A Study of Milvexian in Healthy Adult Females

Healthy Female Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05706753
• Other study ID #: CR109284
• Secondary ID: 2022-002828-1270
• Status: Completed
• Phase: Phase 1
• Start date: January 25, 2023
• Est. completion date: July 20, 2023

Study information

• Verified date: August 2023
• Source: Janssen Pharmaceutica N.V., Belgium
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: July 20, 2023
• Est. primary completion date: July 20, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Female

Intervention

Drug:
• Milvexian
Milvexian will be administered orally.
• Midazolam
Midazolam will be administered orally.
• Ethinylestradiol
Ethinylestradiol will be administered orally.
• Drospirenone
Drospirenone will be administered orally.

Locations

Country	Name	City	State
Belgium	SGS Belgium NV	Edegem

Sponsors (2)

Lead Sponsor	Collaborator
Janssen Pharmaceutica N.V., Belgium	Bristol Myers Squibb Company (BMS)

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Maximum Observed Plasma Concentration (Cmax) of Milvexian	Cmax is defined as the maximum observed plasma concentration of milvexian.	Up to Day 19
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of Participants with Abnormalities in Electrocardiograms (ECGs)	Number of participants with abnormalities in ECGs will be reported.	Up to 16 weeks
Secondary	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