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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Medicure
ClinicalTrials.gov Identifier:
NCT01766154
First received: December 21, 2012
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to evaluate tirofiban concentration in the blood over a period of 24 hours after tirofiban administration. Subjects with varying degrees of renal insufficiency (i.e. kidney function) will be included in the study. Tirofiban is known to be cleared from the blood by the kidneys and so people with kidney problems clear tirofiban to a slower extent compared to people without kidney problems. By comparing the tirofiban concentration profile between subjects with healthy kidney function versus with impaired kidney function, a tirofiban dosing recommendation for subjects with impaired kidney function can be made.

This is a non-randomized, single-center, open-label study. A single dose of tirofiban (25 µg/kg administered intravenously over a 3 min period) will be administered to 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


Condition Intervention Phase
Renal Insufficiency
Drug: Tirofiban
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pharmacokinetic, Pharmacodynamic, and Safety Evaluation of Tirofiban Using a Single High-Dose Bolus In Subjects With Normal Renal Function and Subjects With Moderate-to-Severe Renal Impairment With Non-Dialysis-Dependent Renal Insufficiency (NDDRI)

Resource links provided by NLM:


Further study details as provided by Medicure:

Primary Outcome Measures:
  • An analysis of tirofiban plasma concentration in normal, moderate and severe renal impaired adult subjects following a single high-dose bolus (3 min IV infusion) of tirofiban (25 µg/kg). [ Time Frame: Subject's participation in this study will last 3 days (confinement of 48 hours). ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • An analysis of platelet aggregation inhibition in normal, moderate and severe renal impaired adult subjects following a single high-dose bolus (3 min IV infusion) of tirofiban (25 µg/kg). [ Time Frame: Baseline (prior to administration of tirofiban), 15 minutes, 1 hour, and 6 hours following the end of the tirofiban administration. ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • A safety analysis of high-dose bolus tirofiban [ Time Frame: Adverse events will be assessed on Day 1 (baseline), Day 2 (dosing) and Day 3 (study exit). For most subjects, no further assessment will occur after Day 3. ] [ Designated as safety issue: Yes ]

    To evaluate the safety profile in normal, moderate and severe renal impaired adult subjects following a single high-dose bolus (3 min IV infusion) of tirofiban (25 µg/kg).

    Safety will be assessed for the duration of the subject's participation in the study which will last 3 days. If a serious adverse event is experienced the subject will be followed until the event resolves or the clinical course is stabilized.

    The most common adverse event associated with tirofiban is bleeding.



Enrollment: 25
Study Start Date: January 2013
Study Completion Date: March 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Subjects with normal renal function given tirofiban
Subjects with normal renal function (CrCl >90 mL/min)
Drug: Tirofiban
A single high-dose bolus (3 min IV infusion) of tirofiban (25 µg/kg)
Other Name: Aggrastat
Experimental: Subjects with moderate renal insufficiency given tirofiban
Subjects with moderate renal insufficiency (CrCl 30-59 mL/min)
Drug: Tirofiban
A single high-dose bolus (3 min IV infusion) of tirofiban (25 µg/kg)
Other Name: Aggrastat
Experimental: Subjects with severe renal insufficiency given tirofiban
Subjects with severe renal insufficiency (CrCl <30 mL/min).
Drug: Tirofiban
A single high-dose bolus (3 min IV infusion) of tirofiban (25 µg/kg)
Other Name: Aggrastat

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01766154

Locations
United States, Florida
Avail Clinical Research, LLC
DeLand, Florida, United States, 32720
Sponsors and Collaborators
Medicure
Investigators
Principal Investigator: John Hill, MD Avail Clinical Research, LLC
  More Information

No publications provided

Responsible Party: Medicure
ClinicalTrials.gov Identifier: NCT01766154     History of Changes
Other Study ID Numbers: Medicure 12001
Study First Received: December 21, 2012
Last Updated: March 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Medicure:
tirofiban
pharmacokinetic
renal insufficiency
Phase 1
pharmacodynamic

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Tirofiban
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents
Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014