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

NCT02275156 | Completed Phase 1 Results

• 1 other identifier: 20140213
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Hyperlipidemia; Mixed Dyslipidemia

Keywords

Subjects with normal renal function or severe renal impairment (RI) or end stage renal disease (ESRD) receiving hemodialysis

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (5)

• Number of Participants With Adverse Events

  From the first dose of study drug up until Day 57

• Number of Participants With Clinically Relevant Vital Sign or Clinical Laboratory Changes

  57 days

• Number of Participants With Anti-evolocumab Antibodies

  57 days

• 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

• 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

Study Arms (1)

Evolocumab

EXPERIMENTAL

Participants received a single 140 mg dose of evolocumab subcutaneously on Day 1.

Biological: Evolocumab

Interventions

Evolocumab BIOLOGICAL

Administered by subcutaneous injection

Also known as: AMG 145, Repatha

Evolocumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (1)

Research Site

Denver, Colorado, 80230, United States

Location

Related 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.

  PMID: 29353350 BACKGROUND

• 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.

  PMID: 30676701 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hyperlipidemias; Renal Insufficiency; Kidney Failure, Chronic

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2014
• First Posted: October 27, 2014
• Study Start: August 19, 2014
• Primary Completion: December 19, 2014
• Study Completion: December 19, 2014
• Last Updated: November 7, 2022
• Results First Posted: January 29, 2016

Record last verified: 2022-11

Locations

US (1)