A Study to Test the Effectiveness and Safety of MK0893 in... | NCT00631488

ID	Type	Description	Link
2007_646

A Study to Test the Effectiveness and Safety of MK0893 in... | NCT00631488 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
MK-0893 + Sitagliptin	Experimental	Drug: MK-0893 Drug: Sitagliptin Drug: Placebo for Metformin
MK-0893 + Metformin	Experimental	Drug: MK-0893 Drug: Metformin Drug: Placebo for Sitagliptin
Sitagliptin + Metformin	Active Comparator	Drug: Sitagliptin Drug: Metformin Drug: Placebo for MK-0893

Interventions

Name	Type	Description	Arm Group Labels	Other Names
MK-0893	Drug	Initial loading dose of 200 mg MK-0893 at randomization, followed by MK-0893 administered orally as 40 mg tablets daily throughout the double-blind treatment period (4 weeks).

Outcomes Module

Measure	Description	Time Frame
Change From Baseline (BL) to Week 4 in 24-hour Weighted Mean Glucose (WMG) Levels		BL, 4 weeks (end of double-blind treatment period)

Secondary Outcomes

Measure	Description	Time Frame
Change From BL to Week 4 in Fasting Plasma Glucose (FPG)		BL, 4 weeks (end of double-blind treatment period)
Change From BL to Week 4 in 2-hr Glucose Area Under The Curve (AUC)		BL, 4 weeks (end of double-blind treatment period)

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

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	MK-0893 + Sitagliptin	Participants received an initial loading dose of 200 mg MK-0893 at randomization, followed by MK-0893 administered orally as 40 mg tablets daily throughout the double-blind treatment period. Sitagliptin was administered orally as 100 mg tablets daily before the morning meal throughout the double-blind treatment period.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Comment	Reasons
Adverse Event		FG0001 subjects FG0010 subjects FG0020 subjects
Lost to Follow-up		FG0002 subjects FG0012 subjects FG0020 subjects
Physician Decision		FG0001 subjects FG0010 subjects FG0021 subjects
Protocol Violation		FG0000 subjects FG0010 subjects FG0021 subjects

Arm/Group Information

ID	Title	Description
BG000	MK-0893 + Sitagliptin	Participants received an initial loading dose of 200 mg MK-0893 at randomization, followed by MK-0893 administered orally as 40 mg tablets daily throughout the double-blind treatment period. Sitagliptin was administered orally as 100 mg tablets daily before the morning meal throughout the double-blind treatment period.
BG001	MK-0893 + Metformin	Participants received an initial loading dose of 200 mg MK-0893 at randomization, followed by MK-0893 orally (40 mg tablets) administered daily throughout the double-blind treatment period. Participants received Metformin orally (500 mg tablets) over an initial 2-week titration period starting at 500 mg administered twice daily before the morning and evening meals, increasing to 1500 mg daily, and ending with 1000 mg twice daily. Metformin was then administered throughout the double-blind treatment period.
BG002	Sitagliptin + Metformin	Sitagliptin was administered orally as 100 mg tablets daily before the morning meal throughout the double-blind treatment period. Participants received Metformin orally (500 mg tablets) over an initial 2-week titration period starting at 500 mg administered twice daily before the morning and evening meals, increasing to 1500 mg daily, and ending with 1000 mg twice daily. Metformin was then administered throughout the double-blind treatment period.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00048 BG00149 BG00249 BG003146

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG000-85.7± 4.6(4.6 to -117.4) OG001-117.4± 4.6(-99.6 to 4.6) OG002-99.6± 4.6

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 OG002	Hypothesis: After 4 weeks of treatment, MK-0893+sitagliptin provide greater reduction in 24-hour WMG than sitagliptin+metformin. Using a standard deviation (SD) of 23.5 mg/dL, a sample size of 40 participants per group had 80% power to detect a true difference of 15 mg/dL in the mean change from BL in 24-hour WMG between any 2 treatment groups for a two-sided test at alpha=0.05, with a half-width of 10.3 mg/dL around the 95% confidence interval (CI) for the between group difference.	Longitudinal Data Analysis		0.002		Mean Difference (Final Values)	13.9			2-Sided	95	5.2	22.7				No	Superiority or Other

Secondary

Change From BL to Week 4 in Fasting Plasma Glucose (FPG)

Full Analysis Set Population

Posted

Least Squares Mean

Standard Error

mg/dL

BL, 4 weeks (end of double-blind treatment period)

ID	Title	Description
OG000	MK-0893 + Sitagliptin	Participants received an initial loading dose of 200 mg MK-0893 at randomization, followed by MK-0893 administered orally as 40 mg tablets daily throughout the double-blind treatment period. Sitagliptin was administered orally as 100 mg tablets daily before the morning meal throughout the double-blind treatment period.
OG001	MK-0893 + Metformin	Participants received an initial loading dose of 200 mg MK-0893 at randomization, followed by MK-0893 orally (40 mg tablets) administered daily throughout the double-blind treatment period. Participants received Metformin orally (500 mg tablets) over an initial 2-week titration period starting at 500 mg administered twice daily before the morning and evening meals, increasing to 1500 mg daily, and ending with 1000 mg twice daily. Metformin was then administered throughout the double-blind treatment period.
OG002	Sitagliptin + Metformin	Sitagliptin was administered orally as 100 mg tablets daily before the morning meal throughout the double-blind treatment period. Participants received Metformin orally (500 mg tablets) over an initial 2-week titration period starting at 500 mg administered twice daily before the morning and evening meals, increasing to 1500 mg daily, and ending with 1000 mg twice daily. Metformin was then administered throughout the double-blind treatment period.

Secondary

Change From BL to Week 4 in 2-hr Glucose Area Under The Curve (AUC)

Full Analysis Set Population

Posted

Least Squares Mean

Standard Error

mg.h/dL

BL, 4 weeks (end of double-blind treatment period)

ID	Title	Description
OG000	MK-0893 + Sitagliptin	Participants received an initial loading dose of 200 mg MK-0893 at randomization, followed by MK-0893 administered orally as 40 mg tablets daily throughout the double-blind treatment period. Sitagliptin was administered orally as 100 mg tablets daily before the morning meal throughout the double-blind treatment period.
OG001	MK-0893 + Metformin	Participants received an initial loading dose of 200 mg MK-0893 at randomization, followed by MK-0893 orally (40 mg tablets) administered daily throughout the double-blind treatment period. Participants received Metformin orally (500 mg tablets) over an initial 2-week titration period starting at 500 mg administered twice daily before the morning and evening meals, increasing to 1500 mg daily, and ending with 1000 mg twice daily. Metformin was then administered throughout the double-blind treatment period.
OG002	Sitagliptin + Metformin	Sitagliptin was administered orally as 100 mg tablets daily before the morning meal throughout the double-blind treatment period. Participants received Metformin orally (500 mg tablets) over an initial 2-week titration period starting at 500 mg administered twice daily before the morning and evening meals, increasing to 1500 mg daily, and ending with 1000 mg twice daily. Metformin was then administered throughout the double-blind treatment period.

Secondary

Change From BL to Week 4 in the 2-Hour Total GLP-1 Total AUC

Glucagon-Like Peptide-1 (GLP-1) is an incretin hormone that acts as a potent insulin secretegogue in response to nutrient ingestion and stimulates glucose disposition. The total AUC of Total GLP-1 levels was calculated from blood sample data measured after the morning meal.

Full Analysis Set Population

Posted

Least Squares Mean

Standard Error

pmol*h/L

BL, 4 weeks (end of double-blind treatment period)

ID	Title	Description
OG000	MK-0893 + Sitagliptin	Participants received an initial loading dose of 200 mg MK-0893 at randomization, followed by MK-0893 administered orally as 40 mg tablets daily throughout the double-blind treatment period. Sitagliptin was administered orally as 100 mg tablets daily before the morning meal throughout the double-blind treatment period.
OG001	MK-0893 + Metformin	Participants received an initial loading dose of 200 mg MK-0893 at randomization, followed by MK-0893 orally (40 mg tablets) administered daily throughout the double-blind treatment period. Participants received Metformin orally (500 mg tablets) over an initial 2-week titration period starting at 500 mg administered twice daily before the morning and evening meals, increasing to 1500 mg daily, and ending with 1000 mg twice daily. Metformin was then administered throughout the double-blind treatment period.

Secondary

Change From BL to Week 4 in the 2-Hour Active GLP-1 Total AUC

GLP-1 is cleaved from proglucagon to form the active peptide GLP-1. The active form promotes suppression of glucagon secretion. The total AUC of Active GLP-1 levels was calculated from blood sample data measured after the morning meal.

Full Analysis Set Population

Posted

Least Squares Mean

Standard Error

pmole*h/L

BL, 4 weeks (end of double-blind treatment period)

ID	Title	Description
OG000	MK-0893 + Sitagliptin	Participants received an initial loading dose of 200 mg MK-0893 at randomization, followed by MK-0893 administered orally as 40 mg tablets daily throughout the double-blind treatment period. Sitagliptin was administered orally as 100 mg tablets daily before the morning meal throughout the double-blind treatment period.
OG001	MK-0893 + Metformin	Participants received an initial loading dose of 200 mg MK-0893 at randomization, followed by MK-0893 orally (40 mg tablets) administered daily throughout the double-blind treatment period. Participants received Metformin orally (500 mg tablets) over an initial 2-week titration period starting at 500 mg administered twice daily before the morning and evening meals, increasing to 1500 mg daily, and ending with 1000 mg twice daily. Metformin was then administered throughout the double-blind treatment period.
OG002

Arm/Groups

ID	Title	Description	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	MK-0893 + Sitagliptin	Participants received an initial loading dose of 200 mg MK-0893 at randomization, followed by MK-0893 administered orally as 40 mg tablets daily throughout the double-blind treatment period. Sitagliptin was administered orally as 100 mg tablets daily before the morning meal throughout the double-blind treatment period.	48	7	48
EG001	MK-0893 + Metformin	Participants received an initial loading dose of 200 mg MK-0893 at randomization, followed by MK-0893 orally (40 mg tablets) administered daily throughout the double-blind treatment period. Participants received Metformin orally (500 mg tablets) over an initial 2-week titration period starting at 500 mg administered twice daily before the morning and evening meals, increasing to 1500 mg daily, and ending with 1000 mg twice daily. Metformin was then administered throughout the double-blind treatment period.	49	10	49
EG002	Sitagliptin + Metformin	Sitagliptin was administered orally as 100 mg tablets daily before the morning meal throughout the double-blind treatment period. Participants received Metformin orally (500 mg tablets) over an initial 2-week titration period starting at 500 mg administered twice daily before the morning and evening meals, increasing to 1500 mg daily, and ending with 1000 mg twice daily. Metformin was then administered throughout the double-blind treatment period.	49	8	49

Other Adverse Events

Term	Organ System	Source Vocabulary	Statistical Information
diarrhoea	Gastrointestinal disorders	MedDRA 11.1	EG0001 events1 affected48 at risk EG0017 events6 affected49 at risk EG0029 events6 affected49 at risk
nausea	Gastrointestinal disorders	MedDRA 11.1	EG0002 events2 affected48 at risk EG0015 events4 affected49 at risk EG0022 events2 affected49 at risk
upper respiratory tract infection	Infections and infestations	MedDRA 11.1	EG0004 events4 affected48 at risk EG0011 events1 affected49 at risk EG0021 events1 affected49 at risk

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

ID	Term
D003924	Diabetes Mellitus, Type 2

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
C575263	N-((4-(1-(3-(3,5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl)ethyl)phenyl)carbonyl)-beta-alanine
D000068900	Sitagliptin Phosphate
D008687	Metformin

Ancestor Terms

ID	Term
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011719	Pyrazines
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals

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 OG002	Hypothesis: After 4 weeks of treatment, MK-0893+sitagliptin provide greater reduction in 24-hour FPG than sitagliptin+metformin. Using a standard deviation (SD) of 23.5 mg/dL, a sample size of 40 participants per group had 80% power to detect a true difference of 15 mg/dL in the mean change from BL in 24-hour FPG between any 2 treatment groups for a two-sided test at alpha=0.05, with a half-width of 10.3 mg/dL around the 95% confidence interval for the between group difference.	Longitudinal Data Analysis		0.050		Mean Difference (Final Values)	9.1			2-Sided	95	0.0	18.2				No	Superiority or Other
OG001 OG002	Hypothesis: After 4 weeks of treatment, MK-0893+metformin provide greater reduction in 24-hour FPG than sitagliptin+metformin. Using a standard deviation (SD) of 23.5 mg/dL, a sample size of 40 participants per group had 80% power to detect a true difference of 15 mg/dL in the mean change from BL in 24-hour FPG between any 2 treatment groups for a two-sided test at alpha=0.05, with a half-width of 10.3 mg/dL around the 95% confidence interval for the between group difference.	Longitudinal Data Analysis		<0.001		Mean Difference (Final Values)	-19.1			2-Sided	95	-28.0	-10.1				No	Superiority or Other

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 OG002	Hypothesis: After 4 weeks of treatment, MK-0893+sitagliptin provide greater reduction in 2-hr Glucose AUC than sitagliptin+metformin. Using a SD of 23.5 mg/dL, a sample size of 40 participants per group had 80% power to detect a true difference of 15 mg/dL in the mean change from BL in 2-Hour Glucose Total AUC between any 2 treatment groups for a two-sided test at alpha=0.05, with a half-width of 10.3 mg/dL around the 95% confidence interval for the between group difference.	Longitudinal Data Analysis		0.056		Mean Difference (Final Values)	22.6			2-Sided	95	-0.6	45.8				No	Superiority or Other
OG001 OG002	Hypothesis: After 4 weeks of treatment, MK-0893+metformin provide greater reduction in 2-hr Glucose AUC than sitagliptin+metformin. Using a SD of 23.5 mg/dL, a sample size of 40 participants per group had 80% power to detect a true difference of 15 mg/dL in the mean change from BL in 2-Hour Glucose Total AUC between any 2 treatment groups for a two-sided test at alpha=0.05, with a half-width of 10.3 mg/dL around the 95% confidence interval for the between group difference.	Longitudinal Data Analysis		<0.001		Mean Difference (Final Values)	-44.6			2-Sided	95	-67.3	-21.8				No	Superiority or Other

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 OG002	Hypothesis: After 4 weeks of treatment, MK-0893+sitagliptin provide greater reduction in 2-Hour Total GLP-1 Total AUC than sitagliptin+metformin. Using a SD of 23.5 mg/dL, a sample size of 40 participants/group had 80% power to detect a true difference of 15 mg/dL in the mean change from BL in 2-Hour Total GLP-1 Total AUC between any 2 treatment groups for a 2-sided test at alpha=0.05, with a half-width of 10.3 mg/dL around the 95% CI for the between group difference.	Longitudinal Data Analysis		0.001		Mean Difference (Final Values)	4.2			2-Sided	95	1.7	6.7				No	Superiority or Other
OG001 OG002	Hypothesis: After 4 weeks of treatment, MK-0893+metformin provide greater reduction in 2-Hour Total GLP-1 Total AUC than sitagliptin+metformin. Using a SD of 23.5 mg/dL, a sample size of 40 participants/group had 80% power to detect a true difference of 15 mg/dL in the mean change from BL in 2-Hour Total GLP-1 Total AUC between any 2 treatment groups for a 2-sided test at alpha=0.05, with a half-width of 10.3 mg/dL around the 95% CI for the between group difference.	Longitudinal Data Analysis		<0.001		Mean Difference (Final Values)	13.2			2-Sided	95	10.7	15.7				No	Superiority or Other

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 OG002	Hypothesis: After 4 weeks of treatment, MK-0893+sitagliptin provide greater reduction in 2-Hour Active GLP-1 Total AUC than sitagliptin+metformin. Using a SD of 23.5 mg/dL, a sample size of 40 participants/group had 80% power to detect a true difference of 15 mg/dL in the mean change from BL in 2-Hour Active GLP-1 Total AUC between any 2 treatment groups for a 2-sided test at alpha=0.05, with a half-width of 10.3 mg/dL around the 95% CI for the between group difference	Longitudinal Data Analysis		<0.001		Mean Difference (Final Values)	-6.7			2-Sided	95	-9.5	-3.8				No	Superiority or Other
OG001 OG002	Hypothesis: After 4 weeks of treatment, MK-0893+metformin provide greater reduction in 2-Hour Active GLP-1 Total AUC than sitagliptin+metformin. Using a SD of 23.5 mg/dL, a sample size of 40 participants/group had 80% power to detect a true difference of 15 mg/dL in the mean change from BL in 2-Hour Active GLP-1 Total AUC between any 2 treatment groups for a 2-sided test at alpha=0.05, with a half-width of 10.3 mg/dL around the 95% CI for the between group difference.	Longitudinal Data Analysis		<0.001		Mean Difference (Final Values)	-11.3			2-Sided	95	-14.1	-8.5				No	Superiority or Other