Drug Interaction Study of Isavuconazole and Midazolam

A Phase 1, Open-Label, Drug Interaction Study of the Pharmacokinetics of Isavuconazole and Midazolam After Separate and Concomitant Administration to Healthy Adult Subjects

The purpose of this study is to determine the effect of isavuconazole at steady state on the pharmacokinetics of midazolam in healthy adult subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Pharmacokinetics of Isavuconazole; Pharmacokinetics of Midazolam
• Intervention / Treatment: Drug: Isavuconazole; Drug: Midazolam

Detailed Description

Subjects will check-in on Day -1 and remain confined to the study center until the completion of study procedures on Day 14. Subjects will return to the study center for an outpatient follow-up visit on Day 21. Blood and urine samples will be taken at various times during the study.

Subjects will receive a single dose of oral midazolam syrup on Day 1. On Days 3 and 4, isavuconazole will be dosed orally three times daily (TID). On Days 5 through 13, isavuconazole will be dosed orally once daily (QD). A single dose of oral midazolam syrup will be administered on Day 12.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Covance Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The subject agrees to sexual abstinence, is surgically sterile, is postmenopausal, or is using a medically acceptable method to prevent pregnancy during the study period
• The subject must weigh at least 45 kg and have a body mass index (BMI) of 18-32 kg/m2
• The subject's has a normal 12-lead electrocardiogram (ECG)
• The subject is a non-smoker and has not used tobacco or nicotine products for a minimum of 6 months
• The subject's clinical laboratory test results are within normal limits

Exclusion Criteria:

• The subject has a previous history of any clinically significant gastro-intestinal, neurological, renal, hepatic, pulmonary, metabolic, cardio-vascular, psychiatric, endocrine, hematological disorder or disease, malignancy excluding non-melanoma skin cancer
• The subject has a known or suspected hypersensitivity to midazolam, isavuconazole, or the azole class of compounds
• The subject has a history of consuming more than 14 units of alcoholic beverages per week, has a history of drug or alcohol abuse within the past 2 years, or has a positive screen for alcohol or drugs of abuse/illegal drugs (Note: one unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits)
• The subject has had treatment with prescription drugs or complementary and alternative medicines within 14 days prior to study drug administration, or over-the-counter medication within 1 week prior to study drug administration, with the exception of acetaminophen up to 2g/day
• The subject anticipates an inability to abstain from caffeine or alcohol use for 48 hours prior to clinic admission and throughout the duration of the study
• The subject anticipates an inability to abstain from grapefruit, Seville oranges, star fruit, or any products containing these items from 72 hours prior to clinic admission and throughout the duration of the study
• The subject has/had a symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to clinic admission
• The subject has a positive test for hepatitis C antibody or hepatitis B surface antigen or a known history of human immunodeficiency virus
• The subject has been vaccinated within 30 days prior to study drug administration
• The subject has received an experimental agent within 30 days or five half-lives, whichever is longer, prior to study drug administration
• The subject has had any significant blood loss, donated one unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days, or donated plasma within 7 days prior to clinic admission
• The subject has any other condition which precludes the subject's participation in the trial

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Isavuconazole and Midazolam; Isavuconazole three times per day (TID) for 2 days followed by once a day (QD) for 9 days. Midazolam single doses on days 1 and 12	Drug: Isavuconazole; oral; Other Names: ASP9766; BAL8557; Drug: Midazolam; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic assessment of AUC through the analysis of blood samples	Up to Day 13
Pharmacokinetic assessment of maximum concentration (Cmax) through the analysis of blood samples	Up to Day 13

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Collaborators: Basilea Pharmaceutica

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: July 6, 2011
• First Submitted That Met QC Criteria: July 28, 2011
• First Posted (Estimate): August 1, 2011

Study Record Updates

• Last Update Posted (Estimate): August 1, 2011
• Last Update Submitted That Met QC Criteria: July 28, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: Healthy volunteers; Midazolam; Isavuconazole; ASP9766; BAL8557
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Antifungal Agents; Midazolam; Isavuconazole
• Other Study ID Numbers: 9766-CL-0023

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No