Estimation Study to Assess the Effect of Severe Renal Impairment and End-stage Renal Disease Hemodialysis on the Pharmacokinetics of Evolocumab

Phase 1

Completed

Conditions: Hyperlipidemia
Mixed Dyslipidemia

Interventions: Biological: Evolocumab

Registration Number: NCT02275156

Lead Sponsor: Amgen

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 18

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Evolocumab	Evolocumab	Participants received a single 140 mg dose of evolocumab subcutaneously on Day 1.

Primary Outcome Measures

Name	Time	Method
Maximum Observed Serum Concentration (Cmax) of Evolocumab	Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose	Serum concentrations of evolocumab were measured by a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) of the assay was 800 ng/mL.
Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-last) for Evolocumab	Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Clinically Relevant Vital Sign or Clinical Laboratory Changes	57 days	The investigator reviewed vital signs and laboratory test results and determined whether an abnormal value in an individual participant represented a clinically significant change from the participant's baseline values.
Number of Participants With Adverse Events	From the first dose of study drug up until Day 57	The severity of each adverse event was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: * fatal; * life threatening (places the participant at immediate risk of death); * requires in patient hospitalization or prolongation of existing hospitalization; * results in persistent or significant disability/incapacity; * congenital anomaly/birth defect; * other medically important serious event. The investigator assessed whether each adverse event was possibly related to the study drug.
Mean Percent Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)	Baseline and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose	Serum PCSK9 concentrations were determined using a qualified ELISA. The LLOQ of the assay was 15 ng/mL. Log-transformed baseline PCSK9 was included in the model as a covariate and participant as a random effect.
Number of Participants With Anti-evolocumab Antibodies	57 days	Blood samples were tested using an electrochemiluminescence-based bridging immunoassay to detect antibodies capable of binding to evolocumab.
Area Under the Effect Curve From Baseline to Day 57 (AUECday1-57) for Low-density Lipoprotein Cholesterol (LDL-C)	4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose	The derived log-transformed AUECday1-57 for direct LDL-C was analyzed using a mixed-effect analysis of variance model. Log-transformed baseline LDL-C was the covariate.