Safety and Efficacy of Co-Administration of Sitagliptin a... | NCT01076088

ID	Type	Description	Link
2010_514	Other Identifier	Merck Registration Number

Safety and Efficacy of Co-Administration of Sitagliptin a... | NCT01076088 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Sitagliptin 50 mg + metformin 500 mg	Experimental	Sitagliptin 50 mg and metformin 500 mg twice a day for 24 weeks.	Drug: Sitagliptin 50 mg Drug: Metformin 500 mg
Sitagliptin 50 mg + metformin 850 mg	Experimental	Sitagliptin 50 mg and metformin 850 mg twice a day for 24 weeks.	Drug: Sitagliptin 50 mg Drug: Metformin 850 mg
Metformin 500 mg	Active Comparator	Metformin 500 mg twice daily for 24 weeks.	Drug: Metformin 500 mg
Metformin 850 mg	Active Comparator	Metformin 850 mg twice daily for 24 weeks.	Drug: Metformin 850 mg
Sitagliptin 100 mg	Experimental	Sitagliptin 100 mg once daily for 24 weeks.	Drug: Sitagliptin 100 mg
Placebo	Placebo Comparator	Matching placebo tablets for 24 weeks.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Sitagliptin 50 mg	Drug	Sitagliptin 50 mg tablet twice a day, prior to the morning and evening meal, for 24 weeks.	Sitagliptin 50 mg + metformin 500 mg Sitagliptin 50 mg + metformin 850 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Hemoglobin A1C (A1C) at Week 24	A1C is measured as percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.	Baseline and Week 24

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in 2-hour Post Meal Glucose (2-h PMG) at Week 24	Change from baseline in 2-h PMG at Week 24 is defined as Week 24 2-h PMG minus Week 0 2-h PMG.	Baseline and Week 24
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24

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

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
27181998	Result	Ji L, Han P, Wang X, Liu J, Zheng S, Jou YM, O'Neill EA, Golm GT, Engel SS, Kaufman KD, Shankar RR. Randomized clinical trial of the safety and efficacy of sitagliptin and metformin co-administered to Chinese patients with type 2 diabetes mellitus. J Diabetes Investig. 2016 Sep;7(5):727-36. doi: 10.1111/jdi.12511. Epub 2016 May 19.

Arm/Group Information

ID	Title	Description
FG000	Sitagliptin 50 mg + Metformin 500 mg	Sitagliptin 50 mg twice daily + metformin 500 mg twice daily
FG001	Sitagliptin 50 mg + Metformin 850 mg	Sitagliptin 50 mg twice daily + metformin 850 mg twice daily
FG002	Metformin 500 mg	Metformin 500 mg twice daily
FG003	Metformin 850	Metformin 850 mg twice daily
FG004	Sitagliptin 100 mg	Sitagliptin 100 mg once daily
FG005	Placebo	Matching placebo to sitagliptin and/or metformin. Population includes 1 participant who did not receive any study medication.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG000122 subjects FG001125 subjects FG002126 subjects FG003124 subjects FG004120 subjects FG005127 subjects
COMPLETED		FG000111 subjects FG001107 subjects FG002109 subjects FG003109 subjects FG004
NOT COMPLETED		FG00011 subjects FG00118 subjects FG00217 subjects FG00315 subjects FG004

Type	Comment	Reasons
Adverse Event		FG0001 subjects FG0016 subjects FG0023 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Sitagliptin 50 mg + Metformin 500 mg	Sitagliptin 50 mg twice daily + metformin 500 mg twice daily
BG001	Sitagliptin 50 mg + Metformin 850 mg	Sitagliptin 50 mg twice daily + metformin 850 mg twice daily

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

Change From Baseline in Hemoglobin A1C (A1C) at Week 24

A1C is measured as percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.

Full Analysis Set, all randomized participants except those who: failed to take at least 1 dose of study treatment, lacked all post-randomization data for the A1C subsequent to at least 1 dose of study treatment, or lacked baseline data for the A1C. Last observation carried forward (missing data approach).

Posted

Least Squares Mean

95% Confidence Interval

Percent of glycosylated hemoglobin

Baseline and Week 24

ID	Title	Description
OG000	Sitagliptin 50 mg + Metformin 500 mg	Sitagliptin 50 mg twice daily + metformin 500 mg twice daily
OG001	Sitagliptin 50 mg + Metformin 850 mg

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	Sitagliptin 50 mg + Metformin 500 mg	Sitagliptin 50 mg twice daily + metformin 500 mg twice daily

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Coagulopathy	Blood and lymphatic system disorders	MedDRA 15.1	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 15.1	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
D003924	Diabetes Mellitus, Type 2

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

Intervention Browse Module

ID	Term
D000068900	Sitagliptin Phosphate
D008687	Metformin

ID	Term
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds

Hemoglobin A1c (A1C)

Mean

Standard Deviation

Percent of glycosylated hemoglobin

Title

Denominators

Categories

Title	Measurements
	BG0008.46± 0.97 BG0018.66± 0.95 BG0028.69± 0.99 BG0038.67± 1.08 BG0048.74± 1.14 BG0058.97± 1.05 BG0068.70± 1.04

Fasting plasma glucose (FPG)

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG000175.6± 40.6 BG001181.9± 43.0 BG002184.6± 46.8 BG003183.5± 47.7 BG004182.5± 44.0 BG005185.8± 47.3 BG006182.3± 45.0

2-hour post meal glucose (2-h PMG)

Participants with data: sita50/met500, n=121; sita50/met850, n=125; met500, n=125; met850, n=123; sita100, n=119; placebo; n=126; total, n=739

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG000292.7± 81.2 BG001292.9± 68.4 BG002303.2± 74.1 BG003298.8± 74.6 BG004297.7± 74.7 BG005308.3± 83.6 BG006299.0± 76.2

Title

Denominators

Categories

Title	Measurements
	OG000-1.67(-1.92 to -1.43) OG001-1.83(-2.07 to -1.58) OG002-1.29(-1.54 to -1.04) OG003-1.56(-1.80 to -1.32) OG004-0.99(-1.24 to -0.75) OG005-0.59(-0.84 to -0.34)

Group IDs	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG001 OG003	ANCOVA	The ANCOVA model included terms for treatment and prior antihyperglycemic agent (AHA) therapy status (yes/no) and a covariate for baseline A1C.	0.087	Pairwise comparison, sitagliptin 50 mg + metformin 850 mg vs. metformin 850 mg. The normality assumption required for validity of ANCOVA was violated due to a biologically implausible extreme outlier. See below for results using robust regression.	Difference in Least Squares Mean	-0.27	2-Sided	95	-0.58	0.04	Superiority or Other
OG001 OG004	ANCOVA	The ANCOVA model included terms for treatment and prior AHA therapy status (yes/no) and a covariate for baseline A1C.	<0.001	Pairwise comparison, sitagliptin 50 mg + metformin 850 mg vs. sitagliptin 100 mg. The normality assumption required for validity of ANCOVA was violated due to a biologically implausible extreme outlier. See below for results using robust regression.	Difference in Least Squares Mean	-0.84	2-Sided	95	-1.15	-0.52	Superiority or Other
OG000 OG002	ANCOVA	The ANCOVA model included terms for treatment and prior AHA therapy status (yes/no) and a covariate for baseline A1C.	0.014	Pairwise comparison, sitagliptin 50 mg + metformin 500 mg vs. metformin 500 mg. The normality assumption required for validity of ANCOVA was violated due to a biologically implausible extreme outlier. See below for results using robust regression.	Difference in Least Squares Mean	-0.39	2-Sided	95	-0.69	-0.08	Superiority or Other
OG000 OG004	ANCOVA	The ANCOVA model included terms for treatment and prior AHA therapy status (yes/no) and a covariate for baseline A1C.	<0.001	Pairwise comparison, sitagliptin 50 mg + metformin 500 mg vs. sitagliptin 100 mg. The normality assumption required for validity of ANCOVA was violated due to a biologically implausible extreme outlier. See below for results using robust regression.	Difference in Least Squares Mean	-0.68	2-Sided	95	-0.99	-0.37	Superiority or Other
OG001 OG005	ANCOVA	The ANCOVA model included terms for treatment and prior AHA therapy status (yes/no) and a covariate for baseline A1C.	<0.001	Pairwise comparison, sitagliptin 50 mg + metformin 850 mg vs. placebo. The normality assumption required for validity of ANCOVA was violated due to a biologically implausible extreme outlier. See below for results using robust regression.	Difference in Least Squares Mean	-1.24	2-Sided	95	-1.55	-0.93	Superiority or Other
OG003 OG005	ANCOVA	The ANCOVA model included terms for treatment and prior AHA therapy status (yes/no) and a covariate for baseline A1C.	<0.001	Pairwise comparison, metformin 850 mg vs. placebo. The normality assumption required for validity of ANCOVA was violated due to a biologically implausible extreme outlier. See below for results using robust regression.	Difference in Least Squares Mean	-0.97	2-Sided	95	-1.28	-0.66	Superiority or Other
OG000 OG005	ANCOVA	The ANCOVA model included terms for treatment and prior AHA therapy status (yes/no) and a covariate for baseline A1C.	<0.001	Pairwise comparison, sitagliptin 50 mg + metformin 500 mg vs. placebo. The normality assumption required for validity of ANCOVA was violated due to a biologically implausible extreme outlier. See below for results using robust regression.	Difference in Least Squares Mean	-1.08	2-Sided	95	-1.39	-0.78	Superiority or Other
OG002 OG005	ANCOVA	The ANCOVA model included terms for treatment and prior AHA therapy status (yes/no) and a covariate for baseline A1C.	<0.001	Pairwise comparison, metformin 500 mg vs. placebo. The normality assumption required for validity of ANCOVA was violated due to a biologically implausible extreme outlier. See below for results using robust regression.	Difference in Least Squares Mean	-0.70	2-Sided	95	-1.01	-0.39	Superiority or Other
OG004 OG005	ANCOVA	The ANCOVA model included terms for treatment and prior AHA therapy status (yes/no) and a covariate for baseline A1C.	0.011	Pairwise comparison, sitagliptin 100 mg vs. placebo. The normality assumption required for validity of ANCOVA was violated due to a biologically implausible extreme outlier. See below for results using robust regression.	Difference in Least Squares Mean	-0.40	2-Sided	95	-0.71	-0.09	Superiority or Other
OG001 OG003	Regression, Robust	The Robust Regression model included terms for treatment and prior AHA therapy status (yes/no) and a covariate for baseline A1C.	0.008	Pairwise comparison, sitagliptin 50 mg + metformin 850 mg vs. metformin 850 mg. This is a post-hoc analysis using robust regression, a valid method in the presence of outliers.	Difference in least squares mean	-0.36	2-Sided	95	-0.62	-0.09	Superiority or Other
OG001 OG004	Regression, Robust	The Robust Regression model included terms for treatment and prior AHA therapy status (yes/no) and a covariate for baseline A1C.	<0.001	Comparing co-administration with individual components. This is a post-hoc analysis using robust regression, a valid method in the presence of outliers.	Difference in Least Squares Mean	-0.87	2-Sided	95	-1.13	-0.60	Superiority or Other
OG000 OG002	Regression, Robust	The Robust Regression model included terms for treatment and prior AHA therapy status (yes/no) and a covariate for baseline A1C.	0.007	Comparing co-administration with individual components. This is a post-hoc analysis using robust regression, a valid method in the presence of outliers.	Difference in Least Squares Mean	-0.36	2-Sided	95	-0.63	-0.10	Superiority or Other
OG000 OG004	Regression, Robust	The Robust Regression model included terms for treatment and prior AHA therapy status (yes/no) and a covariate for baseline A1C.	<0.001	Comparing co-administration with individual components. This is a post-hoc analysis using robust regression, a valid method in the presence of outliers.	Difference in Least Squares Mean	-0.61	2-Sided	95	-0.88	-0.35	Superiority or Other
OG001 OG005	Regression, Robust	The Robust Regression model included terms for treatment and prior AHA therapy status (yes/no) and a covariate for baseline A1C.	<0.001	Comparing co-administration with individual components. This is a post-hoc analysis using robust regression, a valid method in the presence of outliers.	Difference in Least Squares Mean	-1.25	2-Sided	95	-1.52	-0.99	Superiority or Other
OG003 OG005	Regression, Robust	The Robust Regression model included terms for treatment and prior AHA therapy status (yes/no) and a covariate for baseline A1C.	<0.001	Comparing co-administration with individual components. This is a post-hoc analysis using robust regression, a valid method in the presence of outliers.	Difference in Least Squares Mean	-0.90	2-Sided	95	-1.16	-0.63	Superiority or Other
OG000 OG005	Regression, Robust	The Robust Regression model included terms for treatment and prior AHA therapy status (yes/no) and a covariate for baseline A1C.	<0.001	Comparing co-administration with individual components. This is a post-hoc analysis using robust regression, a valid method in the presence of outliers.	Difference in Least Squares Mean	-1.00	2-Sided	95	-1.26	-0.74	Superiority or Other
OG002 OG005	Regression, Robust	The Robust Regression model included terms for treatment and prior AHA therapy status (yes/no) and a covariate for baseline A1C.	<0.001	Comparing co-administration with individual components. This is a post-hoc analysis using robust regression, a valid method in the presence of outliers.	Difference in Least Squares Mean	-0.64	2-Sided	95	-0.90	-0.37	Superiority or Other
OG004 OG005	Regression, Robust	The Robust Regression model included terms for treatment and prior AHA therapy status (yes/no) and a covariate for baseline A1C.	0.004	Comparing co-administration with individual components. This is a post-hoc analysis using robust regression, a valid method in the presence of outliers.	Difference in Least Squares Mean	-0.39	2-Sided	95	-0.65	-0.12	Superiority or Other

Secondary

Change From Baseline in 2-hour Post Meal Glucose (2-h PMG) at Week 24

Change from baseline in 2-h PMG at Week 24 is defined as Week 24 2-h PMG minus Week 0 2-h PMG.

Full Analysis Set, all randomized participants except those who: failed to take at least 1 dose of study treatment, lacked all post-randomization data for 2-h PMG subsequent to at least 1 dose of study treatment, or lacked baseline data for 2-h PMG. Last observation carried forward (missing data approach).

Posted

Least Squares Mean

95% Confidence Interval

mg/dL

Baseline and Week 24

ID	Title	Description
OG000	Sitagliptin 50 mg + Metformin 500 mg	Sitagliptin 50 mg twice daily + metformin 500 mg twice daily
OG001	Sitagliptin 50 mg + Metformin 850 mg	Sitagliptin 50 mg twice daily + metformin 850 mg twice daily
OG002	Metformin 500 mg	Metformin 500 mg twice daily
OG003	Metformin 850	Metformin 850 mg twice daily
OG004	Sitagliptin 100 mg	Sitagliptin 100 mg once daily
OG005	Placebo	Matching placebo to sitagliptin and/or metformin

Units	Counts
Participants	OG000110 OG001110 OG002112 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-97.05(-109.01 to -85.09) OG001-109.46(-121.47 to -97.44) OG002-65.67(-77.76 to -53.58)

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
OG001 OG003		ANCOVA	The ANCOVA model included terms for treatment and prior antihyperglycemic agent (AHA) therapy status (yes/no) and a covariate for baseline 2-H PMG.	0.017	Pairwise comparison, sitagliptin 50 mg + metformin 850 mg vs. metformin 850 mg.	Difference in Least Squares Mean	-18.52			2-Sided	95	-33.75	-3.29					Superiority or Other

Secondary

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24

Change from baseline in FPG at Week 24 is defined as Week 24 FPG minus Week 0 FPG.

Full Analysis Set, all randomized participants except those who: failed to take at least 1 dose of study treatment, lacked all post-randomization data for FPG subsequent to at least 1 dose of study treatment, or lacked baseline data for FPG. Last observation carried forward (missing data approach).

Posted

Least Squares Mean

95% Confidence Interval

mg/dL

Baseline and Week 24

ID	Title	Description
OG000	Sitagliptin 50 mg + Metformin 500 mg	Sitagliptin 50 mg twice daily + metformin 500 mg twice daily
OG001	Sitagliptin 50 mg + Metformin 850 mg	Sitagliptin 50 mg twice daily + metformin 850 mg twice daily
OG002	Metformin 500 mg	Metformin 500 mg twice daily
OG003	Metformin 850	Metformin 850 mg twice daily
OG004	Sitagliptin 100 mg	Sitagliptin 100 mg once daily
OG005	Placebo	Matching placebo to sitagliptin and/or metformin

Units	Counts
Participants	OG000118 OG001116 OG002119 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-39.38(-46.29 to -32.47) OG001-47.74(-54.73 to -40.75) OG002-33.66(-40.66 to -26.66) OG003

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
OG001 OG003		ANCOVA	The ANCOVA model included terms for treatment and prior antihyperglycemic agent (AHA) therapy status (yes/no) and a covariate for baseline FPG.	0.069	Pairwise comparison, sitagliptin 50 mg + metformin 850 mg vs. metformin 850 mg	Difference in Least Squares Mean	-8.11			2-Sided	95	-16.86	0.64					Superiority or Other