Investigating how renal impairment affects the drug 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 is testing how well the drug AZD6234 works and is tolerated in people with different levels of kidney problems compared to healthy individuals.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: AstraZeneca (industry)
• Locations: 4 sites (Lake Forest, California and 3 other locations)
• Trial ID: NCT06845813 on ClinicalTrials.gov

What this trial studies

This Phase I multicenter, open-label study evaluates the pharmacokinetics, safety, and tolerability of a single subcutaneous dose of AZD6234 in participants with varying degrees of renal impairment, including end-stage renal disease and severe renal impairment. Participants will be compared to a matched control group of healthy individuals with normal renal function. The study aims to understand how renal function impacts the drug's behavior in the body, using body surface area-adjusted estimated glomerular filtration rate (eGFR) for participant grouping. The study will include both male and female participants aged 18 to 85 years.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 85 with varying degrees of renal impairment or healthy individuals with normal renal function.

Not a fit: Patients with acute renal failure or those not meeting the specific inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide critical insights into the safe use of AZD6234 in patients with renal impairment.

How similar studies have performed: Previous studies have shown success in evaluating pharmacokinetics in patients with renal impairment, making this approach both relevant and necessary.

Eligibility criteria

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.

Where this trial is running

Lake Forest, California and 3 other locations

• Research Site — Lake Forest, California, United States (NOT_YET_RECRUITING)
• Research Site — Orlando, Florida, United States (RECRUITING)
• Research Site — Orlando, Florida, United States (NOT_YET_RECRUITING)
• Research Site — Tampa, Florida, United States (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: Fadi Saba, M.D. — Servico Integrado de Tecnicas Endovasculares
• Study coordinator: AstraZeneca Clinical Study Information Center

Conditions: Renal Impairment, Healthy Participants, AZD6234, Pharmacokinetics, Safety