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

Primary Purpose

Renal Impairment

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AZD9977
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Renal Impairment

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment - AZD9977

Arm Description

There are 4 cohorts in this arm based on renal function (mild, moderate, severe, and normal). Each cohort will have 8 participants.

Outcomes

Primary Outcome Measures

Maximum observed plasma concentration (Cmax)
To assess the PK of AZD9977 following administration of AZD9977
Area under the plasma concentration-time curve from time zero to infinity (AUC)
To assess the PK of AZD9977 following administration of AZD9977
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
Time to reach maximum observed plasma concentration (tmax)
To assess the PK of AZD9977 following administration of AZD9977
Half-life associated with terminal slope of a semi-logarithmic concentration time curve (t½λz)
To assess the PK of AZD9977 following administration of AZD9977
Terminal elimination rate constant (λz)
To assess the PK of AZD9977 following administration of AZD9977
Apparent total body clearance of drug from plasma after oral administration (CL/F)
To assess the PK of AZD9977 following administration of AZD9977
Non-renal clearance of drug from plasma after oral administration (CLNR/F)
To assess the PK of AZD9977 following administration of AZD9977
Apparent volume of distribution during the terminal phase after oral administration (Vz/F)
To assess the PK of AZD9977 following administration of AZD9977
Mean residence time (MRT)
To assess the PK of AZD9977 following administration of AZD9977
Renal clearance of the drug from plasma (CLR)
To assess the PK of AZD9977 following administration of AZD9977
Cumulative amount of unchanged drug excreted into the urine (Ae)
To assess the PK of AZD9977 following administration of AZD9977
Fraction of the drug excreted into the urine (fe)
To assess the PK of AZD9977 following administration of AZD9977

Secondary Outcome Measures

Number of participants with adverse events and serious adverse events
To evaluate the safety and tolerability of AZD9977
Estimated Glomerular Filtration Rate (eGFR)
To determine eGFR based on creatinine and cystatin C using CKD-EPI formula

Full Information

First Posted
June 19, 2020
Last Updated
March 10, 2022
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT04469907
Brief Title
Study to Assess the Pharmacokinetics and Safety of AZD9977 in Participants With Renal Impairment
Official Title
A Single Dose, Non-Randomized, Open-Label, Parallel Group Study to Assess the Pharmacokinetics, Safety and Tolerability of AZD9977 in Participants With Renal Impairment
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
June 22, 2020 (Actual)
Primary Completion Date
October 28, 2021 (Actual)
Study Completion Date
October 28, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Impairment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment - AZD9977
Arm Type
Experimental
Arm Description
There are 4 cohorts in this arm based on renal function (mild, moderate, severe, and normal). Each cohort will have 8 participants.
Intervention Type
Drug
Intervention Name(s)
AZD9977
Intervention Description
Participants will receive a single oral dose of AZD9977 under fasted conditions.
Primary Outcome Measure Information:
Title
Maximum observed plasma concentration (Cmax)
Description
To assess the PK of AZD9977 following administration of AZD9977
Time Frame
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
Title
Area under the plasma concentration-time curve from time zero to infinity (AUC)
Description
To assess the PK of AZD9977 following administration of AZD9977
Time Frame
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
Title
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC0-t)
Description
To assess the PK of AZD9977 following administration of AZD9977
Time Frame
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
Title
Time to reach maximum observed plasma concentration (tmax)
Description
To assess the PK of AZD9977 following administration of AZD9977
Time Frame
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
Title
Half-life associated with terminal slope of a semi-logarithmic concentration time curve (t½λz)
Description
To assess the PK of AZD9977 following administration of AZD9977
Time Frame
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
Title
Terminal elimination rate constant (λz)
Description
To assess the PK of AZD9977 following administration of AZD9977
Time Frame
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
Title
Apparent total body clearance of drug from plasma after oral administration (CL/F)
Description
To assess the PK of AZD9977 following administration of AZD9977
Time Frame
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
Title
Non-renal clearance of drug from plasma after oral administration (CLNR/F)
Description
To assess the PK of AZD9977 following administration of AZD9977
Time Frame
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
Title
Apparent volume of distribution during the terminal phase after oral administration (Vz/F)
Description
To assess the PK of AZD9977 following administration of AZD9977
Time Frame
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
Title
Mean residence time (MRT)
Description
To assess the PK of AZD9977 following administration of AZD9977
Time Frame
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
Title
Renal clearance of the drug from plasma (CLR)
Description
To assess the PK of AZD9977 following administration of AZD9977
Time Frame
Day 1 to 3 (Pre-dose, 0-4, 4-8, 8-12, 12-24, 24-36, and 36-48 hours post-dose)
Title
Cumulative amount of unchanged drug excreted into the urine (Ae)
Description
To assess the PK of AZD9977 following administration of AZD9977
Time Frame
Day 1 to 3 (Pre-dose, 0-4, 4-8, 8-12, 12-24, 24-36, and 36-48 hours post-dose)
Title
Fraction of the drug excreted into the urine (fe)
Description
To assess the PK of AZD9977 following administration of AZD9977
Time Frame
Day 1 to 3 (Pre-dose, 0-4, 4-8, 8-12, 12-24, 24-36, and 36-48 hours post-dose)
Secondary Outcome Measure Information:
Title
Number of participants with adverse events and serious adverse events
Description
To evaluate the safety and tolerability of AZD9977
Time Frame
Day -2 to Day 14
Title
Estimated Glomerular Filtration Rate (eGFR)
Description
To determine eGFR based on creatinine and cystatin C using CKD-EPI formula
Time Frame
Screening, Day -1, Day 1 to 3 (Pre-dose, 4, 12, 24 , 36, and 48 hours)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy matched control participants only (Cohort 4): Participants who are overtly healthy. Stable renal function, with eGFR of ≥ 90 mL/min/1.73m^2. Renally impaired participants only (Cohorts 1-3): Participants who have renal impairment: Cohort 1 participants with severe renal impairment must have an eGFR lesser than 30 mL/min/1.73m^2 not on dialysis 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 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): 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. Male or female of non-childbearing potential. Male participants should not donate sperm for the duration of the study. Female participants must have a negative pregnancy test at time of study entry. Capable of giving signed informed consent. Exclusion Criteria: Healthy matched control participants only (Cohort 4): Evidence of clinically significant cardiovascular, hematological, renal, endocrine, pulmonary, gastrointestinal, hepatic, neurologic, psychiatric, inflammatory or allergic disease. Renally impaired participants only (Cohorts 1-3): Renal transplant participants, participants on dialysis and those with a history of acute kidney injury. All participants (Cohorts 1-4): Any positive result on Screening for serum hepatitis B surface antigen, hepatitis C virus antibody, and human immunodeficiency virus antibody. Known history of drug or alcohol abuse. History of QT prolongation and arrhythmia. Any moderate or potent inhibitors or inducers of CYP3A4. Participants with a known hypersensitivity to AZD9977 or any of the excipients of the product. For women only - currently pregnant or breast-feeding. 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.
Facility Information:
Facility Name
Research Site
City
Northridge
State/Province
California
ZIP/Postal Code
91324
Country
United States
Facility Name
Research Site
City
DeLand
State/Province
Florida
ZIP/Postal Code
32720
Country
United States
Facility Name
Research Site
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33014
Country
United States
Facility Name
Research Site
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32216
Country
United States
Facility Name
Research Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States
Facility Name
Research Site
City
Blue Ash
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home

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

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