Clinical trial NCT04844424: A Study of JNJ-70033093 (Milvexian) in Healthy Adult Participants
Official title: An Open-Label, Randomized, Crossover Study to Evaluate the Relative Oral Bioavailability, Pharmacokinetics, and Food Effect After Single Dose (for Part 1, Part 3, Part 4 and Part 5) or Multiple-Dose (for Part 2) Administration of JNJ-70033093 (Milvexian) in Healthy Adult Participants Using Tablet, Capsule and Dispersed Tablet Formulations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2021-04-14
Enrollment: 115
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 relative bioavailability and food effect of a single dose of milvexian administered as direct compression (DC) oral tablets and roller compacted (RC) oral tablets compared with milvexian administered as Phase 2 oral capsules (Part 1) and of new concept tablets consisting of a single dose of milvexian administered as oral Tablet 1 and Tablet 2 compared with milvexian administered as Phase 2 oral capsules (Part 3) in healthy participants under fasting and fed conditions; to characterize the pharmacokinetics (PK) of multiple twice daily (BID) doses for 5 days of milvexian administered as DC oral tablets and Phase 2 oral capsules in healthy participants (Part 2) and to assess the effects of dosing time and food timing on the PK of single-dose of milvexian Phase 3 oral tablet formulation in healthy participants (Part 4) and to evaluate the relative bioavailability of a single dose of milvexian administered as oral film-coated DC whole tablets, oral film-coated DC tablets dispersed in water and then mixed with apple sauce, and oral film-coated DC tablets dispersed in water and administered as a suspension using a nasogastric (NG) tube in healthy participants under fasting conditions (Part 5).


Eligibility criteria: Inclusion Criteria:

* Healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening and on Day -1 of Treatment Period 1. If there are abnormalities, the investigator may decide that the abnormalities or deviations from normal are not clinically significant, in which case the participant may be included
* Body mass index (BMI equals to \[=\] weight/height\^2) between 18 and 30 kilograms per meter square (kg/m\^2) (inclusive), and body weight not less than 50 kg at screening
* Healthy on the basis of safety laboratory tests performed at screening and on Day -1 of Treatment Period 1. If the results of the safety laboratory tests are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant except as specified in Exclusion Criteria 2. This determination must be recorded in the participant's source documents and initialed by the investigator
* A woman must have a negative highly sensitive serum (beta-human chorionic gonadotropin \[beta-hCG\]) at screening and urine pregnancy test on Day 1 of Treatment Period 1
* Before randomization, a woman must be either: a) Not of childbearing potential defined as: postmenopausal: A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level greater than (\>) 40 international units per liter IU/L or milli-international units per milliliter (mIU/mL) in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal replacement therapy (HRT), however in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient; permanently sterile: Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy; b) Of childbearing potential and; practicing a highly effective method of contraception (failure rate of less than \[\<\] 1 percent \[%\] per year when used consistently and correctly) for at least 3 months prior to the study entry and; agrees to remain on a highly effective method of contraception throughout the study and for at least 34 days after the last dose of study drug
* During the study, a man who is sexually active with a woman of childbearing potential or with a woman who is pregnant must agree to use a barrier method of contraception (example, condom with spermicidal foam/gel/ film/cream/suppository)

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 drug to the participant or that could prevent, limit or confound the protocol-specified assessments. This may include but is not limited to any known bleeding or clotting disorder, a history of arterial or venous thrombosis, liver or renal dysfunction, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplasm, metabolic disturbances, or poor venous access
* Clinically significant abnormal values for hematology, coagulation, clinical chemistry, or urinalysis at screening or on Day -1 of Treatment Period 1 as determined by the investigator or appropriate designee. Any of the following laboratory results outside of the normal ranges specified below at screening or Day -1 of Treatment Period 1 which must be confirmed by repeat: Hemoglobin or hematocrit less than (\<) lower limit of normal; Platelet count \< lower limit of normal; activated partial thromboplastin time (aPTT) or prothrombin time (PT) \>1.2\*upper limit of normal (ULN)
* Use of any agent, including but not limited to non-steroidal anti-inflammatory drugs (NSAIDs), aspirin or other anti-platelet agents, anticoagulants, fish oil capsules, ginkgo or any agent that can potentially increase the risk of bleeding within 14 days prior to the first dose of study drug administration
* History of any clinically significant drug or food allergies (such as anaphylaxis or hepatotoxicity) and known allergy to the study drugs or any of the excipients of the formulation
* History of allergy to or unwillingness to consume any component of the standardized high-fat breakfast menu to be provided in this study
* Woman with history of excessive menstrual bleeding as determined by the investigator or appropriate designee
* Does not tolerate venipuncture

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve of Milvexian from Time Zero to Infinity (AUC [0-Infinity])
timeFrame: Up to 16 months
measure: Part 2: Area under the Plasma Concentration-time Curve of Milvexian From Time Zero to Time of Last Quantifiable Concentration (AUC [0-Last])
timeFrame: Up to 16 months
measure: Maximum Observed Analyte Concentration (Cmax) of Milvexian
timeFrame: Up to 16 months
measure: Parts 1 and 3: AUC (0-Infinity) of Milvexian (Food effect)
timeFrame: Up to 16 months
measure: Parts 1 and 3: AUC (0-Last) of Milvexian (Food effect)
timeFrame: Up to 16 months
measure: Parts 1 and 3: Cmax of Milvexian (Food effect)
timeFrame: Up to 16 months
measure: Actual Sampling Time to Reach the Maximum Observed Analyte Concentration (Tmax) of Milvexian
timeFrame: Up to 16 months
measure: Parts 1 and 3: Tmax of Milvexian (Food effect)
timeFrame: Up to 16 months
Secondary outcomes:
measure: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: Up to 16 months
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: PRA Health Sciences
state: Utah
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: