The Effect of Rifampin on the Metabolism of Istradefylline in Healthy Volunteers.

Effect of a Strong Enzyme Inducer, Rifampin, on the Single-Dose Pharmacokinetics of Istradefylline in Healthy Subjects

The purpose of this study is to test whether Rifampin affects blood levels of istradefylline in humans. Rifampin could possibly decrease istradefylline levels.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Istradefylline 40 mg; Drug: Rifampin 300mg BID + istradefylline 40mg Day 8 only

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy non-smoking male and post-menopausal female subjects
• Body Mass Index: 18.0-35.0 kg/m2, inclusive
• Subjects must not be taking drugs that are moderate to potent inhibitors of CYP3A4 or CYP1A2.
• Subjects without clinically significant medical history in the judgment of the investigator
• Subjects without clinically significant laboratory or ECG abnormalities

Exclusion Criteria:

• Females that are pregnant or lactating
• Administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug, whichever is longer, prior to study drug administration, or planned administration of another investigational product or procedure during the subject's participation in this study;
• Known history of treatment for drug or alcohol addiction within the previous 12 months;
• Subjects with an average alcohol intake of more than 2 units per day or 14 units per week up to 48 hours prior to the istradefylline dose on Day 1. One unit of alcohol is ½ pint of beer (285 mL) or 1 glass of spirits (25 mL) or 1 glass of wine (125 mL);
• Donated or lost > 500 mL of blood within 3 months prior to istradefylline dose on Day 1 of Period 1;
• Positive test results for human immunodeficiency virus (HIV) or Hepatitis B surface antigen, or Hepatitis C;
• Positive test results for drugs of abuse at screening;
• Unable, or unwilling to tolerate multiple venipunctures;
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Istradefylline 40mg; Period 1: Day 1, istradefylline 40mg then crossover to Period 2	Drug: Istradefylline 40 mg; On Day 1, istradefylline 1 × 40-mg tablet administered alone; Other Names: KW-6002
Experimental: Rifampin 300mg BID + istradefylline 40mg; Period 2: Days 1-20 rifampin 300mg BID + istradefylline 40mg Day 8 only	Drug: Istradefylline 40 mg; On Day 1, istradefylline 1 × 40-mg tablet administered alone; Other Names: KW-6002; Drug: Rifampin 300mg BID + istradefylline 40mg Day 8 only; On Days 1 - 20, rifampin 300mg BID; On Day 8, istradefylline 40 mg administered first with rifampin about 2 hours after istradefylline administration; Other Names: rifadin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration-time curve from time zero to infinity (AUC0 ∞) and Observed maximum plasma concentration (Cmax) of istradefylline	Intermittently for a total of 62 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of serious adverse events, and non-serious adverse events	Continuously for up to 74 days

Collaborators and Investigators

• Sponsor: Kyowa Hakko Kirin Pharma, Inc.
• Investigators: Study Chair: Marc Cantillon, M.D., Kyowa Hakko Kirin Pharma, Inc.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: June 24, 2014
• First Submitted That Met QC Criteria: June 24, 2014
• First Posted (Estimate): June 25, 2014

Study Record Updates

• Last Update Posted (Estimate): September 3, 2015
• Last Update Submitted That Met QC Criteria: September 2, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: PD
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Purinergic P1 Receptor Antagonists; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Adenosine A2 Receptor Antagonists; Rifampin; Istradefylline
• Other Study ID Numbers: 6002-015