A Study to Assess Isavuconazole Following a Single Dose of Isavuconazonium Sulfate Intravenous Solution Via Nasogastric (NG) Tube Compared to a Single Dose of Oral Capsules Under Fasting Conditions in Healthy Participants

NCT04096157 | Completed Phase 1 FDA Drug

• 1 other identifier: 9766-CL-0112
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Subjects

Keywords

Cresemba; isavuconazonium sulfate; isavuconazole

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetics (PK) of isavuconazole in plasma: area under the concentration-time curve from the time of dosing extrapolated to time infinity (AUCinf)

  AUCinf will be recorded from the PK plasma samples collected.

  Predose on Day 1 and up to Day 21 postdose in each period

• PK of isavuconazole in plasma: area under the concentration-time curve from 0 to 72 hours (AUC72)

  AUC72 will be recorded from the PK plasma samples collected.

  Predose on Day 1 and up to Day 3 postdose in each period

• PK of isavuconazole in plasma: area under the concentration-time curve from the time of dosing to the last measurable concentration (AUClast)

  AUClast will be recorded from the PK plasma samples collected.

  Predose on Day 1 and up to Day 21 postdose in each period

• PK of isavuconazole in plasma: maximum concentration (Cmax)

  Cmax will be recorded from the PK plasma samples collected.

  Predose on Day 1 and up to Day 21 postdose in each period

Secondary Outcomes (9)

• 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

• Number of participants with vital sign abnormalities and/or adverse events

  Up to 61 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

• Pharmacokinetics (PK) of isavuconazole in plasma: apparent clearance (CL/F)

  Predose on Day 1 and up to Day 21 postdose in each period

Study Arms (2)

Isavuconazonium sulfate IV solution then capsules

EXPERIMENTAL

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.

Drug: Isavuconazonium sulfate IV; Drug: Isavuconazonium sulfate capsules

Isavuconazonium sulfate capsules then IV solution

EXPERIMENTAL

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.

Drug: Isavuconazonium sulfate IV; Drug: Isavuconazonium sulfate capsules

Interventions

Isavuconazonium sulfate IV DRUG

Intravenous (IV) via nasogastric (NG) tube

Also known as: Cresemba

Isavuconazonium sulfate IV solution then capsules; Isavuconazonium sulfate capsules then IV solution

Isavuconazonium sulfate capsules DRUG

Oral

Also known as: Cresemba

Isavuconazonium sulfate IV solution then capsules; Isavuconazonium sulfate capsules then IV solution

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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 -1. 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 -1.
• Subject has any clinically significant abnormality following the physical examination, ECG (including familial short QT syndrome) and protocol-defined clinical laboratory tests at screening or on day -1.
• Subject has a mean pulse of \< 45 or \> 90 bpm; mean systolic blood pressure (SBP) \>140 mmHg; diastolic blood pressure (DBP) \> 90 mmHg (measurements taken in triplicate after the subject has been resting in the supine position for at least 5 minutes; pulse will be measured automatically) on day -1. If mean blood pressure exceeds the limits above, 1 additional triplicate may be taken.
• Subject has a history of peptic or gastric ulcers.
• Subject has a history of sinus disease, sinus allergy, renoplasty or any surgery of the nose, septum or nasal passages or any other abnormality that could impact NG tube placement (e.g., nasal polyps).
• Subject has taken medication or substances via inhalation through the nasal passages within 3 months prior to screening.
• Subject has used any prescribed or nonprescribed drugs (including vitamins and natural and herbal remedies, e.g., St. John's Wort) in the 2 weeks prior to first IP administration, except for occasional use of acetaminophen (up to 2 g/day), topical dermatological products, including corticosteroid products, local anesthetic spray and/or gel (2% Xylocaine) for NG tube placement, hormonal contraceptives and hormone replacement therapy (HRT).

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (1)

Parexel International

Baltimore, Maryland, 21225, United States

Location

MeSH Terms

Interventions

isavuconazole

Study Officials

• Executive Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2019
• First Posted: September 19, 2019
• Study Start: September 24, 2019
• Primary Completion: January 16, 2020
• Study Completion: January 16, 2020
• Last Updated: November 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)