Study to Evaluate the Safety and Efficacy of the Addition... | NCT01841697

NCT01841697

ID	Type	Description	Link
2013-000059-42	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Omarigliptin 25 mg once weekly	Experimental	Participants receive omarigliptin 25 mg once a week plus placebo to sitagliptin once daily for 24 weeks. Participants continue pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may receive glimepiride (total daily dose of 1-6 mg) as rescue therapy.	Drug: Omarigliptin Drug: Placebo to Sitagliptin Drug: Open-label Metformin Drug: Open-label Glimepiride
Sitagliptin 100 mg once daily	Active Comparator	Participants receive sitagliptin 100 mg once daily plus placebo to omarigliptin once a week for 24 weeks. Participants continue pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may receive glimepiride (total daily dose of 1-6 mg) as rescue therapy.	Drug: Sitagliptin Drug: Placebo to omarigliptin Drug: Open-label Metformin Drug: Open-label Glimepiride

Name	Type	Description	Arm Group Labels	Other Names
Omarigliptin	Drug	Omarigliptin (MK-3102) 25 mg oral capsule once a week for 24 weeks	Omarigliptin 25 mg once weekly

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in A1C at Week 24	A1C is a measure of the percentage of glycated hemoglobin in the blood. Participant whole blood samples were collected at baseline and Week 24 to determine the least squares mean A1C change from baseline.	Baseline and Week 24
Percentage of Participants Who Experienced at Least One Adverse Event	An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after initiation of glycemic rescue therapy.	Up to 27 weeks (including 3-week follow-up)
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event	An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after initiation of glycemic rescue therapy.	Up to 24 weeks

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in FPG at Week 24	Participant whole blood samples were collected after an overnight fast at baseline and Week 24 to determine the least squares mean change from baseline in participant FPG.	Baseline and Week 24
Percentage of Participants Achieving an A1C Goal <7.0% After 24 Weeks of Treatment

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Type 2 diabetes mellitus
Currently on a stable dose of metformin monotherapy (≥1500 mg per day) for at least 12 weeks prior to study participation
Male, or female who is not of reproductive potential or if of reproductive potential agrees to abstain from heterosexual activity or use (or have their partner use) 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
Has been treated with any antihyperglycemic agent (AHA) other than the protocol-required metformin within 12 weeks prior to study participation or with omarigliptin at any time prior to signing informed consent
History of hypersensitivity to a dipeptidyl peptidase IV (DPP-4) inhibitor
Is currently participating in, or has participated in, a trial in which the participant received an investigational compound or used an investigational device within the prior 12 weeks of signing the informed consent or is not willing to refrain from participating in any other trial
History of intolerance, hypersensitivity, or any other contraindication to metformin or sitagliptin
Is 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
Has undergone a surgical procedure within 4 weeks of study participation or has planned major surgery during the study
Is on or likely to require treatment ≥14 consecutive days or repeated courses of corticosteroids (inhaled, nasal and topical corticosteroids are permitted)
Currently being treated for hyperthyroidism or is on thyroid hormone replacement therapy and has not been on a stable dose for at least 6 weeks
Is expecting to undergo hormonal therapy in preparation to donate eggs during the period of the trial, including 21 days after the last dose of trial medication
History of active liver disease (other than non-alcoholic steatosis) including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gall bladder disease
Human immunodeficiency virus (HIV)
New or worsening signs or symptoms of coronary heart disease or congestive heart failure within the past 3 months, or myocardial infarction, unstable angina, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, stroke, or transient ischemic attacks in 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
Hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
Positive urine pregnancy test
Pregnant or breastfeeding, or is expecting to conceive during the study including 21 days following the last dose of blinded study drug
User of recreational or illicit drugs or has had a recent history of drug abuse
Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking
Has donated blood products or has had phlebotomy of >300 mL within 8 weeks of study participation, or intends to donate blood products within the projected duration of the trial or has received, or is anticipated to receive, blood products within 12 weeks of study participation or within the projected duration of the trial

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

PubMed Identifier	Type	Citation	Retractions
28093853	Result	Goldenberg R, Gantz I, Andryuk PJ, O'Neill EA, Kaufman KD, Lai E, Wang YN, Suryawanshi S, Engel SS. Randomized clinical trial comparing the efficacy and safety of treatment with the once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor omarigliptin or the once-daily DPP-4 inhibitor sitagliptin in patients with type 2 diabetes inadequately controlled on metformin monotherapy. Diabetes Obes Metab. 2017 Mar;19(3):394-400. doi: 10.1111/dom.12832. Epub 2017 Jan 17.

ID	Type	URL	Comment
	CSR Synopsis	View IPD

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Omarigliptin 25 mg Once Weekly	Participants received omarigliptin 25 mg once a week plus placebo to sitagliptin once daily for 24 weeks. Participants continued pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may have received glimepiride (total daily dose of 1-6 mg) as rescue therapy.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Omarigliptin 25 mg Once Weekly	Participants received omarigliptin 25 mg once a week plus placebo to sitagliptin once daily for 24 weeks. Participants continued pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may have received glimepiride (total daily dose of 1-6 mg) as rescue therapy.
BG001	Sitagliptin 100 mg Once Daily	Participants received sitagliptin 100 mg once daily plus placebo to omarigliptin once a week for 24 weeks. Participants continued pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may have received glimepiride (total daily dose of 1-6 mg) as rescue therapy.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000322 BG001320 BG002642

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 A1C at Week 24

A1C is a measure of the percentage of glycated hemoglobin in the blood. Participant whole blood samples were collected at baseline and Week 24 to determine the least squares mean A1C change from baseline.

Full analysis set population consists of all randomized participants who received at least one dose of study treatment and have a baseline measurement or a post-randomization measurement for the analysis endpoint subsequent to at least one dose of study treatment.

Posted

Least Squares Mean

95% Confidence Interval

Percent

Baseline and Week 24

ID	Title	Description
OG000	Omarigliptin 25 mg Once Weekly	Participants received omarigliptin 25 mg once a week plus placebo to sitagliptin once daily for 24 weeks. Participants continued pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may have received glimepiride (total daily dose of 1-6 mg) as rescue therapy.
OG001	Sitagliptin 100 mg Once Daily	Participants received sitagliptin 100 mg once daily plus placebo to omarigliptin once a week for 24 weeks. Participants continued pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may have received glimepiride (total daily dose of 1-6 mg) as rescue therapy.

Units	Counts
Participants	OG000322 OG001320

Title

Denominators

Categories

Title	Measurements
	OG000-0.47(-0.55 to -0.38) OG001-0.43(-0.51 to -0.35)

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	Constrained longitudinal data analysis					Difference in least squares mean	-0.03			2-Sided	95	-0.15	0.08			Difference is omarigliptin minus sitagliptin.		Non-Inferiority or Equivalence	If the upper bound of the two-sided 95% confidence interval for the mean difference between omarigilptin and sitagliptin is less than the non-inferiority margin, δ =0.3%, then omarigliptin will be declared non-inferior to sitagliptin in terms of A1C reduction at Week 24.

Primary

Percentage of Participants Who Experienced at Least One Adverse Event

An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after initiation of glycemic rescue therapy.

All participants as treated population consists of all randomized participants who received at least one dose of trial treatment. Participants are included in the treatment group corresponding to the trial treatment they actually received.

Posted

Number

Percentage of participants

Up to 27 weeks (including 3-week follow-up)

ID	Title	Description
OG000	Omarigliptin 25 mg Once Weekly	Participants received omarigliptin 25 mg once a week plus placebo to sitagliptin once daily for 24 weeks. Participants continued pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may have received glimepiride (total daily dose of 1-6 mg) as rescue therapy.
OG001	Sitagliptin 100 mg Once Daily	Participants received sitagliptin 100 mg once daily plus placebo to omarigliptin once a week for 24 weeks. Participants continued pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may have received glimepiride (total daily dose of 1-6 mg) as rescue therapy.

Primary

Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event

Posted

Number

Percentage of participants

Up to 24 weeks

ID	Title	Description
OG000	Omarigliptin 25 mg Once Weekly	Participants received omarigliptin 25 mg once a week plus placebo to sitagliptin once daily for 24 weeks. Participants continued pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may have received glimepiride (total daily dose of 1-6 mg) as rescue therapy.
OG001	Sitagliptin 100 mg Once Daily	Participants received sitagliptin 100 mg once daily plus placebo to omarigliptin once a week for 24 weeks. Participants continued pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may have received glimepiride (total daily dose of 1-6 mg) as rescue therapy.

Secondary

Change From Baseline in FPG at Week 24

Participant whole blood samples were collected after an overnight fast at baseline and Week 24 to determine the least squares mean change from baseline in participant FPG.

Posted

Least Squares Mean

95% Confidence Interval

mg/dL

Baseline and Week 24

ID	Title	Description
OG000	Omarigliptin 25 mg Once Weekly	Participants received omarigliptin 25 mg once a week plus placebo to sitagliptin once daily for 24 weeks. Participants continued pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may have received glimepiride (total daily dose of 1-6 mg) as rescue therapy.
OG001	Sitagliptin 100 mg Once Daily	Participants received sitagliptin 100 mg once daily plus placebo to omarigliptin once a week for 24 weeks. Participants continued pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may have received glimepiride (total daily dose of 1-6 mg) as rescue therapy.

Secondary

Percentage of Participants Achieving an A1C Goal <7.0% After 24 Weeks of Treatment

Participant whole blood samples were collected at Week 24 to determine the number of participants achieving A1C <7.0% at Week 24.

Posted

Number

Percentage of participants

Week 24

ID	Title	Description
OG000	Omarigliptin 25 mg Once Weekly	Participants received omarigliptin 25 mg once a week plus placebo to sitagliptin once daily for 24 weeks. Participants continued pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may have received glimepiride (total daily dose of 1-6 mg) as rescue therapy.
OG001	Sitagliptin 100 mg Once Daily	Participants received sitagliptin 100 mg once daily plus placebo to omarigliptin once a week for 24 weeks. Participants continued pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may have received glimepiride (total daily dose of 1-6 mg) as rescue therapy.

Secondary

Percentage of Participants Achieving an A1C Goal <6.5% After 24 Weeks of Treatment

Participant whole blood samples were collected at Week 24 to determine the percentage of participants achieving A1C <6.5% at Week 24.

Posted

Number

Percentage of participants

Week 24

ID	Title	Description
OG000	Omarigliptin 25 mg Once Weekly	Participants received omarigliptin 25 mg once a week plus placebo to sitagliptin once daily for 24 weeks. Participants continued pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may have received glimepiride (total daily dose of 1-6 mg) as rescue therapy.
OG001	Sitagliptin 100 mg Once Daily	Participants received sitagliptin 100 mg once daily plus placebo to omarigliptin once a week for 24 weeks. Participants continued pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may have received glimepiride (total daily dose of 1-6 mg) as rescue therapy.

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 25 mg Once Weekly	Participants received omarigliptin 25 mg once a week plus placebo to sitagliptin once daily for 24 weeks. Participants continued pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may have received glimepiride (total daily dose of 1-6 mg) as rescue therapy.			11	322	0	322
EG001	Sitagliptin 100 mg Once Daily	Participants received sitagliptin 100 mg once daily plus placebo to omarigliptin once a week for 24 weeks. Participants continued pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may have received glimepiride (total daily dose of 1-6 mg) as rescue therapy.			9	320	0	320

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected322 at risk EG0011 events1 affected320 at risk
Angina pectoris	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected322 at risk EG0010 events0 affected320 at risk
Arrhythmia supraventricular	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected322 at risk EG0011 events1 affected320 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected322 at risk EG0011 events1 affected320 at risk
Myocardial infarction	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected322 at risk EG0011 events1 affected320 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected322 at risk EG0010 events0 affected320 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected322 at risk EG0011 events1 affected320 at risk
Hypothyroidism	Endocrine disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected322 at risk EG0010 events0 affected320 at risk
Non-cardiac chest pain	General disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected322 at risk EG0011 events1 affected320 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected322 at risk EG0010 events0 affected320 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected322 at risk EG0010 events0 affected320 at risk
Pyelonephritis acute	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected322 at risk EG0010 events0 affected320 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected322 at risk EG0010 events0 affected320 at risk
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected322 at risk EG0010 events0 affected320 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1	Systematic Assessment	EG0002 events2 affected322 at risk EG0010 events0 affected320 at risk
Sebaceous adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected322 at risk EG0011 events1 affected320 at risk
Cerebrovascular disorder	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected322 at risk EG0011 events1 affected320 at risk
Diabetic neuropathy	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected322 at risk EG0010 events0 affected320 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected322 at risk EG0011 events1 affected320 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected322 at risk EG0011 events1 affected320 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected322 at risk EG0011 events1 affected320 at risk
Dematitis contact	Skin and subcutaneous tissue disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected322 at risk EG0010 events0 affected320 at risk
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected322 at risk EG0010 events0 affected320 at risk
Hypertension	Vascular disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected322 at risk EG0011 events1 affected320 at risk

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

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
D000068900	Sitagliptin Phosphate
D008687	Metformin
C057619	glimepiride

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