Dyslipidemia
Conditions
Brief summary
This study will evaluate the lipid-modifying effect and tolerability of MK1903 when compared to placebo in patients with dyslipidemia who are not on a statin or other lipid-modifying therapy.
Interventions
DRUGMK1903
Three 50 mg capsules MK1903 by mouth every 8 hours for 4 weeks. All participants will receive placebo for a 2 week run-in period.
DRUGComparator: Placebo
Three 50 mg capsules placebo to MK1903 every 8 hours for 4 weeks. All participants will receive placebo for a 2 week run-in 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 70 Years
Healthy volunteers
No
Inclusion criteria
* Participant is not on a statin or other lipid-modifying therapy * Low or moderate risk participant * Male participants, and female participants not of reproductive potential
Exclusion criteria
* Female participant of reproductive potential * Participant is pregnant, breastfeeding, or expecting to conceive during the study * Participant has history of cancer within 5 years of study (except certain types of skin and cervical cancer) * Participant is a user of recreational or illicit drugs or has a recent history of drug and/or alcohol abuse * Participant has donated or received blood within 8 weeks of study start or intends to give/receive blood during the study * Participant consumes more than 3 alcoholic drinks per day or more than 14 alcoholic drinks per week * Participant is currently experiencing menopausal hot flashes * Participant currently engages in vigorous exercise or an aggressive diet regimen * Participant is at high risk for heart conditions * Participant has Type 1 or Type 2 diabetes mellitus * Participant has poorly controlled cardiac arrhythmias * Participant has a history of stroke or other hemorrhage * Participant has poorly controlled high blood pressure * Participant has a thyroid condition or other endocrine/metabolic disease that would affect serum lipids * Participant has a disease of the kidney or liver * Participant has an ulcer within 3 months of screening * Participant is Human Immunodeficiency Virus (HIV) positive * Participant is taking cyclical hormonal contraceptives or non-continuous hormone replacement therapy * Participant is taking or has taken an Organic Anion Transporter (OAT1/3) inhibitor/substrate within 3 days of screening * Participant has taken an anti-obesity medication within 3 months of screening * Participant is taking coumarins * Participant is taking Non-steroidal Anti-inflammatory Drugs (NSAIDs) (acetaminophen and Cyclooxygenase-2 (COX-2) inhibitors are allowed) * Participant is taking more than 100 mg aspirin per day * Participant is being treated with oral, intravenous, or injected corticosteroids or anabolic agents
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) (mg/dL) | Baseline and Week 4 |
| Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) (mg/dL) | Baseline and Week 4 |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in Triglycerides (mg/dL) | Baseline and 4 Weeks |
Participant flow
Recruitment details
Participants were recruited at 26 sites in 8 different countries from February 2009 to August 2009.
Pre-assignment details
Participants had a 2-week placebo run-in period prior to randomization. 402 participants were screened of which 211 participants were excluded (194 participants did not meet inclusion criteria, 15 participants withdrew, 1 participant was lost to follow-up and 1 participant had an adverse event).
Participants by arm
| Arm | Count |
|---|---|
| MK1903 Three 50 mg capsules MK1903 by mouth every 8 hours for 4 weeks. All participants will receive placebo for a 2 week run-in period. | 116 |
| Placebo Three 50 mg capsules placebo to MK1903 every 8 hours for 4 weeks. All participants will receive placebo for a 2 week run-in period. | 75 |
| Total | 191 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 21 | 3 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | MK1903 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 52.6 years STANDARD_DEVIATION 10.4 | 50.9 years STANDARD_DEVIATION 11.1 | 51.9 years STANDARD_DEVIATION 10.7 |
| Body Mass Index | 28.7 kg/m^2 STANDARD_DEVIATION 5 | 28.7 kg/m^2 STANDARD_DEVIATION 4.5 | 28.7 kg/m^2 STANDARD_DEVIATION 4.8 |
| Body Mass Index (BMI) Category < 25 | 20 participants | 14 participants | 34 participants |
| Body Mass Index (BMI) Category 25 - 30 | 65 participants | 42 participants | 107 participants |
| Body Mass Index (BMI) Category 31 - 39 | 28 participants | 17 participants | 45 participants |
| Body Mass Index (BMI) Category => 40 | 3 participants | 2 participants | 5 participants |
| Coronary Heart Disease (CHD) Risk Category Low Risk | 90 Participants | 59 Participants | 149 Participants |
| Coronary Heart Disease (CHD) Risk Category Multiple Risk | 26 Participants | 16 Participants | 42 Participants |
| Diastolic Blood Pressure | 77.9 mm Hg STANDARD_DEVIATION 8.9 | 77.1 mm Hg STANDARD_DEVIATION 9 | 77.6 mm Hg STANDARD_DEVIATION 8.9 |
| Glycemic Status Impaired Fasting Glucose ( ≥ 100 & ≤ 125 mg/dL) | 36 Participants | 21 Participants | 57 Participants |
| Glycemic Status Normal (< 100 mg/dL) | 79 Participants | 53 Participants | 132 Participants |
| Glycemic Status Others (> 125 mg/dL) | 1 Participants | 1 Participants | 2 Participants |
| Height | 168.3 Centimeter STANDARD_DEVIATION 10.5 | 167.9 Centimeter STANDARD_DEVIATION 10.2 | 168.2 Centimeter STANDARD_DEVIATION 10.3 |
| Prior Niacin History No | 106 Participants | 64 Participants | 170 Participants |
| Prior Niacin History Yes | 10 Participants | 11 Participants | 21 Participants |
| Pulse | 67.8 beats/minute STANDARD_DEVIATION 8.8 | 68.5 beats/minute STANDARD_DEVIATION 8.9 | 68.1 beats/minute STANDARD_DEVIATION 8.8 |
| Region Ex-United States | 60 participants | 37 participants | 97 participants |
| Region United States | 56 participants | 38 participants | 94 participants |
| Sex: Female, Male Female | 45 Participants | 28 Participants | 73 Participants |
| Sex: Female, Male Male | 71 Participants | 47 Participants | 118 Participants |
| Systolic Blood Pressure | 122.9 mm Hg STANDARD_DEVIATION 13.6 | 122.3 mm Hg STANDARD_DEVIATION 13.5 | 122.7 mm Hg STANDARD_DEVIATION 13.5 |
| Weight | 81.9 Kilogram STANDARD_DEVIATION 17.9 | 81.6 Kilogram STANDARD_DEVIATION 17.5 | 81.7 Kilogram STANDARD_DEVIATION 17.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 76 / 116 | 26 / 75 |
| serious Total, serious adverse events | 0 / 116 | 0 / 75 |
Outcome results
Primary
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) (mg/dL)
Time frame: Baseline and Week 4
Population: The Full Analysis Set (FAS) population served as the primary population for the analysis of efficacy data. FAS is a subset of all randomized participants with following reasons for exclusion: 1. failure to receive at least 1 dose of study treatment 2. lack of any post-randomization endpoint data subsequent to at least 1 dose of study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK1903 | Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) (mg/dL) | 6.0 Percent Change | Standard Deviation 13 |
| Placebo | Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) (mg/dL) | 0.7 Percent Change | Standard Deviation 11.7 |
Comparison: For the analysis of percent change from baseline in LDL-C at study endpoint, a Longitudinal Analysis of Covariance (ANCOVA) method was used. The repeated measures model included terms for treatment, time (Day 15, 29), and the interaction of time-by-treatment. The analysis model also adjusted for baseline, baseline-by-time interaction, region and gender.p-value: 0.01395% CI: [1, 8.1]Mixed Models Analysis
Primary
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) (mg/dL)
Time frame: Baseline and Week 4
Population: The Full Analysis Set (FAS) population served as the primary population for the analysis of efficacy data. FAS is a subset of all randomized participants with following reasons for exclusion: 1. failure to receive at least 1 dose of study treatment 2. lack of any post-randomization endpoint data subsequent to at least 1 dose of study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK1903 | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) (mg/dL) | -0.3 Percent Change | Standard Deviation 16.3 |
| Placebo | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) (mg/dL) | -1.5 Percent Change | Standard Deviation 12.9 |
Comparison: For the analysis of percent change from baseline in LDL-C at study endpoint, a Longitudinal Analysis of Covariance (ANCOVA) method was used. The repeated measures model included terms for treatment, time (Day 15, 29), and the interaction of time-by-treatment. The analysis model also adjusted for baseline, baseline-by-time interaction, region and gender.p-value: 0.92695% CI: [-3.9, 4.3]Mixed Models Analysis
Secondary
Percent Change From Baseline in Triglycerides (mg/dL)
Time frame: Baseline and 4 Weeks
Population: The Full Analysis Set (FAS) population served as the primary population for the analysis of efficacy data. FAS is a subset of all randomized participants with following reasons for exclusion: 1. failure to receive at least 1 dose of study treatment 2. lack of any post-randomization endpoint data subsequent to at least 1 dose of study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK1903 | Percent Change From Baseline in Triglycerides (mg/dL) | -13.2 Percent Change | Standard Deviation 32.7 |
| Placebo | Percent Change From Baseline in Triglycerides (mg/dL) | -2.0 Percent Change | Standard Deviation 39.5 |
Comparison: Triglycerides was analyzed by non-parametric methods with terms for treatment, gender and region. Specifically, the analysis of variance (ANOVA) model was applied to the Tukey's normal scores of the percent change from baseline. The estimate of the difference in medians between MK1903 and the placebo groups utilizing the Hodges-Lehmann estimate and a distribution-free 95% CI for the difference based on Wilcoxon's rank sum test was provided.p-value: 0.0295% CI: [-18.9, -1.9]Wilcoxon's Rank Sum Test