Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD6234

A Phase I, Multicentre, Single-Dose, Non-Randomised, Open-Label, Parallel-Group Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD6234

This study will evaluate the pharmacokinetics (PK), safety, and tolerability of single subcutaneous dose of AZD6234 with end stage renal disease, severe, and possibly moderate and mild renal impairment in comparison to a matched healthy control group.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: AZD6234

Detailed Description

This Phase I multicentre, single-dose, non-randomised, open-label, parallel-group study aims to examine the pharmacokinetics, safety, and tolerability of AZD6234 in both male and female participants. Participants include those with end-stage renal disease (ESRD) on intermittent haemodialysis (HD), severe renal impairment not on dialysis, and optional groups for moderate and mild renal impairment. These are compared to participants with normal renal function. All participants are grouped based on body surface area-adjusted estimated glomerular filtration rate (eGFR), and those with normal renal function are matched at a group level by sex, age, and body mass index (BMI) to the participants with impaired renal function.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Lake Forest, California, United States, 92630
      • Research Site
  • Florida
    • Orlando, Florida, United States, 32809
      • Research Site
    • Orlando, Florida, United States, 32808
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participant must be 18 to 85 years of age, inclusive, at the time of signing the informed consent.
• Body weight ≥ 50 kg; BMI within the range of ≥ 18 to ≤ 40 kg/m2, as measured at screening.

Healthy Matched Control Participants:

• Participant must be medically healthy with no clinically significant medical history, or abnormalities in physical examination, clinical laboratory profiles, vital signs, or 12-lead ECGs, as deemed by the investigator at screening and Day -1.
• Have an eGFR of ≥ 90 mL/min determined at screening.

Renally-impaired Participants:

• Diagnosis of chronic kidney disease, stable renal function in the 3 months prior to dosing,
• Participants with renal impairment based on BSA-adjusted CKD-EPI equation at screening.
• All renally-impaired participants should be on a stable dose of cardio-renal relevant treatment for at least 2 weeks prior to screening.
• If participants with renal impairment have diabetes mellitus, it must be controlled
• Female(s) of childbearing potential: must use adequate contraception. Oral contraceptives are not permitted as there is a potential effect of the IMP on the absorption of oral drugs.
• Male Participants: Condom use is required for the duration of the study and until at least 28 days after the last dose of IMP. Additional contraception must be used for the sexual partners of male study participants throughout the clinical trial and for 28 days following the last dose of IMP.

Exclusion Criteria:

- History or presence of: significant GI disease or previous upper GI surgery

• Clinically significant cardiovascular disease, as judged by the investigator, d. Neuromuscular or neurogenic disease e. Severe vitamin D deficiency < 12 ng/dL.
• History or presence of any condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
• History of psychosis, bipolar disorder
• History of major depressive disorder within the past 2 years
• History of suicide attempt or history of suicidal ideation within the past year.

Healthy Matched Control Participants:

• History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
• Use of any prescription or non-prescription drugs, unless, in the opinion of the investigator and sponsor, the medication will not interfere with the study.

Renally-impaired Participants:

• Presence of unstable medical condition or any evidence of additional severe or uncontrolled systemic disease or laboratory finding which, in the opinion of the investigator, would compromise the participant's safety or successful participation in this study.
• Renal transplant patients, participants waiting for organ transplant scheduled to occur during the study, and those with a history of acute kidney injury occurring within 3 months prior to screening. Nonfunctioning renal allografts are allowed.
• Use of concurrent medication which affects calculation of eGFR by affecting serum creatinine within 7 days of Day -1.
• Unable to refrain from phosphate binders, cholestyramine/colestipol, and ranitidine/nizatidine within 10 hours before and 10 hours after study intervention.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Subjects with end stage renal disease will receive a single subcutaneous dose of AZD6234 under fasted conditions	Drug: AZD6234; Dose 1; Other Names: Dose 1
Experimental: Group 2; Subjects with severe renal impairment will receive a single subcutaneous dose of AZD6234 under fasted conditions	Drug: AZD6234; Dose 1; Other Names: Dose 1
Experimental: Group 3; Healthy participants will receive a single subcutaneous dose of AZD6234 under fasted conditions	Drug: AZD6234; Dose 1; Other Names: Dose 1
Experimental: Group 4 (optional); Subjects with moderate renal impairment will receive a single subcutaneous dose of AZD6234 under fasted conditions	Drug: AZD6234; Dose 1; Other Names: Dose 1
Experimental: Group 5 (optional); Subjects with mild renal impairment will receive a single subcutaneous dose of AZD6234 under fasted conditions	Drug: AZD6234; Dose 1; Other Names: Dose 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUClast	Area under plasma concentration-time curve from time zero to the last measurable concentration	Day 1 to Day 36
AUCinf	Area under plasma concentration-time curve from zero to infinity	Day 1 to Day 36
Cmax	Maximum observed plasma concentration	Day 1 to Day 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax	Time to reach maximum observed plasma concentration	Day 1 to Day 36
PK parameter (t1/2λz)	Terminal elimination half-life	Day 1 to Day 36
PK parameter (CL/F)	Apparent plasma clearance	Day 1 to Day 36
PK parameter (Vz/F)	Apparent volume of distribution during the terminal phase	Day 1 to Day 36
Number of participants with adverse events (AEs)	To assess the safety and tolerability of a single subcutaneous dose of AZD6234 in participants with end stage renal disease, severe, moderate (optional), and mild (optional) renal impairment and those with normal renal function.	Day 1 to Day 54
Number of participants with abnormal vital signs	To assess the safety and tolerability of a single subcutaneous dose of AZD6234 in participants with end stage renal disease, severe, moderate (optional), and mild (optional) renal impairment and those with normal renal function.	Day 1 to Day 54
Number of participants with abnormal ECGs	To assess the safety and tolerability of a single subcutaneous dose of AZD6234 in participants with end stage renal disease, severe, moderate (optional), and mild (optional) renal impairment and those with normal renal function.	Day 1 to Day 54
Number of participants with abnormal physical examination findings	To assess the safety and tolerability of a single subcutaneous dose of AZD6234 in participants with end stage renal disease, severe, moderate (optional), and mild (optional) renal impairment and those with normal renal function.	Day 1 to Day 54
Number of participants with abnormal laboratory test results	To assess the safety and tolerability of a single subcutaneous dose of AZD6234 in participants with end stage renal disease, severe, moderate (optional), and mild (optional) renal impairment and those with normal renal function.	Day 1 to Day 54
Number of participants with confirmed positive anti-drug antibody testing	Prevalence and incidence of ADAs to AZD6234 ADA titre	Day 1 to Day 54
Number of participants with serious adverse events (SAEs)	To assess the safety and tolerability of a single subcutaneous dose of AZD6234 in participants with end stage renal disease, severe, moderate (optional), and mild (optional) renal impairment and those with normal renal function.	Day 1 to Day 54

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Thomas C Marbury, M.D., Servico Integrado de Tecnicas Endovasculares; Principal Investigator: Fadi Saba, M.D., Servico Integrado de Tecnicas Endovasculares; Principal Investigator: Joel M Neutel, M.D., Servico Integrado de Tecnicas Endovasculares; Principal Investigator: Kwabena Ayesu, M.D., Servico Integrado de Tecnicas Endovasculares

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2025
• Primary Completion (Actual): September 30, 2025
• Study Completion (Actual): September 30, 2025

Study Registration Dates

• First Submitted: February 24, 2025
• First Submitted That Met QC Criteria: February 24, 2025
• First Posted (Actual): February 25, 2025

Study Record Updates

• Last Update Posted (Estimated): November 3, 2025
• Last Update Submitted That Met QC Criteria: October 31, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Renal Impairment; Healthy Participants; AZD6234
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency
• Other Study ID Numbers: D8750C00007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request 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.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No