Clinical trial NCT02275156: Estimation Study to Assess the Effect of Severe Renal Impairment and End-stage Renal Disease Hemodialysis on the Pharmacokinetics of Evolocumab
Official title: Phase 1, Open-label, Single-dose Study of Evolocumab (AMG 145) Administered Subcutaneously to Subjects With Normal Renal Function or Severe Renal Impairment or End Stage Renal Disease Receiving Hemodialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hyperlipidemia
Mixed Dyslipidemia
Keywords: Subjects with normal renal function or severe renal impairment (RI) or end stage renal disease (ESRD) receiving hemodialysis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2014-10-27
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study was to evaluate the pharmacokinetics of evolocumab after a single 140 mg subcutaneous (SC) dose in aduts with normal renal function or severe renal impairment or end-stage renal disease (ESRD) receiving hemodialysis.


Eligibility criteria: Inclusion Criteria:

* Body mass index (BMI) of ≥ 18 and ≤ 35 kg/m² at screening.
* Subjects will have low-density lipoprotein cholesterol (LDL-C) of 70-190 mg/dL (inclusive) and on statin therapy.
* Other inclusion criteria may apply.

Exclusion Criteria:

* Subject with current or prior history of statin intolerance
* Subject has previously received Evolocumab (AMG 145) or any other investigational therapy directed against PCSK9
* Known substance abuse (eg, alcohol, licit or illicit drugs) within 12 months of day -1
* Testing positive for alcohol and/or drugs-of-abuse at screening, day -1, or day 1 (alcohol only)
* History of hypersensitivity or allergic reaction to mammalian-derived drug preparations
* Known sensitivity to any of the active substances or their excipients to be administered during dosing, eg, carboxymethylcellulose
* Other exclusion criteria may apply.

Primary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of Evolocumab
timeFrame: Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose
measure: Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-last) for Evolocumab
timeFrame: Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: From the first dose of study drug up until Day 57
measure: Number of Participants With Clinically Relevant Vital Sign or Clinical Laboratory Changes
timeFrame: 57 days
measure: Number of Participants With Anti-evolocumab Antibodies
timeFrame: 57 days
measure: Area Under the Effect Curve From Baseline to Day 57 (AUECday1-57) for Low-density Lipoprotein Cholesterol (LDL-C)
timeFrame: 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose
measure: Mean Percent Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)
timeFrame: Baseline and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose
Other outcomes:
Locations:
city: Denver
country: United States
facility: Research Site
state: Colorado
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7.
citation: Lee E, Gibbs JP, Emery MG, Block G, Wasserman SM, Hamilton L, Kasichayanula S, Hanafin P, Somaratne R, Egbuna O. Influence of Renal Function on Evolocumab Exposure, Pharmacodynamics, and Safety. Clin Pharmacol Drug Dev. 2019 Apr;8(3):281-289. doi: 10.1002/cpdd.650. Epub 2019 Jan 24.