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

Dyslipidemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00593047
• Other study ID #: KBT004
• Secondary ID: 2007-004413-33
• Status: Completed
• Phase: Phase 2
• First received: December 17, 2007
• Last updated: November 27, 2008
• Start date: November 2007
• Est. completion date: September 2008

Study information

• Verified date: May 2008
• Source: Karo Bio AB
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Medical Products AgencyFinland: Finnish Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: September 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dyslipidemia
• Dyslipidemias

Intervention

Drug:
• KB2115
tablet formulation given once daily for 12 weeks

Locations

Country	Name	City	State
Sweden	Carl-Peter Anderberg	Gothemburg

Sponsors (1)

Lead Sponsor	Collaborator
Karo Bio AB

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	LDL cholesterol		12 weeks	No
Secondary	Triglyceride		12 weeks	No