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

Primary Purpose

Renal Insufficiency

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Tirofiban

About this trial

This is an interventional treatment trial for Renal Insufficiency focused on measuring tirofiban, pharmacokinetic, renal insufficiency, Phase 1, pharmacodynamic

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Avail Clinical Research, LLC

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Subjects with normal renal function given tirofiban

Subjects with moderate renal insufficiency given tirofiban

Subjects with severe renal insufficiency given tirofiban

Arm Description

Subjects with normal renal function (CrCl >90 mL/min)

Subjects with moderate renal insufficiency (CrCl 30-59 mL/min)

Subjects with severe renal insufficiency (CrCl <30 mL/min).

Outcomes

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).

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).

Full Information

NCT ID

NCT01766154

First Posted

December 21, 2012

Last Updated

March 25, 2014

Sponsor

Medicure

1. Study Identification

Unique Protocol Identification Number

NCT01766154

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2014

Overall Recruitment Status

Completed

Study Start Date

January 2013 (undefined)

Primary Completion Date

February 2013 (Actual)

Study Completion Date

March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Medicure

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Renal Insufficiency

Keywords

tirofiban, pharmacokinetic, renal insufficiency, Phase 1, pharmacodynamic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Subjects with normal renal function given tirofiban

Arm Type

Experimental

Arm Description

Subjects with normal renal function (CrCl >90 mL/min)

Arm Title

Subjects with moderate renal insufficiency given tirofiban

Arm Type

Experimental

Arm Description

Subjects with moderate renal insufficiency (CrCl 30-59 mL/min)

Arm Title

Subjects with severe renal insufficiency given tirofiban

Arm Type

Experimental

Arm Description

Subjects with severe renal insufficiency (CrCl <30 mL/min).

Intervention Type

Drug

Intervention Name(s)

Tirofiban

Other Intervention Name(s)

Aggrastat

Intervention Description

A single high-dose bolus (3 min IV infusion) of tirofiban (25 µg/kg)

Primary Outcome Measure Information:

Title

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).

Secondary Outcome Measure Information:

Title

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.

Other Pre-specified Outcome Measures:

Title

A safety analysis of high-dose bolus tirofiban

Description

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.

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John Hill, MD

Organizational Affiliation

Avail Clinical Research, LLC

Official's Role

Principal Investigator

Facility Information:

Facility Name

Avail Clinical Research, LLC

City

DeLand

State/Province

Florida

ZIP/Postal Code

32720

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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