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

CIN-107-115

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.

2021-08-10

2022-04-15

2022-04-15

Completed

Early phase I

20

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 20, 'type': 'ACTUAL'}}

2023-08-14