Drug Interaction Study of Isavuconazole and Midazolam

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

Detailed Description
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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.

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

Conditions
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Pharmacokinetics of Isavuconazole, Pharmacokinetics of Midazolam, Healthy Volunteers

Intervention / Treatment
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* Drug: Isavuconazole
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Isavuconazole and Midazolam<br>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<br>* oral<br>* Other names: BAL8557;Drug: Midazolam<br>* Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Isavuconazole, ASP9766, BAL8557, Midazolam, Healthy volunteers