Clinical trial NCT02256033: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: Mild hepatic impairment
Healthy volunteer
Istradefylline
Lead sponsor: Kyowa Kirin Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Kyowa Hakko Kirin Pharma, Inc.
First posted: 2014-10-03
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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:

  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

Primary outcomes:
measure: 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
timeFrame: Intermittently for a total of 36 days
Secondary outcomes:
measure: Number of adverse events and serious adverse events
timeFrame: Continuously for 36 days
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Knoxville
country: United States
facility: Noccr/Vrg
state: Tennessee
Study officials:
affiliation: Kyowa Hakko Kirin Pharma, Inc.
name: Marc Cantillon, M.D.
role: STUDY_CHAIR
affiliation: Kyowa Hakko Kirin Pharma, Inc.
name: Amy Zhang, PhD.
role: STUDY_DIRECTOR
References: