MK0524B Bioequivalence Study (0524B-070) | NCT00943124

MK0524B Bioequivalence Study (0524B-070) | NCT00943124 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
MK0524B then Simvastatin + MK0524A	Experimental	Period 1: 1 tablet of MK0524B (ER niacin 900 mg/ laropiprant 20 mg/ simvastatin 20 mg). Period 2: 1 tablet of simvastatin 20 mg (Zocor™) and 1 tablet of MK0524A (ER niacin 1000 mg/ laropiprant 20 mg) as separate tablets.	Drug: MK0524B (ER niacin (+) laropiprant (+) simvastatin) Drug: MK0524A (ER niacin + laropiprant) Drug: Simvastatin
Simvastatin + MK0524A then MK0524B	Experimental	Period 1: 1 tablet of simvastatin 20 mg (Zocor™) and 1 tablet of MK0524A (ER niacin 1000 mg/ laropiprant 20 mg) as separate tablets. Period 2: 1 tablet of MK0524B (ER niacin 900 mg/ laropiprant 20 mg/ simvastatin 20 mg).	Drug: MK0524B (ER niacin (+) laropiprant (+) simvastatin) Drug: MK0524A (ER niacin + laropiprant) Drug: Simvastatin

Interventions

Name	Type	Description	Arm Group Labels	Other Names
MK0524B (ER niacin (+) laropiprant (+) simvastatin)	Drug	Single dose of MK0524B (ER niacin 900 mg/ laropiprant 20 mg/ simvastatin 20 mg) in one of two treatment periods.	MK0524B then Simvastatin + MK0524A

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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	Through 48 Hours Post Dose
Peak Plasma Concentration (Cmax) of Simvastatin Acid	Peak Plasma Concentration (Cmax) for Simvastatin Acid, the active metabolite of simvastatin	48 Hours Post Dose
Plasma Area Under the Curve (AUC(0 to 48 Hour)) for Simvastatin	Plasma Area Under the Curve of simvastatin	Through 48 Hours Post Dose
Peak Plasma Concentration (Cmax) of Simvastatin		48 Hours Post Dose
Plasma Area Under the Curve (AUC(0 to Infinity)) for Laropiprant	Plasma Area Under the Curve of Laropiprant	48 Hours Post Dose
Peak Plasma Concentration (Cmax) of Laropiprant		48 Hours Post Dose
Peak Plasma Concentration (Cmax) of Nicotinuric Acid	Peak Plasma Concentration (Cmax) for Nicotinuric Acid, one of the active metabolites of Niacin	24 Hours Post Dose
Total Urinary Excretion of Niacin and Its Metabolites		96 Hours Post Dose

Name	Affiliation	Role
Medical Monitor	Merck Sharp & Dohme LLC	Study Director

Arm/Group Information

ID	Title	Description
FG000	MK0524B Then Simvastatin + MK0524A	Period 1: 1 tablet of MK0524B (ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet). Period 2: 1 tablet of simvastatin and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets.
FG001	Simvastatin + MK0524A Then MK0524B	Period 1: 1 tablet of simvastatin and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets. Period 2: 1 tablet of MK0524B (ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet).

Periods

Title

Milestones

Reasons Not Completed

Period 1

Type	Comment	Milestone Data
STARTED		FG000110 subjects FG001110 subjects
COMPLETED		FG000108 subjects FG001108 subjects
NOT COMPLETED		FG0002 subjects FG0012 subjects

Type	Comment	Reasons
Withdrawal by Subject		FG0001 subjects FG0011 subjects
Did Not Follow Study Procedures		FG0001 subjects FG001

Period 2

Type	Comment	Milestone Data
STARTED		FG000108 subjects FG001108 subjects
COMPLETED		FG000108 subjects FG001

Baseline Characteristics Module

ID	Title	Description
BG000	Overall Study Population	All randomized patients

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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

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.

Posted

Least Squares Mean

Standard Deviation

ng/mL * Hour

Through 48 Hours Post Dose

ID	Title	Description
OG000	MK0524B	MK0524B: 1 tablet of ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet.
OG001	Simvastatin + MK0524A

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	MK0524B	MK0524B: 1 tablet of ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Palpitations	Cardiac disorders	MedDRA 10.0	Non-systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Senior Vice President, Global Clinical Development	Merck Sharp & Dohme Corp.	1-800-672-6372		ClinicalTrialsDisclosure@merck.com

Condition Browse Module

ID	Term
D050171	Dyslipidemias

ID	Term
D052439	Lipid Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

Intervention Browse Module

ID	Term
C518174	MK-0524
D019821	Simvastatin

ID	Term
D008148	Lovastatin
D009281	Naphthalenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Least-Squares Mean Ratio (Fixed Dose Combination (FDC)/Co-administration)					Least-Squares Mean Ratio	1.14				90	1.09	1.20				Yes	Non-Inferiority or Equivalence	Power: If the true geometric mean ratio (GMR MK0524B/Simvastatin + MK0524A) is 1.00 for all the eight primary endpoints, then a sample size of N=220 subjects provides this study with greater than 99.2% probability of observing the 90% confidence intervals (CIs) of all the eight endpoints to be contained within [0.80, 1.25], assuming nonnegative associations among the 8 endpoints.

Primary

Peak Plasma Concentration (Cmax) of Simvastatin Acid

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

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.

Posted

Least Squares Mean

Standard Deviation

ng/mL

48 Hours Post Dose

ID	Title	Description
OG000	MK0524B	MK0524B: 1 tablet of ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet.
OG001	Simvastatin + MK0524A	Simvastatin + MK0524A : 1 tablet of simvastatin 20 mg (ZOCOR) and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets

Units	Counts
Participants	OG000201 OG001202

Title

Denominators

Categories

Title	Measurements
	OG0001.016± 0.946 OG0010.918± 0.906

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Least-Squares Mean Ratio (Fixed Dose Combination (FDC)/Co-administration)					Least-Squares Mean Ratio	1.11				90	1.05	1.16				Yes	Non-Inferiority or Equivalence	Power: If the true geometric mean ratio (GMR MK0524B/Simvastatin + MK0524A) is 1.00 for all the eight primary endpoints, then a sample size of N=220 subjects provides this study with greater than 99.2% probability of observing the 90% confidence intervals (CIs) of all the eight endpoints to be contained within [0.80, 1.25], assuming nonnegative associations among the 8 endpoints.

Primary

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

Plasma Area Under the Curve of simvastatin

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.

Posted

Least Squares Mean

Standard Deviation

ng/mL * Hour

Through 48 Hours Post Dose

ID	Title	Description
OG000	MK0524B	MK0524B: 1 tablet of ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet.
OG001	Simvastatin + MK0524A	Simvastatin + MK0524A : 1 tablet of simvastatin 20 mg (ZOCOR) and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets

Units	Counts
Participants	OG000208 OG001210

Title

Denominators

Categories

Title	Measurements
	OG00015.03± 9.88 OG00115.56± 9.11

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Least-Squares Mean Ratio (Fixed Dose Combination (FDC)/Co-administration)					Least-Squares Mean Ratio	0.97				90	0.93	1.00				Yes	Non-Inferiority or Equivalence	Power: If the true geometric mean ratio (GMR MK0524B/Simvastatin + MK0524A) is 1.00 for all the eight primary endpoints, then a sample size of N=220 subjects provides this study with greater than 99.2% probability of observing the 90% confidence intervals (CIs) of all the eight endpoints to be contained within [0.80, 1.25], assuming nonnegative associations among the 8 endpoints.

Primary

Peak Plasma Concentration (Cmax) of Simvastatin

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.

Posted

Least Squares Mean

Standard Deviation

ng/mL

48 Hours Post Dose

ID	Title	Description
OG000	MK0524B	MK0524B: 1 tablet of ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet.
OG001	Simvastatin + MK0524A	Simvastatin + MK0524A : 1 tablet of simvastatin 20 mg (ZOCOR) and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets

Units	Counts
Participants	OG000209 OG001210

Title

Denominators

Categories

Title	Measurements
	OG0005.81± 4.31 OG0016.33± 4.64

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Least-Squares Mean Ratio (Fixed Dose Combination (FDC)/Co-administration)					Least-Squares Mean Ratio	0.92				90	0.87	0.97				Yes	Non-Inferiority or Equivalence	Power: If the true geometric mean ratio (GMR MK0524B/Simvastatin + MK0524A) is 1.00 for all the eight primary endpoints, then a sample size of N=220 subjects provides this study with greater than 99.2% probability of observing the 90% confidence intervals (CIs) of all the eight endpoints to be contained within [0.80, 1.25], assuming nonnegative associations among the 8 endpoints.

Primary

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

Plasma Area Under the Curve of Laropiprant

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

Posted

Least Squares Mean

Standard Deviation

nmol/L * hour

48 Hours Post Dose

ID	Title	Description
OG000	MK0524B	MK0524B: 1 tablet of ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet.
OG001	Simvastatin + MK0524A	Simvastatin + MK0524A : 1 tablet of simvastatin 20 mg (ZOCOR) and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets

Units	Counts
Participants	OG000217 OG001216

Title

Denominators

Categories

Title	Measurements
	OG0005486± 2832 OG0015405± 2618

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Least-Squares Mean Ratio (Fixed Dose Combination (FDC)/Co-administration)					Least-Squares Mean Ratio	1.02				90	0.99	1.04				Yes	Non-Inferiority or Equivalence	Power: If the true geometric mean ratio (GMR MK0524B/Simvastatin + MK0524A) is 1.00 for all the eight primary endpoints, then a sample size of N=220 subjects provides this study with greater than 99.2% probability of observing the 90% confidence intervals (CIs) of all the eight endpoints to be contained within [0.80, 1.25], assuming nonnegative associations among the 8 endpoints.

Primary

Peak Plasma Concentration (Cmax) of Laropiprant

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

Posted

Least Squares Mean

Standard Deviation

nmol/L

48 Hours Post Dose

ID	Title	Description
OG000	MK0524B	MK0524B: 1 tablet of ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet.
OG001	Simvastatin + MK0524A	Simvastatin + MK0524A : 1 tablet of simvastatin 20 mg (ZOCOR) and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets

Units	Counts
Participants	OG000217 OG001216

Title

Denominators

Categories

Title	Measurements
	OG0001030± 642 OG001953± 542

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Least-Squares Mean Ratio (Fixed Dose Combination (FDC)/Co-administration)					Least-Squares Mean Ratio	1.08				90	1.02	1.14				Yes	Non-Inferiority or Equivalence	Power: If the true geometric mean ratio (GMR MK0524B/Simvastatin + MK0524A) is 1.00 for all the eight primary endpoints, then a sample size of N=220 subjects provides this study with greater than 99.2% probability of observing the 90% confidence intervals (CIs) of all the eight endpoints to be contained within [0.80, 1.25], assuming nonnegative associations among the 8 endpoints.

Primary

Peak Plasma Concentration (Cmax) of Nicotinuric Acid

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

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.

Posted

Least Squares Mean

Standard Deviation

ng/mL

24 Hours Post Dose

ID	Title	Description
OG000	MK0524B	MK0524B: 1 tablet of ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet.
OG001	Simvastatin + MK0524A	Simvastatin + MK0524A : 1 tablet of simvastatin 20 mg (ZOCOR) and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets

Units	Counts
Participants	OG000215 OG001216

Title

Denominators

Categories

Title	Measurements
	OG000620± 536 OG001807± 469

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Least-Squares Mean Ratio (Fixed Dose Combination (FDC)/Co-administration)					Least-Squares Mean Ratio	0.77				90	0.72	0.82				Yes	Non-Inferiority or Equivalence	Power: If the true geometric mean ratio (GMR MK0524B/Simvastatin + MK0524A) is 1.00 for all the eight primary endpoints, then a sample size of N=220 subjects provides this study with greater than 99.2% probability of observing the 90% confidence intervals (CIs) of all the eight endpoints to be contained within [0.80, 1.25], assuming nonnegative associations among the 8 endpoints.

Primary

Total Urinary Excretion of Niacin and Its Metabolites

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

Posted

Least Squares Mean

Standard Deviation

µmol

96 Hours Post Dose

ID	Title	Description
OG000	MK0524B	MK0524B: 1 tablet of ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet.
OG001	Simvastatin + MK0524A	Simvastatin + MK0524A : 1 tablet of simvastatin 20 mg (ZOCOR) and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets

Units	Counts
Participants	OG000216 OG001216

Title

Denominators

Categories

Title	Measurements
	OG0005339± 968 OG0015825± 1188

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Least-Squares Mean Ratio (Fixed Dose Combination (FDC)/Co-administration)					Least-Squares Mean Ratio	0.92				90	0.89	0.94				Yes	Non-Inferiority or Equivalence	Power: If the true geometric mean ratio (GMR MK0524B/Simvastatin + MK0524A) is 1.00 for all the eight primary endpoints, then a sample size of N=220 subjects provides this study with greater than 99.2% probability of observing the 90% confidence intervals (CIs) of all the eight endpoints to be contained within [0.80, 1.25], assuming nonnegative associations among the 8 endpoints.

ID	Type	Description	Link
MK0524B-070
2009_612