Dose-escalating Safety Study in Subjects on Stable Statin Therapy

This study has been completed.
Sponsor:
Collaborator:
Isis Pharmaceuticals
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00231569
First received: October 3, 2005
Last updated: December 2, 2013
Last verified: December 2013

October 3, 2005
December 2, 2013
September 2005
June 2007   (final data collection date for primary outcome measure)
Percent reduction in LDL-cholesterol from baseline [ Time Frame: From baseline measurement ] [ Designated as safety issue: No ]
Percent reduction in LDL-cholesterol from baseline
Complete list of historical versions of study NCT00231569 on ClinicalTrials.gov Archive Site
  • Percent reduction in apoB-100 [ Time Frame: From baseline measurement ] [ Designated as safety issue: No ]
  • Percent change in HDL-cholesterol, triglycerides, total cholesterol, non-HDL cholesterol, VLDL plus LDL-cholesterol and LDL-cholesterol particle size and concentration [ Time Frame: From baseline measurement ] [ Designated as safety issue: No ]
  • Percent change from baseline in LDL/HDL and apoB-100/apo-A1 ratios [ Time Frame: From baseline measurement ] [ Designated as safety issue: No ]
  • AEs, SAEs, physical examination data, vital signs, and laboratory analyzes [ Time Frame: Duration of study ] [ Designated as safety issue: Yes ]
  • Percent reduction in apoB-100 from baseline
  • Percent change from baseline in HDL-cholesterol, triglycerides, total cholesterol, non-HDL cholesterol, VLDL plus LDL-cholesterol and LDL-cholesterol particle size and concentration
  • Percent change from baseline in LDL/HDL and apoB-100/apo-A1 ratios
Not Provided
Not Provided
 
Dose-escalating Safety Study in Subjects on Stable Statin Therapy
A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Dose‑Escalation Study to Assess the Safety and Pharmacodynamics of ISIS 301012 in Hypercholesterolemic Subjects on Stable Statin Therapy

The aim of this study is to assess the safety of varying doses of ISIS 301012 in subjects on Stable statin therapy.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hypercholesterolemia
  • Drug: ISIS 301012 or Placebo
    30 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
  • Drug: ISIS 301012 or Placebo
    100 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
  • Drug: ISIS 301012 or Placebo
    200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
  • Drug: ISIS 301012 or Placebo
    300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
  • Drug: ISIS 301012 or Placebo
    400 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
  • Drug: ISIS 301012 or Placebo
    200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
  • Drug: ISIS 301012 or Placebo
    300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
  • Experimental: Cohort A
    Loading doses followed by weekly maintenance doses
    Intervention: Drug: ISIS 301012 or Placebo
  • Experimental: Cohort B
    Loading doses followed by weekly maintenance doses
    Intervention: Drug: ISIS 301012 or Placebo
  • Experimental: Cohort C
    Loading doses followed by weekly maintenance doses
    Intervention: Drug: ISIS 301012 or Placebo
  • Experimental: Cohort D
    Loading doses followed by weekly maintenance doses
    Intervention: Drug: ISIS 301012 or Placebo
  • Experimental: Cohort E
    Loading doses followed by weekly maintenance doses
    Intervention: Drug: ISIS 301012 or Placebo
  • Experimental: Cohort F
    Loading doses followed by extended weekly maintenance doses
    Intervention: Drug: ISIS 301012 or Placebo
  • Experimental: Cohort G
    Loading doses followed by extended weekly maintenance doses
    Intervention: Drug: ISIS 301012 or Placebo
Akdim F, Stroes ES, Sijbrands EJ, Tribble DL, Trip MD, Jukema JW, Flaim JD, Su J, Yu R, Baker BF, Wedel MK, Kastelein JJ. Efficacy and safety of mipomersen, an antisense inhibitor of apolipoprotein B, in hypercholesterolemic subjects receiving stable statin therapy. J Am Coll Cardiol. 2010 Apr 13;55(15):1611-8. doi: 10.1016/j.jacc.2009.11.069.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
74
December 2007
June 2007   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • On a stable dose of >/= 40 mg Simvastatin or atorvastatin daily for >/= 3 months prior to baseline and expected to remain on this dose for the remainder of the study
  • LDL-cholesterol between 2.60 and 5.70 mmol/L (100 and 220 mg/dL), inclusive at screening
  • Females not of childbearing potential.

Exclusion Criteria:

  • History of CHD or CHD-equivalent (such as diabetes mellitus, or another clinical form of atherosclerotic disease, e.g., peripheral arterial disease, abdominal aortic aneurysm, or symptomatic carotid artery disease)
  • Fasting triglyceride >2.26 mmol/L (200 mg/dL) at screening
  • Any uncontrolled medical/surgical/psychiatric condition, including conditions that may predispose to secondary hypercholesterolemia
  • Current diagnosis or known history of complement deficiency or abnormality
  • A positive hepatitis B surface antigen or hepatitis C antibody, or a known positive HIV status
  • Current diagnosis or known history of liver disease, or has an ALT >ULN at screening
  • Known history of fibromyalgia, myopathy, myositis, rhabdomyolysis, any unexplained muscle pain, or has a CPK >ULN at screening
  • Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin that has been adequately treated
  • The advisability of a subject taking any prescription medication (apart from simvastatin or atorvastatin) within 6 weeks prior to screening should be discussed with the Isis Medical Monitor
  • Subject unwilling to discontinue taking alternative/herbal medication for the duration of the study
  • History of drug abuse within 2 years of screening
  • Subject unwilling to limit alcohol consumption for the duration of the study: male subjects to a maximum of 3 drinks (30 g) per day, and <12 drinks (120 g) per week; female subjects to a maximum of 2 drinks (20 g) per day, and <8 drinks (80 g) per week
  • Known allergy or hypersensitivity to simvastatin
  • Undergoing or has undergone treatment with another investigational drug, biologic agent, or device within 3 months, or 3 half lives, prior to screening, whichever is longer
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Netherlands
 
NCT00231569
301012CS4, EudraCT No.: 2005-002119-26
Yes
Medical Monitor, Genzyme Coporation
Genzyme, a Sanofi Company
Isis Pharmaceuticals
Study Director: Medical Monitor Genzyme, a Sanofi Company
Sanofi
December 2013

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