Dose-escalating Safety Study in Subjects on Stable Statin Therapy

NCT00231569 | Completed Phase 2 DMC

• 2 other identifiers: 301012CS4EudraCT No.: 2005-002119-26
• Study Type: interventional
• Target: 74
• Locations: 2 countries
• Sites: 5

Brief Summary

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

Conditions

Hypercholesterolemia

Keywords

LDL-cholesterol; apoB-100; apoB-48

Outcome Measures

Primary Outcomes (1)

• Percent reduction in LDL-cholesterol from baseline

  From baseline measurement

Secondary Outcomes (4)

• Percent reduction in apoB-100

  From baseline measurement

• Percent change in HDL-cholesterol, triglycerides, total cholesterol, non-HDL cholesterol, VLDL plus LDL-cholesterol and LDL-cholesterol particle size and concentration

  From baseline measurement

• Percent change from baseline in LDL/HDL and apoB-100/apo-A1 ratios

  From baseline measurement

• AEs, SAEs, physical examination data, vital signs, and laboratory analyzes

  Duration of study

Study Arms (7)

Cohort A

EXPERIMENTAL

Loading doses followed by weekly maintenance doses

Drug: ISIS 301012 or Placebo

Cohort B

EXPERIMENTAL

Loading doses followed by weekly maintenance doses

Drug: ISIS 301012 or Placebo

Cohort C

EXPERIMENTAL

Loading doses followed by weekly maintenance doses

Drug: ISIS 301012 or Placebo

Cohort D

EXPERIMENTAL

Loading doses followed by weekly maintenance doses

Drug: ISIS 301012 or Placebo

Cohort E

EXPERIMENTAL

Loading doses followed by weekly maintenance doses

Drug: ISIS 301012 or Placebo

Cohort F

EXPERIMENTAL

Loading doses followed by extended weekly maintenance doses

Drug: ISIS 301012 or Placebo

Cohort G

EXPERIMENTAL

Loading doses followed by extended weekly maintenance doses

Drug: ISIS 301012 or Placebo

Interventions

ISIS 301012 or Placebo DRUG

30 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29

Cohort A

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Kastle Therapeutics, LLC: lead
• Ionis Pharmaceuticals, Inc.: collaborator

Study Sites (5)

Unknown Facility

Auburn, Maine, 04210, United States

Location

Unknown Facility

Amsterdam, 1105 AZ, Netherlands

Location

Unknown Facility

Leiden, 2311 GZ, Netherlands

Location

Unknown Facility

Rotterdam, 3021 HC, Netherlands

Location

Unknown Facility

Utrecht, 3584 CX, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 20378080 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

mipomersen

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 3, 2005
• First Posted: October 4, 2005
• Study Start: September 1, 2005
• Primary Completion: June 1, 2007
• Study Completion: December 1, 2007
• Last Updated: August 3, 2016

Record last verified: 2013-12

Locations

NL (4); US (1)