A Safety and Pharmacokinetics Study of a Recombinant Fusion Protein Linking Coagulation Factor VIIa With Albumin (rVIIa-FP) in Healthy Male Volunteers

• The frequency of related Adverse Events (AEs) to rVIIa-FP. [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
• Number of subjects who develop inhibitors against Factor VII (FVII). [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
• Number of subjects who develop antibodies against rVIIa-FP. [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

• Area under curve to the last sample with quantifiable drug concentration (AUC0-t) of a single dose of rVIIa-FP [ Time Frame: 120 hours ] [ Designated as safety issue: No ]
• Half- life (t1/2) of a single dose of rVIIa-FP [ Time Frame: 120 hours ] [ Designated as safety issue: No ]
• Incremental recovery (IR) of rVIIa-FP [ Time Frame: 120 hours ] [ Designated as safety issue: No ]
• Clearance (Cl) of a single dose of rVIIa-FP [ Time Frame: 120 hours ] [ Designated as safety issue: No ]

This is a first in man, prospective, single-center, randomized, double-blind, dose-escalation cohort study to investigate tolerability, safety and pharmacokinetics of rVIIa-FP in comparison to placebo.

• Biological: rVIIa-FP
  Recombinant VIIa-FP (rVIIa-FP) is a fusion protein linking coagulation factor VIIa with albumin and will be administered by intravenous infusion in escalating doses up to 1000 mcg/kg. Participants will receive pre-treatment with an oral anticoagulant starting 7 days prior to administration of study product and continuing for 7 days after study product has been administered.
• Biological: Placebo (0.9% normal saline)
  Placebo will be administered by intravenous infusion. Participants will receive pre-treatment with an oral anticoagulant starting 7 days prior to administration of placebo and continuing for 7 days after placebo has been administered.

• Experimental: rVIIa-FP
  Intervention: Biological: rVIIa-FP
• Placebo Comparator: Placebo (0.9% normal saline)
  Intervention: Biological: Placebo (0.9% normal saline)

Inclusion Criteria:

• Healthy male subjects between 18 and 35 years of age, both inclusive.
• Body weight between 50.0 and 100.0 kg, both inclusive.
• Body mass index (BMI) between 18.0 and 29.9 kg/m2, both inclusive.
• Written informed consent for study participation obtained before undergoing any study specific procedures.

Exclusion Criteria:

• Subjects at increased cardiovascular risk.
• Any clinical sign or known history of atherosclerosis or thromboembolic events.
• A subject considered at high risk of thromboembolic events confirmed either from history or by thrombophilia screening test.
• Subjects with significant elevation of cholesterol level.
• Renal dysfunction.
• Overt bleeding.
• Smokers with positive cotinine test at screening.
• Participation in any other trial investigating a procoagulant within the last six months prior to screening.
• Known or suspected hypersensitivity to the investigational medicinal product (IMP), or to any excipients of the IMP.
• Contraindications to Warfarin (Coumadin®).