Effect of Mild Hepatic Impairment on the Pharmacokinetics of Istradefylline

NCT ID: NCT02256033

Last Updated: 2024-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-31
• Study Completion Date: 2014-12-31

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.

Detailed Description

This is a multicenter, open-label, parallel group, single-dose study to determine the single-dose PK of istradefylline in subjects with mild hepatic impairment (HI) (Child-Pugh Class A) and in subjects with normal hepatic function. Ten subjects with mild HI (Child-Pugh Class A) and 10 subjects with normal hepatic function (matched for age, gender, race, and BMI) will be enrolled. Enrollment of the subjects with normal hepatic function will be subsequent to the HI subjects.

Conditions

Hepatic Impairment

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Istradefylline

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

Group Type: EXPERIMENTAL

Istradefylline

Intervention Type: DRUG

One 40 mg-tablet administered on Day 1

Interventions

Istradefylline

One 40 mg-tablet administered on Day 1

Intervention Type: DRUG

Other Intervention Names

KW-6002

Eligibility Criteria

Inclusion Criteria

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;

Exclusion Criteria

• 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:

1. Serum ALT > 5 × the upper limit of normal range (ULN);

2. Serum albumin < 2.4 g/dL;

3. Platelet count < 80,000/mm3;

4. Hemoglobin < 11 g/dL;

5. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Kyowa Hakko Kirin Pharma, Inc.

INDUSTRY

Sponsor Role: collaborator

Kyowa Kirin Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc Cantillon, M.D.

Role: STUDY_CHAIR

Kyowa Hakko Kirin Pharma, Inc.

Amy Zhang, PhD.

Role: STUDY_DIRECTOR

Kyowa Hakko Kirin Pharma, Inc.

Locations

Orlando Clinical Research Center

Orlando, Florida, United States

Noccr/Vrg

Knoxville, Tennessee, United States

Countries

United States

Other Identifiers

6002-016

Identifier Type: -

Identifier Source: org_study_id