Pharmacokinetic Evaluation of Tirofiban Using a Single High-Dose Bolus In Subjects With Varying Degrees of Renal Function

Tirofiban is cleared from the plasma largely by renal excretion. As a consequence, a dosage adjustment of 50% of the tirofiban label dosing regimen (0.4 μg/kg/min for a period of 30 minutes, followed by an infusion of 0.10 μg/kg/min) is recommended in patients with severe renal impairment (<30 mL/min CrCl), including those who require hemodialysis. The dosage adjustment for the tirofiban high-dose bolus regimen (25 μg/kg bolus followed by a 0.15 μg/kg/min maintenance) for patients with varying degrees of renal insufficiency is however unknown. The purpose of this study is to determine the extent of dosage adjustment for the high-dose bolus regimen for patients with moderate (30-59 mL/min CrCl), and severe (<30 mL/min CrCl) renal insufficiency.

This non-randomized, single-center, open-label study evaluating the pharmacokinetic (PK), pharmacodynamic (PD), and safety profile of a single high-dose IV bolus injection of tirofiban (25 µg/kg). A single dose of tirofiban will be administered to the subjects with normal renal function (>90 mL/min CrCl), moderate (30-59 mL/min CrCl), and severe (<30 mL/min CrCl) renal impairment with non-dialysis-dependent renal insufficiency (NDDRI).

Inclusion criteria

• Male or female 18-85 years of age. The mean age for the subjects with normal renal function (CrCl >90 mL/min) should match the mean age for the subjects with moderate or severe renal impairment (CrCl 30-59 mL/min, or CrCl <30 mL/min).
• BMI ≥18.5 and ≤32.0.
• Subjects who are able and willing to provide informed consent.

Exclusion criteria

• Taking a medication from a Prohibited Medication List.
• Active pericarditis.
• Presumed or documented history of vasculitis.
• Uncontrolled hypertension (blood pressure >180/110 mm Hg).
• Dependency on renal dialysis.
• Active internal bleeding or bleeding diathesis, surgery, trauma or gastrointestinal/genitourinary tract bleeding within 6 weeks prior to dosing.
• Prior intracranial hemorrhage, hemorrhagic stroke, cerebrovascular accident (CVA) within 2 years or CVA with significant residual neurological deficit, intracranial neoplasm, arteriovenous malformation, intracranial aneurysm, or intracranial structural abnormality.
• Thrombocytopenia (platelet count <100 x 10³ µL) or history of thrombocytopenia following heparin, tirofiban, or eptifibatide administration.
• Taking Over-the-Counter (OTC) vitamins and/or herbal supplements including garlic oil supplements, fish oil supplements, ginger supplements or onion extract pills within 14 days before dosing.
• Participation in another clinical trial 30 days prior to participation in the current study.
• Any other condition that in the opinion of the Investigator may compromise the safety or compliance of the subject or would preclude subject successfully completing the trial.
• Female subjects who have a positive pregnancy test at Screening or Admission (Day 1), or who are breastfeeding.
• Inability to comply with the protocol for the duration of the study.