A Phase 1 interventional study of AZD8233 in End Stage Renal Disease, sponsored by AstraZeneca. Terminated at 1 site in Poland. Open to participants aged 18 Years to 80 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-12-22.
Sponsored by AstraZeneca · Phase 1, Interventional, and Treatment
The study is intended to assess the pharmacokinetics (PK), proprotein convertase subtilisin/kexin type 9 (PCSK9) reduction, safety and tolerability of AZD8233 in male and female participants with severe renal impairment and participants with ESRD compared to matched healthy control participants.
This is an open-label, single dose, non-randomised, parallel group study. Participant will be enrolled in 3 cohorts.
Cohort 3 will include 8 participants with ESRD on dialysis (eGFR of \< 15 mL/min/1.73 m\^2).
Participant will receive the study drug on Day 1, discharged on Day 2 followed by out-patient follow-up visits on Day 3, 7, 14, 28, 42, 56, and 90.
3,840 studies on the registry are indexed under Kidney Diseases; 500 are open to participants now.
This study's enrollment of 3 is below the median of 70 across 2,640 interventional studies indexed under Kidney Diseases.
Browse Kidney Diseases studies →AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.
Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.
Counted across the registry records on this site, refreshed daily.
For Cohort 1 (CKD): Participants who are severely renally impaired.
(a) Have an eGFR of ≥15 to \< 30 mL/min/1.73 m\^2 as determined at Screening (Visit 1) via the CKD-EPI formula.
For Cohort 3 (ESRD): Participants with ESRD on dialysis.
Exclusion Criteria:
Any laboratory values with the following deviations at the Screening Visit (Visit 1); test may be repeated at the discretion of the Investigator if abnormal:
(a) Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and HIV. (b) Alanine aminotransferase > 1.5 × ULN (c) Aspartate aminotransferase > 1.5 × ULN (d) Total bilirubin > ULN (e) Haemoglobin \< 9 g/dL (f) Platelet count ≤ LLN
Participants with severe renal impairment will receive a single dose of AZD8233 on Day 1.
Drug: AZD8233
Participants who are healthy will receive a single dose of AZD8233 on Day 1.
Drug: AZD8233
Participants with ESRD on dialysis will receive a single dose of AZD8233 on Day 1.
Drug: AZD8233
Participants will receive a single subcutaneous (SC) dose of AZD8233 into the region of the abdomen.
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Day 1 to Day 90
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.
Time frame: Baseline, 24 hour post-dose, Day 3, 7, 14, 28, 42, 56 and 90
Plan to share: Yes — Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the requests portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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This study is terminated, as verified in Dec 2022. You cannot join it, but the record below documents what was studied.
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