A double-blind, double dummy, randomized, parallel group, multi-centre Phase III study to evaluate the efficacy and safety of TAK-475 100 mg and TAK-475 100 mg administered in combination with ezetimibe 10 mg versus ezetimibe 10 mg in subjects with primary dyslipidemia.
- Conditions
- Treatment of patients with primary dyslipidaemiaMedDRA version: 8Level: PTClassification code 10058108
- Registration Number
- EUCTR2005-002315-25-EE
- Lead Sponsor
- Takeda Global Research & Development Centre (Europe) Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1267
1. Male or female aged = 18 years.
2. If female and of child bearing potential, the subject is not pregnant, not lactating, not planning on 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.
3. The subject has documented history of dyslipidemia (fasting LDL-c levels = 160 mg/dL (=4.14 mmol/L) and = 220mg/dL (= 5.6mmol/L) and triglycerides = 400 mg/dL (4.52 mmol/L) within 6 months prior to Screening. If this is not the case, an initial blood sample should be taken and analyzed at the local laboratory to confirm this. These results should be confirmed at Screening (Visit 1)).
4. Willing and able to comply with a standardized diet (e.g. TLC)
5. Not have taken any lipid lowering therapy for at least 30 days prior to Screening (Visit 1) (see Prohibited Medication section 5.5).
6. Otherwise is in good physical and mental health as determined by a physician (i.e. via medical history and physical examination).
7. Capable of understanding and willing to sign the Informed Consent Form.
8. At Randomization, in addition to the criteria above, the subject must have mean fasting LDL-c levels = 130 mg/dL (3.36mmol/L) and = 220 mg/dL (5.6 mmol/L) and mean triglyceride levels = 400 mg/dL (= 4.52 mmol/L). The mean values will be calculated from measurements made at Visit 2 (Week -2) and 3 (Week -1) for each subject. In order for the subject to be Randomized, the individual LDL-c values must not differ by more than 15 % of the upper value, and for triglycerides the upper value must be = 450mg/dl (5.0 mmol/L). If the inclusion range is not attained for either triglycerides or LDL-c then the investigator will repeat these assessments at an additional Visit (Visit 3.1). If the LDL and TG criteria then fulfil the above criteria, at two consecutive visits at least 1 week apart then the subject may enter the active treatment phase.
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
At Screening (Visit 1) and at Randomisation (Visit 4) or when specified below, the subjects must not be/have:
1. Between screening and randomisation, (i) ALT or AST level > 1.5 times the upper limit of normal (ULN). However, if a repeat test is <1.5 ULN then contact the Takeda Safety representative contact for consideration of inclusion - see Section 6.3.1 (ii) serum creatinine > 133 µmol/L (>1.5mg/dL) or (iii) prior to Screening and/or (iii) CPK > 3 times the upper limit of normal ULN.
2. Active liver disease or jaundice.
3. A previous history of cancer, other than basal cell carcinoma, 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.
4. 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 Screening (Visit 1) 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.
5. A positive hepatitis B surface antigen, or hepatitis C virus antibody, as determined by medical history and/or subject’s verbal report.
6. A positive human immunodeficiency virus (HIV) status or taking anti-retroviral medications, as determined by medical history and/or subject’s verbal report.
7. 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).
8. Participated in any other clinical studies with TAK-475, is currently participating in another investigational study, has participated in an investigational study within the past 30 days or, for drugs with a long half life, within a period of less than 5 times the drug’s half life.
9. A known hypersensitivity or history of intolerance to TAK-475 or ezetimibe.
10. A history or presence of clinically significant food allergy that would prevent adherence to the specialized diet.
11. A known heterozygous or homozygous familial hypercholesteroleamia or known Type III hyperlipoproteinaemia (familial dysbetalipoproteinaemia).
12. Fibromyalgia, myopathy, rhabdomyolysis or unexplained muscle pain and/or discontinuation of HMG-CoA reductase inhibitors due to myalgia at any time.
13. Uncontrolled hypertension despite medical treatment (Stage 2 hypertension defined as mean resting diastolic blood pressure > 100 mmHg or mean resting systolic blood pressure > 160 mmHg) at Screening (Visit 1).
14. Inflammatory bowel or any other malabsorption syndrome or has had gastric bypass surgery or any other surgical procedure for weight loss.
15. Unwilling or unable, in the opinion of the investigator, to comply with the protocol or scheduled appointments.
16. Unable to understand verbal or written English or any other language for which a certified translation of the approved informed consent is available.
17. A history of drug abuse (defined as illicit drug use) or a history of high alcohol intake (defined as regular or daily consumption of more than 3 (males) and 2 (females) alcoholic drinks p
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