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

NCT04469907 | Completed Phase 1 FDA Drug

• 1 other identifier: D6401C00008
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 6

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.

Conditions

Renal Impairment

Outcome Measures

Primary Outcomes (13)

• 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 Outcomes (2)

• Number of participants with adverse events and serious adverse events

  Day -2 to Day 14

• Estimated Glomerular Filtration Rate (eGFR)

  Screening, Day -1, Day 1 to 3 (Pre-dose, 4, 12, 24 , 36, and 48 hours)

Study Arms (1)

Treatment - AZD9977

EXPERIMENTAL

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

Drug: AZD9977

Interventions

AZD9977 DRUG

Participants will receive a single oral dose of AZD9977 under fasted conditions.

Treatment - AZD9977

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (6)

Research Site

Northridge, California, 91324, United States

Location

Research Site

DeLand, Florida, 32720, United States

Location

Research Site

Hialeah, Florida, 33014, United States

Location

Research Site

Jacksonville, Florida, 32216, United States

Location

Research Site

Orlando, Florida, 32809, United States

Location

Research Site

Blue Ash, Ohio, 45242, United States

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

AZD9977

Condition Hierarchy (Ancestors)

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

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 19, 2020
• First Posted: July 14, 2020
• Study Start: June 22, 2020
• Primary Completion: October 28, 2021
• Study Completion: October 28, 2021
• Last Updated: March 11, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• 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.
• 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.

Locations

US (6)