Heterozygous Familial Hypercholesterolemia MedDRA version: 7.1 Level: LLT Classification code 10057079
Conditions
Interventions
Product Name: Torcetrapib (CP-529,414)/Atorvastatin
Product Code: CP-529,414/Atorvastatin
Pharmaceutical Form: Tablet
Current Sponsor code: CP-429,414/Atorvastatin
Other descriptive name: N/A
Concentr
Sponsors
Pfizer AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men and women at least 18 years of age. 2. Signed informed consent prior to the initiation of any study procedures. 3. Subjects who have heFH. The diagnosis of heterozygous familial hypercholesterolemia will be defined by two alternative methods: (a) clinical criteria (patient and family history, physical examination, and plasma lipid levels) or (b) LDL receptor genotyping. Secondary causes for hypercholesterolemia should be absent (eg, nephrotic syndrome, steroid treatment and obstructive jaundice). 4.1.1. Genotyping Diagnostic Criteria LDL receptor genotype performed prior to this protocol. 4.1.2. Clinical Diagnostic Criteria At the time of diagnosis, with a fasting triglyceride level of =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Women who are pregnant or lactating, or planning to become pregnant, or women of child bearing potential who have not successfully been using acceptable contraceptive methods over the previous three months. 2. Subjects who are unable to tolerate 20 mg atorvastatin during the run in period or who have been intolerant of atorvastatin prior to screening. 3. Subjects with active cardiac disease such as unstable angina, myocardial infarction, coronary angioplasty, coronary artery bypass graft, moderate or severe congestive heart failure (NYHA Class III or IV) within the last 1 month prior to the screening visit and through to randomization. 4. Subjects with uncontrolled hypertension, defined as an average systolic blood pressure >140 mmHg or an average diastolic blood pressure >90 mmHg from the last visit before randomization (at run-in Visit 3, 4 or 5) and the randomization visit (Visit 6). 5. Subjects with a clinically indicated need for statin (HMG CoA reductase inhibitor) therapy other than atorvastatin (including Cholestin™) or other concomitant therapy with known lipid altering effects on LDL C and HDL C, including, but not limited to lipid lowering combination therapies (eg, amlodipine/atorvastatin or simvastatin/ezetimibe), fibrates, bile acid sequestrants if administered with study medication, and nicotinic acid (>500 mg/day). Bile acid sequestrants and cholesterol absorption inhibitors such as ezetimibe are allowed if already being taken at Visit 1 and the dose remains the same throughout the study. Bile acid sequestrants should be administered at least 2 hours before or 4 hours after study medication. 6. Subjects taking any drugs known to be associated with an increased risk of myositis in combination with HMG CoA reductase inhibitors, including but not limited to erythromycin, clarithromycin, telithromycin, any chronic systemic antifungal use, nefazodone, fluvoxamine, any immunosuppressive drugs including cyclosporine, any protease inhibitors and other potent inhibitors of cytochrome P450 3A4 (CYP3A4). Should these medications be necessary during the course of the trial, consideration should be given to temporarily withholding study drug and restarting it only after time has elapsed to allow for sufficient clearance of the medication. 7. Subjects with any other medical condition or laboratory abnormality prior to randomization, which in the opinion of the principal investigator could affect subject safety, preclude evaluation of response, or render unlikely that the subject would complete the study, including but not limited to: a. Subjects with fasting triglycerides >500 mg/dL (5.65 mmol/L) at Visit 1; b. Subjects with uncontrolled diabetes mellitus, as determined by the PI; c. Subjects with renal disease including 1. any history of nephrotic syndrome; 2. chronic renal failure; 3. serum creatinine >1.7 times the upper limit of the reference range (ULRR); d. Subjects with uncontrolled hypothyroidism defined as a TSH >2 times ULRR at Visit 1; e. Subjects with any active hepatobiliary disease, serologic evidence of past or active hepatitis B or hepatitis C infection, or an AST(SGOT) or ALT(SGPT) >2 times the ULRR, alkaline phosphatase >1.5 times ULRR (with elevated liver isoform of alkaline phosphatase), or total bilirubin >1.5 times ULRR at Visit 1. f. Subjects with unexplained serum CK >3 times ULRR at Visit 1 (eg, recent trauma, intramuscular injections, heavy exercise). A repeat CK >3 times ULRR in the absence of condit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to demonstrate the efficacy of fixed combination torcetrapib/atorvastatin in lowering LDL-C, raising levels of HDL-C and favorably altering the levels of other lipid parameters and biomarkers, when compared to atorvastatin alone, in subjects with heFH.;Secondary Objective: Additional objectives include assessing the safety and tolerability of torcetrapib/atorvastatin in subjects with heFH.;Primary end point(s): Percent change in LDL-C and HDL-C from baseline [defined as the arithmetic mean of values from the last run-in period visit, the randomization visit (Week 0, Visit 6)] as measured at the end of the study (EOS) (Week 24, Visit 9) or early termination (ET). | — |
Countries
Denmark, Iceland, Sweden
Outcome results
None listed