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

Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05961397
• Other study ID #: CIN-107-115
• Status: Completed
• Phase: Phase 1
• Start date: August 10, 2021
• Est. completion date: April 15, 2022

Study information

• Verified date: August 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 15, 2022
• Est. primary completion date: April 15, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• baxdrostat
single oral dose of baxdrostat 10 mg

Locations

Country	Name	City	State
United States	Alliance for Multispecialty Research	Knoxville	Tennessee
United States	Advanced Pharma CR	Miami	Florida
United States	Orlando Clinical Research Center	Orlando	Florida
United States	Inland Empire Clinical Trials	Rialto	California
United States	American Research Corporation at the Texas Liver Institute	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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

External Links

•   Redacted CSR Synopsis