Dyslipidemia
Conditions
Brief summary
The study will evaluate the use of extended release niacin/laropiprant (ERN/LRPT) combination tablets in a primary prevention population currently not taking or eligible for lipid-modifying therapy (LMT); the population will comprise participants with low to moderate risk for coronary heart disease (CHD), low high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) at or below goal level, and normal or mildly elevated triglyceride (TG) levels.
Interventions
DRUGERN/LRPT
ERN/LRPT combination tablets (each containing 1 g of extended release niacin and 20 mg of laropiprant), orally, one tablet once per day for 4 weeks, then 2 tablets once per day for 12 weeks
DRUGplacebo
ERN/LRPT-matched placebo, orally, one tablet once per day for 4 weeks, then 2 tablets once per day for 12 weeks
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* LMT ineligible * Participants must meet the lipid criteria of low to moderate CHD risk as defined by National Cholesterol Education Program Adult Treatment Panel III Framingham Point Scores (NCEP ATP III) * HDL-C \<40 mg/dL (1.03 mmol/L) in males and \<50 mg/dL (1.29 mmol/L) in females * Triglyceride (TG) level \<300 mg/dL (3.39 mmol/L). * Fasting serum glucose (FSG) at Visit 1 AND Visit 2 \<126 mg/dL (\<7 mmol/L) * Hemoglobin A1c (HbA1c) level \<6.5% * Participant willing to use acceptable method of contraception during the study, including the 14-day follow-up period
Exclusion criteria
* History of malignancy ≤5 years prior to signing informed consent, except for adequately-treated basal cell or squamous cell skin cancer or in situ cervical cancer * Participation in a study with an investigational compound (non-lipid-modifying) within 30 days * Pregnant, breastfeeding, or expecting to conceive, or father a child during the study, including the 14-day follow-up period * Consumption of more than 3 alcoholic drinks on any given day or more than 14 drinks per week * Engages in or plans to engage in vigorous exercise or an aggressive diet regimen during the study * Diabetes mellitus, based on medical history, FSG ≥126 mg/dL (7 mmol/L), and HbA1c ≥6.5% * Risk factors for coronary heart disease * Active or chronic hepatobiliary or hepatic disease * Active peptic ulcer disease within 3 months of Visit 1 * History of hypersensitivity or allergic reaction to niacin or niacin-containing products * Episode of gout within 1 year of Visit 1, unless currently stable on allopurinol * Taking an LMT (including statins, bile acid sequestrants, fibrates and niacin \>50 mg as monotherapy or coadministered with other LMTs) * Use of over-the- counter or traditional medicine (e.g. red yeast rice products) for lipid-lowering * Receiving treatment with systemic corticosteroids (unless on stable therapy for at lest 6 weeks for replacement for pituitary/adrenal/hypogonadal disease) * Uncontrolled illness or infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) Averaged Across Week 12 and Week 16 | Baseline and Weeks 12 to 16 | The percentage change from baseline in the participants' LDL-C was to be evaluated and averaged across treatment Week 12 and Week 16. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in HDL-C at Week 16 | Baseline and Week 16 | The percentage change from baseline in the participants' HDL-C was to be evaluated at study Week 16. |
| Percent Change From Baseline in Triglycerides (TG) at Week 16 | Baseline and Week 16 | The percentage change from baseline in participants' TG level was to be evaluated at study Week 16. |
| Percent Change From Baseline in Non-HDL-C at Week 16 | Baseline and Week 16 | The percentage change from baseline in participants' non-HDL-C was to be calculated at study Week 16. |
| Percent Change From Baseline in the Ratio of LDL-C to High-Desity Lipoprotein Cholesterol (HDL-C) at Week 16 | Baseline and Week 16 | The percentage from baseline in the participants' ration of LDL-C to HDL-C was to be evaluated at study Week 16. |
| Percent Change From Baseline in Lipoprotein(a) (LP[a]) at Week 16 | Baseline and Week 16 | The pecentage change from baseline in participants LP(a) was to be evaluated at study Week 16. |
| Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16 | Baseline and Week 16 | The percentage change from baseline in participants' Apo B was to be evaluated at study Week 16. |
| Percent Change From Baseline in Apolipoprotein A-I (Apo A-I) at Week 16 | Baseline and Week 16 | The percentage change from baseline in participants' Apo A-I was to be evaluated at study Week 16. |
| Percent Change From Baseline in the Ratio of Total Cholesterol (TC) to HDL-C at Week 16 | Baseline and Week 16 | The percentage change from baseline in the ratio of TC to HDL-C was to be evaluated at study Week 16. |
Participant flow
Recruitment details
This study took place at 37 centers in 2 countries (29 sites in India and 8 sites in Philippines).
Participants by arm
| Arm | Count |
|---|---|
| ERN/LPRT Extended-release niacin 1 g in combination with laropiprant 20 mg administered orally once daily for 4 weeks, followed by ERN 2 g LPRT 40 mg administered orally once daily for 12 weeks, to South and Southeast Asian participants with low HDL-C and low-to-moderate coronary heart disease risk. | 122 |
| Placebo Matching placebo to ERN/LRPT administered orally once daily for 16 weeks to South and Southeast Asian participants with low HDL-C and low-to-moderate coronary heart disease risk. | 122 |
| Total | 244 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 2 |
| Overall Study | Lost to Follow-up | 4 | 1 |
| Overall Study | Non-compliance with study drug | 2 | 0 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Study terminated by Sponsor | 68 | 75 |
| Overall Study | Withdrawal by Subject | 3 | 5 |
Baseline characteristics
| Characteristic | ERN/LPRT | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 45.8 Years STANDARD_DEVIATION 9.3 | 45.3 Years STANDARD_DEVIATION 10.18 | 45.5 Years STANDARD_DEVIATION 9.73 |
| Sex: Female, Male Female | 93 Participants | 79 Participants | 172 Participants |
| Sex: Female, Male Male | 29 Participants | 43 Participants | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 42 / 120 | 17 / 121 |
| serious Total, serious adverse events | 1 / 120 | 0 / 121 |
Outcome results
Primary
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) Averaged Across Week 12 and Week 16
The percentage change from baseline in the participants' LDL-C was to be evaluated and averaged across treatment Week 12 and Week 16.
Time frame: Baseline and Weeks 12 to 16
Population: Due to early study termination, this efficacy endpoint was not analyzed.
Secondary
Percent Change From Baseline in Apolipoprotein A-I (Apo A-I) at Week 16
The percentage change from baseline in participants' Apo A-I was to be evaluated at study Week 16.
Time frame: Baseline and Week 16
Population: Due to early study termination, this efficacy endpoint was not analyzed.
Secondary
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16
The percentage change from baseline in participants' Apo B was to be evaluated at study Week 16.
Time frame: Baseline and Week 16
Population: Due to early study termination, this efficacy endpoint was not analyzed.
Secondary
Percent Change From Baseline in HDL-C at Week 16
The percentage change from baseline in the participants' HDL-C was to be evaluated at study Week 16.
Time frame: Baseline and Week 16
Population: Due to early study termination, this efficacy endpoint was not analyzed.
Secondary
Percent Change From Baseline in Lipoprotein(a) (LP[a]) at Week 16
The pecentage change from baseline in participants LP(a) was to be evaluated at study Week 16.
Time frame: Baseline and Week 16
Population: Due to early study termination, this efficacy endpoint was not analyzed.
Secondary
Percent Change From Baseline in Non-HDL-C at Week 16
The percentage change from baseline in participants' non-HDL-C was to be calculated at study Week 16.
Time frame: Baseline and Week 16
Population: Due to early study termination, this efficacy endpoint was not analyzed.
Secondary
Percent Change From Baseline in the Ratio of LDL-C to High-Desity Lipoprotein Cholesterol (HDL-C) at Week 16
The percentage from baseline in the participants' ration of LDL-C to HDL-C was to be evaluated at study Week 16.
Time frame: Baseline and Week 16
Population: Due to early study termination, this efficacy endpoint was not analyzed
Secondary
Percent Change From Baseline in the Ratio of Total Cholesterol (TC) to HDL-C at Week 16
The percentage change from baseline in the ratio of TC to HDL-C was to be evaluated at study Week 16.
Time frame: Baseline and Week 16
Population: Due to early study termination, this efficacy endpoint was not analyzed.
Secondary
Percent Change From Baseline in Triglycerides (TG) at Week 16
The percentage change from baseline in participants' TG level was to be evaluated at study Week 16.
Time frame: Baseline and Week 16
Population: Due to early study termination, this efficacy endpoint was not analyzed.