Subjects With Hypercholesterolemia MedDRA version: 9.1 Level: PT Classification code 10058108 Term: Dyslipidaemia
Conditions
Interventions
Product Name: Lapaquistat acetate
Product Code: TAK-475
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: lapaquistat
Current Sponsor code: TAK-475
Other descriptive name: Lapaquistat aceta
Sponsors
Takeda Global Research & Development Centre (Europe) Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The subject is a male or female and at least 18 years of age. 2. A female subject of childbearing potential who is sexually active agrees to use adequate contraception from screening throughout the duration of the study and for 30 days following the last dose. Women NOT of child bearing potential are defined as those who have been surgically sterilized (hysterectomy, oophorectomy, tubal ligation) or who are postmenopausal (defined as at least 2 years since last regular menses). Acceptable methods of contraception are defined in Section 9.1.10 Contraception and Pregnancy Avoidance Procedure. 3. The subject is capable of understanding and complying with protocol requirements. 4. The subject or the subject’s legally acceptable representative signs a written informed consent form prior to the initiation of any study procedures. 5. Prior to Randomization, the subject has a mean LDL-C > or equal to 130 mg/dL (3.37 mmol/L) and = 190 mg/dL (4.92 mmol/L) for 2 consecutive samples (at least 1 week apart). The difference between the 2 individual LDL-C values must not exceed 15% of the higher value. 6. Prior to Randomization, the subject has mean TG =400 mg/dL (4.52 mmol/L) for 2 consecutive samples (at least 1 week apart). The upper value for either sample must be =450 mg/dL (5.08 mmol/L). 7. The subject is willing and able to comply with a standardized diet (TLC or equivalent). 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. The subject has an ALT or AST level >1.5 times the upper limit of normal (ULN), identified during screening (e.g., from the V1 blood sample). 2. The subject has a serum creatinine >133 mmol/L (>1.5mg/dL), identified during screening (e.g., from the V1 blood sample). 3. The subject has a CK >3 times the upper limit of normal (ULN), identified during screening (e.g., from the V1 blood sample). 4. The subject has active liver disease or jaundice. 5. The subject has taken any fibrates within 42 days of Visit 1 or any lipid-lowering therapy for at least 30 days prior to Screening (Visit 1). (See Excluded Medications) 6. The subject has a previous history of cancer that has been in remission for less than 5 years prior to the first dose of study medication. This criterion does not include those subjects with basal cell or stage 1 squamous cell carcinoma of the skin. 7. The subject has an endocrine disorder, such as Cushing’s syndrome, hyperthyroidism, or inappropriately treated hypothyroidism affecting lipid metabolism. Subjects with hypothyroidism on appropriate replacement therapy (defined as stable thyroid hormone replacement at least 3 months prior to Screening and TSH levels =1.5 times ULN) will be eligible for enrollment. 8. The subject has a history of myocardial infarction, angina pectoris, unstable angina, transient ischemic attacks, cerebrovascular accident, peripheral vascular disease, abdominal aortic aneurysm, coronary angioplasty, coronary or peripheral arterial surgery (bypass graft surgery), or multiple risk factors that confer a 10-year risk for cardiovascular heart disease (CHD) >20% based on Framingham risk scoring. 9. The subject has a positive hepatitis B surface antigen or hepatitis C virus antibody test, as determined by medical history and/or subject’s verbal report. 10. The subject has a positive human immunodeficiency virus (HIV) status or is taking antiretroviral medications, as determined by medical history and/or subject’s verbal report. 11. The subject is unable or unwilling to discontinue excluded medications or to continue stable doses of “stable dose” medications. (See Excluded Medications and Concomitant Medications.) 12. The subject has received any investigational medication 30 days prior to screening, (for drugs with a long half-life, within a period of less than 5 times the drug’s half-life) or has participated in an investigational study 13. The subject has received lapaquistat acetate in a previous clinical study or as a therapeutic agent 14. The subject has a history or presence of clinically significant food allergy that would prevent adherence to the specialized diet. 15. The subject has a known heterozygous or homozygous familial hypercholesterolemia or known type III hyperlipoproteinemia (familial dysbetalipoproteinemia). 16. The subject has fibromyalgia, myopathy, rhabdomyolysis, or unexplained muscle pain. 17. The subject has uncontrolled hypertension (defined as resting diastolic blood pressure >100 mmHg and/or a resting systolic blood pressure >160 mmHg) at Screening. 18. The subject has had inflammatory bowel disease or any other malabsorption syndrome, or has had gastric bypass or any other surgical procedure for weight loss. 19. The subject is unwilling or unable, in the opinion of the investigator, to comply with the protocol or scheduled appointments. 20. The subject is unable to understand verbal or written English or any other language for which a certified translation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the reduction in plasma low-density lipoprotein cholesterol (LDL-C) in subjects with hypercholesterolemia when treated with lapaquistat acetate 50 mg once daily (QD) or placebo QD for 12 weeks.;Secondary Objective: To evaluate safety and tolerability (adverse events [AE]), safety laboratory tests, physical examination (PE), vital signs and electrocardiogram (ECG)) To evaluate changes in lipid variables non high-density lipoprotein cholesterol (non-HDL-C), (total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), very-low-density lipoprotein cholesterol (VLDL-C), apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B) To evaluate changes in derived ratios LDL-C/HDL-C, TC/HDL-C, ApoB/ApoA1 To evaluate changes in high-sensitivity C-reactive protein (hs-CRP) Secondary Objectives (Open-label Extension Period): To evaluate long-term safety and lipid variables of lapaquistat acetate 50 mg QD after 48 weeks of open-label treatment. ;Primary end point(s): Primary Efficacy Variable: The primary efficacy variable for this study is fasting plasma LDL-C. Secondary Efficacy Variables: The secondary efficacy variables for this study include: TC, Apo B, TG, HDL-C, Apo A1, VLDL-C, derived variables (non-HDL-C, and ratios LDL-C/HDL-C, TC/HDL-C, Apo B/Apo A1), and hs-CRP. The percentage of subjects reaching LDL-C levels of <160 mg/dL (4.1 mmol/L), <130 mg/dL (3.37 mmol/L) and <100 mg/dL (2.59 mmol/L) at Week 12 (or ET) during the double-blind will be evaluated. Safety Assessments: The safety variables will include: AEs, safety laboratory tests, PE, vital signs and ECG | — |
Countries
Estonia, Hungary, Latvia, Netherlands, Spain, United Kingdom
Outcome results
None listed