A placebo-controlled, double-blind, randomised study to evaluate the efficacy and safety of TAK-475 100mg in subjects with type 2 diabetes currently treated with lipid-lowering therapy.

Phase 1

Conditions: treatment of patients with primary dyslipidaemia
MedDRA version: 8 Level: pt Classification code 10058108

Registration Number: EUCTR2005-002316-24-GB

Lead Sponsor: Takeda Europe R &D Centre Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 0

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

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 <1.5 times ULN then contact the Takeda Safety Contact for
consideration of inclusion – see Section 6.6.1,
(ii) serum creatinine >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) will be eligible for enrolment. If the subject’s TSH >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,

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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