Pharmacokinetics of Elinogrel in Healthy Volunteers and Patients With Mild, Moderate, and Severe Renal Impairment

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to determine the pharmacokinetics and safety of elinogrel and its metabolite in patients with mild, moderate, and severe renal impairment compared to healthy volunteers.

Detailed Description
-----------------
Multiple-dose, open-label parallel-group design in patients with mild, moderate or severe renal impairment and age (±7 years), sex and weight (±15% BMI) matched healthy subjects. mild renal impairment: CrCl from 50 to ≤80 ml/min moderate renal impairment: CrCl from 30 to <50 ml/min severe renal impairment: CrCl of <30 ml/min

Official Title
-----------------
An Open-label, Parallel-group Study to Determine the Single and Multiple Dose Pharmacokinetics of Elinogrel and Its Metabolite in Patients With Mild, Moderate, and Severe Renal Impairment Compared to Healthy Subjects

Conditions
-----------------
Renal Impairment

Intervention / Treatment
-----------------
* Drug: Elinogrel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Able to understand and sign the written informed consent Subjects should have either normal renal function or have stable renal disease Exclusion Criteria: History of heart disease Unstable or clinically significant other disorders such as respiratory, hepatic, metabolic, psychiatric or gastrointestinal disorder

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A-Patients with mild renal impairment<br> | Drug: Elinogrel<br>* 100 mg elinogrel b.i.d. with aspirin q.d. for 7 days and aspirin alone for 4 days (Dose of aspirin is 81 mg in the US and 100 mg in Germany)<br>* Other names: PRT060128;|
| Experimental: B-Healthy subjects matched to Group A<br> | Drug: Elinogrel<br>* 100 mg elinogrel b.i.d. with aspirin q.d. for 7 days and aspirin alone for 4 days (Dose of aspirin is 81 mg in the US and 100 mg in Germany)<br>* Other names: PRT060128;|
| Experimental: C-Patients with moderate renal impairment<br> | Drug: Elinogrel<br>* 100 mg elinogrel b.i.d. with aspirin q.d. for 7 days and aspirin alone for 4 days (Dose of aspirin is 81 mg in the US and 100 mg in Germany)<br>* Other names: PRT060128;|
| Experimental: D-Healthy subjects matched to Group C<br> | Drug: Elinogrel<br>* 100 mg elinogrel b.i.d. with aspirin q.d. for 7 days and aspirin alone for 4 days (Dose of aspirin is 81 mg in the US and 100 mg in Germany)<br>* Other names: PRT060128;|
| Experimental: E-Patients with severe renal impairment<br> | Drug: Elinogrel<br>* 100 mg elinogrel b.i.d. with aspirin q.d. for 7 days and aspirin alone for 4 days (Dose of aspirin is 81 mg in the US and 100 mg in Germany)<br>* Other names: PRT060128;|
| Experimental: F-Healthy subjects matched to Group E<br> | Drug: Elinogrel<br>* 100 mg elinogrel b.i.d. with aspirin q.d. for 7 days and aspirin alone for 4 days (Dose of aspirin is 81 mg in the US and 100 mg in Germany)<br>* Other names: PRT060128;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of elinogrel and its metabolite | The PK parameters calculated for both elinogrel and PRT060301 were: AUC0-12h, Cmax, and Tmax on Day 1/Day 7 and T1/2, RACC & CLR on Day 7 For elinogrel only, CLss/F and Vss/F were also calculated | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessments will include vital signs, electrocardiograms and adverse events | Safety assessments consisted of collecting all adverse events (AEs), serious adverse events (SAEs), with their severity and relationship to study drug, and pregnancies, regular monitoring of hematology, blood chemistry and urinalysis performed at study center. Safety assessments also included periodic ECG evaluations, assessments of vital signs, physical condition, and body weight. | 9 days | 
| Measures of platelet function | Platelet aggregation using VerifyNOW P2Y12 assay and thrombi formation using Portola's proprietary PCA (Perfusion Chamber Assay). | 7 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Elinogrel, Renal impairment, Healthy, Kidney dysfunction