Dose-escalating Safety Study in Subjects on Stable Statin Therapy

NCT ID: NCT00231569

Last Updated: 2016-08-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

74 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-09-30

Study Completion Date

2007-12-31

Brief Summary

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

Detailed Description

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Conditions

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Hypercholesterolemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Cohort A

Loading doses followed by weekly maintenance doses

Group Type EXPERIMENTAL

ISIS 301012 or Placebo

Intervention Type DRUG

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

Cohort B

Loading doses followed by weekly maintenance doses

Group Type EXPERIMENTAL

ISIS 301012 or Placebo

Intervention Type DRUG

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

Cohort C

Loading doses followed by weekly maintenance doses

Group Type EXPERIMENTAL

ISIS 301012 or Placebo

Intervention Type DRUG

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

Cohort D

Loading doses followed by weekly maintenance doses

Group Type EXPERIMENTAL

ISIS 301012 or Placebo

Intervention Type DRUG

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

Cohort E

Loading doses followed by weekly maintenance doses

Group Type EXPERIMENTAL

ISIS 301012 or Placebo

Intervention Type DRUG

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

Cohort F

Loading doses followed by extended weekly maintenance doses

Group Type EXPERIMENTAL

ISIS 301012 or Placebo

Intervention Type DRUG

200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85

Cohort G

Loading doses followed by extended weekly maintenance doses

Group Type EXPERIMENTAL

ISIS 301012 or Placebo

Intervention Type DRUG

300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85

Interventions

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ISIS 301012 or Placebo

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

Intervention Type DRUG

ISIS 301012 or Placebo

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

Intervention Type DRUG

ISIS 301012 or Placebo

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

Intervention Type DRUG

ISIS 301012 or Placebo

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

Intervention Type DRUG

ISIS 301012 or Placebo

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

Intervention Type 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

Intervention Type 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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role collaborator

Kastle Therapeutics, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Genzyme Coporation

Principal Investigators

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Medical Monitor

Role: STUDY_DIRECTOR

Genzyme, a Sanofi Company

Locations

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Auburn, Maine, United States

Site Status

Amsterdam, , Netherlands

Site Status

Leiden, , Netherlands

Site Status

Rotterdam, , Netherlands

Site Status

Utrecht, , Netherlands

Site Status

Countries

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United States Netherlands

References

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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.

Reference Type DERIVED
PMID: 20378080 (View on PubMed)

Other Identifiers

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EudraCT No.: 2005-002119-26

Identifier Type: -

Identifier Source: secondary_id

301012CS4

Identifier Type: -

Identifier Source: org_study_id

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