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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: baxdrostat

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Rialto, California, United States, 92377
      • Inland Empire Clinical Trials
  • Florida
    • Miami, Florida, United States, 33147
      • Advanced Pharma Cr
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Alliance for Multispecialty Research
  • Texas
    • San Antonio, Texas, United States, 78215
      • American Research Corporation at the Texas Liver Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal hepatic function group; Subjects with normal hepatic function	Drug: baxdrostat; single oral dose of baxdrostat 10 mg; Other Names: CIN-107
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: CIN-107

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: AstraZeneca
• 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

Publications and helpful links

Helpful Links

• Redacted CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2021
• Primary Completion (Actual): April 15, 2022
• Study Completion (Actual): April 15, 2022

Study Registration Dates

• First Submitted: July 3, 2023
• First Submitted That Met QC Criteria: July 18, 2023
• First Posted (Actual): July 27, 2023

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: PK; hepatic impairment; baxdrostat
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: CIN-107-115

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No