Clinical trial NCT04388501: A Study Evaluating Drug Drug Interaction Between Milvexian and Atorvastatin in Healthy Participants
Official title: A Single-center, Open-label, Randomized, Three-way Cross-over Study Evaluating Drug Drug Interaction Between JNJ-70033093 and Atorvastatin in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Pharmaceutica N.V., Belgium
Sponsor class: INDUSTRY
First posted: 2020-05-14
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The purpose of this study is to evaluate the potential pharmacokinetics (PK) interaction between milvexian and atorvastatin (and its metabolites) in healthy participants at steady state.


Eligibility criteria: Inclusion Criteria:

* Healthy on the basis of physical examination, medical history, vital signs, Electrocardiogram (ECG), and laboratory test results, including serum chemistry, blood coagulation, hematology, and urinalysis, performed at screening.
* Normal renal function at screening as evidenced by an estimated glomerular filtration rate (eGFR) of greater than or equal to (\>=) 90 milliliter per minute per 1.73 square meters (mL/min/1.73 m\^2) calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
* Must sign an informed consent form (ICF) indicating they understand the purpose of, and procedures required for, the study and are willing to participate in the study
* If a woman, except for postmenopausal women, must have a negative highly sensitive serum (beta-human chorionic gonadotropin \[beta-hCG\]) at screening and urine (beta-hCG) pregnancy test on Day 1 of each treatment period
* Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies

Exclusion Criteria:

* Participant is a woman who is pregnant, breastfeeding, or planning to become pregnant during this study or within 34 days after the last study drug administration
* History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, gastrointestinal disease, diabetes mellitus, hepatic or renal insufficiency, thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results
* Clinically significant abnormal values for hematology, coagulation, clinical chemistry (including thyroid-stimulating hormone \[TSH\] at screening only), or urinalysis at screening or on Day 1 prior to the first dosing, including: Hemoglobin and hematocrit less than (\<) lower limit of normal; Platelet count \< lower limit of normal; and activated partial thromboplastin time (aPTT) or prothrombin time (PT) greater than (\>) 1.2\* upper limit of normal (ULN)
* Clinically significant abnormal physical examination, vital signs, or 12 lead ECG at screening or at admission to the study center on Day 1 prior to first dosing, as deemed appropriate by the investigator
* Participants with a history of excessive menstrual bleeding

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Milvexian at Steady State
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 10, 12, 14 hours after drug administration on Day 5 in Period 1, 2, 3
measure: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24hours]) of Milvexian at Steady State
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 10, 12, 14 hours after drug administration on Day 5 in Period 1, 2 and 3
measure: Maximum Observed Plasma Concentration (Cmax) of Atorvastatin at Steady State
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 10, 12, 14 hours after drug administration on Day 5 in Period 1, 2, 3
measure: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24hours]) of Atorvastatin in Healthy Participants at Steady State
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 10, 12, 14 hours after drug administration on Day 5 in Period 1, 2 and 3
Secondary outcomes:
measure: Cmax of Milvexian After a Single Dose Administration
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 10, 12, 14, 24, 48, 72 hours after drug administration on Day 1 in Period 1, 2, 3
measure: AUC(0-24 hours) of Milvexian After a Single Dose Administration
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 10, 12, 14, 24 hours after drug administration on Day 1 in Period 1, 2, 3
measure: Cmax of Atorvastatin After a Single Dose Administration
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 10, 12, 14, 24, 48, 72 hours after drug administration on Day 1 in Period 1, 2, 3
measure: AUC(0-24 hours) of Atorvastatin After a Single Dose Administration
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 10, 12, 14, 24 hours after drug administration on Day 1 in Period 1, 2, 3
measure: Number of Participants with Adverse Event as a Measure of Safety and Tolerability
timeFrame: Up to 3.4 months
measure: Change From Baseline in Activated Partial Thromboplastin Time (aPTT)
timeFrame: Baseline, Day 2 and Day 6
Other outcomes:
Locations:
city: Merksem
country: Belgium
facility: Clinical Pharmacology Unit
Study officials:
affiliation: Janssen Pharmaceutica N.V., Belgium
name: Janssen Pharmaceutica N.V., Belgium Clinical Trial
role: STUDY_DIRECTOR
References: