treatment of patients with primary dyslipidaemia MedDRA version: 8 Level: pt Classification code 10058108
Conditions
Sponsors
Takeda Europe R &D Centre Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female subjects aged = 18 years, 2. Capable of understanding and willing to sign the Informed Consent Form, 3. Documented diagnosis of Type 2 diabetes mellitus for > 6 months (Random venous plasma glucose = 200 mg/dL (11.1 mmol/L), 2-hour glucose tolerance during a 75g oral glucose tolerance test (OGTT) = 200mg/dL (11.1 mmol/L) or Fasting Plasma Glucose (FPG) =126 mg/dL (7 mmol/L)), with stable glycaemic control over a period of at least 3 months and HbA1c of 9.5 % or less. 4. On a stable antidiabetic regimen, which may include oral antidiabetic medication and/or insulin, for at least 3 months prior to Screening (Visit 1). 5. The most recent value of LDL-c = 100 mg/dL (2.59 mmol/L) and triglycerides = 400mg/dl (4.52 mmol/L), within the previous 6 months, currently treated with one of the following lipid-lowering drugs: atorvastatin (10 mg, 20 mg, or 40 mg), simvastatin (20mg or 40 mg), rosuvastatin (10 mg or 20 mg), or fenofibrate (not to exceed 200 mg), and no changes in the medication for at least 4 Weeks before Screening (Visit 1). If no value is available, then confirm acceptability for enrolment from result on sample taken at screening visit 1. 6. The subject is otherwise in good health as determined by a physician (ie, via medical history and physical examination) 7. At Randomisation (Visit 4) in order to be randomised subjects must have fulfilled the above criteria and also have: Mean LDL-cholesterol levels of =100mg/dL (2.59 mmol/L) and mean triglycerides level of = 400 mg/dL (4.52 mmol/L). The mean values will be calculated from measurements made at Week –2 (Visit 2) and Week –1 (Visit 3) for each subject. For LDL-cholesterol the difference between the two individual values must not differ by more than 15% of the upper value. For triglycerides, the upper value for either sample must be = 450 mg/dL (5.1 mmol/L). If the inclusion range is not attained for either LDL-c or triglycerides levels then the investigator will repeat these assessments at an additional Visit (Visit 3.1). If the LDL-c and triglycerides level then fulfil the above criteria at two consecutive visits, at least 1 week apart, then the subject may enter the active phase of treatment with TAK-475 100mg or placebo. 8. If female and of childbearing potential, the subject is not pregnant, not lactating or becoming pregnant between Screening and 30 days following the last dose of study medication, and agrees to use acceptable forms of contraception during the study. 9. At Randomisation (Visit 4) in order to be randomised subjects must have fulfilled the above criteria and also have: Mean LDL-cholesterol levels of =100mg/dL (2.59 mmol/L) and mean triglycerides level of = 400 mg/dL (4.52 mmol/L). The mean values will be calculated from measurements made at Week –2 (Visit 2) and Week –1 (Visit 3) for each subject. For LDL-cholesterol the difference between the two individual values must not differ by more than 15% of the upper value. For triglycerides, the upper value for either sample must be = 450 mg/dL (5.1 mmol/L). If the inclusion range is not attained for either LDL-c or triglycerides levels then the investigator will repe
Exclusion criteria
Exclusion criteria: At Screening (Visit 1) to enter the 4-Week Run-In period the subjects must not be/have: 1. Type 1 Diabetes Mellitus 2. Between screening and randomisation, (i) ALT or AST level >1.5 times the upper limit of normal (ULN). If a repeat test is 133 µmol/L (>1.5mg/dL) or (iii) CPK >3 times the upper limit of normal (ULN) 3. Active liver disease, gallbladder disease (with or without cholelithiasis) or jaundice 4. Positive hepatitis B surface antigen, or hepatitis C virus antibody, as determined by medical history and/or subject’s verbal report 5. Positive human immunodeficiency virus status or is taking anti-retroviral medications, as determined by medical history and/or subject’s verbal report 6. Known hypersensitivity or intolerance to TAK-475 or to the planned companion medication or its components 7. Myocardial infarction, unstable angina, transient ischemic attacks, cerebrovascular accident, coronary angioplasty, coronary or peripheral arterial surgery (bypass graft surgery) in the 6 months prior to Screening (Visit 1) 8. Cancer that has been in remission for less than 5 years prior to the first dose of study drug. This criterion does not include those subjects with basal cell or Stage 1 squamous cell carcinoma of the skin 9. 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 therapy at least 3 months prior to Lead-In and TSH levels 1.5 x ULN, a free thyroxine T4 level will be determined. If the free thyroxine T4 is within normal limits for that subject, the subject may continue in the study 10. Known heterozygous or homozygous familial hypercholesterolaemia or known Type III hyperlipoproteinaemia (familial dysbetalipoproteinaemia) 11. Fibromyalgia, myopathy, rhabdomyolysis or unexplained muscle pain 12. Uncontrolled hypertension despite treatment (defined as mean resting diastolic blood pressure >100 mm Hg or mean resting systolic blood pressure >160 mm Hg) at Screening (Visit 1). 13. Inflammatory bowel disease or any other malabsorption syndrome or has had gastric bypass or any other surgical procedure for weight loss. 14. Unwilling or unable, in the opinion of the investigator, to comply with the protocol or scheduled appointments. 15. Unable or unwilling to discontinue excluded medications or to continue stable doses of “stable dose” medications or would require treatment with any excluded medication during the study. See Prohibited Medications Section 5.5 16. Participating in another investigational study or has participated in an investigational study within the past 30 days or,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of TAK-475 compared to placebo on low-density lipoprotein cholesterol (LDL-c) levels in subjects with Type 2 Diabetes currently treated with doses of other lipid-lowering drugs.; Secondary Objective: To evaluate the effects of TAK-475 compared to placebo on total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-c), very-low densitylipoproteins (VLDL-c), apolipoprotein A1 (Apo A1) and apolipoprotein B (Apo B), in this population. The percentage of subjects achieving LDL-c levels of <130 mg/dL, <100mg/dL and < 70 mg/dL after 24 weeks of treatment and the overall safety and tolerability will be evaluated. Other secondary objectives are to evaluate the effects of TAK-475 compared to placebo on other lipid variables, high-sensitivity C-reactive protein (hs-CRP), apolipoprotein (a) and Hb A1c. Blood samples for the determination of biomarkers, including cardiovascular morbidity markers will also be collected. ; Primary end point(s): Efficacy: The primary efficacy variable for this study is the fasting direct plasma LDL-c. Secondary: The secondary efficacy variables are lipid parameters including: non-HDL-c, TC, Apo B, HDL-c, Apo A1, TG, VLDL-c, ratios (LDL-c/HDL-c, TC/HDL-c, Apo B/Apo A1), hs-CRP and Hb A1c.TC/HDL-c, LDL-c/HDL-c, Apo B/Apo A1 ratios and non-HDL-c will also be derived. Cardiovascular morbidity markers (e.g. Interleukin 6 (IL-6), Oxidazed-LDL, fibrinogen, plasminogen activated inhibitor-1 (PAI-1)) will also be evaluated, if determined.Safety: Safety variables are: Adverse events, clinical chemistry, hematology, urinalysis, electrocardiogram (ECG), vital signs, weight, physical examination and Best Corrected Visual Acuity (BCVA). | — |
Countries
Czech Republic, Denmark, Estonia, Finland, Germany, Latvia, Slovakia, United Kingdom
Outcome results
None listed