Renal Impairment
Conditions
Keywords
Renal Impairment, Healthy participants, AZD5004, Pharmacokinetics, Safety
Brief summary
This is a Phase I, multicentre, single-dose, non-randomised, open-label, parallel-group study to examine the PK, safety, and tolerability of AZD5004 in male and female participants with severe renal impairment and moderate renal impairment (optional) compared with male and female participants with normal renal function.
Detailed description
This is a Phase I, multicentre, single-dose, non-randomised, open-label, parallel-group study to examine the PK, safety, and tolerability of AZD5004 in male and female participants with severe renal impairment and moderate renal impairment (optional) compared with male and female participants with normal renal function. Participants will be assigned to the following groups based on eGFR determined at screening by a local laboratory using serum creatinine: Group 1: Participants with severe renal impairment (eGFR \< 30 mL/min), not on dialysis. Group 2: Participants with normal renal function (eGFR of ≥ 90 mL/min) matched by sex, age, and body weight on a group level to the impaired participants. Group 3 (optional): Participants with moderate renal impairment (eGFR ≥ 30 to \< 60 mL/min).
Interventions
DRUGAZD5004
Dose 1
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Up to three groups (two renal impairment groups and controls with normal renal function) will be enrolled into this study. All subjects will receive the study intervention: Group 1 will enroll 7 participants with severe renal impairment Group 2 will enroll \ 7 participants with normal renal function matched by sex, age, and body weight Group 3 (optional) will enroll 7 participants with moderate renal impairment
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Adults 18-80 years of age * Weight \>50kg and BMI between 18-40 kg/m2 For participants with normal renal function: -Participant must be medically healthy with no significant findings on medical evaluation and an eGFR ≥90 ml/min at screening. For participants with renal impairment: Group 1 (severe) must have an eGFR \<30 ml/min and Group 3 (moderate) must have an eGFR 30 to \<60 ml/min based on CKD-EPI calculations for at least 6 months prior to enrollment.
Exclusion criteria
* Poorly controlled diabetes mellitus (A1C \>10% at screening or recent history of diabetic ketoacidosis or symptomatic hypoglycemia). * Unwillingness to use adequate contraception * Uncontrolled hypertension or hypotension. * Positive screening for HIV, Hepatitis B, or Hepatitis C * Presence of unstable systemic disease or psychologic conditions. Abnormal laboratory values to include but not limited to liver function tests (thresholds differ for renal impairment and health controls) * Any change in baseline medication within 2 weeks of planned study initiation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUCinf | Day 1 to Day 5 | Area under the concentration-time curve from zero to infinity |
| AUClast | Day 1 to Day 5 | Area under the concentration-time curve from zero to the last measurable concentration |
| Cmax | Day 1 to Day 5 | Maximum observed plasma concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK parameter CLNR/F | Day 1 to Day 5 | non-renal clearance of drug from plasma after oral administration |
| PK parameter Vz/F | Day 1 to Day 5 | Apparent volume of distribution during the terminal phase after extravascular administration |
| PK parameter CLr | Day 1 to Day 5 | Renal clearance of the drug from plasma |
| PK parameter Ae | Day 1 to Day 5 | Cumulative amount of unchanged drug excreted into the urine |
| fe | Day 1 to Day 5 | Fraction of the drug excreted into the urine |
| Tmax | Day 1 to Day 5 | Time to reach maximum observed plasma concentration |
| PK parameter t1/2λz | Day 1 to Day 5 | Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve |
| PK parameter CL/F | Day 1 to Day 5 | Apparent total body clearance of drug from plasma after extravascular administration |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events (AEs) | Day 1 to Day 10 | To assess the safety and tolerability of a single oral dose of AZD5004 for participants with severe and moderate (optional) renal impairment and those with normal renal function |
| Number of participants with abnormal Vital signs, abnormal ECGs, and abnormal physical examination findings | Day 1 to Day 5 | To assess the safety and tolerability of a single oral dose of AZD5004 for participants with severe and moderate (optional) renal impairment and those with normal renal function |
| Number of participants with abnormal laboratory tests results | Day 1 to Day 5 | To assess the safety and tolerability of a single oral dose of AZD5004 for participants with severe and moderate (optional) renal impairment and those with normal renal function |
Countries
United States
Outcome results
None listed