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MK0524B Bioequivalence Study (0524B-070)

An Open-Label, Definitive Bioequivalence Study to Compare the Pharmacokinetics of the Simvastatin, Nicotinic Acid, and MK0524 (Laropiprant) Components of a Formulation of MK0524B With That of Zocor™ and MK0524A Tablets

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00943124
Enrollment
220
Registered
2009-07-22
Start date
2007-07-31
Completion date
2007-08-31
Last updated
2015-06-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Dyslipidemia

Brief summary

This study will evaluate: 1. the bioequivalence of simvastatin and simvastatin acid following dose of simvastatin (ZOCOR™) given together with one tablet of MK0524A or as a component of the triple combination tablet MK0524B. 2. the bioequivalence of laropiprant and ER niacin when administered as the triple combination tablet MK0524B or as the double combination tablet MK0524A given together with simvastatin.

Interventions

DRUGMK0524B (ER niacin (+) laropiprant (+) simvastatin)

Single dose of MK0524B (ER niacin 900 mg/ laropiprant 20 mg/ simvastatin 20 mg) in one of two treatment periods.

DRUGMK0524A (ER niacin + laropiprant)

Single dose of MK0524A (ER niacin 1000 mg/ laropiprant 20 mg) in one of two treatment periods.

DRUGSimvastatin

Single dose simvastatin (Zocor™) 20 mg in one of two treatment periods.

Sponsors

Merck Sharp & Dohme LLC
Lead SponsorINDUSTRY

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 a nonsmoker * Subject is willing to follow the study guidelines

Exclusion criteria

* Subject has or has a history of any illness that might confound the results of the study or make participation in the study unsafe for the subject

Design outcomes

Primary

MeasureTime frameDescription
Plasma Area Under the Curve (AUC(0 to 48hr)) for Simvastatin AcidThrough 48 Hours Post DosePlasma Area Under the Curve of simvastatin acid, the active metabolite of simvastatin
Peak Plasma Concentration (Cmax) of Simvastatin Acid48 Hours Post DosePeak Plasma Concentration (Cmax) for Simvastatin Acid, the active metabolite of simvastatin
Plasma Area Under the Curve (AUC(0 to 48 Hour)) for SimvastatinThrough 48 Hours Post DosePlasma Area Under the Curve of simvastatin
Peak Plasma Concentration (Cmax) of Simvastatin48 Hours Post Dose—
Plasma Area Under the Curve (AUC(0 to Infinity)) for Laropiprant48 Hours Post DosePlasma Area Under the Curve of Laropiprant
Peak Plasma Concentration (Cmax) of Laropiprant48 Hours Post Dose—
Peak Plasma Concentration (Cmax) of Nicotinuric Acid24 Hours Post DosePeak Plasma Concentration (Cmax) for Nicotinuric Acid, one of the active metabolites of Niacin
Total Urinary Excretion of Niacin and Its Metabolites96 Hours Post Dose—

Participant flow

Participants by arm

ArmCount
Overall Study Population
All randomized patients
220
Total220

Withdrawals & dropouts

PeriodReasonFG000FG001
Period 1Did Not Follow Study Procedures10
Period 1Personal Reasons01
Period 1Withdrawal by Subject11

Baseline characteristics

CharacteristicOverall Study Population
Age, Continuous35.11 years
Height169.58 Centimeters
Sex: Female, Male
Female
92 Participants
Sex: Female, Male
Male
128 Participants
Weight72.99 Kilograms

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
61 / 22058 / 220
serious
Total, serious adverse events
0 / 2200 / 220

Outcome results

Primary

Peak Plasma Concentration (Cmax) of Laropiprant

Time frame: 48 Hours Post Dose

Population: Two hundred-twenty (220) subjects were enrolled in this study. Due to early dropout (N=4), data from a total of 217 and 216 subjects were available for laropiprant Cmax analysis for MK0524B and Simvastatin + MK0524A, respectively

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
MK0524BPeak Plasma Concentration (Cmax) of Laropiprant1030 nmol/LStandard Deviation 642
Simvastatin + MK0524APeak Plasma Concentration (Cmax) of Laropiprant953 nmol/LStandard Deviation 542
Comparison: Least-Squares Mean Ratio (Fixed Dose Combination (FDC)/Co-administration)90% CI: [1.02, 1.14]
Primary

Peak Plasma Concentration (Cmax) of Nicotinuric Acid

Peak Plasma Concentration (Cmax) for Nicotinuric Acid, one of the active metabolites of Niacin

Time frame: 24 Hours Post Dose

Population: Two hundred-twenty (220) subjects were enrolled in this study. Due to early dropout (N=4) and missing samples (N=1), data from a total of 215 and 216 subjects available for plasma nicotinuric acid analysis for MK0524B and Simvastatin + MK0524A, respectively.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
MK0524BPeak Plasma Concentration (Cmax) of Nicotinuric Acid620 ng/mLStandard Deviation 536
Simvastatin + MK0524APeak Plasma Concentration (Cmax) of Nicotinuric Acid807 ng/mLStandard Deviation 469
Comparison: Least-Squares Mean Ratio (Fixed Dose Combination (FDC)/Co-administration)90% CI: [0.72, 0.82]
Primary

Peak Plasma Concentration (Cmax) of Simvastatin

Time frame: 48 Hours Post Dose

Population: Two hundred-twenty (220) subjects were enrolled in this study. Due to early dropout (N=4), mis-handling of plasma samples (N=2) and the limitation of the assay (N=10), data from a total of 209 and 210 subjects were available for simvastatin Cmax analysis for MK0524B and Simvastatin + MK0524A, respectively.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
MK0524BPeak Plasma Concentration (Cmax) of Simvastatin5.81 ng/mLStandard Deviation 4.31
Simvastatin + MK0524APeak Plasma Concentration (Cmax) of Simvastatin6.33 ng/mLStandard Deviation 4.64
Comparison: Least-Squares Mean Ratio (Fixed Dose Combination (FDC)/Co-administration)90% CI: [0.87, 0.97]
Primary

Peak Plasma Concentration (Cmax) of Simvastatin Acid

Peak Plasma Concentration (Cmax) for Simvastatin Acid, the active metabolite of simvastatin

Time frame: 48 Hours Post Dose

Population: Two hundred-twenty (220) subjects were enrolled in this study. Due to early dropout (N=4), mis-handling of plasma samples (N=10) and the limitation of the assay (N=10), data from a total of 201 and 202 subjects were available for simvastatin acid Cmax analysis for MK0524B and Simvastatin + MK0524A, respectively.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
MK0524BPeak Plasma Concentration (Cmax) of Simvastatin Acid1.016 ng/mLStandard Deviation 0.946
Simvastatin + MK0524APeak Plasma Concentration (Cmax) of Simvastatin Acid0.918 ng/mLStandard Deviation 0.906
Comparison: Least-Squares Mean Ratio (Fixed Dose Combination (FDC)/Co-administration)90% CI: [1.05, 1.16]
Primary

Plasma Area Under the Curve (AUC(0 to 48 Hour)) for Simvastatin

Plasma Area Under the Curve of simvastatin

Time frame: Through 48 Hours Post Dose

Population: Two hundred-twenty (220) subjects were enrolled in this study. Due to early dropout (N=4), mis-handling of plasma samples (N=2) and the limitation of the assay (N=10), data from a total of 208 and 210 subjects were available for simvastatin AUC(0-48 hour) analysis for MK0524B and Simvastatin + MK0524A, respectively.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
MK0524BPlasma Area Under the Curve (AUC(0 to 48 Hour)) for Simvastatin15.03 ng/mL * HourStandard Deviation 9.88
Simvastatin + MK0524APlasma Area Under the Curve (AUC(0 to 48 Hour)) for Simvastatin15.56 ng/mL * HourStandard Deviation 9.11
Comparison: Least-Squares Mean Ratio (Fixed Dose Combination (FDC)/Co-administration)90% CI: [0.93, 1]
Primary

Plasma Area Under the Curve (AUC(0 to 48hr)) for Simvastatin Acid

Plasma Area Under the Curve of simvastatin acid, the active metabolite of simvastatin

Time frame: Through 48 Hours Post Dose

Population: Two hundred-twenty (220) subjects were enrolled in this study. Due to early dropout (N=4), mis-handling of plasma samples (N=10) and the limitation of the assay (N=10), data from a total of 200 and 202 subjects were available for simvastatin acid AUC(0 to 48 hour) analysis for MK0524B and Simvastatin + MK0524A, respectively.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
MK0524BPlasma Area Under the Curve (AUC(0 to 48hr)) for Simvastatin Acid9.19 ng/mL * HourStandard Deviation 8.38
Simvastatin + MK0524APlasma Area Under the Curve (AUC(0 to 48hr)) for Simvastatin Acid8.03 ng/mL * HourStandard Deviation 7.78
Comparison: Least-Squares Mean Ratio (Fixed Dose Combination (FDC)/Co-administration)90% CI: [1.09, 1.2]
Primary

Plasma Area Under the Curve (AUC(0 to Infinity)) for Laropiprant

Plasma Area Under the Curve of Laropiprant

Time frame: 48 Hours Post Dose

Population: Two hundred-twenty (220) subjects were enrolled in this study. Due to early dropout (N=4), data from a total of 217 and 216 subjects were available for laropiprant AUC(0 to infinity) analysis for MK0524B and Simvastatin + MK0524A, respectively

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
MK0524BPlasma Area Under the Curve (AUC(0 to Infinity)) for Laropiprant5486 nmol/L * hourStandard Deviation 2832
Simvastatin + MK0524APlasma Area Under the Curve (AUC(0 to Infinity)) for Laropiprant5405 nmol/L * hourStandard Deviation 2618
Comparison: Least-Squares Mean Ratio (Fixed Dose Combination (FDC)/Co-administration)90% CI: [0.99, 1.04]
Primary

Total Urinary Excretion of Niacin and Its Metabolites

Time frame: 96 Hours Post Dose

Population: Two hundred-twenty (220) subjects were enrolled in this study. Due to early dropout (N=4), data from a total of 216 subjects were available for both MK0524B and Simvastatin + MK0524A for analysis of urinary excretion of nicotinuric acid and metabolites

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
MK0524BTotal Urinary Excretion of Niacin and Its Metabolites5339 µmolStandard Deviation 968
Simvastatin + MK0524ATotal Urinary Excretion of Niacin and Its Metabolites5825 µmolStandard Deviation 1188
Comparison: Least-Squares Mean Ratio (Fixed Dose Combination (FDC)/Co-administration)90% CI: [0.89, 0.94]

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026