Heterozygous Familial Hypercholesterolemia
Conditions
Interventions
Product Name: Anacetrapib
Product Code: MK-0859
Pharmaceutical Form: Tablet
INN or Proposed INN: Anacetrapib
CAS Number: 875446-37-0
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Visit 1 Patients will be eligible to continue to Visit 2 if they meet the following criteria at Visit 1: a. Patient is male or female and =18 and =80 years of age on day of signing informed consent. b. A patient who is of reproductive potential agrees to remain abstinent* or use (or have their partner use) 2 acceptable methods of birth control for the duration of the study. Acceptable methods of birth control are: intrauterine device (IUD), diaphragm with spermicide, condom, vasectomy and hormonal contraception. Note: If oral hormonal contraception is used as one of the methods, hormonal contraceptives must have been used for at least 2 months prior to randomization for patients to be eligible for entry into the study. A female patient who is not of reproductive potential is eligible without requiring the use of contraception. A female patient who is not of reproductive potential is defined as: one who has either 1) reached natural menopause defined as age 46 or older with a) 12 months of spontaneous amenorrhea or b) 6 months of spontaneous menorrhea with serum FSH levels in the postmenopausal range as determined by the central laboratory, 2) 6 weeks post surgical bilateral oophorectomy with or without hysterectomy, or 3) bilateral tubal ligation. *if required locally, two acceptable birth control methods must be used a. Patient has been diagnosed with HeFH defined as: - Documentation of known mutation in a copy of the patient’s LDL receptor, Apo B, or PCSK9 genes OR - In the absence of a genetic diagnosis, a patient must have a documented history of one or more of the following: - Documented history of untreated TC >290 mg/dL (7.5 mmol/L) OR - untreated LDL-C >190 mg/dL (4.9 mmol/L) AND at least ONE of the following: -Documented history or presence of a tendinous or cutaneous xanthoma in the patient or a first-degree relative - Documented history or presence of a mutated copy of the LDL receptor or apo B gene in an adult first-degree relative or biological offspring - Documented history in a first-degree adult relative with untreated TC >350 mg/dL (9.1 mmol/L) or untreated LDL->190 mg/dL (4.9 mmol/L) - Documented history in a first degree relative 280 mg/dL (7.2 mmol/L) or LDL-C >160 mg/dL (4.1 mmol/L) - Documented history in a first degree relative of premature coronary artery disease or sudden death from natural causes prior to age 55 years if male or prior to age 60 years if female b. LDL-C >100 mg/dL (2.59 mmol/L) without documented history of CVD or LDLC >70 mg/dL (1.81 mmol/L) with documented history of CVD c. Patients have been treated with an optimal dose of statin (i.e. one of the following) for at least 6 weeks prior to Visit 1: - simvastatin 40 mg or 80 mg - atorvastatin 20 mg, 40 mg or 80 mg - rosuvastatin 5 mg, 10 mg, 20 mg or 40 mg - pitavastatin 4 mg - lovastatin 80 mg - pravastatin 80 mg Note: Patients are expected to take statin under supervision of their treating physician in accordance with statin product circular in that region. d. Patient
Exclusion criteria
Exclusion criteria: Visit 1 Exclusion Criteria Based on Medical History or Laboratory Abnormalities a. Patient receives treatment with LDL apheresis within 4 weeks of Visit 1 or expected to undergo treatment with LDL aphresis during the course of the study. b. Patient has homozygous familial hypercholesterolemia. c. Patient has severe chronic heart failure defined by New York Heart Association (NYHA) Classes III or IV. d. Patient has uncontrolled cardiac arrhythmias, MI, PCI, CABG, unstable angina, or stroke within 3 months prior to Visit 1. e. Patient has uncontrolled hypertension defined as follows: - Sitting diastolic blood pressure =100 mmHg, or sitting systolic blood pressure =160 mm Hg (non-diabetic patients). OR - Sitting diastolic blood pressure =90 mmHg, or sitting systolic blood pressure =150 mm Hg (diabetic patients). f. Patient has uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins (i.e., secondary causes of hyperlipidemia). Note: Patients with thyroid stimulating hormone (TSH) values outside the central laboratory normal range who are determined to be without symptoms of either hypo- or hyperthyroidism may be allowed in the study if, after review by the Investigator and Project Physician, the patient is deemed not to have clinically significant thyroid hormone excess or deficiency. g. Patient has active or chronic hepatobiliary, hepatic or gall bladder disease. Note: Patients with chronic hepatitis B or C or non-alcoholic steatosis are allowed in the study if ALT and AST are within protocol-specified range listed in the inclusion criteria. h. Patient has eGFR 300 mL within 8 weeks of signing informed consent, or intends to donate 250 mL of blood products or receive blood products within the projected duration of the study. o. Patient has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might confound the results of the study, or interfere with the patient’s participation for the full duration of the study, such that it is not in the best interest of the patient to participate. Exclusion Criteria Based on Concomitant Therapy p. Patient is currently taking medications tha
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. Evaluate the efficacy of adding anacetrapib 100 mg for 52 weeks relative to placebo on plasma concentrations of LDL-C (beta quantification method). 2. Evaluate the safety and tolerability of 52 weeks of treatment with anacetrapib 100 mg. ; Secondary Objective: 1. Evaluate the efficacy of adding anacetrapib 100 mg for 52 weeks relative to placebo on plasma concentrations of HDL-C. 2. Evaluate the efficacy of adding anacetrapib 100 mg for 52 weeks relative to placebo on plasma concentrations of non-HDL-C. 3. Evaluate the efficacy of adding anacetrapib 100 mg for 52 weeks relative to placebo on plasma concentrations of apo B. 4. Evaluate the efficacy of adding anacetrapib 100 mg for 52 weeks relative to placebo on plasma concentrations of apo A-1. 5. Evaluate the efficacy of adding anacetrapib 100 mg for 52 weeks relative to placebo on plasma concentrations of Lp(a). 6. Evaluate the effects of cessation of anacetrapib 100 mg for 12 weeks on LDL-C, HDL-C, non-HDL-C, apo B, apo A-1, and Lp(a). 7. Evaluate the safety and tolerability of anacetrapib 12 weeks after cessation of treatment. ;Primary end point(s): The primary efficacy endopoint is the percentage change from baseline in LDL-C using betaquantification method at Week 52;Timepoint(s) of evaluation of this end point: Multiple timepoints. Please refer to protocol for details. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): HDL-C, non HDL-C, Apo B, ApoA-I, Lp(a), TC, TC/HDL-C, LDL-C/HDL-C, Apo B/Apo A-1, LDL-C/Apo B, Apo E, and lipoprotein sub-fractions.;Timepoint(s) of evaluation of this end point: Multiple timepoints. Please refer to protocol for details. | — |
Countries
Canada, Czech Republic, France, Germany, Netherlands, Norway, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Trial Operations
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Outcome results
None listed