Phase 1 PK Study to Evaluate the PK of CIN-107 in Subjects With Hepatic Impairment
Study Details
Study Description
Brief Summary
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:
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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
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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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Normal hepatic function group Subjects with normal hepatic function |
Drug: baxdrostat
single oral dose of baxdrostat 10 mg
Other Names:
|
| Experimental: Moderate hepatic impairment group Subjects with a Child-Pugh score of 7 to 9 (Category B) at screening |
Drug: baxdrostat
single oral dose of baxdrostat 10 mg
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Incidence of treatment emergent adverse events following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function. [up to 72 hours post-dose]
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.
- 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 [up to 72 hours post-dose]
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.
- 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. [up to 72 hours post-dose]
Cmax will be determined for baxdrostat and the CIN-107M metabolite
- 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. [up to 72 hours post-dose]
Tmax will be determined for baxdrostat and the CIN-107M metabolite
- 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. [up to 72 hours post-dose]
Terminal elimination half-life will be determined for baxdrostat and the CIN-107M metabolite
Eligibility Criteria
Criteria
Inclusion Criteria:
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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.)
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Is a non-nicotine user or smokes =<10 cigarettes/day;
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Has a BMI between 18 and 42 kg/m2, inclusive;
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Is able to understand and willing to comply with study procedures and restrictions and provide written informed consent;
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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.
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if male, must agree to abstain from sperm donation for 90 days; and
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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:
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Personal or family history of long QT syndrome, torsades de pointes, or other complex ventricular arrhythmias, or family history of sudden death;
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History of, or current, clinically significant arrhythmias;
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Prolonged QTcF (>460 msec) based on the average of triplicate ECGs;
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Estimated glomerular filtration rate (or creatinine clearance) <50 mL/min/1.73 m2;
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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
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Current treatment with weight loss medication or prior weight loss surgery;
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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;
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Corticosteroid use (systemic or extensive topical use) within 3 months prior to study drug dosing
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Pregnant, breastfeeding, or planning to become pregnant during the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Inland Empire Clinical Trials | Rialto | California | United States | 92377 |
| 2 | Advanced Pharma CR | Miami | Florida | United States | 33147 |
| 3 | Orlando Clinical Research Center | Orlando | Florida | United States | 32809 |
| 4 | Alliance for Multispecialty Research | Knoxville | Tennessee | United States | 37920 |
| 5 | American Research Corporation at the Texas Liver Institute | San Antonio | Texas | United States | 78215 |
Sponsors and Collaborators
- CinCor Pharma, Inc.
Investigators
- Principal Investigator: Kimberly Cruz, MD, Advanced Pharma CR
- Principal Investigator: William B Smith,, MD, Alliance for Multispecialty Research
- Principal Investigator: Zeid Kayali, MD, Inland Empire Clinical Trials
- Principal Investigator: Thomas Marbury, MD, Orlando Clinical Research Center
- Principal Investigator: Eric Lawitz, MD, American Research Corporation at the Texas Liver Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CIN-107-115