Investigation of the Effects of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of Opemalirsen (AZD2373)

This study is being conducted to investigate the PK, safety, and tolerability of opemalirsen in participants with renal impairment, compared to participants with normal renal function.

This is a Phase I, multicentre, single-dose, non-randomised, open-label, parallel-group study, that will be conducted in 2 parts, to examine the PK, safety, and tolerability of opemalirsen in male and female participants with severe renal impairment to matched participants with normal renal function; and, if necessary, participants with mild and moderate renal impairment to matched participants with normal renal function. Potential participants will be screened to assess their eligibility to enter the study within 28 days prior to first dose administration. Participants will be assigned to the following groups based on BSA-adjusted eGFR at screening using the creatinine-based CKD-EPI (2021) race-free estimation of eGFR: * Part 1: * Group 1: Participants with normal renal function (eGFR ≥ 90 mL/min; n = 8 to 20 participants) * Group 2: Participants with severe renal impairment not on dialysis (eGFR \< 30 mL/min; n = 8 to 10 participants) * Part 2 (Optional): * Group 3: Participants with moderate renal impairment (eGFR ≥ 30 mL/min to \< 60 mL/min; n = 8 to 10 participants) * Group 4: Participants with mild renal impairment (eGFR ≥ 60 mL/min to \< 90 mL/min; n = 8 to 10 participants) If the data from Part 1 demonstrate that severe renal impairment does not alter PK of opemalirsen to an extent which would warrant dose adjustment, then Part 2 will not be pursued. If the PK data of the study support a dosage adjustment in patients with severe renal impairment, then participants will be enrolled Group 3 and/or Group 4 in Part 2. Additional participants may be enrolled in Group 1 (not exceeding n = 20) and dosed in parallel with Part 2, if required, to match participants in Groups 3 and/or 4. Each matched participant with normal renal function (Group 1) enrolled in the study will be demographically matched by sex, age (± 10 years), and BMI (± 20%), data obtained at screening, to an enrolled participant with renal impairment. Participants with normal renal function cannot be matched to more than one participant with renal impairment within an impairment group; however, participants with normal renal function may be matched to 1 participant from more than 1 renal impairment group. Eligible participants will be admitted to the study site on Day -1. On Day 1, participants will receive a single SC injection of opemalirsen. Participants will be confined to the study site until Day 3 and will return for follow-up visits 1, 2, 3, and 8 weeks post-dose. Serial PK (venous) blood samples and urine samples will be collected up to 48 hours post-dose (Day 3) for the measurement of opemalirsen in plasma and urine. Additional blood samples will be collected the follow-up visits 1, 2, and 3 weeks post-dose for the measurement of opemalirsen in plasma. Adverse events and serious adverse events will be recorded and physical examinations, 12-lead electrocardiograms, vital sign measurements, and clinical laboratory tests will be performed to assess safety and tolerability.