Phase 3, Multi-center, double-blind, randomized, parallel group study of the efficacy, safety, and tolerability of fixed combination torcetrapib (CP-529,414)/Atorvastatin administered orally, once daily (QD) for six months, compared with maximally tolerated Atorvastatin therapy alone, in subjects with heterozygous familial hypercholesterolemia. - N/A

Conditions: Heterozygous Familial Hypercholesterolemia
MedDRA version: 7.1Level: LLTClassification code 10057079

Registration Number: EUCTR2004-004269-14-SE

Lead Sponsor: Pfizer AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 360

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 <400 mg/dL (4.52 mmol/L), the subject must meet one of criteria (a) to (e). (Please see Table 1 in the protocol).

a. The subject meets the first degree relative LDL C criteria (see Table 1) in the absence of lipid lowering treatment and the subject has tendinous xanthomas, or

b. The subject is an adult relative of previously diagnosed FH subject (homozygous FH or heFH by genotyping or heFH by the clinical criteria as outlined here) and the subject meets the appropriate first, second or third degree relative LDL C criteria for first, second or third degree relatives, or

c. The subject meets the first degree relative LDL C criteria and the subject has 2 or more first degree relatives who meet the general population LDL C criteria for general population in the absence of lipid lowering treatment, or

d. The subject meets the 100% probability criteria in the absence of lipid lowering treatment and the subject has a relative who meets the appropriate first, second or third degree criteria for LDL C or the subject has a pediatric relative (<18 years of age) who meets the appropriate first, second or third degree relative LDL C or TC criteria, or

e. The subject meets the general population criteria for LDL C and the subject has a first degree relative <20 years old who meets first-degree relative LDL C or TC criteria.

NOTE: Diagnostic criteria for each subject must be noted in source documents.
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

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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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).

Secondary Outcome Measures