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.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Participants will receive a single oral dose of AZD9977 under fasted conditions.
Research Site
Northridge, California, United States
Research Site
DeLand, Florida, United States
Research Site
Hialeah, Florida, United States
Research Site
Jacksonville, Florida, United States
Maximum observed plasma concentration (Cmax)
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
Area under the plasma concentration-time curve from time zero to infinity (AUC)
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
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 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
Time to reach maximum observed plasma concentration (tmax)
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
Half-life associated with terminal slope of a semi-logarithmic concentration time curve (t½λz)
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
Terminal elimination rate constant (λz)
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
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Research Site
Orlando, Florida, United States
Research Site
Blue Ash, Ohio, United States
Apparent total body clearance of drug from plasma after oral administration (CL/F)
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
Non-renal clearance of drug from plasma after oral administration (CLNR/F)
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
Apparent volume of distribution during the terminal phase after oral administration (Vz/F)
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
Mean residence time (MRT)
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
Renal clearance of the drug from plasma (CLR)
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)
Cumulative amount of unchanged drug excreted into the urine (Ae)
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)
Fraction of the drug excreted into the urine (fe)
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)
Number of participants with adverse events and serious adverse events
To evaluate the safety and tolerability of AZD9977
Time frame: Day -2 to Day 14
Estimated Glomerular Filtration Rate (eGFR)
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)