| Outcome Measures: |
Primary: Observed maximum plasma concentration (Cmax), The pharmacokinetics (PK) parameter of AZD8233 full-length antisense oligonucleotide (ASOs) in participants with severe renal impairment and ESRD compared to matched healthy control participants will be assessed using plasma concentrations. Cmax is defined as observed maximum plasma concentration of AZD8233., Baseline, 24 hour post-dose, Day 3, 7, 14, 28, 42, 56 and 90|Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUCinf), The PK of AZD8233 full-length ASOs in participants with severe renal impairment and ESRD compared to matched healthy control participants will be assessed using plasma concentrations. AUCinf is defined as area under the plasma concentration-time curve from time zero extrapolated to infinity of AZD8233. AUCinf is estimated by AUClast + Clast/λz where Clast is the observed last quantifiable drug concentration., Baseline, 24 hour post-dose, Day 3, 7, 14, 28, 42, 56 and 90|Area under the plasma concentration-curve from time zero to time of last quantifiable concentration (AUClast), The PK of AZD8233 full-length ASOs in participants with severe renal impairment and ESRD compared to matched healthy control participants will be assessed using plasma concentrations. AUClast is defined as area under the plasma concentration-curve from time zero to time of last quantifiable concentration of AZD8233., Baseline, 24 hour post-dose, Day 3, 7, 14, 28, 42, 56 and 90|Area under the concentration-time curve from time zero to 24 hours after dosing (AUC0-24), The PK of AZD8233 full-length ASOs in participants with severe renal impairment and ESRD compared to matched healthy control participants will be assessed using plasma concentrations. AUC0-24 is defined as area under the concentration-time curve from time zero to 24 hours after dosing of AZD8233., Baseline, 24 hour post-dose|Renal clearance (CLR), The PK of AZD8233 full-length ASOs in participants with severe renal impairment and ESRD compared to matched healthy control participants will be assessed using urine concentrations. CLR is defined as renal clearance of AZD8233 from plasma., Post-dose (0-8 hour and 8-24 hour) at Day 1|Amount excreted in urine (Ae), The PK of AZD8233 full-length ASOs in participants with severe renal impairment and ESRD compared to matched healthy control participants will be assessed using urine concentrations. The PK urine parameters for AZD8233 full-length ASOs will be derived from Ae. Ae(0-last) is defined as cumulative amount of analyte excreted unchanged in urine at the last sampling interval of AZD8233., Post-dose (0-8 hour and 8-24 hour) at Day 1|Fraction unbound in plasma (fe), The PK of AZD8233 full-length ASOs in participants with severe renal impairment and ESRD compared to matched healthy control participants will be assessed using urine concentrations. The PK urine parameters for AZD8233 full-length ASOs will be derived from fe. fe(0-last) is defined as percentage of dose excreted unchanged in urine from time zero to the last measured time-point for an analyte of AZD8233., Post-dose (0-8 hour and 8-24 hour) at Day 1|Number of participants with adverse events (AEs), To assess safety and tolerability of AZD8233 in participants with severe renal impairment, ESRD and their healthy matched controls., Day 1 to Day 90 | Secondary: Percentage reduction in proprotein convertase subtilisin/kexin type 9 (PCSK9) plasma levels from baseline, To asses the percentage change from baseline in PCSK9 plasma levels over-time in participants with severe renal impairment and ESRD compared to their healthy matched controls., Baseline, 24 hour post-dose, Day 3, 7, 14, 28, 42, 56 and 90
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