Renal Impairment
Conditions
Keywords
End State Renal Disease (ESRD), Renal Insufficiency, Renal Impairment, Renal Disease, Hemodialysis
Brief summary
Evaluation of the pharmacokinetics (PK) of SPR206 in subjects with normal renal function, subjects with various degrees of renal insufficiency, and subjects with end-stage renal disease (ESRD) receiving hemodialysis (HD) therapy.
Interventions
DRUGSPR206
SPR206 100 mg single-dose IV infused over 1 hour
Sponsors
United States Department of Defense
Spero Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * BMI ≥ 18.5 and ≤ 39.9 (kg/m2) and weight between 50.0 and 130.0 kg (inclusive) * Medically healthy without clinically significant abnormalities (Healthy Volunteers) or medically stable without clinically significant acute or chronic illness (Subjects with varying degrees of Renal Disease) * Normal renal function with eGFR ≥90 mL/min/1.73m2 (Cohort 1), or renal insufficiency with eGFR 60 to \<90 mL/min/1.73m2 (Cohort 2), 30 to \<60 mL/min/1.73m2 (Cohort 3), or \<30 mL/min/1.73m2 (Cohort 4), calculated using Modification of Diet in Renal Disease (MDRD). Subjects with ESRD must be receiving hemodialysis at least 3 times per week for at least 3 months at Screening (Cohort 5 only) * Non-smoker for at least 1 month prior to screening for the study * Ability and willingness to abstain from alcohol, caffeine, xanthine-containing beverages or food * Other inclusion criteria per protocol Key
Exclusion criteria
* Any clinically significant medical history or abnormal findings upon physical examination, or clinical laboratory tests, not specifically excluded in other criteria below that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject * Electrocardiogram (ECG) with QTcF interval duration equal or greater than 500 msec * Hemoglobin (HB), hematocrit (HCT), white blood cell count (WBC), or platelet count less than the lower limit of normal range of the reference laboratory (Cohort 1). HB \<8.5 gm/dL, WBC ≤3,000 cells/μL or platelet count ≤100,000 cells/μL (Cohorts 2-5) * Results of biochemistry tests for alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin greater than 1.5 X the upper limit of normal (ULN) for the reference laboratory * Recent history (within 6 months) of known or suspected Clostridium difficile infection * History of chronic liver disease, cirrhosis, or biliary disease * History of seizure disorder except childhood history of febrile seizures * Positive urine drug/alcohol testing * Positive testing for human immunodeficiency virus1/2 (HIV 1/2), hepatitis B surface antigen (HBsAg) or hepatitis C (HCV) antibodies * History of substance abuse or alcohol abuse * Known history of clinically significant hypersensitivity reaction or anaphylaxis to any medication * Other
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to the maximum plasma concentration (Tmax) | 36 hours after start of study drug IV infusion |
| Maximum plasma concentration (Cmax) | 36 hours after start of study drug IV infusion |
| Area under the concentration-time curve from time 0 to last measurable timepoint (AUC0-t) | 36 hours after start of study drug IV infusion |
| Area under the concentration-time curve from time 0 to infinity (AUC0-∞) | 36 hours after start of study drug IV infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Terminal Elimination Rate Constant (kel) | 36 hours after start of study drug IV infusion | — |
| Terminal half-life (t1/2) | 36 hours after start of study drug IV infusion | — |
| Amount of drug excreted in urine by interval (Aet) for Cohorts 1-4 | 36 hours after start of study drug IV infusion | — |
| Cumulative amount of drug excreted in urine at the end of each interval (Aeu) for Cohorts 1-4 | 36 hours after start of study drug IV infusion | — |
| Fraction of drug excreted in the urine expressed as a percentage (Ae%) for Cohorts 1-4 | 36 hours after start of study drug IV infusion | — |
| Fraction of dose excreted in the urine over a collection interval (Fe) for Cohorts 1-4 | 36 hours after start of study drug IV infusion | — |
| Cumulative fraction of dose excreted in the urine over (Feu) for Cohorts 1-4 | 36 hours after start of study drug IV infusion | — |
| Extraction ratio (ER) for subjects on dialysis (Cohort 5) | Up to 1 day post dose - between start and end of hemodialysis | — |
| Total body clearance (CL) | 36 hours after start of study drug IV infusion | — |
| Amount of the dose removed by hemodialysis (XHD) for subjects on dialysis (Cohort 5) | Up to 1 day post dose - between start and end of hemodialysis | — |
| Incidence of Treatment-Emergent Adverse Events | 14 days post start of last study drug IV infusion | To assess the incidents of treatment-emergent adverse events following SPR206 intravenous dose administration. AEs will be classified by System Organ Class (SOC) and Preferred Term (PT). Incidence, frequency, severity and duration will be presented. |
| Incidence of abnormal vital sign assessments - blood pressure | 14 days post study drug IV infusion | To assess the incidents of abnormal systolic and diastolic blood pressure assessments following SPR206 intravenous dose administration. Values and changes from baseline at each scheduled time-point will be summarized using descriptive statistics (n, mean, SD, median, minimum, and maximum). Significant changes from baseline will be presented. |
| Incidence of abnormal vital sign assessments - body temperature | 14 days post study drug IV infusion | To assess the incidents of abnormal body temperature assessments following SPR206 intravenous dose administration. Values and changes from baseline at each scheduled time-point will be summarized using descriptive statistics (n, mean, SD, median, minimum, and maximum). Significant changes from baseline will be presented. |
| Incidence of abnormal physical exam assessments | 14 days post study drug IV infusion | To assess the incidents of abnormal body system assessments following SPR206 intravenous dose administration. Changes from baseline in physical examination findings will be classified as Normal, Abnormal NCS, and Abnormal CS. Frequency counts will be presented. |
| Incidence of abnormal ECG assessments - heart rate | 14 days post study drug IV infusion | To assess the incidents of abnormal heart rate assessment following SPR206 intravenous dose administration. Cardiac (12-Lead ECG) for heart rate will be classified as normal, abnormality that is NCS, and CS abnormality. Frequency counts by dose group and timepoint of collection will be presented. |
| Incidence of abnormal ECG assessments - PR, RR, QRS, QT and QTcF interval | 14 days post study drug IV infusion | To assess the incidents of abnormal PR interval, RR interval, QRS interval, QT interval and QTcF interval assessments following SPR206 intravenous dose administration. Cardiac (12-Lead ECG) results will be classified as normal, abnormality that is NCS, and CS abnormality. Frequency counts by dose group and timepoint of collection will be presented. |
| Incidence of abnormal safety laboratory assessments | 14 days post study drug IV infusion | To assess the incidents of abnormal hematology, serum chemistry, coagulation and urinalysis assessments following SPR206 intravenous dose administration. Values and changes from baseline at each scheduled time-point will be summarized using descriptive statistics (n, mean, SD, median, minimum, and maximum). Frequency counts of significant changes from baseline will be presented. |
| Estimated hemodialysis clearance (CLHD) for subjects on dialysis (Cohort 5) | Up to 1 day post dose - between start and end of hemodialysis | — |
| Renal clearance (CLR) | 36 hours after start of study drug IV infusion | — |
| Steady-state volume of distribution (Vss) | 36 hours after start of study drug IV infusion | — |
| Area under the concentration-time curve from time 0 to 8 hours (AUC0-8) | 8 hours after start of study drug IV infusion | — |
Countries
New Zealand
Outcome results
None listed