Ascending Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Evolocumab (AMG 145) in Adults With Hyperlipidemia on Stable Doses of a Statin

NCT ID: NCT01133522

Last Updated: 2018-11-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-01
• Study Completion Date: 2011-09-14

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.

Detailed Description

Participants receiving low-to-moderate-dose statins were randomized in a 1:3 ratio to receive subcutaneous placebo or evolocumab and enrolled sequentially into one of 5 dose-escalation cohorts:

1. Evolocumab 14 mg/placebo once weekly (QW) × 6 doses

2. Evolocumab 35 mg/placebo once weekly (QW) × 6 doses

3. Evolocumab 140 mg/placebo every 2 weeks (Q2W) × 3 doses

4. Evolocumab 280 mg/placebo every 2 weeks (Q2W) × 3 doses

5. Evolocumab 420 mg/placebo every 4 weeks (Q2W) × 2 doses.

Participants receiving high-dose statins were randomized 1:3 to receive subcutaneous placebo or evolocumab 140 mg every 2 weeks × 3 doses (Cohort 6).

Participants diagnosed with familial hypercholesterolemia (HeFH) were randomized 1:2 to receive subcutaneous placebo or evolocumab 140 mg every 2 weeks × 3 doses (Cohort 7).

Conditions

Hyperlipidemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Evolocumab

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

Group Type: EXPERIMENTAL

Evolocumab

Intervention Type: BIOLOGICAL

Administered by subcutaneous injection

Placebo

Participants received matching placebo dose regimens by subcutaneous injection.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Administered by subcutaneous injection

Interventions

Evolocumab

Administered by subcutaneous injection

Intervention Type: BIOLOGICAL

Placebo

Administered by subcutaneous injection

Intervention Type: BIOLOGICAL

Other Intervention Names

AMG 145; Repatha

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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:

1. known microvascular or macrovascular disease

2. HbA1c > 8.0% at screening

3. 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

References

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.

Reference Type: BACKGROUND

PMID: 23083772 (View on PubMed)

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

20080398

Identifier Type: -

Identifier Source: org_study_id