Hypercholesterolemia, Familial
Conditions
Brief summary
This is a 105-week clinical study in patients with heterozygous familial hypercholesterolemia on intensive Low Density Lipoprotein-cholesterol (LDL-C) lowering therapy intended to assess the affects of MK0524A on carotid intima media thickening using ultrasound compared to patients taking placebo. There will be 12 scheduled clinic visits involving review of medical history, physical exam, vital signs, laboratory testing, ultrasound imaging, and electrocardiograms.
Interventions
DRUGComparator: niacin (+) laropiprant (MK0524A)
niacin (+) laropiprant (2 g) po qd.
DRUGComparator: placebo
niacin (+) laropiprant (2 g) placebo po qd.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Patients who are 18 to 70 years of age with Heterozygous Familial Hypercholesterolemia and a LDL-C greater than or equal to 100mg/dL and triglycerides less than or equal to 400mg/dL at Visit 1 while on a stable dose of intensive LDL-C lowering therapy
Exclusion criteria
* A condition which, in the opinion of the investigator, might pose a risk to the patient or interfere with participating in the study * Patients with less than 80% drug study compliance * Patients with chronic medical conditions known to influence serum lipids or lipoproteins or significantly affect the ultrasound acoustic window * Patients with unstable dose of medications * Pregnant or lactating women, or women intending to become pregnant are excluded * Patient with diabetes mellitus that is poorly controlled, or is taking new or recently adjusted antidiabetic pharmacotherapy (with the exception of +/- 10 units of insulin) * Patients with the following conditions: high grade stenosis (greater than 75%) of the carotid artery, chronic heart failure, uncontrolled/unstable cardiac arrhythmias, unstable hypertension, active or chronic hepatobiliary or hepatic disease, HIV positive, episode of gout (within 1 year)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Carotid Intima Media Thickness | after 96 weeks of postrandomization treatment | change in mean carotid intima media thickness defined as a composite measure of the left and right common, bulb, and internal carotid artery. |
Secondary
| Measure | Time frame |
|---|---|
| Change in Lipid Profile | after 96 weeks of postrandomization treatment |
Participant flow
Pre-assignment details
There was an MK0524A active run-in period prior to randomization. Per protocol, patients were scheduled to receive MK0524A 1g orally once daily for 4 weeks. The MK0524A dose was then increased to 2g (2x 1g tablets), once daily, for an additional 4 weeks prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| MK0524A, 2 g (Postrandomization Period) Patients who were randomized to MK0524A, 2 g (oral administration) once daily. | 214 |
| Placebo (Postrandomization Period) Patients who were randomized to placebo | 218 |
| Total | 432 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| MK0524A Active Run-In, Pre-randomization | Adverse Event | 120 | 0 | 0 |
| MK0524A Active Run-In, Pre-randomization | Certified Sonographer Not Available | 2 | 0 | 0 |
| MK0524A Active Run-In, Pre-randomization | Lost to Follow-up | 1 | 0 | 0 |
| MK0524A Active Run-In, Pre-randomization | Not cIMT eligible at Visit 3 | 340 | 0 | 0 |
| MK0524A Active Run-In, Pre-randomization | Patient Unable to Complete cIMT Scan | 1 | 0 | 0 |
| MK0524A Active Run-In, Pre-randomization | Trial Termination | 16 | 0 | 0 |
| MK0524A Active Run-In, Pre-randomization | Withdrawal by Subject | 24 | 0 | 0 |
| Post-randomization Period | Adverse Event | 0 | 23 | 7 |
| Post-randomization Period | Lost to Follow-up | 0 | 2 | 1 |
| Post-randomization Period | Patient Randomized in Error | 0 | 0 | 1 |
| Post-randomization Period | Protocol Violation | 0 | 1 | 0 |
| Post-randomization Period | Trial Termination | 0 | 180 | 204 |
| Post-randomization Period | Withdrawal by Subject | 0 | 8 | 6 |
Baseline characteristics
| Characteristic | MK0524A, 2 g (Postrandomization Period) | Placebo (Postrandomization Period) | Total |
|---|---|---|---|
| Age, Continuous | 53.1 years STANDARD_DEVIATION 8.94 | 54.5 years STANDARD_DEVIATION 8.22 | 53.8 years STANDARD_DEVIATION 8.6 |
| Sex: Female, Male Female | 76 Participants | 82 Participants | 158 Participants |
| Sex: Female, Male Male | 138 Participants | 136 Participants | 274 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 395 / — | 74 / — | 54 / — |
| serious Total, serious adverse events | 10 / — | 5 / — | 8 / — |
Outcome results
Primary
Change in Mean Carotid Intima Media Thickness
change in mean carotid intima media thickness defined as a composite measure of the left and right common, bulb, and internal carotid artery.
Time frame: after 96 weeks of postrandomization treatment
Population: study prematurely terminated, no efficacy analyses were performed
Secondary
Change in Lipid Profile
Time frame: after 96 weeks of postrandomization treatment
Population: study prematurely terminated, no efficacy analyses were performed