A Phase 1/2 study of the dose-response in pharmacodynamics and safety of prothrombin complex concentrate Cofact in healthy subjects under vitamin K antagonist anticoagulatio
- Conditions
- Treatment of bleeding and perioperative prophylaxisblood clottingblood clotting factors
- Registration Number
- NL-OMON51966
- Lead Sponsor
- Prothya Biosolutions BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 85
1. Sex: Male or female of nonchildbearing potential.
2. Age: 18 to 55 years, inclusive, at screening.
3. Body mass index (BMI):18.0 to 30.0 kg/m2, inclusive, at screening. Body
weight is not less than 50 kg and not more than 100 kg.
4. Status: Healthy subjects.
5. Female subjects will be included if they are of nonchildbearing potential.
Female subjects should have a documented history of tubal ligation more than 6
months prior to the onset of the study, or with a documented hysterectomy.
Postmenopausal women will be included in the study if the postmenopausal status
is confirmed with a history of 12 months uninterrupted spontaneous amenorrhea,
or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone
(FSH) levels >40 mIU/ml, or 6 weeks postsurgical bilateral oophorectomy with
or without hysterectomy.
6. Male subjects, if not surgically sterilized, must agree to use adequate
contraception and not donate sperm from first admission to the clinical
research center until 90 days after the follow-up visit. Adequate contraception
for the male subject (and his female partner, if she is of childbearing
potential) is defined as using hormonal contraceptives or an intrauterine
device combined with at least 1 of the following forms of contraception: a
diaphragm, a cervical cap, or a condom. Total abstinence from heterosexual
intercourse, in accordance with the lifestyle of the subject, is also
acceptable.
Further criteria apply, see protocol.
1. Employee of PRA or the Sponsor.
2. History of relevant drug and/or food allergies.
3. Any of the following laboratory results outside of the ranges, at screening:
lupus anticoagulants (LA screen) and/or anti-beta2-glycoprotein I, low levels
of protein C (activity), low levels of protein S (activity), or low levels of
antithrombin.
4. Abnormal aPTT or PT levels, or Fe or ferritin levels.
5. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma
glutamyl transferase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase
(ALP), and total bilirubin are not more than about 1.2 times the upper limit of
normal at screening (per the Investigator*s discretion).
Further criteria apply, see protocol.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Establish dose-response relationship for Cofact in vitamine K antagonist (VKA)<br /><br>reversal with respect to thrombin generation in subjects anticoagulated with<br /><br>acenocoumarol therapy</p><br>
- Secondary Outcome Measures
Name Time Method <p>Kinetics of thrombin generation<br /><br><br /><br>Assessment of global parameters of coagulation over 14 days<br /><br><br /><br>To evaluate the effects of Cofact in healthy subjects receiving acenocoumarol<br /><br>on biomarkers reflective of coagulation activation<br /><br><br /><br>To assess the safety and tolerability of Cofact in healthy subjects receiving<br /><br>acenocoumarol</p><br>