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

Completed · Phase 1

Conditions studied: Hepatic Impairment

In brief

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.

Key facts

Study ID

NCT06388616

Run by

AstraZeneca

People needed

30

Starts

2024-05-02

Expected to finish

2024-09-05

Last updated by the study team

2024-11-12

Who can join

Age: 18 and older, up to 79. Sex: any. Healthy volunteers: accepted.

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:
• Women < 55 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and FSH levels in the postmenopausal range.
• Women ≥ 55 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment.
• Postmenopausal status for participants with hepatic impairment based on FSH levels may be at the discretion of the investigator.
• Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
• Provision of signed and dated written ICF prior to any mandatory study-specific procedures, sampling, and analyses.

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.
• Participant is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or Day -1 or expected during the conduct of the study.
• History of any major surgical procedure within 30 days prior to study intervention.
• Any clinically or surgically significant condition that may affect balcinrenone absorption and/or excretion in the opinion of the investigator, including gastric restrictions and bariatric surgery (eg, gastric bypass). Uncomplicated appendectomy and hernia repair will be allowed. Uncomplicated cholecystectomy is allowed at the discretion of the investigator.
• Judgment by the investigator that the participant should not participate in the study if they have any ongoing or recent (ie, during the screening period) minor medical complaints that may interfere with the interpretation of study data or if they are considered unlikely to comply with study procedures, restrictions, and requirements.
• Use of any medication defined as prohibited medication (see Appendix E) within 2 weeks prior to study intervention or longer if the medication has a long half-life.
• Unable to refrain from the following for 10 hours prior to and 10 hours after study intervention: Phosphate binders (eg, aluminium hydroxide and calcium carbonanate).
• Acid reducing agents (eg, ranitidine/nizatidine or proton pump inhibitors). Cholestyramine/colestipol. MRA agents (eg, spironolactone, eplerenone, finerenone).
• Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days of study intervention in this study or, if known, 5 half-lives from last dose in the previous study to study intervention in this study, whichever is longest.
• Previous enrolment in the present study. Note: participants consented and screened, but not receiving study intervention in this study or a previous Phase I study, are not excluded.
• Participant smokes more than 10 cigarettes (ie, 1/2 pack) per day or equivalent (eg, e-vapor cigarette, pipe, cigar, chewing tobacco, nicotine patch, nicotine gum) and is unable to comply with the nicotine restrictions (Section 5.3.2) during the study.

Where it is running

• Research Site — Hialeah, Florida, United States
• Research Site — Orlando, Florida, United States
• Research Site — San Antonio, Texas, United States

Full record on ClinicalTrials.gov

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