Clinical trial NCT05961397: Phase 1 PK Study to Evaluate the PK of CIN-107 in Subjects With Hepatic Impairment
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension
Keywords: hepatic impairment
PK
baxdrostat
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-07-27
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

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

Primary outcomes:
measure: Incidence of treatment emergent adverse events following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function.
timeFrame: up to 72 hours post-dose
measure: 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
timeFrame: up to 72 hours post-dose
measure: 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.
timeFrame: up to 72 hours post-dose
measure: 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.
timeFrame: up to 72 hours post-dose
measure: 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.
timeFrame: up to 72 hours post-dose
Secondary outcomes:
Other outcomes:
Locations:
city: Rialto
country: United States
facility: Inland Empire Clinical Trials
state: California
city: Miami
country: United States
facility: Advanced Pharma CR
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Knoxville
country: United States
facility: Alliance for Multispecialty Research
state: Tennessee
city: San Antonio
country: United States
facility: American Research Corporation at the Texas Liver Institute
state: Texas
Study officials:
affiliation: Advanced Pharma CR
name: Kimberly Cruz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Alliance for Multispecialty Research
name: William B Smith,, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Inland Empire Clinical Trials
name: Zeid Kayali, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Orlando Clinical Research Center
name: Thomas Marbury, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: American Research Corporation at the Texas Liver Institute
name: Eric Lawitz, MD
role: PRINCIPAL_INVESTIGATOR
References: