dyslipidemia (eg hyperlipidaemia, hypertriglyceridaemia) MedDRA version: 18.0 Level: LLT Classification code 10020667 Term: Hyperlipidemia System Organ Class: 100000004861
Conditions
Interventions
Product Code: K-877
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: K-877
CAS Number: 848259–27–8
Current Sponsor code: K-877
Other descriptive name: K-877
Concentration unit: µg microgra
Sponsors
Kowa Research Europe
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to understand and comply with study procedures and give written informed consent 2. Aged =18 years 3. Have no clinically significant abnormal findings on medical history, physical examination, vital signs, 12 lead electrocardiogram (ECG), and clinical laboratory profiles of both blood and urine that would impair participation or safety in the trial or clinically relevant abnormal findings that in the opinion of the investigator could interfere with the objectives of the study or the safety of the patient. 4. After treatment with stable statin therapy for at least 12 weeks prior to screening, have a screening LDL C of no more than 10 mg/dL above the NCEP ATP III target (see note 2 below): • LDL C =65 years) yes F.1.3.1 Number of subjects for this age range 350
Exclusion criteria
Exclusion criteria: 1. Patients who require other lipid lowering treatments in addition to study drug (K 877) and statin 2. Patients with body mass index =40 kg/m2 3. Patients with homozygous familial hypercholesterolaemia (heterozygous is permitted) or familial hypoalphalipoproteinaemia 4. Patients with type 1 diabetes mellitus 5. Patients with poorly controlled type 2 diabetes mellitus (haemoglobin A1c [HbA1c] >10%) 6. Patients who are receiving insulin or insulin analog treatment except for stable basal insulin therapy with a single insulin 7. Patients with moderate or severe renal impairment (ie, estimated glomerular filtration rate 3 × upper limit of the normal (ULN) of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) at any screening visit 9. Patients with a creatine kinase (CK) level >3 × ULN at screening 10. Patients with hepatic insufficiency (including biliary cirrhosis and unexplained persistent liver function abnormalities, eg, persistent increase in serum transaminase), gall bladder disease, or pancreatitis 11. Patients with a history of drug or alcohol abuse; allowed amounts are 20 g for women and 30 g for men per day (see Appendix D for details on calculating alcohol use) 12. Patients who have a hypersensitivity/intolerance to PPARa agonists or statins, contraindications as per approved statin SPC 13. Patients who had MI, artery angioplasty, bypass graft surgery, or severe/unstable angina pectoris within 3 months prior to screening 14. Patients who had symptomatic cerebrovascular disease including cerebrovascular haemorrhage, ischaemia, or carotid endarterectomy within 3 months of screening 15. Patients with symptomatic heart failure (New York Heart Association class III or IV) 16. Patients who have uncontrolled hypertension (seated systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg) Note: An average of 3 readings within an adequate time interval during the study visit may be used to determine blood pressure level 17. Patients who have used lipid modifying treatment other than statins within 28 days prior to screening 18. Patients with a history of chronic active hepatitis B or hepatitis C, or known to be infected with human immunodeficiency virus (HIV) 1 or HIV 2 19. Patients with known muscular or neuromuscular disease 20. Patients with known active or history (<10 years from previous event) of neoplastic disease (excluding basal cell cancer) or patients who may need to take antineoplastic treatment during the study period 21. Patients with uncontrolled hypothyroidism or hyperthyroidism Note: controlled thyroid disease (normal serum thyroid stimulating hormone [TSH] and stable therapy for at least 3 months) is permitted 22. Patients who have participated in any other clinical studies within 3 months of screening 23. Patients who have experienced a loss of more than 400 mL of blood during the 3 months prior to screening, eg, as a blood donor 24. Patients with a clinically relevant abnormal history, physical examination findings, 12 lead ECG, or laboratory values at screening that in the opinion of the investigator could interfere with the objectives of the study or the safety of the patient 25. Patient has a high possibility they will not be compliant with the requirements of the protocol 26. Patients who have a mental condition rendering them unable to understand th
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the dose response of the following parameters: •% change in non high density lipoprotein cholesterol (non HDL C) from baseline to Week 12 •% change in TG from baseline to Week 12 To assess the safety and tolerability of K 877 in patients with residual cardiovascular risk despite statin controlled LDL C concentration as particularly evaluated by: •Change and % change in serum creatinine from baseline to Week 12 •Change and % change in homocysteine from baseline to Week 12 ;Secondary Objective: To assess the response of the following parameters: •% change in HDL C, total cholesterol (TC), and apolipoprotein (Apo) B from baseline to Week 12 •% change in Apo A1 and Apo A2 from baseline to Week 12 •% change in LDL C, small LDL particles (small and dense LDL), very low density lipoprotein (VLDL C), Apo B48, Apo B100, Apo C2, Apo C3, adiponectin, fibroblast growth factor 21 (FGF21), high sensitivity C reactive protein (hsCRP), lecithin cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP) mass and activity, proprotein convertase subtilisin/kexin type 9 (PCSK9) mass, HDL function (reverse cholesterol transport, HDL driven endothelial production of nitric oxide, ion mobility analysis, HDL sub fractions (including pre beta HDL) and lipid and lipoprotein ratios TC/HDL C, non HDL C/HDL C, Apo B/Apo A1, LDL C/Apo B, and Apo C3/Apo C2, from baseline to Week 12 •To measure PK parameters in a subset of patients per dose group;Primary end point(s): The primary efficacy endpoints of the study include the following: • % change in non HDL C from baseline to Week 12 • % change in TG from baseline to Week 12 For the primary endpoints, non HDL C and TG, the primary analysis will be carried out using an analysis of covariance (ANCOVA) model with percent change from baseline to Week 12, baseline non HDL C, and baseline TG values as covariates, respectively. The superiority of K 877 groups compared to placebo will be assessed by Dunnett’s | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints include the following: • % change in HDL C, TC, and Apo B from baseline to Week 12 • % change in Apo A1 and Apo A2 from baseline to Week 12 • % change in LDL C, small LDL particles (small and dense LDL), VLDL C, Apo B48, Apo C2, Apo C3, FGF21, hsCRP, LCAT, CETP mass and activity, PCSK9 mass, HDL function (reverse cholesterol transport, HDL driven endothelial production of nitric oxide, HDL oxidative capacity, Ion mobility analysis, 2 D gel analysis for HDL sub fractions including pre beta HDL, Calculation: TC/HDL C, non HDL C/HDL C, Remnant C (TC LDL C HDL C), Apo A1/Apo B, LDL C/Apo B, Apo B100, and Apo C3/C2 from baseline to Week 12 The secondary efficacy endpoints will be analysed using the same statistical method used for the primary analysis; however, Dunnett’s test will not be used to evaluate the superiority of the K 877 groups to the placebo group.;Timepoint(s) of evaluation of this end point: 12 weeks | — |
Countries
Czech Republic, Denmark, Germany, Hungary, Netherlands, Poland, Russian Federation, Sweden, United Kingdom
Contacts
Public ContactYusuke Senko
Kowa Research Europe
Outcome results
None listed