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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
  Purpose

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


Condition Intervention Phase
Hypercholesterolemia
Drug: ISIS 301012 or Placebo
Phase 2

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 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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Percent reduction in LDL-cholesterol from baseline [ Time Frame: From baseline measurement ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 74
Study Start Date: September 2005
Study Completion Date: December 2007
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A
Loading doses followed by weekly maintenance doses
Drug: ISIS 301012 or Placebo
30 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
Experimental: Cohort B
Loading doses followed by weekly maintenance doses
Drug: ISIS 301012 or Placebo
100 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
Experimental: Cohort C
Loading doses followed by weekly maintenance doses
Drug: ISIS 301012 or Placebo
200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
Experimental: Cohort D
Loading doses followed by weekly maintenance doses
Drug: ISIS 301012 or Placebo
300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
Experimental: Cohort E
Loading doses followed by weekly maintenance doses
Drug: ISIS 301012 or Placebo
400 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
Experimental: Cohort F
Loading doses followed by extended weekly maintenance doses
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
Experimental: Cohort G
Loading doses followed by extended weekly maintenance doses
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00231569

Locations
United States, Maine
Auburn, Maine, United States, 04210
Netherlands
Amsterdam, Netherlands, 1105 AZ
Leiden, Netherlands, 2311 GZ
Rotterdam, Netherlands, 3021 HC
Utrecht, Netherlands, 3584 CX
Sponsors and Collaborators
Genzyme, a Sanofi Company
Isis Pharmaceuticals
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

No publications provided by Sanofi

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Medical Monitor, Genzyme Coporation
ClinicalTrials.gov Identifier: NCT00231569     History of Changes
Other Study ID Numbers: 301012CS4, EudraCT No.: 2005-002119-26
Study First Received: October 3, 2005
Last Updated: December 2, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United States: Food and Drug Administration

Keywords provided by Sanofi:
LDL-cholesterol
apoB-100
apoB-48

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

ClinicalTrials.gov processed this record on November 25, 2014