Clinical trial NCT02427035: A Study of CSL112 in Healthy Adults and in Adults With Moderate Renal Impairment
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myocardial Infarction
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2015-04-27
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Plasma apolipoprotein A-I (apoA-I) and phosphatidylcholine (PC) area under the curve (AUC)
timeFrame: Before and at up to 10 time points (during up to 7 days) after infusion
measure: Plasma apoA-I and PC AUC0-last and AUC 0-t
timeFrame: Before and at up to 10 time points (during up to 7 days) after infusion
measure: Plasma apoA-I and PC Cmax
timeFrame: Before and at up to 10 time points (during up to 7 days) after infusion
measure: Plasma apoA-I and PC Tmax
timeFrame: Before and at up to 10 time points (during up to 7 days) after infusion
measure: Plasma apoA-I and PC Volume of distribution during terminal phase
timeFrame: Before and at up to 10 time points (during up to 7 days) after infusion
measure: Plasma apoA-I and PC clearance
timeFrame: Before and at up to 10 time points (during up to 7 days) after infusion
measure: Plasma apoA-I and PC t1/2
timeFrame: Before and at up to 10 time points (during up to 7 days) after infusion
measure: Urinary excretion of apoA-I (Ae0-t)
timeFrame: Before and up to 48 hours after infusion
measure: Urinary excretion of apoA-I (%fe0-t)
timeFrame: Before and up to 48 hours after infusion
measure: Renal clearance of apoA-I
timeFrame: Before and up to 48 hours after infusion
Secondary outcomes:
measure: Urinary excretion of sucrose(Ae0-t)
timeFrame: Before and up to 48 hours after infusion
measure: Urinary excretion of sucrose (%fe0-t)
timeFrame: Before and up to 48 hours after infusion
measure: Urinary excretion of sucrose (clearance)
timeFrame: Before and up to 48 hours after infusion
measure: Adverse drug reaction (ADR) or suspected ADR frequency (%)
timeFrame: Up to approximately 127 days
measure: Clinically significant changes in routine safety assessments
timeFrame: Up to approximately 97 days
measure: Clinically important change in drug-induced liver injury
timeFrame: From baseline (before infusion) up to Day 16.
measure: Clinically important change in renal status
timeFrame: From baseline (before infusion) up to Day 16.
measure: Plasma sucrose AUC
timeFrame: Before and at up to 7 time points (during up to 2 days) after infusion
measure: Plasma sucrose AUC0-last and AUC 0-t
timeFrame: Before and at up to 7 time points (during up to 2 days) after infusion
measure: Plasma sucrose Cmax
timeFrame: Before and at up to 7 time points (during up to 2 days) after infusion
measure: Plasma sucrose Tmax
timeFrame: Before and at up to 7 time points (during up to 2 days) after infusion
measure: Plasma sucrose Volume of distribution during terminal phase
timeFrame: Before and at up to 7 time points (during up to 2 days) after infusion
measure: Plasma sucrose Clearance
timeFrame: Before and at up to 7 time points (during up to 2 days) after infusion
measure: Plasma sucrose t1/2
timeFrame: Before and at up to 7 time points (during up to 2 days) after infusion
measure: Adverse drug reaction (ADR) or suspected ADR frequency
timeFrame: Up to approximately 127 days
measure: Number of subjects with AEs
timeFrame: After the start of infusion up to approximately 127 days
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Study Site - 17101
city: Munich
country: Germany
facility: Study Site - 17102
city: London
country: United Kingdom
facility: Study Site - 24101
city: Manchester
country: United Kingdom
facility: Study Site - 24102
Study officials:
affiliation: CSL Behring
name: Denise D'Andrea, M.D.
role: STUDY_DIRECTOR
References:
citation: Zheng B, Duffy D, Tricoci P, Kastrissios H, Pfister M, Wright SD, Gille A, Tortorici MA. Pharmacometric analyses to characterize the effect of CSL112 on apolipoprotein A-I and cholesterol efflux capacity in acute myocardial infarction patients. Br J Clin Pharmacol. 2021 Jun;87(6):2558-2571. doi: 10.1111/bcp.14666. Epub 2020 Dec 23.
citation: Tortorici MA, Duffy D, Evans R, Feaster J, Gille A, Mant TGK, Wright SD, D'Andrea D. Pharmacokinetics and Safety of CSL112 (Apolipoprotein A-I [Human]) in Adults With Moderate Renal Impairment and Normal Renal Function. Clin Pharmacol Drug Dev. 2019 Jul;8(5):628-636. doi: 10.1002/cpdd.618. Epub 2018 Sep 21.