How fluconazole, carbamazepine, and itraconazole affect ASP3082 processing in healthy adults

A Phase 1 Crossover Design Study to Assess the Effect of CYP3A Moderate and Strong Inhibitors (Fluconazole and Itraconazole) and Strong Inducer (Carbamazepine) on the Single-dose Pharmacokinetics of ASP3082 in Healthy Adults

This test will see if fluconazole, carbamazepine, and itraconazole change how healthy adults' bodies absorb and clear ASP3082.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Astellas Pharma Inc (Industry-sponsored)
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT07395024 on ClinicalTrials.gov

What this trial studies

This is a Phase 1 pharmacokinetic drug-drug interaction study in healthy adult volunteers. Participants are assigned to one of three groups to receive ASP3082 together with either fluconazole, itraconazole, or carbamazepine. Blood samples will be collected over time to measure ASP3082 concentrations and compare absorption, distribution, metabolism, and clearance with and without the coadministered drugs. Safety monitoring, including physical exams and ECGs, will be performed throughout the study.

Who should consider this trial

Good fit: Healthy adults who pass medical screening, are not pregnant or breastfeeding, and agree to the study's contraception and follow-up requirements are eligible.

Not a fit: People seeking direct cancer treatment or those with active medical conditions are unlikely to receive therapeutic benefit from participating in this healthy-volunteer pharmacokinetic study.

Why it matters

Potential benefit: If successful, the results could help clinicians avoid harmful interactions and set safe dosing when ASP3082 is given with these commonly used medications in future patients.

How similar studies have performed: Drug-drug interaction and pharmacokinetic studies like this are standard and have successfully guided dosing and safety precautions for many cancer drugs.

Eligibility criteria

Inclusion Criteria:

* Participant is healthy and has no clinically significant medical condition based on the physical examination, electrocardiograms (ECGs) and protocol-defined clinical laboratory tests at screening or on day -1.
* Female participant is not pregnant and is not a woman of childbearing potential (WOCBP)
* Female participant must not be breastfeeding or lactating starting at screening and throughout the investigational period and for 5 half-lives (approximately 28 days after final study intervention administration).
* Female participant must not donate ova starting at first administration of study intervention and throughout the investigational period and for 3 months after final study intervention administration.
* Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period and for 3 months after final study intervention administration.
* Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 3 months after final study intervention administration.
* Male participant must not donate sperm during the treatment period and for 3 months after final study intervention administration.
* Participant agrees not to participate in another interventional study while participating in the present study.
* Participant has a Body Mass Index (BMI) range of 18.0 to 32.0 kg/m\^2, inclusive, and weighs at least 50 kg at screening.

Exclusion Criteria:

* Participant is positive for Human Leukocyte Antigen (HLA) -B15:02 or HLA-A31:01, for Group 2 only.
* Participant has been pregnant within 6 months prior to screening.
* Participant 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.
* Participant has a history of malignancy within 2 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that is considered cured with minimal risk of recurrence).
* Participant has had major surgery (e.g., requiring general anesthesia) within 90 days before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study or within 5 half-lives (approximately 28 days) after the last dose of study drug administration or end-of-study visit (ESV), whichever is longer.
* Participant has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 28 days prior to day -1.
* Participant has a history of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) DSM-5 criteria within 2 years before screening.
* Participant 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.
* Participant has used any prescribed or nonprescribed drugs (including vitamins, and natural and herbal remedies, e.g., St. John's wort) in the 28 days prior to day -1, except for occasional use of acetaminophen (up to 2 g/day), topical dermatological products (including corticosteroid products) and hormone replacement therapy (HRT).
* Participant has used any inducer of metabolism (e.g., barbiturates and rifampin) in the 28 days prior to day -1.
* Participant has received a coronavirus disease 2019 (COVID-19) vaccine within the 14 days prior to day -1 or will have a COVID-19 vaccine dose before the ESV.
* Participant has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening.
* Participant has any liver test result alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin (TBL )) ≥ 1.5 ×upper limit of normal (ULN ) on day -1.
* Participant has a creatinine level outside normal limits on day -1.
* Participant has any of the following conditions on day -1: a mean pulse \< 45 or \> 90 bpm, mean systolic blood pressure (SBP ) \> 140 mmHg, or mean diastolic blood pressure (DBP) \> 90 mmHg (measurements taken in triplicate after participant has been resting in the supine position for at least 5 minutes; pulse measured automatically). If the mean blood pressure exceeds the limits above, 1 additional triplicate measurement may be taken.
* Participant has a mean corrected QT interval using Fridericia's formula (QTcF ) of \> 450 msec on day -1.
* Participant tests positive for alcohol at screening or on day -1.
* Participant tests positive for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine and opiates) at screening or on day -1.
* Participant tests positive for cannabinoids on day -1.
* Participant has a positive serology test for hepatitis A virus (HAV) antibodies immunoglobulin M (IgM), hepatitis B (HBc) antibodies, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies or antibodies to human immunodeficiency virus (HIV ) type 1 and/or type 2 at screening.
* Participant has a positive rapid COVID-19 antigen test on day -1.
* Participant has any condition that makes the participant unsuitable for study participation.
* Participant has a known or suspected hypersensitivity to ASP3082 or any components of the formulation used.
* Participant has a history of smoking \> 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to day -1 or the participant tests positive for cotinine at screening or day -1.
* Participant has a history of consuming \> 10 units of alcoholic beverages per week within 3 months prior to screening (Note: 1 unit = 12 ounces of beer, 5 ounces of wine, 1.5 ounces of spirits/hard liquor).
* Participant has used any drugs of abuse (e.g., amphetamines, barbiturates, benzodiazepines, cocaine and/or opiates) within 3 months prior to day -1.
* Participant 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 prior to day -1.
* Participant has had previous exposure to ASP3082.
* Participant is an employee of Astellas, the study-related contract research organizations (CROs) or the clinical unit.

Where this trial is running

Baltimore, Maryland

• Parexel — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Study coordinator: Astellas Pharma Global Development Inc.

Conditions Healthy Volunteer; ASP3082; Pharmacokinetics; Setidegrasib; Healthy Volunteers; Fluconazole; Itraconazole; Carbamazepine