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

NCT05961397 | Completed Phase 1 FDA Drug

• 1 other identifier: CIN-107-115
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 5

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.

Conditions

Hypertension

Keywords

hepatic impairment; PK; baxdrostat

Outcome Measures

Primary Outcomes (5)

• 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

Study Arms (2)

Normal hepatic function group

EXPERIMENTAL

Subjects with normal hepatic function

Drug: baxdrostat

Moderate hepatic impairment group

EXPERIMENTAL

Subjects with a Child-Pugh score of 7 to 9 (Category B) at screening

Drug: baxdrostat

Interventions

baxdrostat DRUG

single oral dose of baxdrostat 10 mg

Also known as: CIN-107

Moderate hepatic impairment group; Normal hepatic function group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (5)

Inland Empire Clinical Trials

Rialto, California, 92377, United States

Location

Advanced Pharma CR

Miami, Florida, 33147, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

Alliance for Multispecialty Research

Knoxville, Tennessee, 37920, United States

Location

American Research Corporation at the Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Related Links

• Redacted CSR Synopsis

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2023
• First Posted: July 27, 2023
• Study Start: August 10, 2021
• Primary Completion: April 15, 2022
• Study Completion: April 15, 2022
• Last Updated: August 14, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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.

Locations

US (5)