Addition of Omarigliptin (MK-3102) to Participants With T... | NCT01704261

ID	Type	Description	Link
2012-002612-10	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Omarigliptin	Experimental	Omarigliptin (MK-3102) 25 mg capsule administered orally once a week for 24 weeks. Participants continue pre-study concomitant therapy of open-label glimepiride tablet(s) orally once daily (total daily dose >=4 mg per day) and metformin tablet(s) orally once or twice daily (total daily dose >=1500 mg per day).	Drug: Omarigliptin Drug: Glimepiride Drug: Metformin
Placebo	Placebo Comparator	Matching placebo to omarigliptin capsule administered orally once a week for 24 weeks. Participants continue pre-study concomitant therapy of open-label glimepiride tablet(s) orally once daily (total daily dose >=4 mg per day) and metformin tablet(s) orally once or twice daily (total daily dose >=1500 mg per day).	Drug: Matching placebo to Omarigliptin Drug: Glimepiride Drug: Metformin

Name	Type	Description	Arm Group Labels	Other Names
Omarigliptin	Drug	Omarigliptin 25 mg capsule administered orally once a week	Omarigliptin

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Hemoglobin A1c (A1C) at Week 24	A1C is blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%). Thus, this change from baseline reflects the Week 24 A1C minus the Week 0 A1C.	Baseline and Week 24
Percentage of Participants Who Experienced at Least One Adverse Event (AE)	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure.	Up to Week 27
Percentage of Participants Who Discontinued From the Study Due to an AE	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure.	Up to Week 24

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	Blood glucose was measured on a fasting basis. FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 24 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 24 minus FPG at baseline).	Baseline and Week 24

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Diagnosed with type 2 diabetes mellitus
Currently taking stable doses of metformin (>=1500 mg/day) and sulfonylurea
Male, or female not of reproductive potential or female of reproductive potential who agrees to remain abstinent or use (or have their partner use) 2 methods of acceptable contraception to prevent pregnancy during the study and for 21 days after the last dose of study drug

Exclusion Criteria:

History of type 1 diabetes mellitus or a history of ketoacidosis
Treated with any antihyperglycemic agent therapies other than the protocol-required sulfonylurea and metformin within 12 weeks prior to study participation or with omarigliptin at any time prior to study participation.
History of hypersensitivity to a dipeptidyl peptidase IV (DPP-4) inhibitor
On a weight loss program and is not in the maintenance phase; or has been on a weight loss medication in the past 6 months; or has undergone bariatric surgery within 12 months prior to study participation.
Is on or likely to require treatment for >=2 consecutive weeks or repeated courses of corticosteroids (inhaled, nasal or topical corticosteroids are permitted)
Currently being treated for hyperthyroidism or is on thyroid replacement therapy and has not been on a stable dose for at least 6 weeks
Medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease
Human immunodeficiency virus (HIV)
New or worsening coronary heart disease, congestive heart failure, myocardial infarction, unstable angina, coronary artery intervention, stroke, or transient ischemic neurological disorder within the past 3 months
Poorly controlled hypertension
History of malignancy <=5 years prior to study participation, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer
Clinically important hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
Pregnant or breast feeding, or is expecting to conceive or donate eggs during the trial, including 21 days following the last dose of study drug
Current user of recreational or illicit drugs or has had a recent history of drug abuse or routinely consumes >2 alcoholic drinks per day or >14 drinks per week, or engages in binge drinking
Donated blood products within 8 weeks of study participation, or intends to donate blood products during the study or has received or anticipates receiving blood products within 12 weeks prior to study participation or during the study

Name	Affiliation	Role
Medical Director, MD	Merck Sharp & Dohme LLC	Study Director

PubMed Identifier	Type	Citation	Retractions
29110647	Result	Lee SH, Gantz I, Round E, Latham M, O'Neill EA, Ceesay P, Suryawanshi S, Kaufman KD, Engel SS, Lai E. A randomized, placebo-controlled clinical trial evaluating the safety and efficacy of the once-weekly DPP-4 inhibitor omarigliptin in patients with type 2 diabetes mellitus inadequately controlled by glimepiride and metformin. BMC Endocr Disord. 2017 Nov 6;17(1):70. doi: 10.1186/s12902-017-0219-x.

ID	Type	URL	Comment
	CSR Synopsis Links	View IPD

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Omarigliptin	Omarigliptin 25 mg capsule administered orally once a week for 24 weeks. Participants continue pre-study concomitant therapy of open-label glimepiride tablet(s) orally once daily (total daily dose >=4 mg per day) and metformin tablet(s) orally once or twice daily (total daily dose >=1500 mg per day).
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Omarigliptin	Omarigliptin 25 mg capsule administered orally once a week for 24 weeks. Participants continue pre-study concomitant therapy of open-label glimepiride tablet(s) orally once daily (total daily dose >=4 mg per day) and metformin tablet(s) orally once or twice daily (total daily dose >=1500 mg per day).
BG001	Placebo	Matching placebo to omarigliptin capsule administered orally once a week for 24 weeks. Participants continue pre-study concomitant therapy of open-label glimepiride tablet(s) orally once daily (total daily dose >=4 mg per day) and metformin tablet(s) orally once or twice daily (total daily dose >=1500 mg per day).
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000154 BG001153 BG002307

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 blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%). Thus, this change from baseline reflects the Week 24 A1C minus the Week 0 A1C.

The Full Analysis Set (FAS) population consisted of all randomized participants who received at least 1 dose of study medication and had a baseline measurement or a measurement for the analysis endpoint after receiving study medication. One participant was in 2 clinical trials in parallel and was excluded from all efficacy and safety analysis.

Posted

Least Squares Mean

95% Confidence Interval

%A1C

Baseline and Week 24

ID	Title	Description
OG000	Omarigliptin	Omarigliptin 25 mg capsule administered orally once a week for 24 weeks. Participants continue pre-study concomitant therapy of open-label glimepiride tablet(s) orally once daily (total daily dose >=4 mg per day) and metformin tablet(s) orally once or twice daily (total daily dose >=1500 mg per day).
OG001	Placebo	Matching placebo to omarigliptin capsule administered orally once a week for 24 weeks. Participants continue pre-study concomitant therapy of open-label glimepiride tablet(s) orally once daily (total daily dose >=4 mg per day) and metformin tablet(s) orally once or twice daily (total daily dose >=1500 mg per day).

Units	Counts
Participants	OG000153 OG001153

Title

Denominators

Categories

Title	Measurements
	OG000-0.67(-0.84 to -0.50) OG001-0.06(-0.23 to 0.12)

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		Difference in the least squares means	Based on a constrained longitudinal data analysis (cLDA) method with a restriction of the same baseline mean across treatment groups.	<0.001		Mean Difference (Final Values)	-0.61			2-Sided	95	-0.85	-0.38					Superiority or Other

Primary

Percentage of Participants Who Experienced at Least One Adverse Event (AE)

An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure.

All Subjects as Treated (ASaT) population, defined as all randomized participants who received at least 1 dose of study medication. Participants were included in the treatment group corresponding to the study treatment they actually received. One participant was in 2 clinical trials and was excluded from all efficacy and safety analysis.

Posted

Number

Percentage of participants

Up to Week 27

ID	Title	Description
OG000	Omarigliptin	Omarigliptin 25 mg capsule administered orally once a week for 24 weeks. Participants continue pre-study concomitant therapy of open-label glimepiride tablet(s) orally once daily (total daily dose >=4 mg per day) and metformin tablet(s) orally once or twice daily (total daily dose >=1500 mg per day).
OG001	Placebo	Matching placebo to omarigliptin capsule administered orally once a week for 24 weeks. Participants continue pre-study concomitant therapy of open-label glimepiride tablet(s) orally once daily (total daily dose >=4 mg per day) and metformin tablet(s) orally once or twice daily (total daily dose >=1500 mg per day).

Primary

Percentage of Participants Who Discontinued From the Study Due to an AE

The ASaT Population was defined as all randomized participants who received at least 1 dose of study medication. Participants were included in the treatment group corresponding to the study treatment they actually received. One participant was in 2 clinical trials and was excluded from all efficacy and safety analysis.

Posted

Number

Percentage of participants

Up to Week 24

ID	Title	Description
OG000	Omarigliptin	Omarigliptin 25 mg capsule administered orally once a week for 24 weeks. Participants continue pre-study concomitant therapy of open-label glimepiride tablet(s) orally once daily (total daily dose >=4 mg per day) and metformin tablet(s) orally once or twice daily (total daily dose >=1500 mg per day).
OG001	Placebo	Matching placebo to omarigliptin capsule administered orally once a week for 24 weeks. Participants continue pre-study concomitant therapy of open-label glimepiride tablet(s) orally once daily (total daily dose >=4 mg per day) and metformin tablet(s) orally once or twice daily (total daily dose >=1500 mg per day).

Secondary

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

Blood glucose was measured on a fasting basis. FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 24 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 24 minus FPG at baseline).

The FAS population consisted of all randomized participants who received at least 1 dose of study medication and had a baseline measurement or a measurement for the analysis endpoint after receiving study medication. One participant was in 2 clinical trials in parallel and was excluded from all efficacy and safety analysis.

Posted

Least Squares Mean

95% Confidence Interval

mg/dL

Baseline and Week 24

ID	Title	Description
OG000	Omarigliptin	Omarigliptin 25 mg capsule administered orally once a week for 24 weeks. Participants continue pre-study concomitant therapy of open-label glimepiride tablet(s) orally once daily (total daily dose >=4 mg per day) and metformin tablet(s) orally once or twice daily (total daily dose >=1500 mg per day).
OG001	Placebo	Matching placebo to omarigliptin capsule administered orally once a week for 24 weeks. Participants continue pre-study concomitant therapy of open-label glimepiride tablet(s) orally once daily (total daily dose >=4 mg per day) and metformin tablet(s) orally once or twice daily (total daily dose >=1500 mg per day).

Secondary

Percentage of Participants Attaining A1C Glycemic Goals of <7% and <6.5% at Week 24

The percentage of participants who achieved A1C values <6.5% (48 mmol/mol) or <7.0% (53 mmol/mol) in the FAS population at Week 24.

The FAS Population consisted of all randomized participants who received at least 1 dose of study medication and had a baseline measurement or a measurement for the analysis endpoint after receiving study medication. One participant was in 2 clinical trials in parallel and was excluded from all efficacy and safety analysis.

Posted

Number

95% Confidence Interval

Percentage of participants

24 weeks

ID	Title	Description
OG000	Omarigliptin	Omarigliptin 25 mg capsule administered orally once a week for 24 weeks. Participants continue pre-study concomitant therapy of open-label glimepiride tablet(s) orally once daily (total daily dose >=4 mg per day) and metformin tablet(s) orally once or twice daily (total daily dose >=1500 mg per day).
OG001	Placebo	Matching placebo to omarigliptin capsule administered orally once a week for 24 weeks. Participants continue pre-study concomitant therapy of open-label glimepiride tablet(s) orally once daily (total daily dose >=4 mg per day) and metformin tablet(s) orally once or twice daily (total daily dose >=1500 mg per day).

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	Omarigliptin	Omarigliptin 25 mg capsule administered orally once a week for 24 weeks. Participants continue pre-study concomitant therapy of open-label glimepiride tablet(s) orally once daily (total daily dose >=4 mg per day) and metformin tablet(s) orally once or twice daily (total daily dose >=1500 mg per day).			3	153	29	153
EG001	Placebo	Matching placebo to omarigliptin capsule administered orally once a week for 24 weeks. Participants continue pre-study concomitant therapy of open-label glimepiride tablet(s) orally once daily (total daily dose >=4 mg per day) and metformin tablet(s) orally once or twice daily (total daily dose >=1500 mg per day).			5	153	23	153

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vertigo	Ear and labyrinth disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected153 at risk EG0010 events0 affected153 at risk
Duodenal ulcer haemorrhage	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected153 at risk EG0011 events1 affected153 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected153 at risk EG0011 events1 affected153 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected153 at risk EG0011 events1 affected153 at risk
Non-cardiac chest pain	General disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected153 at risk EG0010 events0 affected153 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected153 at risk EG0010 events0 affected153 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected153 at risk EG0011 events1 affected153 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected153 at risk EG0011 events1 affected153 at risk
Cerebrovascular disorder	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected153 at risk EG0010 events0 affected153 at risk

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

ID	Term
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Upper respiratory tract infection	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0004 events4 affected153 at risk EG00111 events9 affected153 at risk
Urinary tract infection	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0009 events9 affected153 at risk EG0014 events3 affected153 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 17.1	Systematic Assessment	EG00065 events18 affected153 at risk EG00144 events13 affected153 at risk

ID	Term
C587539	2-(2,5-difluorophenyl)-5-(2-(methylsulfonyl)-2,6-dihydropyrrolo(3,4-c)pyrazol-5(4H)-yl)tetrahydro-2H-pyran-3-amine
C057619	glimepiride
D008687	Metformin