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:

1. 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).

2. BMI ≥18.5 and ≤32.0.

3. Subjects who are able and willing to provide informed consent.

Exclusion Criteria:

1. Taking a medication from a Prohibited Medication List.

2. Active pericarditis.

3. Presumed or documented history of vasculitis.

4. Uncontrolled hypertension (blood pressure >180/110 mm Hg).

5. Dependency on renal dialysis.

6. Active internal bleeding or bleeding diathesis, surgery, trauma or
gastrointestinal/genitourinary tract bleeding within 6 weeks prior to dosing.

7. 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.

8. Thrombocytopenia (platelet count <100 x 10³ µL) or history of thrombocytopenia
following heparin, tirofiban, or eptifibatide administration.

9. 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.

10. Participation in another clinical trial 30 days prior to participation in the current
study.

11. 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.

12. Female subjects who have a positive pregnancy test at Screening or Admission (Day 1),
or who are breastfeeding.

13. Inability to comply with the protocol for the duration of the study.