from Time 0 to Time of the Last Observed Quantifiable Concentration (AUC[0-last]) of MilvexianUp to Day 19

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.

Area Under the Plasma Concentration-time Curve of Milvexian over the Dosing Interval (tau) at Steady-state (AUCtau,ss)Up to Day 19

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).

Number of Participants with Adverse Events (AEs)Up to 16 weeks

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.

Number of Participants with Abnormalities in Electrocardiograms (ECGs)Up to 16 weeks

Number of participants with abnormalities in ECGs will be reported.

Maximum Observed Plasma Concentration of Milvexian at Steady-state (Cmax,ss)Up to Day 19

Cmax,ss is defined as the maximum observed plasma concentration of milvexian at steady-state.

Maximum Observed Plasma Concentration (Cmax) of MilvexianUp to Day 19

Cmax is defined as the maximum observed plasma concentration of milvexian.

Number of Participants with Abnormalities in Clinical Laboratory TestsUp to 16 weeks

Number of participants with abnormalities in clinical laboratory tests will be reported.

Trial Locations

Locations (1)

SGS Belgium NV

🇧🇪

Edegem, Belgium

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