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

May 27, 2010
March 16, 2012
June 2010
October 2011   (final data collection date for primary outcome measure)
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 ]
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 122 days. ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01133522 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 122 days. ] [ Designated as safety issue: No ]
  • 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 122 days. ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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
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

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.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hyperlipidemia
  • Drug: AMG 145
    5 dose levels of AMG 145 administered as multiple SC doses.
  • Drug: Placebo
    5 dose levels of the equivalent volume of placebo administered as multiple SC doses.
  • Experimental: AMG 145
    Intervention: Drug: AMG 145
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
58
November 2011
October 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT01133522
20080398
Not Provided
Global Development Leader, Amgen Inc.
Amgen
Not Provided
Study Director: MD Amgen
Amgen
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP