Phase 1 PK Study to Evaluate the PK of CIN-107 in Subjects With Hepatic Impairment

A Phase 1, Open-label, Single-dose, Parallel-group Study to Evaluate the Pharmacokinetics of CIN-107 in Subjects With Varying Degrees of Hepatic Function

The goal of this Phase 1, open-label, single-dose, parallel-group study is to evaluate the pharmacokinetics (PK) of a single 10-mg oral dose of baxdrostat in subjects with varying degrees of hepatic function. The main objectives are to:

• To assess the safety and tolerability of baxdrostat following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function; and
• To characterize the PK of baxdrostat following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function.

Participants were administered a single 10-mg oral dose of baxdrostat in the fasted state the morning of Day 1. Plasma samples were drawn at various timepoints. Safety assessments included adverse events, vital signs, 12-lead electrocardiograms (ECGs), clinical laboratory evaluations, and physical examinations.

Twenty subjects in 2 groups based on the Child-Pugh classification in the protocol at screening: up to 10 subjects in the normal hepatic function group and up to 10 subjects in the moderate hepatic impairment group. Twenty subjects entered and completed the study.

Inclusion Criteria:

• Is between the ages of 18 and 80 years, inclusive, and in stable health condition. (For hepatically impaired subjects, their hepatic function category must be stable for a minimum of 3 months prior to screening.)
• Is a non-nicotine user or smokes =<10 cigarettes/day;
• Has a BMI between 18 and 42 kg/m2, inclusive;
• Is able to understand and willing to comply with study procedures and restrictions and provide written informed consent;
• if a male subject with a female partner of childbearing potential must agree to use 2 medically accepted, highly effective methods of birth control for 90 days.
• if male, must agree to abstain from sperm donation for 90 days; and
• if female with a male partner, must be surgically sterile, postmenopausal, or agree to use 2 medically accepted, highly effective methods of birth control from Day -14 until 60 days after study drug dosing

Main Exclusion Criteria:

• Personal or family history of long QT syndrome, torsades de pointes, or other complex ventricular arrhythmias, or family history of sudden death;
• History of, or current, clinically significant arrhythmias;
• Prolonged QTcF (>460 msec) based on the average of triplicate ECGs;
• Estimated glomerular filtration rate (or creatinine clearance) <50 mL/min/1.73 m2;
• Evidence of any of the following: Encephalopathy grade 2 or worse, Seated systolic BP >160 mmHg and/or diastolic BP >100 mmHg, or systolic BP <90 mmHg and/or diastolic BP <50 mmHg, resting heart rate >100 beats per minute (bpm) or <50 bpm, Oral temperature >37.6°C (>99.68°F), Respiration rate <12 or >20 breaths per minute, symptomatic postural tachycardia or orthostatic hypotension, abnormal serum potassium >upper limit of normal range, abnormal serum sodium <130 mEq/L, positive test for HIV antibody, hepatitis C , hepatitis B , or SARS-CoV-2 RNA
• Current treatment with weight loss medication or prior weight loss surgery;
• Use of a moderate or strong inhibitor of CYP3A4 within 14 days prior to the dose of study drug OR use of a moderate or strong inducer of CYP3A4 within 28 days prior to the dose of study drug;
• Corticosteroid use (systemic or extensive topical use) within 3 months prior to study drug dosing
• Pregnant, breastfeeding, or planning to become pregnant during the study