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
Overview
- Phase
- Phase 1
- Intervention
- baxdrostat
- Conditions
- Hypertension
- Sponsor
- AstraZeneca
- Enrollment
- 20
- Locations
- 5
- Primary Endpoint
- 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.
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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:
- 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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
Normal hepatic function group
Subjects with normal hepatic function
Intervention: baxdrostat
Moderate hepatic impairment group
Subjects with a Child-Pugh score of 7 to 9 (Category B) at screening
Intervention: baxdrostat
Outcomes
Primary Outcomes
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.
Time Frame: up to 72 hours post-dose
Cmax will be determined for baxdrostat and the CIN-107M metabolite
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
Time Frame: 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.
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.
Time Frame: up to 72 hours post-dose
Tmax will be determined for baxdrostat and the CIN-107M metabolite
Incidence of treatment emergent adverse events following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function.
Time Frame: 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.
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.
Time Frame: up to 72 hours post-dose
Terminal elimination half-life will be determined for baxdrostat and the CIN-107M metabolite