Drug Interaction Study of Multiple Doses of Isavuconazole and Single Dose of Dextromethorphan in Healthy Adult Subjects

NCT01651325 | Completed Phase 1

• 1 other identifier: 9766-CL-0042
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics of a single dose of dextromethorphan in healthy adult subjects.

Conditions

Pharmacokinetics of Isavuconazole; Pharmacokinetics of Dextromethorphan; Healthy Adult Volunteers

Keywords

Isavuconazole; dextromethorphan; dextrorphan; DXM; Healthy Volunteers; BAL4815

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetic (PK) profile for dextromethorphan (in plasma): AUCinf, Cmax , AUClast

  Area under the concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf), maximum concentration (Cmax), and AUC from time of dosing to the last quantifiable concentration (AUClast).

  Pre-dose on Days 1 and 10, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48 and 72 hours post-dose

Secondary Outcomes (5)

• PK profile for dextromethorphan (in plasma): t1/2, tmax, CL/F, and Vz/F

  Pre-dose on Days 1 and 10, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48 and 72 hours post-dose

• PK profile for dextrorphan (in plasma): AUClast, AUCinf, Cmax, tmax, t1/2

  Pre-dose on Days 1 and 10, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48 and 72 hours post-dose

• PK Isavuconazole (in plasma): trough concentration (Ctrough)

  Pre-dose on Days 8 and 12 and at 24 (Day 13) hours post-dose

• PK profile for Isavuconazole (in plasma): AUCtau, Cmax, and tmax

  Day 9 pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12,16, 20 hours post-dose and Day 10 pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, and 24 (Day 11) hours post-dose

• Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs

  Day 1 through Day 13

Study Arms (1)

Isavuconazole and dextromethorphan

EXPERIMENTAL

Dextromethorphan on Day 1and Day 10, Isavuconazole three times per day (TID) on Days 6 and 7, and once daily (QD) on Days 8 thru 12.

Drug: Isavuconazole; Drug: dextromethorphan

Interventions

Isavuconazole DRUG

oral

Also known as: BAL4815, ASP9766

Isavuconazole and dextromethorphan

dextromethorphan DRUG

oral

Also known as: DXM

Isavuconazole and dextromethorphan

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The subject has a body weight of at least 45.0 kg and has a body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive
• The subject's 12-lead electrocardiogram (ECG) is normal at Screening and Day -1 or, if abnormal, the abnormality is not clinically significant as determined by the investigator, including a QTcF of 430 msec or less for male or 450 msec or less for female subjects
• The subject's clinical laboratory test results at Screening and Day -1 are within normal limits unless the investigator considers the abnormality to be not clinically significant. Results for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be ≤ upper limit of normal, and total bilirubin must be ≤ 1.5 mg/dL
• The female subject agrees to sexual abstinence, or is surgically sterile, postmenopausal (defined as at least 2 years at Screening without menses), or using a medically acceptable double barrier method (e.g. spermicide and diaphragm, or spermicide and condom) to prevent pregnancy and agrees to continue using this method from Screening until 3 weeks after the follow-up visit at the end of the study; and is not lactating or pregnant as documented by negative pregnancy tests at Screening and Day -1
• The male subject agrees to sexual abstinence, is surgically sterile, or is using a medically acceptable method to prevent pregnancy and agrees to continue using this method from Screening until 3 weeks after the follow-up visit at the end of the study

You may not qualify if:

• The subject has any clinically significant (as judged by the Investigator) disease history of the following systems: pulmonary, gastrointestinal, cardiovascular (including a history of clinically significant arrhythmia or clinically significant conduction delays on ECG), hepatic, neurological, psychiatric, renal, genitourinary, endocrine, metabolic, dermatologic, immunologic, hematologic, or malignancy excluding non melanoma skin cancer
• The subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmia or torsade de pointes, structural heart disease, or family history of Long QT syndrome (suggested by sudden death of a close relative at a young age due to possible or probable cardiac causes)
• The subject has/had a symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to clinic check in on Day -1
• The subject has received a vaccination within the last 30 days prior to study drug administration or plans to receive any vaccinations during the study or within 2 weeks after the last dose of study drug
• The subject has a positive result for hepatitis C antibodies or hepatitis B surface antigen at Screening or is known to be positive for human immunodeficiency virus (HIV)
• The subject has a known or suspected allergy to any of the components of the trial products including dextromethorphan or the azole class of compounds, or a history of multiple and/or severe allergies to drugs or foods (as judged by the investigator), or a history of severe anaphylactic reactions
• The subject has smoked (any use of tobacco or nicotine containing products) within 6 months prior to Screening
• The subject has had treatment with prescription drugs or complementary and alternative medicines within 14 days prior to Day -1, or over-the-counter medications within 1 week prior to Day -1, with the exception of occasional use of acetaminophen up to 2 g/day
• The subject has received an experimental agent within 30 days or 5 half-lives, whichever is longer, prior to Day -1
• 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 has donated plasma within 7 days prior to clinic check-in on Day -1
• The subject has taken part in strenuous exercise within 3 days prior to study drug administration
• The subject anticipates an inability to abstain from caffeine or alcohol use for 48 hours prior to clinical check-in on Day -1 and throughout the duration of the study; or from grapefruit, Seville oranges, star fruit, or any products containing these items from 72 hours prior to clinic check-in on Day -1 and throughout the duration of the study
• The subject has a recent history (within the last 2 years) of drug or alcohol abuse, as defined by the investigator, or a positive drug and/or alcohol screen at Screening or Day -1

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Basilea Pharmaceutica International Ltd: collaborator

Study Sites (1)

Parexel

Baltimore, Maryland, 21225, United States

Location

MeSH Terms

Interventions

isavuconazole; Dextromethorphan

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Medical Director

  Astellas Pharma Global Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2012
• First Posted: July 27, 2012
• Study Start: May 1, 2012
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: February 23, 2015

Record last verified: 2015-02

Locations

US (1)