A Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of Repaglinide and Caffeine

A Phase 1 Open Label Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of Repaglinide and Caffeine

The purpose of this study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics of Repaglinide and possible metabolites after single dose administration. In addition, this study will assess the effect of multiple doses of isavuconazole on the pharmacokinetics of caffeine and possible metabolites after single dose administration. Safety and tolerability of isavuconazole alone and in combination with Repaglinide or in combination with caffeine will be assessed.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Pharmacokinetics of Caffeine; Pharmacokinetics of Repaglinide
• Intervention / Treatment: Drug: Isavuconazole; Drug: Repaglinide; Drug: Caffeine

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

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • PAREXEL Early Phase Clinical Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• 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 + Repaglinide + Caffeine; Isavuconazole three times a day on Days 5 and 6 and once a day on Days 7 through 17, repaglinide on Days 1 and Day 14, caffeine on Days 3 and 16	Drug: Isavuconazole; oral; Other Names: BAL4815; Drug: Repaglinide; oral; Other Names: Prandin®; Drug: Caffeine; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of plasma repaglinide and possible metabolite concentration: Area under the concentration-time curve from time of dosing to the last quantifiable concentration (AUClast)		Days 1 and 14
Pharmacokinetics of plasma repaglinide and possible metabolite concentration: Area under the concentration-time curve from time 0 extrapolated to infinity (AUCinf)		Days 1 and 14
Pharmacokinetics of plasma repaglinide and possible metabolite concentration: Maximum concentration (Cmax)		Days 1 and 14
Pharmacokinetics of caffeine and possible metabolite concentration: Area under the concentration-time curve from time of dosing to the last quantifiable concentration (AUClast)		Days 3 and 16
Pharmacokinetics of caffeine and possible metabolite concentration: Area under the concentration-time curve from time 0 extrapolated to infinity (AUCinf)		Days 3 and 16
Pharmacokinetics of caffeine and possible metabolite concentration: Maximum concentration (Cmax)		Days 3 and 16
Pharmacokinetics of plasma isavuconazole concentration: Trough concentration (Ctrough)		Days 10-18
Pharmacokinetics of plasma isavuconazole concentration: Area under the concentration-time curve during the time interval between consecutive dosing (AUCtau)		Days 13, 14 and 16
Pharmacokinetics of plasma isavuconazole concentration: Maximum concentration (Cmax)		Days 13, 14 and 16
Pharmacokinetics of plasma isavuconazole concentration: Time after dosing when Cmax occurs (tmax)		Days 13, 14 and 16
Safety assessed through adverse events		up to Day 24
Safety assessed through clinical laboratory evaluations	Laboratory assessments will include hematology, serum chemistry and urinalysis parameters	up to Day 18
Safety assessed by 12-lead electrocardiograms (ECGs)		up to Day 18
Safety assessed through vital signs	Vital signs will be measured including oral temperature, pulse, and sitting blood pressure	up to Day 18

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Collaborators: Basilea Pharmaceutica International Ltd

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: April 29, 2014
• First Submitted That Met QC Criteria: April 29, 2014
• First Posted (Estimate): May 1, 2014

Study Record Updates

• Last Update Posted (Estimate): May 1, 2014
• Last Update Submitted That Met QC Criteria: April 29, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Isavuconazole; Healthy Subjects; Caffeine; BAL4815; BAL8728; Repaglinide
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Antifungal Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Caffeine; Isavuconazole; Repaglinide
• Other Study ID Numbers: 9766-CL-0053