Dyslipidemia
Conditions
Brief summary
This study will evaluate the definitive bioequivalence of tablets of MK0524A (1000 mg Extended Release (ER) Niacin/ 20 mg laropiprant) from two sources.
Interventions
DRUGniacin (+) laropiprant (Source 1)
Single dose of MK0524A (ER Niacin/laropiprant 1000/20 mg) from Source 1 in one of two treatment periods.
DRUGComparator: niacin (+) laropiprant (Source 2)
Single dose of MK0524A (ER Niacin/laropiprant 1000/20 mg) from Source 2 in one of two treatment periods.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject is in good health * Subject is willing to follow all study guidelines
Exclusion criteria
* Subject has or has a history of any disease or condition that might confound the results of the study or make participation unsafe
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of Nicotinuric Acid | Predose and up to 24 hours postdose | Measure of rate of absorption of ER niacin |
| Total Amount of Urinary Excretion of Niacin and Its Metabolites | Predose and up to 96 hours postdose | Measure of extent of absorption of ER niacin |
| Area Under Curve (AUC 0-infinity) of Laropiprant | Predose and up to 48 hours postdose | Measure of extent of absorption of laropiprant |
| Maximum Concentration (Cmax) of Laropiprant | Predose and up to 48 hours postdose | Measure of rate of absorption of laropiprant |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Includes all participants from Both treatment groups; MK0524A Phase III tablet and MK0524A New Site tablet | 188 |
| Total | 188 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 2 | Adverse Event | 1 | 0 |
| Period 2 | Lost to Follow-up | 0 | 3 |
| Period 2 | Withdrawal by Subject | 7 | 6 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 38.5 years FULL_RANGE 1 |
| Height | 166.6 Centimeters |
| Sex: Female, Male Female | 92 Participants |
| Sex: Female, Male Male | 96 Participants |
| Weight | 71.6 Kilograms |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 98 / 188 | 100 / 188 |
| serious Total, serious adverse events | 0 / 188 | 2 / 188 |
Outcome results
Primary
Area Under Curve (AUC 0-infinity) of Laropiprant
Measure of extent of absorption of laropiprant
Time frame: Predose and up to 48 hours postdose
Population: A linear mixed effect model was used to analyze laropiprant AUC0-infinity and uses data available from at least one treatment period. 166 subjects had data from the treatment of MK0524A New Site Tablet, and 167 subjects had data from the treatment of MK0524A Phase III Tablet
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| MK0524A New Site Tablet | Area Under Curve (AUC 0-infinity) of Laropiprant | 6.36 Micro Molar times Hour | Standard Deviation 3.01 |
| MK0524A Phase III Tablet | Area Under Curve (AUC 0-infinity) of Laropiprant | 6.37 Micro Molar times Hour | Standard Deviation 2.66 |
Comparison: Group B: MK0524A (1000 mg ER Niacin/20 mg MK-laropiprant) tablet from new manufacturing site (Source 2)~Group A: MK0524A (1000 mg ER Niacin/20 mg MK-laropiprant) Phase III tablet (Source 1)95% CI: [0.95, 1.05]
Primary
Maximum Concentration (Cmax) of Laropiprant
Measure of rate of absorption of laropiprant
Time frame: Predose and up to 48 hours postdose
Population: A linear mixed effect model was used to analyze laropiprant Cmax and uses data available from at least one treatment period. 166 subjects had data from the treatment of MK0524A New Site Tablet, and 167 subjects had data from the treatment of MK0524A Phase III Tablet.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| MK0524A New Site Tablet | Maximum Concentration (Cmax) of Laropiprant | 0.988 micro Molar | Standard Deviation 0.563 |
| MK0524A Phase III Tablet | Maximum Concentration (Cmax) of Laropiprant | 0.975 micro Molar | Standard Deviation 0.466 |
Comparison: MK0524A (1000 mg ER Niacin/20 mg MK-laropiprant) tablet from new manufacturing site (Source 2)~MK0524A (1000 mg ER Niacin/20 mg MK-laropiprant) Phase III tablet (Source 1)95% CI: [0.96, 1.09]
Primary
Maximum Plasma Concentration (Cmax) of Nicotinuric Acid
Measure of rate of absorption of ER niacin
Time frame: Predose and up to 24 hours postdose
Population: The Hodges-Lehmann estimator was used to analyze nicotinuric acid Cmax and uses only subjects with data available on both treatment periods. 188 subjects were randomized,17 subjects discontinued, 26 subjects were inadvertently overdosed with 5 tablets of MK0524A 1000 mg/20 mg, reducing the available subject population for analysis to 145.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MK0524A New Site Tablet | Maximum Plasma Concentration (Cmax) of Nicotinuric Acid | 1190 ng/mL |
| MK0524A Phase III Tablet | Maximum Plasma Concentration (Cmax) of Nicotinuric Acid | 1260 ng/mL |
Comparison: MK0524A (1000 mg ER Niacin/20 mg MK-laropiprant) tablet from new manufacturing site (Source 2)~MK0524A (1000 mg ER Niacin/20 mg MK-laropiprant) Phase III tablet (Source 1)90% CI: [0.93, 1.03]
Primary
Total Amount of Urinary Excretion of Niacin and Its Metabolites
Measure of extent of absorption of ER niacin
Time frame: Predose and up to 96 hours postdose
Population: A linear mixed effect model was used to analyze total amount of urinary excretion of niacin and its metabolite and uses data available from at least one treatment period. 157 subjects had data from the treatment of MK0524A New Site Tablet, and 161 subjects had data from the treatment of MK0524A Phase III Tablet
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| MK0524A New Site Tablet | Total Amount of Urinary Excretion of Niacin and Its Metabolites | 5280 micro mole | Standard Deviation 1894 |
| MK0524A Phase III Tablet | Total Amount of Urinary Excretion of Niacin and Its Metabolites | 5470 micro mole | Standard Deviation 1330 |
Comparison: MK0524A (1000 mg ER Niacin/20 mg MK-laropiprant) tablet from new manufacturing site (Source 2)~MK0524A (1000 mg ER Niacin/20 mg MK-laropiprant) Phase III tablet (Source 1)90% CI: [0.89, 0.98]