Clinical trial NCT04469907: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2020-07-14
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum observed plasma concentration (Cmax)
timeFrame: 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
measure: Area under the plasma concentration-time curve from time zero to infinity (AUC)
timeFrame: 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
measure: Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC0-t)
timeFrame: 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
measure: Time to reach maximum observed plasma concentration (tmax)
timeFrame: 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
measure: Half-life associated with terminal slope of a semi-logarithmic concentration time curve (t½λz)
timeFrame: 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
measure: Terminal elimination rate constant (λz)
timeFrame: 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
measure: Apparent total body clearance of drug from plasma after oral administration (CL/F)
timeFrame: 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
measure: Non-renal clearance of drug from plasma after oral administration (CLNR/F)
timeFrame: 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
measure: Apparent volume of distribution during the terminal phase after oral administration (Vz/F)
timeFrame: 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
measure: Mean residence time (MRT)
timeFrame: 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
measure: Renal clearance of the drug from plasma (CLR)
timeFrame: Day 1 to 3 (Pre-dose, 0-4, 4-8, 8-12, 12-24, 24-36, and 36-48 hours post-dose)
measure: Cumulative amount of unchanged drug excreted into the urine (Ae)
timeFrame: Day 1 to 3 (Pre-dose, 0-4, 4-8, 8-12, 12-24, 24-36, and 36-48 hours post-dose)
measure: Fraction of the drug excreted into the urine (fe)
timeFrame: Day 1 to 3 (Pre-dose, 0-4, 4-8, 8-12, 12-24, 24-36, and 36-48 hours post-dose)
Secondary outcomes:
measure: Number of participants with adverse events and serious adverse events
timeFrame: Day -2 to Day 14
measure: Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Screening, Day -1, Day 1 to 3 (Pre-dose, 4, 12, 24 , 36, and 48 hours)
Other outcomes:
Locations:
city: Northridge
country: United States
facility: Research Site
state: California
city: DeLand
country: United States
facility: Research Site
state: Florida
city: Hialeah
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Blue Ash
country: United States
facility: Research Site
state: Ohio
Study officials:
References: