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

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

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.

Study Overview

• Status: Completed
• Conditions: Kidney Diseases; Renal Insufficiency; Renal Impairment; Kidney Disease
• Intervention / Treatment: Drug: IDN-6556

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research
    • Miami, Florida, United States, 33136
      • University of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. Mean body weight within ±10 kg
  2. Mean age within ±5 years
  3. 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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Volunteers; All subjects receive a single 50 mg oral dose of IDN-6556	Drug: IDN-6556; Other Names: emricasan; PF-03491390
Experimental: Severe Renal Impairment; All subjects receive a single 50 mg oral dose of IDN-6556	Drug: IDN-6556; Other Names: emricasan; 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

Collaborators and Investigators

• Sponsor: Conatus Pharmaceuticals Inc.
• Investigators: Study Chair: Dave Hagerty, MD, Conatus Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: January 15, 2014
• First Submitted That Met QC Criteria: January 16, 2014
• First Posted (Estimate): January 20, 2014

Study Record Updates

• Last Update Posted (Estimate): January 28, 2016
• Last Update Submitted That Met QC Criteria: December 18, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: pharmacokinetics; renal impairment; pharmacodynamics
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Renal Insufficiency
• Other Study ID Numbers: IDN-6556-05