Clinical trial NCT04865393: Phase 1 Study of PK and Safety of SPR206 in Subjects With Various Degrees Of Renal Function
Official title: A Phase 1, Open-label Study to Assess the Safety and Pharmacokinetics of SPR206 Following a Single IV Dose of SPR206 in Subjects With Varying Degrees of Renal Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Keywords: End State Renal Disease (ESRD)
Renal Insufficiency
Renal Impairment
Renal Disease
Hemodialysis
Lead sponsor: Spero Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: United States Department of Defense
First posted: 2021-04-29
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


Eligibility 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 exclusion criteria per protocol

Primary outcomes:
measure: Time to the maximum plasma concentration (Tmax)
timeFrame: 36 hours after start of study drug IV infusion
measure: Maximum plasma concentration (Cmax)
timeFrame: 36 hours after start of study drug IV infusion
measure: Area under the concentration-time curve from time 0 to last measurable timepoint (AUC0-t)
timeFrame: 36 hours after start of study drug IV infusion
measure: Area under the concentration-time curve from time 0 to infinity (AUC0-∞)
timeFrame: 36 hours after start of study drug IV infusion
Secondary outcomes:
measure: Area under the concentration-time curve from time 0 to 8 hours (AUC0-8)
timeFrame: 8 hours after start of study drug IV infusion
measure: Terminal Elimination Rate Constant (kel)
timeFrame: 36 hours after start of study drug IV infusion
measure: Terminal half-life (t1/2)
timeFrame: 36 hours after start of study drug IV infusion
measure: Total body clearance (CL)
timeFrame: 36 hours after start of study drug IV infusion
measure: Renal clearance (CLR)
timeFrame: 36 hours after start of study drug IV infusion
measure: Steady-state volume of distribution (Vss)
timeFrame: 36 hours after start of study drug IV infusion
measure: Amount of drug excreted in urine by interval (Aet) for Cohorts 1-4
timeFrame: 36 hours after start of study drug IV infusion
measure: Cumulative amount of drug excreted in urine at the end of each interval (Aeu) for Cohorts 1-4
timeFrame: 36 hours after start of study drug IV infusion
measure: Fraction of drug excreted in the urine expressed as a percentage (Ae%) for Cohorts 1-4
timeFrame: 36 hours after start of study drug IV infusion
measure: Fraction of dose excreted in the urine over a collection interval (Fe) for Cohorts 1-4
timeFrame: 36 hours after start of study drug IV infusion
measure: Cumulative fraction of dose excreted in the urine over (Feu) for Cohorts 1-4
timeFrame: 36 hours after start of study drug IV infusion
measure: Extraction ratio (ER) for subjects on dialysis (Cohort 5)
timeFrame: Up to 1 day post dose - between start and end of hemodialysis
measure: Estimated hemodialysis clearance (CLHD) for subjects on dialysis (Cohort 5)
timeFrame: Up to 1 day post dose - between start and end of hemodialysis
measure: Amount of the dose removed by hemodialysis (XHD) for subjects on dialysis (Cohort 5)
timeFrame: Up to 1 day post dose - between start and end of hemodialysis
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 14 days post start of last study drug IV infusion
measure: Incidence of abnormal vital sign assessments - blood pressure
timeFrame: 14 days post study drug IV infusion
measure: Incidence of abnormal vital sign assessments - body temperature
timeFrame: 14 days post study drug IV infusion
measure: Incidence of abnormal physical exam assessments
timeFrame: 14 days post study drug IV infusion
measure: Incidence of abnormal ECG assessments - heart rate
timeFrame: 14 days post study drug IV infusion
measure: Incidence of abnormal ECG assessments - PR, RR, QRS, QT and QTcF interval
timeFrame: 14 days post study drug IV infusion
measure: Incidence of abnormal safety laboratory assessments
timeFrame: 14 days post study drug IV infusion
Other outcomes:
Locations:
city: Auckland
country: New Zealand
facility: Medical Facility
city: Christchurch
country: New Zealand
facility: Medical Facility
Study officials:
affiliation: Spero Therapeutics Inc
name: David Melnick, MD
role: STUDY_DIRECTOR
References: