Back to resultsEstimation Study to Assess the Effect of Severe Renal Impairment and End-stage Renal Disease Hemodialysis on the Pharmacokinetics of Evolocumab
Primary Purpose
Hyperlipidemia, Mixed Dyslipidemia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Evolocumab
Sponsored by
About this trial
This is an interventional treatment trial for Hyperlipidemia focused on measuring Subjects with normal renal function or severe renal impairment (RI) 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.
Sites / Locations
- Research Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Evolocumab
Arm Description
Participants received a single 140 mg dose of evolocumab subcutaneously on Day 1.
Outcomes
Primary Outcome Measures
Maximum Observed Serum Concentration (Cmax) of Evolocumab
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
Secondary Outcome Measures
Number of Participants With Adverse Events
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.
Number of Participants With Clinically Relevant Vital Sign or Clinical Laboratory Changes
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 Anti-evolocumab Antibodies
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)
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.
Mean Percent Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02275156
Brief Title
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
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
August 19, 2014 (Actual)
Primary Completion Date
December 19, 2014 (Actual)
Study Completion Date
December 19, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperlipidemia, Mixed Dyslipidemia
Keywords
Subjects with normal renal function or severe renal impairment (RI) or end stage renal disease (ESRD) receiving hemodialysis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Evolocumab
Arm Type
Experimental
Arm Description
Participants received a single 140 mg dose of evolocumab subcutaneously on Day 1.
Intervention Type
Biological
Intervention Name(s)
Evolocumab
Other Intervention Name(s)
AMG 145, Repatha
Intervention Description
Administered by subcutaneous injection
Primary Outcome Measure Information:
Title
Maximum Observed Serum Concentration (Cmax) of Evolocumab
Description
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.
Time Frame
Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose
Title
Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-last) for Evolocumab
Time Frame
Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose
Secondary Outcome Measure Information:
Title
Number of Participants With Adverse Events
Description
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.
Time Frame
From the first dose of study drug up until Day 57
Title
Number of Participants With Clinically Relevant Vital Sign or Clinical Laboratory Changes
Description
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.
Time Frame
57 days
Title
Number of Participants With Anti-evolocumab Antibodies
Description
Blood samples were tested using an electrochemiluminescence-based bridging immunoassay to detect antibodies capable of binding to evolocumab.
Time Frame
57 days
Title
Area Under the Effect Curve From Baseline to Day 57 (AUECday1-57) for Low-density Lipoprotein Cholesterol (LDL-C)
Description
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.
Time Frame
4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose
Title
Mean Percent Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)
Description
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.
Time Frame
Baseline and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Denver
State/Province
Colorado
ZIP/Postal Code
80230
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
29353350
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.
Results Reference
background
PubMed Identifier
30676701
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.
Results Reference
background
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Estimation Study to Assess the Effect of Severe Renal Impairment and End-stage Renal Disease Hemodialysis on the Pharmacokinetics of Evolocumab
We'll reach out to this number within 24 hrs