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

Hyperlipidemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02275156
• Other study ID #: 20140213
• Status: Completed
• Phase: Phase 1
• Start date: August 19, 2014
• Est. completion date: December 19, 2014

Study information

• Verified date: November 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 19, 2014
• Est. primary completion date: December 19, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dyslipidemias
• Hyperlipidemia
• Hyperlipidemias
• Kidney Diseases
• Kidney Failure, Chronic
• Mixed Dyslipidemia
• Renal Insufficiency

Intervention

Biological:
• Evolocumab
Administered by subcutaneous injection

Locations

Country	Name	City	State
United States	Research Site	Denver	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose
Primary	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	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.	From the first dose of study drug up until Day 57
Secondary	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.	57 days
Secondary	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.	57 days
Secondary	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.	4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose
Secondary	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.	Baseline and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose

External Links

•   AmgenTrials clinical trials website