Study to Assess the Pharmacokinetics and Safety of AZD9977 in Participants With Renal Impairment

A Single Dose, Non-Randomized, Open-Label, Parallel Group Study to Assess the Pharmacokinetics, Safety and Tolerability of AZD9977 in Participants With Renal Impairment

This is a single dose, non-randomized, open-label, parallel group study. The study will be conducted in participants with severe renal impairment and compared with matched participants with normal renal function. The duration of the study for an individual participant from Screening to Follow-up will be approximately 5 weeks.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: AZD9977

Detailed Description

The study will have 4 cohorts, consisting of participants with severe renal impairment who are not on dialysis (Cohort 1), moderate renal impairment (Cohort 2), mild renal impairment (Cohort 3) and participants with normal renal function (Cohort 4). Following completion of Cohort 1 and Cohort 4, pharmacokinetics (PK) and safety data will be reviewed and a decision will be made whether to study unmatched participants with moderate and mild renal impairment (Cohorts 2 and 3, respectively).

Participants will be screened up to 21 days before administration of study drug. Eligible participants will be admitted to the clinical unit either on the evening of Day -2 or on the morning of Day -1. Each participant will receive a single oral dose of the study drug under fasted conditions on Day 1. Participants will be required to remain resident in the clinical unit until the morning of Day 3 but, if participants prefer, may also remain resident until all PK and other study procedures are completed on Day 7. This decision to extend residency will be made at the discretion of the principal investigator. If participants do check out on Day 3, participants will then return to the unit, as scheduled, for collection of PK samples and safety assessments, with a final Follow-up Visit on Day 14.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Northridge, California, United States, 91324
      • Research Site
  • Florida
    • DeLand, Florida, United States, 32720
      • Research Site
    • Hialeah, Florida, United States, 33014
      • Research Site
    • Jacksonville, Florida, United States, 32216
      • Research Site
    • Orlando, Florida, United States, 32809
      • Research Site
  • Ohio
    • Blue Ash, Ohio, United States, 45242
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Healthy matched control participants only (Cohort 4):

1. Participants who are overtly healthy.

2. Stable renal function, with eGFR of ≥ 90 mL/min/1.73m^2.

   Renally impaired participants only (Cohorts 1-3):

3. Participants who have renal impairment:

   1. Cohort 1 participants with severe renal impairment must have an eGFR lesser than 30 mL/min/1.73m^2 not on dialysis
   2. Cohort 2 participants with moderate renal impairment must have an eGFR of greater than or equal to 30 to lesser than 60 mL/min/1.73m^2
   3. Cohort 3 participants with mild renal impairment must have an eGFR of greater than or equal to 60 to lesser than 90 mL/min/1.73m^2.

   All participants (Cohorts 1-4):

4. Body weight of at least 50 kg and BMI within the range greater than or equal to 18 to lesser than or equal to 35 kg/m^2.
5. Male or female of non-childbearing potential.
6. Male participants should not donate sperm for the duration of the study.
7. Female participants must have a negative pregnancy test at time of study entry.
8. Capable of giving signed informed consent.

Exclusion Criteria:

Healthy matched control participants only (Cohort 4):

1. Evidence of clinically significant cardiovascular, hematological, renal, endocrine, pulmonary, gastrointestinal, hepatic, neurologic, psychiatric, inflammatory or allergic disease.

   Renally impaired participants only (Cohorts 1-3):

2. Renal transplant participants, participants on dialysis and those with a history of acute kidney injury.

   All participants (Cohorts 1-4):

3. Any positive result on Screening for serum hepatitis B surface antigen, hepatitis C virus antibody, and human immunodeficiency virus antibody.
4. Known history of drug or alcohol abuse.
5. History of QT prolongation and arrhythmia.
6. Any moderate or potent inhibitors or inducers of CYP3A4.
7. Participants with a known hypersensitivity to AZD9977 or any of the excipients of the product.
8. For women only - currently pregnant or breast-feeding.
9. A positive local diagnostic test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Screening, clinical signs and symptoms consistent with COVID-19, or the patient has been previosuly hospitalised with COVID-19 infection.

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

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment - AZD9977; There are 4 cohorts in this arm based on renal function (mild, moderate, severe, and normal). Each cohort will have 8 participants.	Drug: AZD9977; Participants will receive a single oral dose of AZD9977 under fasted conditions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma concentration (Cmax)	To assess the PK of AZD9977 following administration of AZD9977	Day 1 to 3 (Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 20, 24, 36, and 48 hours post-dose), Day 4 to 7
Area under the plasma concentration-time curve from time zero to infinity (AUC)	To assess the PK of AZD9977 following administration of AZD9977	Day 1 to 3 (Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 20, 24, 36, and 48 hours post-dose), Day 4 to 7
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC0-t)	To assess the PK of AZD9977 following administration of AZD9977	Day 1 to 3 (Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 20, 24, 36, and 48 hours post-dose), Day 4 to 7
Time to reach maximum observed plasma concentration (tmax)	To assess the PK of AZD9977 following administration of AZD9977	Day 1 to 3 (Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 20, 24, 36, and 48 hours post-dose), Day 4 to 7
Half-life associated with terminal slope of a semi-logarithmic concentration time curve (t½λz)	To assess the PK of AZD9977 following administration of AZD9977	Day 1 to 3 (Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 20, 24, 36, and 48 hours post-dose), Day 4 to 7
Terminal elimination rate constant (λz)	To assess the PK of AZD9977 following administration of AZD9977	Day 1 to 3 (Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 20, 24, 36, and 48 hours post-dose), Day 4 to 7
Apparent total body clearance of drug from plasma after oral administration (CL/F)	To assess the PK of AZD9977 following administration of AZD9977	Day 1 to 3 (Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 20, 24, 36, and 48 hours post-dose), Day 4 to 7
Non-renal clearance of drug from plasma after oral administration (CLNR/F)	To assess the PK of AZD9977 following administration of AZD9977	Day 1 to 3 (Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 20, 24, 36, and 48 hours post-dose), Day 4 to 7
Apparent volume of distribution during the terminal phase after oral administration (Vz/F)	To assess the PK of AZD9977 following administration of AZD9977	Day 1 to 3 (Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 20, 24, 36, and 48 hours post-dose), Day 4 to 7
Mean residence time (MRT)	To assess the PK of AZD9977 following administration of AZD9977	Day 1 to 3 (Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 20, 24, 36, and 48 hours post-dose), Day 4 to 7
Renal clearance of the drug from plasma (CLR)	To assess the PK of AZD9977 following administration of AZD9977	Day 1 to 3 (Pre-dose, 0-4, 4-8, 8-12, 12-24, 24-36, and 36-48 hours post-dose)
Cumulative amount of unchanged drug excreted into the urine (Ae)	To assess the PK of AZD9977 following administration of AZD9977	Day 1 to 3 (Pre-dose, 0-4, 4-8, 8-12, 12-24, 24-36, and 36-48 hours post-dose)
Fraction of the drug excreted into the urine (fe)	To assess the PK of AZD9977 following administration of AZD9977	Day 1 to 3 (Pre-dose, 0-4, 4-8, 8-12, 12-24, 24-36, and 36-48 hours post-dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events and serious adverse events	To evaluate the safety and tolerability of AZD9977	Day -2 to Day 14
Estimated Glomerular Filtration Rate (eGFR)	To determine eGFR based on creatinine and cystatin C using CKD-EPI formula	Screening, Day -1, Day 1 to 3 (Pre-dose, 4, 12, 24 , 36, and 48 hours)

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2020
• Primary Completion (Actual): October 28, 2021
• Study Completion (Actual): October 28, 2021

Study Registration Dates

• First Submitted: June 19, 2020
• First Submitted That Met QC Criteria: July 9, 2020
• First Posted (Actual): July 14, 2020

Study Record Updates

• Last Update Posted (Actual): March 11, 2022
• Last Update Submitted That Met QC Criteria: March 10, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: D6401C00008

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 request 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 rerefer 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