A Double-blind, Randomized, Placebo-controlled, Pharmacokinetic, Safety and Tolerability Study of CSL112 in Adult Subjects With Moderate Renal Impairment and in Healthy Adult Subjects With Normal Renal Function
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- CSL Behring
- Enrollment
- 32
- Locations
- 4
- Primary Endpoint
- Plasma apoA-I and PC Tmax
Study Overview
Brief Summary
This is a phase 1 multicenter, randomized, double-blind, placebo-controlled, ascending dose study to investigate the pharmacokinetics (PK), safety, and tolerability of CSL112 in adult subjects with moderate renal impairment and in healthy adult subjects with normal renal function.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Men or women aged 18 to 85 years (inclusive) of age, with body weight 50 kg or more.
- •Subjects with renal impairment (RI) must have stable chronic moderate RI (estimated glomerular filtration rate [eGFR] ≥ 30 and < 60 mL/min/1.73 m2)
- •Healthy subjects must have normal renal function (eGFR ≥ 90 mL/min/1.73 m2)
Exclusion Criteria
- •Evidence of a clinically significant medical condition, disorder or disease
- •Evidence of hepatobiliary disease
- •Any clinically relevant abnormal laboratory test result
- •Known history of allergies, hypersensitivity or deficiencies to CSL112 or any of its components
- •Other severe comorbid condition, concurrent medication, or other issue that renders the subject unsuitable for participation in the study, including: history of cancer, low platelet count, bleeding disorder or coagulopathy, significantly altered electrocardiogram waveform, unstable glycemia control in subjects with diabetes, acute renal failure, recent donation or loss of blood
- •Evidence or history of alcohol or substance abuse
Arms & Interventions
Low
A low dose of either CSL112 or placebo is to be administered as a single intravenous (IV) infusion. The placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Intervention: Placebo (Other)
High
A high dose of either CSL112 or placebo is to be administered as a single intravenous (IV) infusion. The placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Intervention: Placebo (Other)
High
A high dose of either CSL112 or placebo is to be administered as a single intravenous (IV) infusion. The placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Intervention: CSL112 (Biological)
Low
A low dose of either CSL112 or placebo is to be administered as a single intravenous (IV) infusion. The placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Intervention: CSL112 (Biological)
Outcomes
Primary Outcomes
Plasma apoA-I and PC Tmax
Time Frame: Before and at up to 10 time points (during up to 7 days) after infusion
Plasma apoA-I and PC Volume of distribution during terminal phase
Time Frame: Before and at up to 10 time points (during up to 7 days) after infusion
Renal clearance of apoA-I
Time Frame: Before and up to 48 hours after infusion
Renal clearance of apoA-I, calculated as Ae0-48/AUC0-48
Plasma apoA-I and PC AUC0-last and AUC 0-t
Time Frame: Before and at up to 10 time points (during up to 7 days) after infusion
AUC from time point zero to the last quantifiable time point before the analyte first returns to baseline (AUC0-last) and/or a partial AUC from baseline to time point t (AUC0-t) with and without baseline correction
Plasma apolipoprotein A-I (apoA-I) and phosphatidylcholine (PC) area under the curve (AUC)
Time Frame: Before and at up to 10 time points (during up to 7 days) after infusion
Baseline corrected plasma apoA-I and PC AUC0-infinity
Plasma apoA-I and PC Cmax
Time Frame: Before and at up to 10 time points (during up to 7 days) after infusion
Plasma apoA-I and PC clearance
Time Frame: Before and at up to 10 time points (during up to 7 days) after infusion
Plasma apoA-I and PC t1/2
Time Frame: Before and at up to 10 time points (during up to 7 days) after infusion
Urinary excretion of apoA-I (Ae0-t)
Time Frame: Before and up to 48 hours after infusion
Amount excreted (Ae) of apoA-I over a collection interval 0-t.
Urinary excretion of apoA-I (%fe0-t)
Time Frame: Before and up to 48 hours after infusion
Percent fraction excreted (%fe) of apoA-I in urine over time interval 0-t, calculated as Ae0-t/Dose x 100.
Secondary Outcomes
- Adverse drug reaction (ADR) or suspected ADR frequency (%)(Up to approximately 127 days)
- Urinary excretion of sucrose(Ae0-t)(Before and up to 48 hours after infusion)
- Clinically important change in drug-induced liver injury(From baseline (before infusion) up to Day 16.)
- Plasma sucrose AUC(Before and at up to 7 time points (during up to 2 days) after infusion)
- Plasma sucrose Clearance(Before and at up to 7 time points (during up to 2 days) after infusion)
- Plasma sucrose t1/2(Before and at up to 7 time points (during up to 2 days) after infusion)
- Adverse drug reaction (ADR) or suspected ADR frequency(Up to approximately 127 days)
- Urinary excretion of sucrose (%fe0-t)(Before and up to 48 hours after infusion)
- Clinically important change in renal status(From baseline (before infusion) up to Day 16.)
- Plasma sucrose Cmax(Before and at up to 7 time points (during up to 2 days) after infusion)
- Plasma sucrose Volume of distribution during terminal phase(Before and at up to 7 time points (during up to 2 days) after infusion)
- Urinary excretion of sucrose (clearance)(Before and up to 48 hours after infusion)
- Plasma sucrose AUC0-last and AUC 0-t(Before and at up to 7 time points (during up to 2 days) after infusion)
- Plasma sucrose Tmax(Before and at up to 7 time points (during up to 2 days) after infusion)
- Number of subjects with AEs(After the start of infusion up to approximately 127 days)
- Clinically significant changes in routine safety assessments(Up to approximately 97 days)