A Phase I Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD0780

NCT06592482 | Completed Phase 1 FDA Drug

• 1 other identifier: D7960C00007
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

Brief Summary

This is a Phase I, multi-centre, single-dose, non-randomised, open-label, parallel-group study to examine the PK, safety, and tolerability of AZD0780 in male and female participants (females of non-childbearing potential) with severe renal impairment not on dialysis, end-stage renal disease (ESRD) on intermittent haemodialysis (HD), or moderate renal impairment (optional) compared with male and female participants (females of non-childbearing potential) with normal renal function. Potential participants will be screened to assess their eligibility to enter the study up to 4 weeks prior to administration of study intervention. Eligible participants will be admitted to the study site on Day -1. On Day 1, an "A" single oral dose of AZD0780 will be administered, and participants will be confined to the study site until after assessments are completed on Day 11.

Conditions

Renal Impairment

Outcome Measures

Primary Outcomes (3)

• AUClast

  Area under the concentration-time curve from zero to the last measurable concentration

  From Day 1 to Day 11

• Cmax

  Maximum observed plasma concentration

  From Day 1 to Day 11

• AUCinf

  Area under the concentration-time curve from zero to infinity

  From Day 1 to Day 11

Secondary Outcomes (12)

• Number of participants with adverse events (AEs)

  From Day 1 to Day 11

• Number of participants with abnormal vital signs, abnormal ECGs, and abnormal physical examination findings

  From Day 1 to Day 11

• Number of participants with abnormal laboratory test results

  From Day 1 to Day 11

• PK parameters Tmax

  From Day 1 to Day 11

• PK parameters t1/2λz

  From Day 1 to Day 11

Study Arms (4)

Group 1: AZD0780

EXPERIMENTAL

Participants with severe renal impairment (eGFR \< 30 mL/min), not on dialysis.

Drug: AZD0780

Group 2: AZD0780

EXPERIMENTAL

Participants with ESRD (eGFR \< 15 mL/min) on a stable intermittent HD schedule for at least 3 months prior to planned dosing.

Drug: AZD0780

Group 3: AZD0780

EXPERIMENTAL

Participants with normal renal function demographically matched by sex, age, and body mass index (BMI) to the impaired participants (eGFR of ≥ 90 mL/min)

Drug: AZD0780

Group 4 (optional): AZD0780

EXPERIMENTAL

Participants with moderate renal impairment (eGFR ≥ 30 to \< 60 mL/min).

Drug: AZD0780

Interventions

AZD0780 DRUG

A single "A" dose of AZD0780 will be administered in the morning on Day 1 under fasted condition. Study intervention will be administered orally with approximately 240 mL of water.

Group 1: AZD0780; Group 2: AZD0780; Group 3: AZD0780; Group 4 (optional): AZD0780

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Participant must be 18 to 85 years of age, inclusive at the time of signing ICF
• For Participants with normal renal function:
• \- Participant must be medically healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, or 12-lead ECGs, as deemed by the investigator at screening and Day -1
• For Participants with renal impairment:
• Diagnosis of chronic kidney disease, stable renal function in the 6 months prior to dosing
• Received HD for chronic renal failure for at least 3 months prior to dosing (Group 2)
• Participants with renal impairment, as follows, based on CKD-EPI equation (BSA-adjusted eGFR) at screening: Group1 eGFR \< 30 mL/min), not requiring dialysis, Group 2 ESRD (eGFR \< 15 mL/min) on a stable intermittent HD schedule for at least 3 months prior to planned dosing and Group 4 (optional) moderate renal impairment (eGFR ≥ 30 to \< 60 mL/min)
• Male participants:
• Males must be surgically sterile or using, in conjunction with their female partner, a highly effective method of contraception for the duration of the study (from the time of study intervention administration) until 3 months after discharge to prevent pregnancy in a partner.
• Female participants of non-childbearing potential:
• Female participants must not be pregnant and must have a negative pregnancy test at screening and check-in, must not be lactating, and must not be of childbearing potential.

You may not qualify if:

• For Participants with normal renal function:
• 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).
• Use of any prescription or non-prescription drugs (including vitamins, recreational drugs, and dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before study intervention, unless, in the opinion of the investigator and sponsor, the medication will not interfere with the study.
• History of any major surgical procedure within 30 days prior to study intervention.
• For Participants with renal impairment:
• Presence of unstable medical or psychological conditions which, in the opinion of the investigator, would compromise the participant's safety or successful participation in this study.
• Renal transplant patients (participants on HD with non-functioning renal transplants are not excluded), 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.
• History of any major surgical procedure within 30 days prior to study intervention.
• Current or previous treatment with drugs for reduction or inhibition of PCSK9 (eg, evolocumab, alirocumab, or inclisiran).
• Use of moderate/strong inhibitors or inducers of CYP3A4/5.
• Unable to refrain from potassium binders, phosphate binders (eg, aluminium hydroxide and calcium carbonate), cholestyramine/colestipol, and ranitidine/nizatidine within 10 hours before and 10 hours after study intervention.
• Receiving or has received within 14 days of screening, medication that contains a black box warning for significant QT prolongation. A list of prohibited medications can be found in protocol.
• Use of concurrent medication which affects calculation of eGFR by affecting serum creatinine (eg, cephalosporin antibiotics, ascorbic acid, trimethoprim, cimetidine, or quinine) within 7 days of Day -1.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (5)

Research Site

Lake Forest, California, 92630, United States

Location

Research Site

Hialeah, Florida, 33014, United States

Location

Research Site

Orlando, Florida, 32808, United States

Location

Research Site

Orlando, Florida, 32809, United States

Location

Research Site

Saint Paul, Minnesota, 55114, United States

Location

MeSH Terms

Conditions

Renal Insufficiency

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Kwabena Ayesu, Medicine

  Omega Research Orlando

  PRINCIPAL INVESTIGATOR

• Thomas Marbury, Medicine

  Orlando Clinical Research Center

  PRINCIPAL INVESTIGATOR

• Juan Carlos Rondon, Medicine

  Clinical Pharmacology of Miami, Inc.

  PRINCIPAL INVESTIGATOR

• Trisha Shamp, Medicine

  Nucleus Network

  PRINCIPAL INVESTIGATOR

• Joel Neutel, Medicine

  Orange County Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2024
• First Posted: September 19, 2024
• Study Start: August 2, 2024
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: February 20, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

US (5)