Primary hypercholesterolaemia MedDRA version: 9.1 Level: LLT Classification code 10020603 Term: Hypercholesterolaemia
Conditions
Interventions
Product Code: KB2115
Pharmaceutical Form: Tablet
CAS Number: KB2115
Current Sponsor code: KB2115
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical
Sponsors
Karo Bio AB
Eligibility
Sex/Gender
All
Inclusion 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: a. Non-nursing and non-pregnant 12 months prior to enrolment b. 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 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 a. Atorvastatin not more than 20 mg/day or b. 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 electrocardiogram (ECG), eg, QTc interval > 450 msec 8. Body Mass Index of = 40 kg/m^2 9. Recent history ( 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 2 16. Unstable or severe angina pectoris or peripheral artery disease 17. Known thyroid disease or thyroid biomarkers (thyroid-stimulating hormone [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 20. Positive human immunodeficiency virus (HIV) or hepatitis A, B and C, and for Epstein Barr virus and Cytomegalovirus 21. Hepatitis or liver cirrhosis 22. Bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase or -glutamyl transpeptidase > 1.5 ULN at enrollment or visit Week 1 23. History of (past 2 years) or present alcohol or drug abuse as judged by the investigator or patients who consume > 14 alcoholic drinks per week. 24. Involvement in the planning and conduct of the study (applies to both Karo Bio AB staff and clinical research organizations) 25. Participation in a clinical study during the past 30 days anticipated to interfere with the objectives of the study as judged by the investigator 26. Previous randomization of treatment in present study or previous treatment with KB2115
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To assess safety and tolerability of different doses of KB2115 as add on to statin treatment To assess systemic exposure Cmax at different doses of KB2115 & to assess plasma conc time relationship & exposure AUC & Cmax in a subset of approx 24 patients To assess systemic exposure of KB42899 Determine plasma conc of atorvastatin, to assess possible influence on atorvastatin plasma conc of 12W treatment with KB2115 or placebo To assess the influence of add on KB2115 on blood lipids including cholesterol (total and HDL), triglycerides, FFAs, apolipoprotein A-I, A-II, B and apolipoprotein B/apolipoprotein A-1 ratio, lipoprotein (a), bone specific biomarker activity, possibly lathosterol, plant sterol, & cholestan (C4). Analyses of lathosterol, plant sterol & cholestan (C4) may be performed To assess the influence of add on with KB2115 on the pituitary-thyroid axis by determination of biomarkers of thyroid activity To assess potential effects on heart rate and QT/QTc interval;Primary end point(s): Absolute change in LDL-cholesterol from baseline to 12 weeks;Main Objective: To assess the efficacy of different doses of KB2115 on low-density lipoprotein (LDL) cholesterol as add on to statin treatment in patients with hypercholesteremia. | — |
Countries
Finland, Sweden
Outcome results
None listed