E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Hypercholesterolaemia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020603 |
E.1.2 | Term | Hypercholesterolaemia |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
To assess safety & 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 and 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 12 w 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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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 (< 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. 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 (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
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E.5 End points |
E.5.1 | Primary end point(s) |
Absolute change in LDL-cholesterol from baseline to 12 weeks |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |