Hypertension
Conditions
Keywords
hepatic impairment, PK, baxdrostat
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.
Interventions
DRUGbaxdrostat
single oral dose of baxdrostat 10 mg
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed