A Study to Evaluate the Effect of Multiple Doses of Esomeprazole on the Pharmacokinetics of Isavuconazole

Study Overview
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Brief Summary
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The purpose of this study is to assess the effect of multiple doses of esomeprazole on the pharmacokinetics of isavuconazole. In addition, safety and tolerability of isavuconazole alone and in combination with esomeprazole will be assessed

Official Title
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A Phase 1 Randomized Open Label, Parallel Group Study to Evaluate the Effect of Multiple Doses of Esomeprazole on the Pharmacokinetics of Isavuconazole

Conditions
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Pharmacokinetics of Isavuconazole, Healthy Subjects

Intervention / Treatment
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* Drug: Isavuconazole
* Drug: Esomeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject has a body weight of at least 50 kg and a body mass index of 18.5 to 32 kg/m2, inclusive The subject's 12-lead electrocardiogram (ECG) is normal The subject's clinical laboratory test results are within normal limits Exclusion Criteria: The subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy The subject has a history of bowel obstruction, swallowing disorder, severe gastro-intestinal disorders, major gastrointestinal surgery, gastric/duodenal ulcers or any other condition that may interfere with study drug absorption Female subject has been pregnant within 6 months before screening or breast feeding within 3 months before screening The subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmia or torsade de pointes, structural heart disease, or family history of either Short or Long QT syndrome (suggested by sudden death of a close relative at a young age due to possible or probable cardiac causes). QT is the time between the start of the Q wave and the end of the T wave in the heart's electrical system The subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to clinic admission The subject has received a vaccination within the last 30 days prior to study drug administration The subject has a positive serology test for Hepatitis B surface antigen (HBsAg), Hepatitis A Immunoglobulin M antibody (anti HAV (IgM)), Hepatitis C antibody (anti-HCV), or human immunodeficiency virus (anti-HIV 1+2) The subject has a known or suspected allergy to any of the components of the trial products or the azole class of compounds, or a history of multiple and/or severe allergies to drugs or foods, or a history of severe anaphylactic reactions The subject has used tobacco or nicotine containing products in the last 6 months The subject has had treatment with any prescribed or non-prescribed drugs (including vitamins, natural and herbal remedies, e.g. St. John's wort) in the 2 weeks prior with the exception of hormonal methods of contraception, hormone replacement therapy, or occasional use of acetaminophen up to 2 g/day The subject has participated in any interventional clinical study or has received any investigational drugs within past 30 days or 5 half-lives, whichever is longer 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 anticipates an inability to abstain from alcohol or caffeine use for 48 hours prior and throughout the duration of the study; or from grapefruit, grapefruit juice, star fruit, or Seville oranges or any products containing these items from 72 hours prior and throughout the duration of the study The subject has history of consuming more than 14 units of alcoholic beverages per week within 6 months prior to screening or has a history of alcoholism or drug/chemical/substance abuse within past 2 years prior to screening (Note: one unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits/hard liquor) or the subject tests positive for alcohol or drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, and opiates) The subject has taken part in strenuous exercise within 3 days before Day 1

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

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Isavuconazole alone<br>Isavuconazole three times a day on Days 1 and 2 and once a day on Days 3, 4, and 5 | Drug: Isavuconazole<br>* oral<br>* Other names: BAL4815;|
| Experimental: Isavuconazole and Esomeprazole<br>Esomeprazole daily for 10 days starting on Day 1 and isavuconazole three times a day on Days 6 and 7 and once a day on Days 8, 9, and 10 | Drug: Isavuconazole<br>* oral<br>* Other names: BAL4815;Drug: Esomeprazole<br>* oral<br>* Other names: Nexium®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of plasma isavuconazole concentration: Area under the concentration-time curve during the time interval between consecutive dosing (AUCtau) |  | Day 5 (Arm 1) and Day 10 (Arm 2) | 
| Pharmacokinetics of plasma isavuconazole concentration: Maximum concentration (Cmax) |  | Day 5 (Arm 1) and Day 10 (Arm 2) | 
| Pharmacokinetics of plasma isavuconazole concentration: Time after dosing when Cmax occurs (tmax) |  | Day 5 (Arm 1) and Day 10 (Arm 2) | 
| Safety assessed through adverse events |  | up to Day 17 | 
| Safety assessed through clinical laboratory evaluations | Laboratory assessments will include hematology, serum chemistry and urinalysis parameters | up to Day 11 | 
| Safety assessed by 12-lead electrocardiograms (ECGs) |  | up to Day 11 | 
| Safety assessed through vital signs | Vital signs will be measured including oral temperature, pulse, and sitting blood pressure | up to Day 11 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Isavuconazole, Esomeprazole, BAL4815, BAL8728, Healthy Subjects