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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hypertension

Intervention / Treatment
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* Drug: baxdrostat


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normal hepatic function group<br>Subjects with normal hepatic function | Drug: baxdrostat<br>* single oral dose of baxdrostat 10 mg<br>* Other names: CIN-107;|
| Experimental: Moderate hepatic impairment group<br>Subjects with a Child-Pugh score of 7 to 9 (Category B) at screening | Drug: baxdrostat<br>* single oral dose of baxdrostat 10 mg<br>* Other names: CIN-107;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function. | The safety and tolerability of baxdrostat was assessed throughout the study based on incidence of treatment emergent adverse events (AEs), following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function. | up to 72 hours post-dose | 
| Area under the curve (AUC) for baxdrostat and the CIN-107-M metabolite following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function | Measurement of plasma concentrations of baxdrostat and its major metabolite CIN-107-M. AUC [0 to 24 hours, 0 to last quantifiable concentration, and 0 to infinity of baxdrostat] will be determined for baxdrostat and the CIN-107M metabolite. | up to 72 hours post-dose | 
| Maximum Plasma Concentration [Cmax] of baxdrostat and the CIN-107-M metabolite following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function. | Cmax will be determined for baxdrostat and the CIN-107M metabolite | up to 72 hours post-dose | 
| Time to Maximum Plasma Concentration [Tmax] of baxdrostat and the CIN-107-M metabolite following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function. | Tmax will be determined for baxdrostat and the CIN-107M metabolite | up to 72 hours post-dose | 
| Terminal elimination half-life of baxdrostat and the CIN-107-M metabolite following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function. | Terminal elimination half-life will be determined for baxdrostat and the CIN-107M metabolite | up to 72 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PK, hepatic impairment, baxdrostat