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

This study has been completed.
Sponsor:
Information provided by:
Amgen
ClinicalTrials.gov Identifier:
NCT01133522
First received: May 27, 2010
Last updated: March 16, 2012
Last verified: March 2012
  Purpose

AMG 145 is being developed for the treatment of hypercholesterolemia. The purpose of the study is to evaluate the safety and tolerability of multiple doses of AMG 145 when given as an add-on to stable statin therapy. The study hypotheses are that no significant safety issues will be identified following multiple SC doses of AMG 145 when administered as an add-on to stable statin therapy, and there will be a statistically significant decrease in LDL-C (low density lipoprotein cholesterol) levels following multiple SC doses of AMG 145 when administered as an add-on to stable statin therapy compared to placebo.


Condition Intervention Phase
Hyperlipidemia
Drug: AMG 145
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Ascending Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 145 in Subjects With Hyperlipidemia on Stable Doses of a Statin

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • The subject incidence of treatment-emergent adverse events and incidence of binding and neutralizing antibodies to AMG 145 as well as changes in vital signs, clinical laboratory safety tests, and electrocardiograms (ECGs). [ Time Frame: Including a 35-day screening period, the maximum subject participation is 120 days. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • PK (pharmacokinetics) concentrations as well as derived PK parameters of unbound AMG 145 [ Time Frame: Including a 35-day screening period, the maximum subject participation is 120 days. ] [ Designated as safety issue: No ]
  • Ratio to baseline and unadjusted LDL-C and PCSK9 (proprotein convertase subtilisin/kexin type 9) [ Time Frame: Including a 35-day screening period, the maximum subject participation is 120 days. ] [ Designated as safety issue: No ]

Estimated Enrollment: 58
Study Start Date: June 2010
Study Completion Date: November 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AMG 145 Drug: AMG 145
5 dose levels of AMG 145 administered as multiple SC doses.
Placebo Comparator: Placebo Drug: Placebo
5 dose levels of the equivalent volume of placebo administered as multiple SC doses.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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/m2 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 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 (SBP≥ 150 or DBP≥ 90 mmHg) either on or off therapy at screening or at baseline
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01133522

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Global Development Leader, Amgen Inc.
ClinicalTrials.gov Identifier: NCT01133522     History of Changes
Other Study ID Numbers: 20080398
Study First Received: May 27, 2010
Last Updated: March 16, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Amgen:
AMG145
Multiple Dose
Statin
Ascending

Additional relevant MeSH terms:
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on July 29, 2014