- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00231569
Dose-escalating Safety Study in Subjects on Stable Statin Therapy
August 1, 2016 updated by: Kastle Therapeutics, LLC
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.
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
74
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Amsterdam, Netherlands, 1105 AZ
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Leiden, Netherlands, 2311 GZ
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Rotterdam, Netherlands, 3021 HC
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Utrecht, Netherlands, 3584 CX
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Maine
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Auburn, Maine, United States, 04210
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Cohort A
Loading doses followed by weekly maintenance doses
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30 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
100 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
400 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
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Experimental: Cohort B
Loading doses followed by weekly maintenance doses
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30 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
100 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
400 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
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Experimental: Cohort C
Loading doses followed by weekly maintenance doses
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30 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
100 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
400 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
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Experimental: Cohort D
Loading doses followed by weekly maintenance doses
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30 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
100 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
400 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
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Experimental: Cohort E
Loading doses followed by weekly maintenance doses
|
30 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
100 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
400 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
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Experimental: Cohort F
Loading doses followed by extended weekly maintenance doses
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30 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
100 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
400 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
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Experimental: Cohort G
Loading doses followed by extended weekly maintenance doses
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30 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
100 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
400 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Percent reduction in LDL-cholesterol from baseline
Time Frame: From baseline measurement
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From baseline measurement
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Percent reduction in apoB-100
Time Frame: From baseline measurement
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From baseline measurement
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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
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From baseline measurement
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Percent change from baseline in LDL/HDL and apoB-100/apo-A1 ratios
Time Frame: From baseline measurement
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From baseline measurement
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AEs, SAEs, physical examination data, vital signs, and laboratory analyzes
Time Frame: Duration of study
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Duration of study
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2005
Primary Completion (Actual)
June 1, 2007
Study Completion (Actual)
December 1, 2007
Study Registration Dates
First Submitted
October 3, 2005
First Submitted That Met QC Criteria
October 3, 2005
First Posted (Estimate)
October 4, 2005
Study Record Updates
Last Update Posted (Estimate)
August 3, 2016
Last Update Submitted That Met QC Criteria
August 1, 2016
Last Verified
December 1, 2013
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 301012CS4
- EudraCT No.: 2005-002119-26
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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