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

NCT01766154 | Completed Phase 1

• 1 other identifier: Medicure 12001
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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

Conditions

Renal Insufficiency

Keywords

tirofiban; pharmacokinetic; renal insufficiency; Phase 1; pharmacodynamic

Outcome Measures

Primary Outcomes (1)

• 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).

  Subject's participation in this study will last 3 days (confinement of 48 hours).

Secondary Outcomes (1)

• 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).

  Baseline (prior to administration of tirofiban), 15 minutes, 1 hour, and 6 hours following the end of the tirofiban administration.

Other Outcomes (1)

• A safety analysis of high-dose bolus tirofiban

  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.

Study Arms (3)

Subjects with normal renal function given tirofiban

EXPERIMENTAL

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

Drug: Tirofiban

Subjects with moderate renal insufficiency given tirofiban

EXPERIMENTAL

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

Drug: Tirofiban

Subjects with severe renal insufficiency given tirofiban

EXPERIMENTAL

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

Drug: Tirofiban

Interventions

Tirofiban DRUG

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

Also known as: Aggrastat

Subjects with moderate renal insufficiency given tirofiban; Subjects with normal renal function given tirofiban; Subjects with severe renal insufficiency given tirofiban

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medicure: lead

Study Sites (1)

Avail Clinical Research, LLC

DeLand, Florida, 32720, United States

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Tirofiban

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Tyrosine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• John Hill, MD

  Avail Clinical Research, LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2012
• First Posted: January 11, 2013
• Study Start: January 1, 2013
• Primary Completion: February 1, 2013
• Study Completion: March 1, 2013
• Last Updated: March 27, 2014

Record last verified: 2014-03

Locations

US (1)