PK and PD Study of IDN-6556 in Subjects With Severe Renal Impairment and Matched Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
This is an open-label, parallel-group study to compare the pharmacokinetics and pharmacodynamics of IDN-6556 following a single 50 mg oral dose of IDN-6556 in subjects with severe renal impairment and matched healthy volunteers with normal renal function.

Official Title
-----------------
An Open-Label Pharmacokinetic and Pharmacodynamic Study of a Single Dose of IDN-6556 in Subjects With Severe Renal Impairment and in Matched Healthy Volunteers

Conditions
-----------------
Renal Impairment, Renal Insufficiency, Kidney Disease, Kidney Diseases

Intervention / Treatment
-----------------
* Drug: IDN-6556


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All Subjects: Male or female subjects 18 - 75 years of age, able to provide written informed consent, understand and comply with all scheduled visits, and other requirements of the study Body mass index (BMI) 18.0 - 40.0 kg/m2 and body weight >50 kg Willingness to utilize two reliable forms of contraception (for both males and females of childbearing potential) from screening to one month after the last dose of study drug Matched Healthy Volunteers: Medically healthy as determined by the Investigator Screening creatinine clearance ≥90 mL/min using the Cockcroft-Gault equation Supine blood pressure ≤145/90 mmHg No significant uncontrolled systemic or major illness that, in the opinion of the Investigator, would preclude the subject from participating in and completing the study Demographically comparable to subjects with severe renal impairment as follows: Mean body weight within ±10 kg Mean age within ±5 years Similar gender ratio Severe Renal Impaired Subjects: Screening creatinine clearance (CLCR) <30 mL/min using the Cockcroft-Gault equation Supine blood pressure ≤170/110 mmHg Documented renal impairment indicated by reduced creatinine clearance within 12 months of screening or longer Stable renal function as evidenced by ≤30% difference in two measurements of creatinine clearance on two separate occasions separated by at least 28 days with one measurement being the value at screening. Exclusion Criteria: History of renal trasplant Acute renal failure Subjects undergoing any method of dialysis or hemofiltration Evidence or history of clinically significant uncontrolled hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) Disorders or surgery of the gastrointestinal tract which may interfere with drug absorption or may otherwise influence the pharmacokinetics of the investigational medicinal product (e.g., inflammatory bowel disease, resections of the small or large intestine, etc.) History of febrile illness within 5 days prior to dosing Evidence of clinically significant liver disease or liver damage (e.g., hepatitis B or C, autoimmune hepatitis, primary biliary cirrhosis, non-alcoholic fatty liver disease, elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) that is considered clinically significant by the Investigator, etc.) Known infection with human immunodeficiency virus (HIV) upon serological testing History or presence of clinically concerning cardiac arrhythmias, or prolongation of Screening (pre-treatment) QT or QTc interval of >480 milliseconds (msec) for subjects with severe renal impairment or >450 msec for matched healthy volunteers Subjects with active or history of malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 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: Healthy Volunteers<br>All subjects receive a single 50 mg oral dose of IDN-6556 | Drug: IDN-6556<br> <br> * Other names: PF-03491390;|
| Experimental: Severe Renal Impairment<br>All subjects receive a single 50 mg oral dose of IDN-6556 | Drug: IDN-6556<br> <br> * Other names: PF-03491390;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC | Area under the plasma concentration curve (AUC) parameters include AUC0-12, AUCinf, AUClast | 48 hours | 
| Cmax | Maximum concentration (Cmax) | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of cCK18 | Biomarker cCK18 (Cleaved cytokeratin 18) PK evaluations from pre-dose to 48 hours | 48 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pharmacokinetics, pharmacodynamics, renal impairment