Clinical trial NCT01651325: Drug Interaction Study of Multiple Doses of Isavuconazole and Single Dose of Dextromethorphan in Healthy Adult Subjects
Official title: A Phase 1, Open-Label, Sequential Study of the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of a Single Dose of Dextromethorphan in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics of Isavuconazole
Pharmacokinetics of Dextromethorphan
Healthy Adult Volunteers
Keywords: Isavuconazole
dextromethorphan
dextrorphan
DXM
Healthy Volunteers
BAL4815
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Basilea Pharmaceutica International Ltd
First posted: 2012-07-27
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

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.

Detailed description: Subjects will check-in on Day -1 and remain confined to the clinical unit until Day 13. On the morning of Day 1, subjects will receive a single dose of dextromethorphan. On Days 6 and 7, subjects will receive isavuconazole three times daily (TID) administered approximately 8 hours apart. On Day 8 through 12, subjects will receive isavuconazole once daily (QD). On Day 10, subjects will receive a single dose of dextromethorphan. A follow-up visit will be scheduled on Day 21 (± 2 days).

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Pharmacokinetic (PK) profile for dextromethorphan (in plasma): AUCinf, Cmax , AUClast
timeFrame: 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:
measure: PK profile for dextromethorphan (in plasma): t1/2, tmax, CL/F, and Vz/F
timeFrame: 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
measure: PK profile for dextrorphan (in plasma): AUClast, AUCinf, Cmax, tmax, t1/2
timeFrame: 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
measure: PK Isavuconazole (in plasma): trough concentration (Ctrough)
timeFrame: Pre-dose on Days 8 and 12 and at 24 (Day 13) hours post-dose
measure: PK profile for Isavuconazole (in plasma): AUCtau, Cmax, and tmax
timeFrame: 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
measure: Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs
timeFrame: Day 1 through Day 13
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Parexel
state: Maryland
Study officials:
affiliation: Astellas Pharma Global Development
name: Medical Director
role: STUDY_DIRECTOR
References: