A Two-Part, Open-Label, Randomized, Placebo-Controlled, Crossover Study to Assess the Reversal of the Anticoagulant Effects of milvexian by 4-Factor Prothrombin Complex Concentrate (4F-PCC) (Part 1) and Recombinant Human Factor VIIa (rFVIIa) (Part 2) in Healthy Subjects
- Conditions
- thromboembolic disorders10014523
- Registration Number
- NL-OMON54179
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 46
1. Participants must be male or female between 18 and <55 years of age.
2. Participants must be healthy on the basis of medical history, physical
examination, vital signs, ECG, and laboratory test results.
3. If a woman, must have a negative highly sensitive serum (β-human chorionic
gonadotropin [β-hCG]) pregnancy test at screening and urine (β-hCG) pregnancy
test on Day -1 of each study period (Part 1) or on Day -1 of Period 1 (Part 2).
4. Body mass index (weight [kg]/height^2 [m]^2) >=18.0 and <29.9 kg/m^2 body
weight not less than 50 kg and not more than 100 kg.
5. After being supine for 5 minutes, systolic blood pressure between 90 and 140
mmHg, inclusive; and no higher than 90 mmHg diastolic, inclusive.
For a complete overview see the protocol
1. If a woman, pregnant, breast-feeding or planning to become pregnant during
the study.
2. History or family 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 subject or that could prevent,
limit or confound the protocol specified assessments.
3. Participants with current hepatitis B infection, or hepatitis C infection,
or human immunodeficiency virus type1 (HIV-1) or HIV-2 infection at study
screening.
4. History of any significant drug allergy (such as anaphylaxis or
hepatotoxicity) and known allergy to the study intervention or any of the
excipients of the formulations. History of allergy to or unwillingness to
consume any component of high-fat breakfast menu to be provided in this study.
5. Any of the following laboratory results outside of the ranges specified
below at screening or on Day -1 of Period 1, confirmed by repeat: a. Hemoglobin
or hematocrit < lower limit of normal
b. Platelet count < lower limit of normal c. aPTT, or PT > ULN d. Low-density
lipoprotein (LDL), High-density lipoprotein (HDL), apolipoprotein B, or
lipoprotein a, outside the normal reference ranges
(at the screening visit only)
For a complete overview see the protocol
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To evaluate the reversal of the anticoagulant effects of JNJ-70033093 by 4F-PCC<br /><br>and rFVIIa in healthy subjects as measured by changes from baseline of the<br /><br>coagulation testing parameters (aPTT and TGA).</p><br>
- Secondary Outcome Measures
Name Time Method <p>To assess the safety and tolerability of 4F-PCC and rFVIIa when<br /><br>co-administered with milvexian to reverse its anticoagulant effects in healthy<br /><br>participants.<br /><br><br /><br>To assess the pharmacokinetics (PK) of multiple doses of milvexian at 200 mg<br /><br>BID on Days 4 to 7 (Part 1).<br /><br><br /><br>To assess the pharmacokinetics (PK) of single 100 mg and 500 mg doses of<br /><br>milvexian administered under fed condition on Day 1 in healthy participants<br /><br>(Part 2).<br /><br><br /><br>To assess the PK of rFVIIa in healthy participants (Part 2).</p><br>