Mixed Hyperlipidemia, Primary Hypercholesterolemia
Conditions
Brief summary
The purpose of this study is to evaluate the effect of SCH 900271 compared to placebo on the reduction of low-density lipoprotein cholesterol (LDL-C) from baseline to 8 weeks of treatment in participants with primary hypercholesterolemia (familial and nonfamilial) or mixed hyperlipidemia. The study will also evaluate the effect of SCH 900271 on non-high density lipoprotein cholesterol (non-HDL-C) and various other lipids and lipoproteins. The safety of SCH 900271 in this participant population will also be evaluated.
Interventions
DRUGSCH 900271 15mg
oral tablets; SCH 900271 - 15 mg taken once daily for 8 weeks
DRUGSCH 900271
oral tablets; SCH 900271 10 mg taken once daily for 8 weeks
DRUGPlacebo
oral tablets; placebo administered once daily during the 5-week single-blind placebo run-in and diet stabilization period and during the 8 week double-blind treatment period.
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Adults of either sex 18 to 75 years of age, inclusive, with a diagnosis of primary hypercholesterolemia (familial and nonfamilial) or mixed hyperlipidemia (increased LDL-C and triglycerides \[TG\]) * must be free of any clinically significant disease, other than primary hypercholesterolemia or mixed hyperlipidemia that would knowingly interfere with study evaluations * must be willing to adhere to dietary recommendations, protocol requirements, and provide written informed consent
Exclusion criteria
The participant will be excluded from entry if ANY of the criteria listed below are met: * use of any investigational drug within 30 days of study entry * female of childbearing potential or lactating * postmenopausal (or perimenopausal) woman who is currently experiencing hot flashes (e.g. within 30 days of study entry * homozygous familial hypercholesterolemia * congestive heart failure New York Heart Association (NYHA) Class III or IV * uncontrolled hypertension on or off therapy * cardiac arrhythmia requiring medication * clinical atherosclerotic disease that confers high risk for coronary heart disease (CHD) events (e.g. clinical CHD, symptomatic carotid artery disease, peripheral arterial disease, abdominal aortic aneurysm) * Type 1 Diabetes Mellitus * Type 2 Diabetes Mellitus * history of mental instability, drug/alcohol abuse or who has been treated or is being treated for severe psychiatric illness, which in the opinion of the investigator, may interfere with optimal participation in the study * gastrointestinal ulcer within 3 months of study entry * history of coagulopathy * history of gout * known active or chronic hepatic or biliary disease. * known significant impairment of renal function, dysproteinemia, nephrotic syndrome, or other renal disease * body mass index \>40 kg/m\^2 * taking non-steroidal anti-inflammatory drugs (NSAIDS) (acetaminophen and cyclooxygenase-2 \[COX-2\] inhibitors are allowed) * taking more than 100 mg aspirin per day * being treated with corticosteroids (oral, intramuscular, or intravascular) * more than 3 alcoholic beverages per day or its equivalent (one drink equals 1.5 ounces of 80 proof liquor or equivalent) during study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Direct LDL-C at Week 8 | Baseline and Week 8 | The percentage change from baseline in the participants' LDL-C was to be evaluated at study Week 8. Standard error presented below is least squares standard error. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Direct Non-HDL-C at Week 8 | Baseline and Week 8 | The percentage change from baseline in the participants' non-HDL-C was to be evaluated at study Week 8. Standard error presented below is least squares standard error. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SCH 900271 15 mg Participants receive SCH 900271 15 mg tablet and placebo tablet once daily in the morning with water in a fasted state for 8 weeks | 104 |
| SCH 900271 10 mg Participants receive SCH 900271 10 mg tablet and placebo tablet once daily in the morning with water in a fasted state for 8 weeks | 105 |
| SCH 900271 5 mg Participants receive SCH 900271 5 mg tablet and placebo tablet once daily in the morning with water in a fasted state for 8 weeks | 104 |
| SCH 900271 2.5 mg Participants receive SCH 900271 2.5 mg tablet and placebo tablet once daily in the morning with water in a fasted state for 8 weeks | 104 |
| SCH 900271 1 mg Participants receive SCH 900271 1 mg tablet and placebo tablet once daily in the morning with water in a fasted state for 8 weeks | 105 |
| Placebo Participants receive two placebo tablets once daily in the morning with water in a fasted state for 8 weeks | 97 |
| Total | 619 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 10 | 15 | 5 | 1 | 4 | 0 |
| Overall Study | Did not meet protocol eligibility | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | SCH 900271 15 mg | SCH 900271 10 mg | SCH 900271 5 mg | SCH 900271 2.5 mg | SCH 900271 1 mg | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 57.5 Years STANDARD_DEVIATION 9.5 | 56.0 Years STANDARD_DEVIATION 10.8 | 56.1 Years STANDARD_DEVIATION 10.3 | 56.5 Years STANDARD_DEVIATION 8.7 | 57.5 Years STANDARD_DEVIATION 9.4 | 55.2 Years STANDARD_DEVIATION 9.5 | 56.5 Years STANDARD_DEVIATION 9.7 |
| Sex: Female, Male Female | 51 Participants | 51 Participants | 49 Participants | 50 Participants | 52 Participants | 47 Participants | 300 Participants |
| Sex: Female, Male Male | 53 Participants | 54 Participants | 55 Participants | 54 Participants | 53 Participants | 50 Participants | 319 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 41 / 103 | 41 / 105 | 19 / 104 | 8 / 104 | 14 / 105 | 5 / 97 |
| serious Total, serious adverse events | 4 / 103 | 1 / 105 | 3 / 104 | 0 / 104 | 0 / 105 | 0 / 97 |
Outcome results
Primary
Change From Baseline in Direct LDL-C at Week 8
The percentage change from baseline in the participants' LDL-C was to be evaluated at study Week 8. Standard error presented below is least squares standard error.
Time frame: Baseline and Week 8
Population: Intent-to-treat population defined as all participants who receive randomized treatment assignment, and have a baseline and at least one post-baseline LDL-C determination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SCH 900271 15 mg | Change From Baseline in Direct LDL-C at Week 8 | -2.0 Percent change | Standard Error 1.3 |
| SCH 900271 10 mg | Change From Baseline in Direct LDL-C at Week 8 | -1.5 Percent change | Standard Error 1.3 |
| SCH 900271 5 mg | Change From Baseline in Direct LDL-C at Week 8 | -4.2 Percent change | Standard Error 1.3 |
| SCH 900271 2.5 mg | Change From Baseline in Direct LDL-C at Week 8 | 0.2 Percent change | Standard Error 1.3 |
| SCH 900271 1 mg | Change From Baseline in Direct LDL-C at Week 8 | 1.2 Percent change | Standard Error 1.3 |
| Placebo | Change From Baseline in Direct LDL-C at Week 8 | 1.5 Percent change | Standard Error 1.4 |
p-value: 0.0695% CI: [-7.2, 0.2]ANOVA
p-value: 0.195% CI: [-6.7, 0.6]ANOVA
Comparison: LS means and LS standard errors based on ANOVA model extracting effects due to treatment, gender, and primary diagnosis.p-value: <0.0195% CI: [-9.4, -2]ANOVA
p-value: 0.4895% CI: [-5, 2.4]ANOVA
p-value: 0.8595% CI: [-4, 3.3]ANOVA
Secondary
Change From Baseline in Direct Non-HDL-C at Week 8
The percentage change from baseline in the participants' non-HDL-C was to be evaluated at study Week 8. Standard error presented below is least squares standard error.
Time frame: Baseline and Week 8
Population: Intent-to-treat population defined as all participants who receive randomized treatment assignment and have a baseline and at least one post-baseline non-HDL-C determination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SCH 900271 15 mg | Change From Baseline in Direct Non-HDL-C at Week 8 | -2.1 Percent change | Standard Error 1.2 |
| SCH 900271 10 mg | Change From Baseline in Direct Non-HDL-C at Week 8 | -2.7 Percent change | Standard Error 1.2 |
| SCH 900271 5 mg | Change From Baseline in Direct Non-HDL-C at Week 8 | -3.5 Percent change | Standard Error 1.2 |
| SCH 900271 2.5 mg | Change From Baseline in Direct Non-HDL-C at Week 8 | -0.5 Percent change | Standard Error 1.3 |
| SCH 900271 1 mg | Change From Baseline in Direct Non-HDL-C at Week 8 | 1.6 Percent change | Standard Error 1.2 |
| Placebo | Change From Baseline in Direct Non-HDL-C at Week 8 | 0.9 Percent change | Standard Error 1.3 |
p-value: 0.0995% CI: [-6.5, 0.4]ANOVA
p-value: 0.0495% CI: [-7.1, -0.2]ANOVA
p-value: 0.0195% CI: [-7.9, -1]ANOVA
p-value: 0.4195% CI: [-4.9, 2]ANOVA
p-value: 0.6895% CI: [-2.7, 4.2]ANOVA