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Effect of Mild Hepatic Impairment on the Pharmacokinetics of Istradefylline

Primary Purpose

Hepatic Impairment

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Istradefylline
Sponsored by
Kyowa Hakko Kirin Pharma, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Hepatic Impairment focused on measuring Mild hepatic impairment, Healthy volunteer, Istradefylline

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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;

Additional inclusion criteria apply

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.

Additional exclusion criteria apply

Sites / Locations

  • Orlando Clinical Research Center
  • Noccr/Vrg

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Istradefylline

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Number of adverse events and serious adverse events
Safety and tolerability will be assessed through review of recorded adverse events and serious adverse events.

Full Information

First Posted
September 16, 2014
Last Updated
May 19, 2015
Sponsor
Kyowa Hakko Kirin Pharma, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02256033
Brief Title
Effect of Mild Hepatic Impairment on the Pharmacokinetics of Istradefylline
Official Title
Effect of Mild Hepatic Impairment (Child-Pugh Class A) on the Single-dose Pharmacokinetics of Istradefylline
Study Type
Interventional

2. Study Status

Record Verification Date
May 2015
Overall Recruitment Status
Completed
Study Start Date
August 2014 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kyowa Hakko Kirin Pharma, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Impairment
Keywords
Mild hepatic impairment, Healthy volunteer, Istradefylline

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Istradefylline
Arm Type
Experimental
Arm Description
One 40-mg tablet of istradefylline administered on Day 1.
Intervention Type
Drug
Intervention Name(s)
Istradefylline
Other Intervention Name(s)
KW-6002
Intervention Description
One 40 mg-tablet administered on Day 1
Primary Outcome Measure Information:
Title
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
Description
Single-dose pharmacokinetics (PK) of istradefylline in subjects with mild hepatic impairment (HI) (Child-Pugh Class A) and in subjects with normal hepatic function
Time Frame
Intermittently for a total of 36 days
Secondary Outcome Measure Information:
Title
Number of adverse events and serious adverse events
Description
Safety and tolerability will be assessed through review of recorded adverse events and serious adverse events.
Time Frame
Continuously for 36 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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; Additional inclusion criteria apply 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: 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. Additional exclusion criteria apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Cantillon, M.D.
Organizational Affiliation
Kyowa Hakko Kirin Pharma, Inc.
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Amy Zhang, PhD.
Organizational Affiliation
Kyowa Hakko Kirin Pharma, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Orlando Clinical Research Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32908
Country
United States
Facility Name
Noccr/Vrg
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Effect of Mild Hepatic Impairment on the Pharmacokinetics of Istradefylline

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