To assess the pharmacokinetics, safety, and tolerability of AZD8233 in participants with Chronic Kidney Disease (CKD), end stage renal disease (ESRD) and healthy participants.

Study identifier:D7990C00007

ClinicalTrials.gov identifier:NCT05065463

EudraCT identifier:2021-003044-24

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

A Single Dose, Non-randomised, Open-label, Parallel Group Study to Assess the Pharmacokinetics, PCSK9 Reduction, Safety, and Tolerability of AZD8233 in Participants with Severe Renal Impairment, End Stage Renal Disease and Healthy Participants as Controls

Medical condition

End Stage Renal Disease

Phase

Phase 1

Healthy volunteers

Yes

Study drug

AZD8233

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 80 Years

Date

Study Start Date: 10 Aug 2022

Primary Completion Date: 23 Nov 2022

Study Completion Date: 23 Nov 2022

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Aug 2023 by AstraZeneca

Collaborators

Parexel International

Inclusion and exclusion criteria

Inclusion Criteria

1. For Cohort 1 and 3 (CKD/ESRD): Participants that are on statins, ACEi/ARB, beta-blocker, diuretic or on any other cardio-renal relevant treatment, the dose should be stable at least 4 weeks prior to Screening (Visit 1) (no dose adjustments within 4 weeks prior to Screening [Visit 1]).
2. For Cohort 2 (HV): Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. (a) Have an eGFR of ≥ 90 mL/min/1.73 m^2 as determined at Screening (Visit 1) via the CKD-EPI formula.
3. 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.
4. For Cohort 3 (ESRD): Participants with ESRD on dialysis.
(a) Have an eGFR of < 15 mL/min/1.73 m^2.
(b) Have been on stable intermittent haemodialysis for at least 3 months prior to Screening (Visit 1).
5. Body weight of at least 50 kg and BMI within the range ≥ 18 to ≤ 35 kg/m^2 (inclusive).
6. Female of non-childbearing potential or male. Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria

1. Participant has a positive SARS-CoV-2 test result within 2 weeks before screening (Visit 1) or between screening and admission to study centre (Day -22 to Day - 2).
2. Clinical signs and symptoms consistent with COVID-19 (eg, fever, dry cough, dyspnoea, sore throat, fatigue) 2 weeks before screening (Visit 1) or between screening and admission to study centre (Visit 2).
3. Participant has been previously hospitalised with COVID-19 infection within the last 3 months prior to Screening (Visit 1).
4. Known or suspected history of substance dependence or a positive screen for drugs or alcohol abuse at the Screening Visit.
5. 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
6. Previous allogeneic bone marrow transplant.
7. Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection.
9. Participants with a known hypersensitivity to AZD8233 or any of the excipients of the product.
10. For Cohort 2: Any clinically significant disease or disorder (eg, cardiovascular, pulmonary, gastrointestinal, liver, renal, neurological, musculoskeletal including bone fractures, endocrine including adrenal insufficiency, metabolic, malignant, psychiatric, major physical impairment,), skin disorder, history of, or ongoing clinically significant allergy/hypersensitivity.
11. Cohort 1 & 3: Presence of unstable medical (e.g., diabetes) or psychological conditions and renal transplant patients.
12. Previous administration of AZD8233/AZD6615 or inclisiran (LEQVIO®, Novartis).
13. Current or previous treatment with drugs for reduction of PCSK9 (for example evolocumab, alirocumab or inclisiran).

No locations available

Arms	Assigned Interventions
Experimental: Cohort 1 Participants with severe renal impairment 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.
Experimental: Cohort 2 Participants who are healthy 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.
Experimental: Cohort 3 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.

Documents available

CSRsynopsis will be posted on AZ.CT and on EudraCT
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]