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

NCT02121860 | Completed Phase 1 Results

• 1 other identifier: IDN-6556-08
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 3

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 mild, moderate, and severe hepatic impairment (defined as Child-Pugh A, B, and C, respectively) and matched healthy volunteers with normal hepatic function.

Conditions

Hepatic Impairment; Liver Diseases; Digestive System Diseases

Keywords

Hepatic Impairment; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (2)

• AUC

  Area under the plasma concentration curve (AUC) to 12 hours post-dose (AUC0-12); AUC to the last observed plasma concentration (AUClast);

  48 Hours

• Cmax

  Maximum concentration (Cmax)

  48 Hours

Secondary Outcomes (2)

• Levels of cCK18/M30

  predose, 0.5, 1,2,3,4,5,8,12,24, and 48 hours post dose

• Levels of Caspase 3/7 RLU

  predose, 0.5, 1,2,3,4,5,8,12,24, and 48 hours post dose

Study Arms (4)

Chil-Pugh Class A

EXPERIMENTAL

All subjects with mild hepatic impairment received a single 50 mg oral dose of IDN-6556

Drug: IDN-6556

Chil-Pugh Class B

EXPERIMENTAL

All subjects with moderate hepatic impairment received a single 50 mg oral dose of IDN-6556

Drug: IDN-6556

Chil-Pugh Class C

EXPERIMENTAL

All subjects with severe hepatic impairment received a single 50 mg oral dose of IDN-6556

Drug: IDN-6556

Normal Hepatic Function

EXPERIMENTAL

All healthy volunteers subjects received a single 50 mg oral dose of IDN-6556

Drug: IDN-6556

Interventions

IDN-6556 DRUG

Also known as: emricasan, PF-03491390

Chil-Pugh Class A; Chil-Pugh Class B; Chil-Pugh Class C; Normal Hepatic Function

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Subjects:
• Male or female subjects 18 years of age or older, 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 \>45 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
• 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 hepatic impairment as follows:
• Mean body weight within ±15 kg
• Mean age within ±10 years
• Similar gender ratio
• Subjects with Hepatic Impairment:
• Evidence of hepatic disease
• Score ≥ 2 on one of the Child-Pugh parameters, or

You may not qualify if:

• All Subjects:
• Known infection with human immunodeficiency virus (HIV) upon serological testing
• Evidence of clinically significant uncontrolled hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, renal, 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 Note: Subjects can be rescreened once afebrile and more than 5 days have elapsed since the febrile illness.
• Known ongoing drug abuse within one month prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during Screening and/or at Day -1
• Subjects with active or history of malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas)
• Dosing in another clinical trial within 30 days prior to the study drug administration
• If female: known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding
• Matched Healthy Volunteers:
• 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.)
• Screening creatinine clearance \<80 mL/min using the Cockcroft-Gault equation
• History or presence of clinically concerning cardiac arrhythmias, or prolongation of Screening (pre-treatment) QT or QTc interval of \>450 milliseconds (msec)
• History of regular alcohol consumption exceeding 28 drinks/week (1 drink = 150 mL of wine or 360 mL of beer or 45 mL of spirits) within 6 months of Screening
• Subjects with Hepatic Impairment:

Sponsors & Collaborators

• Conatus Pharmaceuticals Inc.: lead

Study Sites (3)

Avail Clinical Research

DeLand, Florida, 32720, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

MeSH Terms

Conditions

Liver Diseases; Digestive System Diseases

Interventions

3-(2-(2-tert-butylphenylaminooxalyl)aminopropionylamino)-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid

Results Point of Contact

• Title: Jean L. Chan, MD
• Organization: Conatus Pharmaceuticals

jchan@conatuspharma.com

(858) 376-2632

Study Officials

• Dave Hagerty, MD

  Conatus Pharmaceuticals Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

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: April 18, 2014
• First Posted: April 24, 2014
• Study Start: April 1, 2014
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: February 24, 2016
• Results First Posted: February 24, 2016

Record last verified: 2016-01

Locations

US (3)