Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Balcinrenone

NCT06388616 | Completed Phase 1 FDA Drug

• 1 other identifier: D6402C00013
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

This study will evaluate the pharmacokinetics (PK), safety, and tolerability of a single oral dose of balcinrenone in patients with mild and moderate hepatic impairment in comparison to a matched healthy control group.

Conditions

Hepatic Impairment

Keywords

Hepatic Impairment; Healthy participants; Balcinrenone; Pharmacokinetics; Safety

Outcome Measures

Primary Outcomes (3)

• Area under plasma concentration-time curve from time zero to the last measurable concentration (AUClast)

  To compare the PK of a single oral dose of balcinrenone in participants with mild and moderate hepatic impairment to those with normal hepatic function

  Day 1 to Day 5

• Area under plasma concentration-time curve from zero to infinity (AUCinf)

  To compare the PK of a single oral dose of balcinrenone in participants with mild and moderate hepatic impairment to those with normal hepatic function

  Day 1 to Day 5

• Maximum observed plasma concentration (Cmax)

  To compare the PK of a single oral dose of balcinrenone in participants with mild and moderate hepatic impairment to those with normal hepatic function

  Day 1 to Day 5

Secondary Outcomes (3)

• AEs and SAEs up to the follow-up telephone call (Day 10 [± 3 days])

  Screening (day -28 to day -2) to day 10

• Number of participants with abnormal Vital signs, abnormal ECGs, and abnormal physical examination findings

  Screening (day -28 to day -2) to day 4

• Number of participants with abnormal laboratory tests results

  Screening (day -28 to day -2) to day 4

Study Arms (3)

Group 1

EXPERIMENTAL

Subjects with Mild Impairment will receive a single oral dose of balcinrenone under fasted conditions.

Drug: Balcinrenone

Group 2

EXPERIMENTAL

Subjects with Moderate Impairment will receive a single oral dose of balcinrenone under fasted conditions.

Drug: Balcinrenone

Group 3

EXPERIMENTAL

Healthy participants will receive a single oral dose of balcinrenone under fasted conditions.

Drug: Balcinrenone

Interventions

Balcinrenone DRUG

50 mg, Immediate release capsule to be taken orally.

Also known as: AZD9977

Group 1; Group 2; Group 3

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Participant must be 18 to 79 years of age, inclusive, at the time of signing the informed consent.
• For participant with hepatic impairment:
• Participant must have a diagnosis of chronic (≥ 6 months) and stable hepatic impairment Child Pugh Class A or B (eg, no clinically significant change in signs, symptoms, or laboratory parameters of hepatic disease status within 30 days prior to study screening, as determined by the investigator at screening and Day -1).
• Supporting documents confirming the participant's hepatic impairment must be available; participant self-report is not acceptable; the participant must be classified by the investigator as CP Class A or B at screening.
• Participants must be stable on a concomitant medication and/or treatment regimen (defined as not starting a new treatment/medication\[s\] or a change in the dosage or frequency of the concomitant medication\[s\] within 2 weeks prior to screening). Minor changes in dosage can be accepted at the discretion of the investigator.
• For participant with normal hepatic function:
• Participant must be medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or 12-lead ECGs, as deemed by the investigator at screening and Day -1.
• Body weight ≥ 50 kg; BMI within the range of 18.0 to 42.0 kg/m2 (inclusive) as measured at screening.
• Sex: male and female.
• Females must not be lactating and must not have a positive pregnancy test at screening and at Day -1.
• Women of childbearing potential (defined as female participants who are neither permanently sterilised \[hysterectomy, bilateral oophorectomy, or bilateral salpingectomy\] nor postmenopausal) must use a highly effective method of contraception (described below).
• A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly. Women of childbearing potential who are sexually active with a non-sterilised male partner must agree to use one highly effective method of birth control, as defined below, from enrolment throughout the study and until at least 4 weeks after study intervention.
• Highly effective methods of contraception include: sexual abstinence (periodic abstinence \[eg, calendar, ovulation, symptothermal, post-ovulation methods\], declaration of abstinence for the duration of exposure to IMP, and withdrawal \[coitus interruptus\], spermicides only, and lactational amenorrhoea method are not acceptable methods of contraception), a vasectomised partner, bilateral tubal occlusion, combined (oestrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system.
• Women of nonchildbearing potential (defined as female participants who are permanently surgically sterilised \[hysterectomy, bilateral oophorectomy, or bilateral salpingectomy\] or postmenopausal).
• Women will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to the planned date of study intervention without an alternative medical cause. The following age-specific requirements apply:

You may not qualify if:

• Participant has eGFR \< 60 mL/minute/1.73 m2 as calculated by CKD-EPI.
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the investigator at screening or Day -1, or history of hypersensitivity to drugs with a similar chemical structure or class to balcinrenone.
• History of long QT syndrome or any clinically significant abnormalities on 12-lead ECG at screening or Day -1, as judged by the investigator, including but not limited to any of the following:
• Any significant arrhythmia.
• Conduction abnormalities (eg, Wolff Parkinson White syndrome, second degree AV block; at the discretion of the investigator).
• Prolonged QTcF \> 450 ms for participants with normal hepatic function; \> 480 ms for participants with mild or moderate hepatic impairment.
• Clinically significant PR (PQ) interval shortening (\< 120 ms) or prolongation (\> 240 ms); intermittent second or third degree AV block, or AV dissociation.
• Complete bundle branch block and/or QRS duration \> 120 ms.
• Any of the following signs or confirmation of COVID-19 infection at screening or Day -1:
• Participant has a positive SARS-CoV-2 test result within 2 weeks prior to screening, at screening, or on Day -1.
• Clinical signs and symptoms consistent with COVID-19 (eg, fever, dry cough, dyspnoea, sore throat, fatigue) within 2 weeks prior to screening or Day -1.
• Positive test for HIV at screening.
• Positive results at screening for hepatitis B surface antigen, hepatitis B core antibody or hepatitis C virus. Participants with impaired hepatic function with positive total hepatitis B core antibody or positive hepatitis C result may be included if a follow-up hepatitis B virus DNA test or follow-up hepatitis C virus RNA test is negative.
• History or presence of clinically significant thyroid disease, in the opinion of the investigator. Participants with clinically significant TSH levels outside normal limits at screening will not be enrolled. Participants on stable thyroid replacement therapy are not excluded.
• History or presence of clinically significant or unstable medical or psychiatric condition or disease in the opinion of the investigator.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (3)

Research Site

Hialeah, Florida, 33014, United States

Location

Research Site

Orlando, Florida, 32809, United States

Location

Research Site

San Antonio, Texas, 78215, United States

Location

MeSH Terms

Interventions

AZD9977

Study Officials

• Thomas C Marbury, M.D.

  Servico Integrado de Tecnicas Endovasculares

  PRINCIPAL INVESTIGATOR

• Eric J Lawitz, M.D.

  Servico Integrado de Tecnicas Endovasculares

  PRINCIPAL INVESTIGATOR

• Juan C Rondon, M.D.

  Servico Integrado de Tecnicas Endovasculares

  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

Model Details: Three cohorts (two hepatic impairment cohorts and controls with normal hepatic function) will be enrolled into this study. All subjects will receive the study intervention: * Cohort 1 will enroll 8 participants with mild hepatic impairment * Cohort 2 will enroll 8 participants with moderate hepatic impairment * Cohort 3 will enroll 8-12 healthy participants matched on a group level regarding age, BMI and sex

Study Record Dates

• First Submitted: April 16, 2024
• First Posted: April 29, 2024
• Study Start: May 2, 2024
• Primary Completion: September 5, 2024
• Study Completion: September 5, 2024
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma 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 de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

US (3)