Pharmacokinetic Study in Healthy Lactating Women Exposed to Ibrexafungerp

Phase 1, Open-Label Pharmacokinetic Study in Healthy Lactating Women After Two Oral Doses of Ibrexafungerp Administered on a Single Day

This is a pharmacokinetic evaluation of lactating women after receiving two doses of Ibrexafungerp. The study population included healthy lactating females who were at least 10 days postpartum with a fully established milk supply and were between the ages of 18 and 50 years at the time of screening

This was a Phase 1 study designed to evaluate the pharmacokinetics of ibrexafungerp after administration of two oral doses in lactating women to determine whether ibrexafungerp is excreted in breast milk, and if so, to characterize ibrexafungerp PK in the breast milk and plasma of lactating women.

Participants received a single day of twice daily (BID) 300-mg (2 x 150-mg) oral ibrexafungerp doses given 12 hours apart (Q12H). Participants received both doses on site. Participants were admitted to the clinic on Day 1 and discharged on Day 5, after the 108-hour procedures were completed.

Inclusion Criteria:

• A healthy lactating woman aged 18 to 50 years, inclusive, at Screening
• At least 10-days postpartum after uncomplicated delivery with a full milk supply established. (There is no specific length of time postpartum)
• Actively breastfeeding or expressing breast milk
• willing to temporarily discontinue breast feeding their infant before the Day 1 morning dose through to 108 hours after the first dose (approximately 4.5 days) AND has the ability to pump breast milk and to provide a reserve for infant feeding, with acceptance of bottle feeding, prior to the study OR has decided to discontinue breastfeeding permanently but has not yet started weaning their infant with acceptance of bottle feeding and must have adequate milk supply
• Has a Body Mass Index (BMI) ≤34 kg/m2 at the screening visit. BMI is calculated by taking the participant's weight in kg and dividing by the participant's height in meters, squared.
• willing to fully express breast milk from both breasts during the duration of the milk collection portion of the study
• Is judged to be in good health based on medical history, physical examination, vital sign measurements, and laboratory safety tests (all within laboratory normal ranges or changes outside the normal range judged to be clinically non-significant by the investigator) performed at the screening visit and prior to administration of the initial dose of study drug
• Has no clinically significant abnormality on electrocardiogram (ECG) performed at the screening visit
• Has been a non-smoker (including vaping) or a light smoker (less than 10 cigarettes per day) for at least 6 months
• Understands the study procedures and agrees to participate in the study by giving written informed consent
• Is willing to comply with the study restrictions and participate for the full length of the study for a complete summary of study restrictions
• Is not pregnant and highly unlikely to become pregnant

Exclusion Criteria:

• Is pregnant or unwilling or unable to comply with the lifestyle guidelines presented in the protocol during the study period and through the Post-Study visit
• Has evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric (including post-natal depression), neurologic, allergic disease (including drug allergies, but excluding untreated asymptomatic, seasonal allergies at time of dosing), or a history of neoplastic disease or any active cancer
• Is mentally or legally incapacitated
• Has a history of any illness or clinical findings that, in the opinion of the study investigator, might confound the results of the study or poses an additional risk to the participant or infant by participation in the study
• Anticipates the use of prescription or non-prescription drugs that are strong CYP3A4 inducers, including vitamins, herbal and dietary supplements (including St. John's Wort) within 7 days of study drug administration (or 14 days if the drug is a potential enzyme inducer)
• Is unable to refrain from consumption of grapefruit juice, grapefruits, grapefruit products, star fruit, Seville and blood oranges, apple and mulberry juice as well as vegetables from the mustard green family (eg, kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, and mustard), charbroiled meats, and fenugreek beginning approximately 7 days prior to administration of the initial dose of study drug and throughout the participant's stay in the clinic
• Consumes significant amounts of alcohol, defined as greater than 2 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces] or distilled spirits [25 mL/1 ounce]) per day. Participant is unable to refrain from all alcohol consumption within one week prior to study dosing throughout the study until the final study visit
• Consumes excessive amounts of caffeine for one month prior to study drug administration, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola or other caffeinated beverages per day
• Has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) or participated in another investigational study within 30 days or 5½ half-lives of the investigational product prior to the screening. The 30-day window will be derived from the date of the last study procedure (ie, poststudy, AE follow-up, etc.) in the previous study to the screening visit of the current study
• Has a history of significant multiple and/or severe allergies [including latex allergy, but with exception of seasonal rhinitis (hay fever)] or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
• Has a known hypersensitivity to ibrexafungerp
• Is currently a user including illicit drugs or has a history of drug (including alcohol) abuse within approximately 1 year
• Is unable to abstain from strenuous exercise from the screening visit until administration of the initial dose of study drug, throughout the study until the poststudy visit