Clinical trial NCT03964038: A Study to Assess the Relative Bioavailability of Gilteritinib Following a Single Dose of Gilteritinib Mini-tablet Oral Suspension and Gilteritinib Mini-tablets Compared to a Single Dose of Gilteritinib Tablet in Healthy Subjects
Official title: A Phase 1 Parallel Study to Assess the Relative Bioavailability of Gilteritinib Following a Single Dose of Gilteritinib Mini-tablet Oral Suspension and Gilteritinib Mini-tablets Compared to a Single Dose of Gilteritinib Tablet in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Keywords: gilteritinib
ASP2215
Healthy volunteer
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2019-05-28
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the relative bioavailability as well as the safety and tolerability of single doses of gilteritinib mini-tablets oral suspension and gilteritinib mini tablets compared to gilteritinib tablets under fasting conditions in healthy male and female participants.

Detailed description: Participants will be screened for up to 28 days prior to investigational product (IP) administration on day 1. Eligible participants will be admitted to the clinical unit on day -1 and will be residential for 10 days/9 nights.

Eligibility criteria: Inclusion Criteria:

* Subject has a body mass index range of 18.5 to 32.0 kg/m2, inclusive and weighs at least 50 kg at screening.
* Female subject is not pregnant and the following condition applies:

  * Subject is not a woman of childbearing potential.
* Male subject with female partner(s) of childbearing potential (including breastfeeding partner\[s\]) must agree to use contraception throughout the treatment period and for 120 days after study treatment administration.
* Male subject must not donate sperm during the treatment period and for 120 days after study treatment 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 120 days after study treatment 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 assessment or breastfeeding within 3 months prior to screening.
* Subject has a known or suspected hypersensitivity to gilteritinib, or any components of the formulations used.
* Subject has had previous exposure with gilteritinib.
* Subject has any of the liver function tests (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase and total bilirubin) ≥ 1.5 × upper limit of normal 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 study treatment 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 investigator's review of the physical examination, electrocardiogram (ECG) and protocol-defined clinical laboratory tests at screening or on day -1.
* Subject has a mean pulse \< 45 or \> 90 bpm; mean systolic blood pressure \> 140 mmHg; mean diastolic blood pressure \> 90 mmHg (measurements taken in triplicate after subject has been resting in the supine position for at least 5 minutes; pulse will be measured automatically) on day -1. If the mean blood pressure exceeds the limits above, 1 additional triplicate may be taken.
* Subject has a mean corrected QT interval using Fridericia's formula (QTcF) interval of \> 430 msec (for male subjects) and \> 450 msec (for female subjects) on day -1. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG may be taken.
* Subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease or a family history of long QT syndrome.
* 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 study treatment administration, except for occasional use of paracetamol (up to 2 g/day), topical dermatological products, including corticosteroid products and hormone replacement therapy (HRT).
* Subject has smoked, used tobacco-containing products and nicotine or nicotine-containing products (e.g., electronic vapes) within 6 months prior to screening.
* Subject has a history of consuming \> 14 units for male subjects or 7 units for female subjects of alcoholic beverages per week within 6 months prior to screening or has a history of alcoholism or drug/chemical/substance abuse within 2 years prior to screening (note: 1 unit = 12 ounces of beer, 4 ounces of wine, 1 ounce of spirits/hard liquor) or the subject tests positive for alcohol at screening or on day -1.
* Subject has used any drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and/or opiates) within 3 months prior to day -1 or the subject tests positive for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates) at screening or on day -1.
* Subject has used any inducer of metabolism (e.g., barbiturates and rifampin) in the 3 months prior to day -1.
* Subject has had significant blood loss, donated ≥ 1 unit (450 mL) of whole blood or donated plasma within 7 days prior to day -1 and/or received a transfusion of any blood or blood products within 60 days.
* Subject has a positive serology test for hepatitis A virus antibodies (immunoglobulin M), hepatitis B core, hepatitis B surface antigen, hepatitis C virus antibodies or antibodies to human immunodeficiency virus type 1 and/or type 2 at screening.
* Subject is an employee of Astellas, the study-related contract research organizations or the clinical unit.

Primary outcomes:
measure: Pharmacokinetics (PK) of gilteritinib in plasma: area under the concentration-time curve from the time of dosing to 72 hours (AUC72)
timeFrame: Up to Day 9
measure: Pharmacokinetics (PK) of gilteritinib in plasma: area under the concentration-time curve from the time of dosing extrapolated to time infinity (AUCinf)
timeFrame: Up to Day 9
measure: Pharmacokinetics (PK) of gilteritinib in plasma: area under the concentration-time curve from the time of dosing to the last measurable concentration (AUClast)
timeFrame: Up to Day 9
measure: Pharmacokinetics (PK) of gilteritinib in plasma: maximum concentration (Cmax)
timeFrame: Up to Day 9
Secondary outcomes:
measure: Safety and tolerability assessed by nature, frequency, and severity of Adverse Events (AEs)
timeFrame: Up to Day 18
measure: Number of participants with laboratory value abnormalities and/or adverse events (AEs)
timeFrame: Up to Day 18
measure: Number of participants with electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)
timeFrame: Up to Day 18
measure: Number of participants with vital sign abnormalities and /or adverse events (AEs)
timeFrame: Up to Day 18
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: EPCU - Parexel
state: Maryland
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: