A Study to Assess the Safety, Tolerability and Glucose-Lo... | NCT02004886

Label	Type	Description	Intervention Names
MK-0893 (40 mg)	Experimental	MK-0893 40-mg q.d. (quaque die, once daily) group will receive MK-0893 40-mg tablets (after loading dose with 160 mg) and matching placebo to metformin and matching placebo to MK-0893.	Drug: MK-0893 Drug: Placebo
MK-0893 (120 mg)	Experimental	MK-0893 at 120 mg q.d. group will receive MK-0893 120 mg q.d. tablets (after loading dose of 500 mg on Day 1) and matching placebo tablets to metformin and matching placebo to MK-0893	Drug: MK-0893 Drug: Placebo
Metformin (2000 mg)	Active Comparator	Metformin taken orally, 500 mg tablets, Day 1 to Day 6: 500 mg b.i.d. (bis in die, twice daily), Day 7 to Day 13: 1000 mg in the morning and 500 mg in the evening, and Day 14 to Day 28: 1000 mg. b.i.d. and matching placebo to MK-0893.	Drug: Metformin Drug: Placebo
Placebo	Placebo Comparator	Placebo tablets matching the MK-0893 and placebo tablets matching metformin.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
MK-0893	Drug	10 mg and 100 mg tablets	MK-0893 (120 mg) MK-0893 (40 mg)

Measure	Description	Time Frame
Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Week 4	Blood samples were collected 30 minutes prior to all meals, and 15, 30, 60, 90, 120, 180 minutes post-meal, then and at midnight, 3 AM, and the next morning at 6:30 AM and 7:30 AM. A 24-hour weighted mean glucose (WMG) was determined by averaging multiple plasma glucose measurements over a 24-hour period.	Baseline and Week 4
Number of Participants Experiencing an Adverse Event (AE)	An adverse event (AE) is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product.	Up to 42 days
Number of Participants Discontinuing Study Treatment Due to an AE	An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product.	Up to 28 days

Measure	Description	Time Frame
Change From Baseline in Fasting Plasma Glucose (FPG)	Plasma Glucose levels were measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value.	Baseline and Week 4
Change From Baseline in Fructosamine at Week 4

ID	Type	URL	Comment
	CSR Synopsis	View IPD

ID	Title	Description
FG000	MK-0893 (40 mg)	MK-0893 40-mg, once daily
FG001	MK-0893 (120 mg)	MK-0893, 120 mg, once daily

ID	Title	Description
BG000	MK-0893 (40 mg)	MK-0893 40-mg, once daily
BG001	MK-0893 (120 mg)	MK-0893, 120 mg, once daily
BG002	Metformin (2000 mg)	Metformin, oral, 1000 mg, twice daily
BG003	Placebo	Placebo
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG00019 BG00118 BG00218 BG00319 BG00474

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 24-hour Weighted Mean Glucose (WMG) at Week 4

Blood samples were collected 30 minutes prior to all meals, and 15, 30, 60, 90, 120, 180 minutes post-meal, then and at midnight, 3 AM, and the next morning at 6:30 AM and 7:30 AM. A 24-hour weighted mean glucose (WMG) was determined by averaging multiple plasma glucose measurements over a 24-hour period.

Completers Population was used for all efficacy analyses, and required that a participant took at least one dose of study therapy, had a baseline measurement, and had a post-randomization measurement in the treatment period at Week 4.

Posted

Least Squares Mean

95% Confidence Interval

mg/dL

Baseline and Week 4

ID	Title	Description
OG000	MK-0893 (40 mg)	MK-0893 40-mg, once daily
OG001	MK-0893 (120 mg)	MK-0893, 120 mg, once daily
OG002	Metformin (2000 mg)	Metformin, oral, 1000 mg, twice daily
OG003	Placebo	Placebo

Units	Counts
Participants	OG00018 OG00117 OG00218 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-37.9(-47.1 to -28.8) OG001-65.7(-74.8 to -56.5) OG002-38.1(-47.0 to -29.2) 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
OG000 OG003		ANCOVA	Terms for treatment, prior AHA therapy status, and baseline 24-hour WMG value as a covariate.	<0.001		Mean Difference (Final Values)	-25.9			2-Sided	95	-38.4	-13.3					Superiority or Other
OG001 OG003		ANCOVA

Primary

Number of Participants Experiencing an Adverse Event (AE)

An adverse event (AE) is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product.

Safety Population included all randomized participants who initiated study therapy.

Posted

Number

Number of Participants

Up to 42 days

ID	Title	Description
OG000	MK-0893 (40 mg)	MK-0893 40-mg, once daily
OG001	MK-0893 (120 mg)	MK-0893, 120 mg, once daily
OG002	Metformin (2000 mg)	Metformin, oral, 1000 mg, twice daily
OG003	Placebo	Placebo

Units	Counts

Primary

Number of Participants Discontinuing Study Treatment Due to an AE

An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product.

Safety Population included all randomized participants who initiated study therapy.

Posted

Number

Number of Participants

Up to 28 days

ID	Title	Description
OG000	MK-0893 (40 mg)	MK-0893 40-mg, once daily
OG001	MK-0893 (120 mg)	MK-0893, 120 mg, once daily
OG002	Metformin (2000 mg)	Metformin, oral, 1000 mg, twice daily
OG003	Placebo	Placebo

Units	Counts

Secondary

Change From Baseline in Fasting Plasma Glucose (FPG)

Plasma Glucose levels were measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value.

Posted

Least Squares Mean

95% Confidence Interval

mg/dL

Baseline and Week 4

ID	Title	Description
OG000	MK-0893 (40 mg)	MK-0893 40-mg, once daily
OG001	MK-0893 (120 mg)	MK-0893, 120 mg, once daily
OG002	Metformin (2000 mg)	Metformin, oral, 1000 mg, twice daily
OG003	Placebo	Placebo

Secondary

Change From Baseline in Fructosamine at Week 4

Fructosamine levels in the blood were measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value.

Posted

Least Squares Mean

95% Confidence Interval

mg/dL

Baseline and Week 4

ID	Title	Description
OG000	MK-0893 (40 mg)	MK-0893 40-mg, once daily
OG001	MK-0893 (120 mg)	MK-0893, 120 mg, once daily
OG002	Metformin (2000 mg)	Metformin, oral, 1000 mg, twice daily
OG003	Placebo	Placebo

Secondary

Change From Baseline in Fasting C-peptide at Week 4

Fasting C-peptide levels in the blood were measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value.

Posted

Least Squares Mean

95% Confidence Interval

ng/mL

Baseline and Week 4

ID	Title	Description
OG000	MK-0893 (40 mg)	MK-0893 40-mg, once daily
OG001	MK-0893 (120 mg)	MK-0893, 120 mg, once daily
OG002	Metformin (2000 mg)	Metformin, oral, 1000 mg, twice daily
OG003	Placebo	Placebo

Secondary

Change From Baseline in Fasting Insulin at Week 4

Fasting insulin levels in the blood were measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value.

Posted

Least Squares Mean

95% Confidence Interval

μIU/mL

Baseline and Week 4

ID	Title	Description
OG000	MK-0893 (40 mg)	MK-0893 40-mg, once daily
OG001	MK-0893 (120 mg)	MK-0893, 120 mg, once daily
OG002	Metformin (2000 mg)	Metformin, oral, 1000 mg, twice daily
OG003	Placebo	Placebo

Secondary

Change From Baseline in 2-hour Post-prandial Glucose Excursion at Week 4

2-hour post-prandial glucose excursion is the change in glucose concentration in the blood 2 hours after a meal. Change from baseline in 2-hour post-prandial glucose excursion at Week 4 is defined as Week 4 minus baseline.

Posted

Least Squares Mean

95% Confidence Interval

mg/dL

Baseline and Week 4

ID	Title	Description
OG000	MK-0893 (40 mg)	MK-0893 40-mg, once daily
OG001	MK-0893 (120 mg)	MK-0893, 120 mg, once daily
OG002	Metformin (2000 mg)	Metformin, oral, 1000 mg, twice daily
OG003	Placebo	Placebo

Secondary

Change From Baseline in 3-hour Area Under the Plasma Concentration Versus Time Curve (AUC) for Glucose at Week 4

Blood samples collected for glucose 30 minutes prior to the breakfast meal and 15, 30, 60, 90, 120, 180 minutes post-meal. AUC is a measure of the amount of drug in the blood over time. 3-hour AUC for Glucose was measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value.

Posted

Least Squares Mean

95% Confidence Interval

mg hr/dL

Baseline and Week 4

ID	Title	Description
OG000	MK-0893 (40 mg)	MK-0893 40-mg, once daily
OG001	MK-0893 (120 mg)	MK-0893, 120 mg, once daily
OG002	Metformin (2000 mg)	Metformin, oral, 1000 mg, twice daily
OG003	Placebo

Secondary

Change From Baseline in 3-hour AUC for C-peptide at Week 4

Blood samples were collected for C-peptide 30 minutes prior to the breakfast meal and 15, 30, 60, 90, 120, 180 minutes post-meal. AUC is a measure of the amount of drug in the blood over time. 3-hour AUC for C-peptide was measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value.

Posted

Least Squares Mean

95% Confidence Interval

ng hr/mL

Baseline and Week 4

ID	Title	Description
OG000	MK-0893 (40 mg)	MK-0893 40-mg, once daily
OG001	MK-0893 (120 mg)	MK-0893, 120 mg, once daily
OG002	Metformin (2000 mg)	Metformin, oral, 1000 mg, twice daily
OG003	Placebo	Placebo

Secondary

Change From Baseline in 3-hour Insulin Total AUC at Week 4

Blood samples were collected for insulin 30 minutes prior to the breakfast meal and 15, 30, 60, 90, 120, 180 minutes post-meal. AUC is a measure of the amount of drug in the blood over time. 3-hour Insulin Total AUC was measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value.

Posted

Least Squares Mean

95% Confidence Interval

µIU hr/mL

Baseline and Week 4

ID	Title	Description
OG000	MK-0893 (40 mg)	MK-0893 40-mg, once daily
OG001	MK-0893 (120 mg)	MK-0893, 120 mg, once daily
OG002	Metformin (2000 mg)	Metformin, oral, 1000 mg, twice daily
OG003	Placebo	Placebo

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
External Ear Pain	Ear and labyrinth disorders	MedDRA 9.1	Systematic Assessment	EG0001 affected19 at risk EG0010 affected18 at risk EG0020 affected18 at risk EG0030 affected19 at risk
Eye Irritation	Eye disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0011 affected18 at risk EG0020 affected18 at risk EG003
Vision Blurred	Eye disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0010 affected18 at risk EG0020 affected18 at risk EG003
Abdominal Pain	Gastrointestinal disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0010 affected18 at risk EG0021 affected18 at risk EG003
Abdominal Pain Lower	Gastrointestinal disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0010 affected18 at risk EG0020 affected18 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0012 affected18 at risk EG0023 affected18 at risk EG003
Dry Mouth	Gastrointestinal disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0011 affected18 at risk EG0020 affected18 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0010 affected18 at risk EG0021 affected18 at risk EG003
Gingival Pain	Gastrointestinal disorders	MedDRA 9.1	Systematic Assessment	EG0001 affected19 at risk EG0010 affected18 at risk EG0020 affected18 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 9.1	Systematic Assessment	EG0001 affected19 at risk EG0010 affected18 at risk EG0021 affected18 at risk EG003
Stomach Discomfort	Gastrointestinal disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0010 affected18 at risk EG0020 affected18 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 9.1	Systematic Assessment	EG0001 affected19 at risk EG0010 affected18 at risk EG0021 affected18 at risk EG003
Asthenia	General disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0010 affected18 at risk EG0021 affected18 at risk EG003
Chest Discomfort	General disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0011 affected18 at risk EG0020 affected18 at risk EG003
Fatigue	General disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0011 affected18 at risk EG0020 affected18 at risk EG003
Feeling Abnormal	General disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0011 affected18 at risk EG0020 affected18 at risk EG003
Nodule	General disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0010 affected18 at risk EG0021 affected18 at risk EG003
Pyrexia	General disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0010 affected18 at risk EG0021 affected18 at risk EG003
Thirst	General disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0010 affected18 at risk EG0020 affected18 at risk EG003
Herpes Simplex	Infections and infestations	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0010 affected18 at risk EG0021 affected18 at risk EG003
Influenza	Infections and infestations	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0011 affected18 at risk EG0020 affected18 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0012 affected18 at risk EG0020 affected18 at risk EG003
Otitis Media	Infections and infestations	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0011 affected18 at risk EG0020 affected18 at risk EG003
Sinusitis	Infections and infestations	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0010 affected18 at risk EG0020 affected18 at risk EG003
Viral Infection	Infections and infestations	MedDRA 9.1	Systematic Assessment	EG0001 affected19 at risk EG0011 affected18 at risk EG0020 affected18 at risk EG003
Blood Glucose Increased	Investigations	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0010 affected18 at risk EG0020 affected18 at risk EG003
Dyslipidaemia	Metabolism and nutrition disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0010 affected18 at risk EG0021 affected18 at risk EG003
Fluid Retention	Metabolism and nutrition disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0011 affected18 at risk EG0020 affected18 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0011 affected18 at risk EG0020 affected18 at risk EG003
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0010 affected18 at risk EG0020 affected18 at risk EG003
Dizziness	Nervous system disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0010 affected18 at risk EG0022 affected18 at risk EG003
Headache	Nervous system disorders	MedDRA 9.1	Systematic Assessment	EG0001 affected19 at risk EG0010 affected18 at risk EG0022 affected18 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0010 affected18 at risk EG0021 affected18 at risk EG003
Testicular Pain	Reproductive system and breast disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0010 affected18 at risk EG0020 affected18 at risk EG003
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0011 affected18 at risk EG0020 affected18 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0011 affected18 at risk EG0020 affected18 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0011 affected18 at risk EG0020 affected18 at risk EG003
Pharyngolaryngeal Pain	Respiratory, thoracic and mediastinal disorders	MedDRA 9.1	Systematic Assessment	EG0001 affected19 at risk EG0011 affected18 at risk EG0020 affected18 at risk EG003
Rales	Respiratory, thoracic and mediastinal disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0011 affected18 at risk EG0020 affected18 at risk EG003
Rash Erythematous	Skin and subcutaneous tissue disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0011 affected18 at risk EG0020 affected18 at risk EG003
Hypertension	Vascular disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected19 at risk EG0011 affected18 at risk EG0020 affected18 at risk EG003

ID	Term
D003924	Diabetes Mellitus, Type 2
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals

ID	Title	Description	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	MK-0893 (40 mg)	MK-0893 40-mg, once daily	19	3	19
EG001	MK-0893 (120 mg)	MK-0893, 120 mg, once daily	18	7	18
EG002	Metformin (2000 mg)	Metformin, oral, 1000 mg, twice daily	18	9	18
EG003	Placebo	Placebo	19	8	19

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