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

This study has been completed.
Sponsor:
Information provided by:
Karo Bio AB
ClinicalTrials.gov Identifier:
NCT00593047
First received: December 17, 2007
Last updated: November 27, 2008
Last verified: May 2008
  Purpose

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 Intervention Phase
Dyslipidemia
Drug: KB2115
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Karo Bio AB:

Primary Outcome Measures:
  • LDL cholesterol [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Triglyceride [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 180
Study Start Date: November 2007
Study Completion Date: September 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00593047

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

No publications provided by Karo Bio AB

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr Jens Kristensen, Chief Medical Officer, Karo Bio AB
ClinicalTrials.gov Identifier: NCT00593047     History of Changes
Other Study ID Numbers: KBT004, 2007-004413-33
Study First Received: December 17, 2007
Last Updated: November 27, 2008
Health Authority: Sweden: Medical Products Agency
Finland: Finnish Medicines Agency

Keywords provided by Karo Bio AB:
hypercholesterolemia

Additional relevant MeSH terms:
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on October 30, 2014