A Phase 1 Crossover Study to Assess the Bioequivalence of Isavuconazole Following a Single Dose of Isavuconazonium Sulfate Intravenous Solution Via Nasogastric Tube Compared to a Single Dose of Oral Capsules Under Fasting Conditions in Healthy Subjects
Overview
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 17
- Locations
- 1
- Primary Endpoint
- PK of isavuconazole in plasma: area under the concentration-time curve from 0 to 72 hours (AUC72)
Overview
Brief Summary
The purpose of this study is to evaluate the bioequivalence of isavuconazole following a single dose of isavuconazonium sulfate intravenous (IV) solution via nasogastric (NG) tube (test formulation) compared to a single dose of isavuconazonium sulfate capsules for oral administration (i.e., oral capsules administered to nonintubated participants)(reference formulation). In addition, this study will evaluate the safety and tolerability of isavuconazole and the general pharmacokinetic (PK) parameters of isavuconazole when administered as a single dose of isavuconazonium sulfate IV solution via NG tube (test formulation) and a single dose of isavuconazonium sulfate capsules for oral administration (i.e., oral capsules administered to nonintubated participants) (reference formulation) under fasting conditions in healthy male and female participants.
Detailed Description
Eligible participants will participate in 2 treatment periods separated by a washout of at least 30 days between investigational product (IP) administrations in each period. Participants will be randomized to 1 of 2 sequences. Participants will be admitted to the clinical unit on day -1 of each period and will be residential for 5 days/4 nights. Participants will receive a single dose of isavuconazonium sulfate IV solution via NG tube (test formulation) or isavuconazonium sulfate capsules for oral administration (i.e., oral capsules administered to nonintubated participants) (reference formulation) under fasting conditions on day 1 of each period. Participants are to remain semirecumbent and avoid lying on either the left or right side for 4 hours postdose. Correct placement of the NG tube will be confirmed using X-ray radiography. Pharmacokinetic samples will be collected predose on day 1 of each period and at multiple time points postdose. Standard safety and tolerability assessments will be conducted. Participants will be discharged from the clinical unit on day 4 of each period on the condition that all required assessments have been performed and that there are no medical reasons for a longer stay in the clinical unit. Participants will return for ambulatory visits to collect pharmacokinetic samples on days 8, 11, 15 and 21 of each period.
The study will be completed with an end-of-study visit (ESV). The ESV will take place 5 to 9 days after day 21 of period 2 or at early discontinuation from the study.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Subject has a body mass index (BMI) range of 18.5 to 32.0 kg/m\^2, inclusive and weighs at least 50 kg at screening.
- •Female subject is not pregnant and at least 1 of the following conditions apply:
- •Not a woman of childbearing potential (WOCBP)
- •WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 30 days after final investigational product (IP) administration.
- •Female subject must agree not to breastfeed starting at screening, throughout the study period and for 30 days after final IP administration.
- •Female subject must not donate ova starting at first administration of IP, throughout the study period and for 30 days after final IP administration.
- •Male subject with female partner(s) of childbearing potential (including breastfeeding partner\[s\]) must agree to use contraception throughout the treatment period and for 30 days after final IP administration.
- •Male subject must not donate sperm during the treatment period and for 30 days after final IP administration.
- •Male subject with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy, throughout the study period and for 30 days after final IP administration.
- •Subject agrees not to participate in another interventional study while participating in the present study.
Exclusion Criteria
- •Subject has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening.
- •Subject has any condition which makes the subject unsuitable for study participation.
- •Female subject who has been pregnant within 6 months prior to screening or breastfeeding within 3 months prior to screening.
- •Subject has a known or suspected hypersensitivity to isavuconazonium sulfate or any components of the formulations used.
- •Subject has had previous exposure with isavuconazonium sulfate.
- •Subject has any of the liver function tests (alkaline phosphatase \[ALP\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\] and total bilirubin \[TBL\]) ≥ 1.5 upper limit of normal (ULN) on day -
- •In such a case, the assessment may be repeated once.
- •Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies) prior to first IP administration.
- •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.
- •Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 1 week prior to day -
Arms & Interventions
Isavuconazonium sulfate IV solution then capsules
Participants will first receive a single dose of isavuconazonium sulfate intravenous (IV) solution via nasogastric (NG) tube (test formulation) under fasting conditions on Day 1 of Period 1. After a washout period of 30 days, the participants then receive a single dose of isavuconazonium sulfate capsules (reference formulation) for oral administration under fasting conditions on Day 1 of Period 2.
Intervention: Isavuconazonium sulfate IV (Drug)
Isavuconazonium sulfate IV solution then capsules
Participants will first receive a single dose of isavuconazonium sulfate intravenous (IV) solution via nasogastric (NG) tube (test formulation) under fasting conditions on Day 1 of Period 1. After a washout period of 30 days, the participants then receive a single dose of isavuconazonium sulfate capsules (reference formulation) for oral administration under fasting conditions on Day 1 of Period 2.
Intervention: Isavuconazonium sulfate capsules (Drug)
Isavuconazonium sulfate capsules then IV solution
Participants will first receive a single dose of isavuconazonium sulfate capsules (reference formulation) for oral administration under fasting conditions on Day 1 of Period 1. After a washout period of 30 days, the participants then receive a single dose of isavuconazonium sulfate intravenous (IV) solution via nasogastric (NG) tube (test formulation) under fasting conditions on Day 1 of Period 2.
Intervention: Isavuconazonium sulfate IV (Drug)
Isavuconazonium sulfate capsules then IV solution
Participants will first receive a single dose of isavuconazonium sulfate capsules (reference formulation) for oral administration under fasting conditions on Day 1 of Period 1. After a washout period of 30 days, the participants then receive a single dose of isavuconazonium sulfate intravenous (IV) solution via nasogastric (NG) tube (test formulation) under fasting conditions on Day 1 of Period 2.
Intervention: Isavuconazonium sulfate capsules (Drug)
Outcomes
Primary Outcomes
PK of isavuconazole in plasma: area under the concentration-time curve from 0 to 72 hours (AUC72)
Time Frame: Predose on Day 1 and up to Day 3 postdose in each period
AUC72 will be recorded from the PK plasma samples collected.
PK of isavuconazole in plasma: area under the concentration-time curve from the time of dosing to the last measurable concentration (AUClast)
Time Frame: Predose on Day 1 and up to Day 21 postdose in each period
AUClast will be recorded from the PK plasma samples collected.
Pharmacokinetics (PK) of isavuconazole in plasma: area under the concentration-time curve from the time of dosing extrapolated to time infinity (AUCinf)
Time Frame: Predose on Day 1 and up to Day 21 postdose in each period
AUCinf will be recorded from the PK plasma samples collected.
PK of isavuconazole in plasma: maximum concentration (Cmax)
Time Frame: Predose on Day 1 and up to Day 21 postdose in each period
Cmax will be recorded from the PK plasma samples collected.
Secondary Outcomes
- Number of participants with vital sign abnormalities and/or adverse events(Up to 61 days)
- Pharmacokinetics (PK) of isavuconazole in plasma: apparent clearance (CL/F)(Predose on Day 1 and up to Day 21 postdose in each period)
- Pharmacokinetics (PK) of isavuconazole in plasma: terminal elimination half-life (t1/2)(Predose on Day 1 and up to Day 21 postdose in each period)
- Pharmacokinetics (PK) of isavuconazole in plasma: time of maximum concentration (tmax)(Predose on Day 1 and up to Day 21 postdose in each period)
- Pharmacokinetics (PK) of isavuconazole in plasma: lag time (tlag)(Predose on Day 1 and up to Day 21 postdose in each period)
- Pharmacokinetics (PK) of isavuconazole in plasma: apparent volume of distribution during terminal phase after oral/intravenous administration (Vz/F)(Predose on Day 1 and up to Day 21 postdose in each period)
- Number of participants with Adverse Events (AEs)(Up to 61 days)
- Number of participants with laboratory value abnormalities and/or adverse events(Up to 32 days)
- Pharmacokinetics (PK) of isavuconazole in plasma: area under the concentration-time curve extrapolated from time to infinity as a percentage of total AUC (AUCinf(%extrap))(Predose on Day 1 and up to Day 21 postdose in each period)