NCT01133522

Brief Summary

The purpose of the study is to evaluate the safety and tolerability of multiple doses of evolocumab when given as an add-on to stable statin therapy.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jun 2010

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 27, 2010

Completed
4 days until next milestone

First Posted

Study publicly available on registry

May 31, 2010

Completed
1 day until next milestone

Study Start

First participant enrolled

June 1, 2010

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 14, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 14, 2011

Completed
4.1 years until next milestone

Results Posted

Study results publicly available

October 22, 2015

Completed
Last Updated

November 2, 2018

Status Verified

November 1, 2018

Enrollment Period

1.3 years

First QC Date

May 27, 2010

Results QC Date

September 23, 2015

Last Update Submit

November 1, 2018

Conditions

Hyperlipidemia

Keywords

AMG145Multiple DoseStatinAscending

Outcome Measures

Primary Outcomes (2)

  • Number of Participants With Adverse Events

    The relationship of each adverse event to the investigational product was assessed by the investigator. A serious adverse event (SAE) is defined as an adverse event that * is fatal * is life threatening (places the subject at immediate risk of death) * requires in-patient hospitalization or prolongation of existing hospitalization * results in persistent or significant disability/incapacity * is a congenital anomaly/birth defect * other significant medical hazard.

    From the first dose of study drug until Day 85

  • Number of Participants With Anti-Evolocumab Antibodies

    Serum samples were analyzed by an electrochemiluminescence (ECL)-based immunoassay for anti-evolocumab binding antibodies. Positive samples were subsequently tested in a receptor-ligand binding bioassay for anti-evolocumab neutralizing antibodies

    From the first dose of study drug until Day 85

Secondary Outcomes (4)

  • Maximum Observed Plasma Concentration (Cmax) of Evolocumab

    Day 1, predose and Days 4, 8, 15, 22, 29, 36, 40, 43, 50, 57, 64, 71, 78, and 85

  • Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Evolocumab

    Day 29 predose (last dose for Cohorts 3-7) and Days 36 (predose for Cohorts 1 and 2), 40, 43, 50, 57, 64, 71, 78, and 85

  • Percent Change From Baseline to End of the Dosing Interval in LDL-C

    Baseline and Day 43 for QW and Q2W groups or Day 57 for Q4W group

  • Percent Change From Baseline to End of the Dosing Interval in PCSK9

    Baseline and Day 43 for QW and Q2W groups or Day 57 for Q4W group

Study Arms (2)

Evolocumab

EXPERIMENTAL

Participants received one of 5 dose levels of evolocumab administered as multiple subcutaneous doses.

Biological: Evolocumab

Placebo

PLACEBO COMPARATOR

Participants received matching placebo dose regimens by subcutaneous injection.

Biological: Placebo

Interventions

EvolocumabBIOLOGICAL

Administered by subcutaneous injection

Also known as: AMG 145, Repatha
Evolocumab
PlaceboBIOLOGICAL

Administered by subcutaneous injection

Placebo

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Men and women ages 18 to 70 years (inclusive) at the time of screening with hyperlipidemia
  • Body mass index (BMI) ≥18 and ≤ 35 kg/m\^2 at the time of screening
  • Low-density lipoprotein cholesterol (LDL-C) level of 70-220 mg/dL (inclusive) at screening as measured by direct assay
  • For Cohorts 1-5: On a stable dose of rosuvastatin (Crestor) \< 40 mg/day, atorvastatin (Lipitor) \< 80 mg/day, or simvastatin (Zocor) 20-80 mg/day for ≥ 1 month prior to enrollment and expected to remain on this dose for the remainder of the study
  • For Cohort 6: On a stable dose of rosuvastatin (Crestor) 40 mg/day or atorvastatin (Lipitor) 80 mg/day for ≥ 1 month prior to enrollment and expected to remain on this dose for the remainder of the study
  • For Cohort 7: Diagnosis of heterozygous familial hypercholesterolemia, based on a score of ≥ 9 points using the World health Organization (WHO) criteria

You may not qualify if:

  • Diagnosis of homozygous familial hypercholesterolemia
  • History of heart failure, coronary artery bypass graft, or cardiac arrhythmia
  • History of acute coronary syndrome (e.g. myocardial infarction, hospitalization for unstable angina) or percutaneous coronary intervention, within 12 months prior to enrollment
  • Planned cardiac surgery or revascularization
  • Known aortic, peripheral vascular or cerebrovascular disease (including history of stroke or transient ischemic attack)
  • Diabetes mellitus with any of the following:
  • known microvascular or macrovascular disease
  • HbA1c \> 8.0% at screening
  • use of any hypoglycemic medication other than metformin
  • Uncontrolled hypertension (systolic blood pressure ≥ 150 or diastolic blood pressure ≥ 90 mmHg) either on or off therapy at screening or at baseline

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (1)

  • Dias CS, Shaywitz AJ, Wasserman SM, Smith BP, Gao B, Stolman DS, Crispino CP, Smirnakis KV, Emery MG, Colbert A, Gibbs JP, Retter MW, Cooke BP, Uy ST, Matson M, Stein EA. Effects of AMG 145 on low-density lipoprotein cholesterol levels: results from 2 randomized, double-blind, placebo-controlled, ascending-dose phase 1 studies in healthy volunteers and hypercholesterolemic subjects on statins. J Am Coll Cardiol. 2012 Nov 6;60(19):1888-98. doi: 10.1016/j.jacc.2012.08.986. Epub 2012 Oct 17.

    PMID: 23083772BACKGROUND

Related Links

MeSH Terms

Conditions

Hyperlipidemias

Interventions

evolocumab

Condition Hierarchy (Ancestors)

DyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

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
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 27, 2010

First Posted

May 31, 2010

Study Start

June 1, 2010

Primary Completion

September 14, 2011

Study Completion

September 14, 2011

Last Updated

November 2, 2018

Results First Posted

October 22, 2015

Record last verified: 2018-11