A Phase I, Single-Dose, Non-Randomised, Open-Label, Parallel-Group Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Balcinrenone
Overview
- Phase
- Phase 1
- Intervention
- Balcinrenone
- Conditions
- Hepatic Impairment
- Sponsor
- AstraZeneca
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Area under plasma concentration-time curve from time zero to the last measurable concentration (AUClast)
- Status
- Completed
- Last Updated
- last year
Overview
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.
Detailed Description
This is an open-label, non-randomised, multicentre, parallel-group, single-dose study to examine the PK, safety, and tolerability of balcinrenone 50 mg administered orally to male and female participants with mild or moderate hepatic impairment compared with control participants with normal hepatic function. Eight participants with mild impairment and 8 participants with moderate impairment per CP classification and 8 to 12 participants with normal hepatic function matched on a group level regarding age, BMI, and sex to the impaired groups are planned for study intervention. All participants will receive a single dose of balcinrenone 50 mg on Day 1 following an overnight fast. Study intervention will be administered orally with approximately 240 mL of water. Child-Pugh scoring will be used to determine the level of hepatic impairment. Participants will be enrolled into the following groups based on their CP classification score as determined at screening: * Group 1: Participants with mild hepatic impairment (CP Class A, score of 5 or 6). * Group 2: Participants with moderate hepatic impairment (CP Class B, score of 7 to 9). * Group 3: Participants with normal hepatic function matched on a group level regarding age, BMI, and sex to the impaired groups.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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 -
- •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 -
Exclusion Criteria
- •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 -
Arms & Interventions
Group 1
Subjects with Mild Impairment will receive a single oral dose of balcinrenone under fasted conditions.
Intervention: Balcinrenone
Group 2
Subjects with Moderate Impairment will receive a single oral dose of balcinrenone under fasted conditions.
Intervention: Balcinrenone
Group 3
Healthy participants will receive a single oral dose of balcinrenone under fasted conditions.
Intervention: Balcinrenone
Outcomes
Primary Outcomes
Area under plasma concentration-time curve from time zero to the last measurable concentration (AUClast)
Time Frame: Day 1 to Day 5
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
Area under plasma concentration-time curve from zero to infinity (AUCinf)
Time Frame: Day 1 to Day 5
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
Maximum observed plasma concentration (Cmax)
Time Frame: Day 1 to Day 5
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
Secondary Outcomes
- 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)