Clinical trial NCT06845813: Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD6234
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Renal Impairment
Keywords: Renal Impairment
Healthy Participants
AZD6234
Pharmacokinetics
Safety
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2025-02-25
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Up to five cohorts (four renal impairment cohorts and controls with normal renal function) will be enrolled into the study.

All subjects will receive the study intervention:

* Cohort 1 will enroll participants with end stage renal disease
* Cohort 2 will enroll participants with severe renal impairment
* Cohort 3 will enroll healthy participants matched on a group level by sex, age, and BMI
* Cohort 4 (optional) will enroll participants with moderate renal impairment
* Cohort 5 (optional) will enroll participants with mild renal impairment
Primary purpose: TREATMENT

Brief summary: 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.

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.

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.

Primary outcomes:
measure: AUClast
timeFrame: Day 1 to Day 36
measure: AUCinf
timeFrame: Day 1 to Day 36
measure: Cmax
timeFrame: Day 1 to Day 36
Secondary outcomes:
measure: Tmax
timeFrame: Day 1 to Day 36
measure: PK parameter (t1/2λz)
timeFrame: Day 1 to Day 36
measure: PK parameter (CL/F)
timeFrame: Day 1 to Day 36
measure: PK parameter (Vz/F)
timeFrame: Day 1 to Day 36
measure: Number of participants with adverse events (AEs)
timeFrame: Day 1 to Day 54
measure: Number of participants with abnormal vital signs
timeFrame: Day 1 to Day 54
measure: Number of participants with abnormal ECGs
timeFrame: Day 1 to Day 54
measure: Number of participants with abnormal physical examination findings
timeFrame: Day 1 to Day 54
measure: Number of participants with abnormal laboratory test results
timeFrame: Day 1 to Day 54
measure: Number of participants with confirmed positive anti-drug antibody testing
timeFrame: Day 1 to Day 54
measure: Number of participants with serious adverse events (SAEs)
timeFrame: Day 1 to Day 54
Other outcomes:
Locations:
city: Lake Forest
country: United States
facility: Research Site
state: California
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
Study officials:
affiliation: Servico Integrado de Tecnicas Endovasculares
name: Fadi Saba, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Servico Integrado de Tecnicas Endovasculares
name: Thomas C Marbury, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Servico Integrado de Tecnicas Endovasculares
name: Joel M Neutel, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Servico Integrado de Tecnicas Endovasculares
name: Kwabena Ayesu, M.D.
role: PRINCIPAL_INVESTIGATOR
References: