Effect of Mild Hepatic Impairment on the Pharmacokinetics of Istradefylline

NCT02256033 | Completed Phase 1

• 1 other identifier: 6002-016
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to test whether mild liver impairment affects blood levels of istradefylline in humans. Decreased liver function could possibly increase istradefylline levels.

Conditions

Hepatic Impairment

Keywords

Mild hepatic impairment; Healthy volunteer; Istradefylline

Outcome Measures

Primary Outcomes (1)

• Comparison of pharmacokinetic parameter istradefylline (Area under the concentration-time curve [AUC]) between subjects with hepatic impairment and healthy subjects with normal hepatic function using an analysis of variance model

  Single-dose pharmacokinetics (PK) of istradefylline in subjects with mild hepatic impairment (HI) (Child-Pugh Class A) and in subjects with normal hepatic function

  Intermittently for a total of 36 days

Secondary Outcomes (1)

• Number of adverse events and serious adverse events

  Continuously for 36 days

Study Arms (1)

Istradefylline

EXPERIMENTAL

One 40-mg tablet of istradefylline administered on Day 1.

Drug: Istradefylline

Interventions

Istradefylline DRUG

One 40 mg-tablet administered on Day 1

Also known as: KW-6002

Istradefylline

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:
• Non-smoking males and females 18-75 years of age, inclusive;
• Men and women with procreative potential must practice medically reliable double barrier methods of birth control;
• Body mass index (BMI): 18.0-35.0 kg/m2, inclusive:
• Must abstain from drugs and nutrients known as moderate to potent inhibitors/inducers of CYP3A4 and CYP1A enzymes. These agents should be discontinued at least 4 weeks before the istradefylline dose (Day 1) until the Follow-up visit.
• Negative results at Screening and Baseline for the following screening laboratory tests: urine drug screen (amphetamines, barbiturates, benzodiazepines, opiates, cannabinoids, and cocaine). Documented prescription use in subjects with mild HI for medications included in the urine drug of abuse test is permitted as long as the dose is stable for at least 2 weeks;
• Subjects with Normal Hepatic Function only
• Medical history without clinically significant or ongoing pathology, which in the opinion of the Investigator will preclude the subject's participation in, or influence the outcome of the study;
• Subjects with Mild Hepatic Impairment only
• Stable, mild liver disease (Child-Pugh A \[5 to 6 points\]); of cryptogenic, post-hepatic, hepatitis B/C virus, or alcoholic origin;
• Stable hepatic impairment, defined as no clinically significant change in disease status within the last 30 days, as documented by the subject's recent medical history;

You may not qualify if:

• Female subjects who are taking oral contraceptives or long-term injectable or implantable hormonal contraceptives, pregnant, lactating, or breast-feeding;
• Known history of treatment for drug or alcohol addiction within the previous 12 months or \> 14 untis of alcohol consumption per week, or alcohol consumption within 1 week prior to dosing;
• Positive test results for human immunodeficiency virus (HIV), or Hepatitis B surface antigen;
• Difficulty fasting or eating the standard meals that will be provided;
• Use of tobacco or nicotine-containing products within 90 days of the study start to the Follow-up visit (to be confirmed by urine cotinine test);
• Subjects with Hepatic Impairment only
• Severe ascites at Screening;
• History of or current severe hepatic encephalopathy (Grade 3 or higher)
• Any of the following laboratory parameters at screening:
• Serum ALT \> 5 × the upper limit of normal range (ULN);
• Serum albumin \< 2.4 g/dL;
• Platelet count \< 80,000/mm3;
• Hemoglobin \< 11 g/dL;
• Absolute neutrophil count (ANC) \< 1.5 × 109/L (\< 1.5 × 103/μL);
• Biliary liver cirrhosis or other causes of HI not related to parenchymal disorder and/or disease of the liver, including hepatocellular carcinoma.

Sponsors & Collaborators

• Kyowa Kirin Co., Ltd.: lead
• Kyowa Hakko Kirin Pharma, Inc.: collaborator

Study Sites (2)

Orlando Clinical Research Center

Orlando, Florida, 32908, United States

Location

Noccr/Vrg

Knoxville, Tennessee, 37920, United States

Location

MeSH Terms

Interventions

istradefylline

Study Officials

• Marc Cantillon, M.D.

  Kyowa Hakko Kirin Pharma, Inc.

  STUDY CHAIR

• Amy Zhang, PhD.

  Kyowa Hakko Kirin Pharma, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2014
• First Posted: October 3, 2014
• Study Start: August 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: April 25, 2024

Record last verified: 2024-04

Locations

US (2)