LDL-Cholesterol Lowering Effect of KB2115 as Add on to Statin

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00593047
Recruitment Status : Completed
First Posted : January 14, 2008
Last Update Posted : December 1, 2008
Information provided by:
Karo Bio AB

Brief Summary:

Thyroid hormones are known to reduce cholesterol levels through regulation of a number of key enzymes involved in synthesis, degradation, and lipid transport. However, the currently marketed thyroid agonists are non-selective, and cannot be used for the treatment of hypercholesterolemia due to extrahepatic consequences of hyperthyroidism, especially on heart, bone, and muscle.

To take advantage of thyroid hormone effect on lipid metabolism for the treatment of hypercholesterolemia, it is necessary to develop a selective thyroid receptor agonist that can induce hyperthyroidism in the liver, while an euthyroid state is preserved in the extrahepatic tissue. KB2115 is a thyroid agonist developed to be liver selective.

The purpose of the study is to assess the efficacy and safety of KB2115 as add on therapy to low and middle doses of statin following 12 weeks of exposure compared to placebo. The aim of the study is to assess efficacy (LDL-cholesterol lowering effects) and safety of KB2115 at doses between 25 and 100 µg and to define a clinically relevant dose or dose range for future studies.

Condition or disease Intervention/treatment Phase
Dyslipidemia Drug: KB2115 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II, Placebo-Controlled, Double-Blind, Randomised, 12-Week, Parallel-Group Study to Assess the Efficacy of Different Doses of KB2115 as Add on to Statin Treatment in Patients With Dyslipidemia
Study Start Date : November 2007
Actual Primary Completion Date : July 2008
Actual Study Completion Date : September 2008

Arm Intervention/treatment
Placebo Comparator: 1
Statin + placebo
Drug: KB2115
tablet formulation given once daily for 12 weeks

Experimental: 2
Statin + KB2115 dose 1
Drug: KB2115
tablet formulation given once daily for 12 weeks

Experimental: 3
Statin + KB2115 dose 2
Drug: KB2115
tablet formulation given once daily for 12 weeks

Experimental: 4
Statin + KB2115 dose 3
Drug: KB2115
tablet formulation given once daily for 12 weeks

Primary Outcome Measures :
  1. LDL cholesterol [ Time Frame: 12 weeks ]

Secondary Outcome Measures :
  1. Triglyceride [ Time Frame: 12 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Signed informed consent
  2. Males or females aged 18 to 75 years. Female patients must be non-fertile. To be considered as non-fertile, females must fulfil the following:

    • Non-nursing and non-pregnant 12 months prior to enrolment
    • Not of child bearing potential ie, either documented irreversible surgically sterile (bilateral oophorectomy or hysterectomy is acceptable, but not tubal ligation) or post-menopausal. Post-menopausal is defined as serum follicle-stimulating hormone (FSH) levels in the post-menopausal range combined with amenorrhea for more than 1 year in a woman above 50 years of age, or amenorrhea for more than 2 years below 50 years of age
  3. Patients with hypercholesterolemia treated with stable doses of the below listed lipid lowering medication for at least 3 months prior to randomization

    • Atorvastatin not more than 20 mg/day or
    • Simvastatin not more than 40 mg/day
  4. LDL-cholesterol > 3.0 mmol/L (Week -1)
  5. Subject able and willing to comply with all study requirements
  6. At randomization, diet as instructed by the investigator during the last 4 weeks prior to randomization and willingness to follow these instructions throughout the study

Exclusion Criteria:

  1. Cholesterol lowering agents other than the defined statins
  2. History of somatic or psychiatric disease/condition, which may interfere with the objectives of the study as judged by the investigator
  3. Clinically significant illness or clinically relevant trauma within 2 weeks before the administration of the investigational product as judged by the investigator
  4. Chronic (> 3 months) pain condition requiring daily medication with pain killers
  5. Glycosylated haemoglobin (HbA1c) > 7.0%
  6. Diabetes requiring medication other than metformin
  7. Clinically abnormal physical findings and laboratory values as judged by the investigator and abnormal resting ECG, eg, QTc interval > 450 msec
  8. Body Mass Index of ≥ 40 kg/m2
  9. Resent history (< 3 month) of stroke or transient ischemic attacks
  10. History of seizure disorder, except febrile convulsions
  11. A current diagnosis of cancer, unless in remission
  12. Blood pressure (BP) of > 160/95 mm Hg
  13. History of cardiac arrhythmia, such as intermittent supraventricular tachyarrhythmia and atrial fibrillation
  14. Unstable angina pectoris, myocardial infarction or coronary bypass graft surgery or percutaneous coronary intervention < 6 month before randomization
  15. Congestive heart failure New York Heart Association Class > 2
  16. Unstable or severe angina pectoris or peripheral artery disease
  17. Known thyroid disease or thyroid biomarkers (TSH, T3, free T3, T4, free T4) outside reference range for normal at enrolment and at baseline
  18. Positive urine pregnancy test in women at enrolment
  19. Use of thyroid replacement therapy and hormone replacement therapy (including contraceptive pills) for last 3 months before randomization

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00593047

Carl-Peter Anderberg
Gothemburg, Sweden
Sponsors and Collaborators
Karo Bio AB
Study Director: Jens Kristensen, MD, PhD Karo Bio AB

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Dr Jens Kristensen, Chief Medical Officer, Karo Bio AB Identifier: NCT00593047     History of Changes
Other Study ID Numbers: KBT004
First Posted: January 14, 2008    Key Record Dates
Last Update Posted: December 1, 2008
Last Verified: May 2008

Keywords provided by Karo Bio AB:

Additional relevant MeSH terms:
Lipid Metabolism Disorders
Metabolic Diseases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Lipid Regulating Agents