A Study to Evaluate the Safety, Tolerability, and Efficac... | NCT01755156

NCT01755156

ID	Type	Description	Link
2012-003670-11	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Omarigliptin (Phase A) → Omarigliptin (Phase B)	Experimental	Phase A: Omarigliptin 25 mg capsule administered orally once weekly for 24 weeks. Phase B: Omarigliptin 25 mg capsule administered orally once weekly and matching placebo to glimepiride tablet/capsule administered orally once daily for 80 weeks. Participants will continue pre-study metformin throughout the duration of the study. If necessary, rescue therapy may be initiated (open-label glimepiride during Phase A and insulin glargine during Phase B).	Drug: Omarigliptin Drug: Matching placebo to glimepiride Drug: Insulin glargine Drug: Metformin
Placebo to omarigliptin (Phase A) → Glimepiride (Phase B)	Placebo Comparator	Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: Matching placebo to omarigliptin capsule administered orally once weekly and glimepiride 1 or 2 mg tablet/capsule administered orally once daily (titrated up to 6 mg daily) for 80 weeks. Participants will continue pre-study metformin throughout the duration of the study. If necessary, rescue therapy may be initiated (open-label glimepiride during Phase A and insulin glargine during Phase B).	Drug: Matching placebo to omarigliptin Drug: Glimepiride Drug: Insulin glargine Drug: Metformin

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Omarigliptin	Drug	Omarigliptin 25 mg capsule administered orally once weekly (preferably on the same day of each week)	Omarigliptin (Phase A) → Omarigliptin (Phase B)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Glycosylated Hemoglobin (A1C) at Week 24 (Phase A)	A1C is measured as a percent. Change from baseline in A1C at Week 24 was analyzed using a constrained longitudinal data analysis (cLDA) method with a restriction of the same baseline mean across treatment groups. The cLDA model included terms for treatment, time, and the interaction of time by treatment.	Baseline and Week 24
Percentage of Participants Who Experienced at Least One Adverse Event (Phase A+B)	An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Presented data exclude data after glycemic rescue.	Up to 107 weeks
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (Phase A+B)	An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Presented data exclude data after glycemic rescue.	Up to 104 weeks
Percentage of Participants Who Experienced an Adverse Event Which Were Included Under the System Order Class of Investigations (Phase A+B)	The following laboratory parameters were included: blood chemistry, hematology, electrocardiograms, lipids, body weight, and vital signs.	Up to 104 weeks

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in 2-hour Post-meal Glucose (PMG) at Week 24 (Phase A)	Change from baseline in 2-hour PMG at Week 24 was analyzed using cLDA method with a restriction of the same baseline mean across treatment groups. The cLDA model included terms for treatment, time, and the interaction of time by treatment.	Baseline and Week 24

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Has 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
History of intolerance, hypersensitivity, or any other contraindication to metformin, glimepiride, or insulin glargine
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 for >=2 consecutive weeks 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 blinded study medication
History of active liver disease (other than non-alcoholic steatosis) including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder 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

Contacts/Locations Module

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

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
28547998	Result	Shankar RR, Inzucchi SE, Scarabello V, Gantz I, Kaufman KD, Lai E, Ceesay P, Suryawanshi S, Engel SS. A randomized clinical trial evaluating the efficacy and safety of the once-weekly dipeptidyl peptidase-4 inhibitor omarigliptin in patients with type 2 diabetes inadequately controlled on metformin monotherapy. Curr Med Res Opin. 2017 Oct;33(10):1853-1860. doi: 10.1080/03007995.2017.1335637. Epub 2017 Jun 23.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Omarigliptin (Phase A) → Omarigliptin (Phase B)	Phase A: Omarigliptin 25 mg capsule administered orally once weekly for 24 weeks. Phase B: Omarigliptin 25 mg capsule administered orally once weekly and matching placebo to glimepiride tablet/capsule administered orally once daily for 80 weeks.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Omarigliptin (Phase A)	Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.
BG001	Placebo to Omarigliptin (Phase A)	Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000201 BG001201 BG002402

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
	BG00057.5± 8.1 BG00156.8± 9.1 BG00257.2± 8.6

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000100 BG00199 BG002

Hemoglobin A1C (A1C)

Mean

Standard Deviation

Percent

Title

Denominators

Categories

Title	Measurements
	BG0008.06± 0.87 BG0018.02± 0.89 BG002

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

Omarigliptin (Phase A), n=192; Placebo to omarigliptin (Phase A), n=193; Total, n=385

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG000240.2± 60.5 BG001236.0± 59.9

Fasting plasma glucose (FPG)

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG000168.8± 37.6 BG001168.6± 37.2 BG002

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 Glycosylated Hemoglobin (A1C) at Week 24 (Phase A)

A1C is measured as a percent. Change from baseline in A1C at Week 24 was analyzed using a constrained longitudinal data analysis (cLDA) method with a restriction of the same baseline mean across treatment groups. The cLDA model included terms for treatment, time, and the interaction of time by treatment.

Full analysis set population included all randomized participants who received at least 1 dose of study medication and had a baseline measurement or a post-randomization measurement.

Posted

Least Squares Mean

95% Confidence Interval

Percent

Baseline and Week 24

ID	Title	Description
OG000	Omarigliptin (Phase A)	Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.
OG001	Placebo to Omarigliptin (Phase A)	Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks

Units	Counts
Participants	OG000201 OG001201

Title

Denominators

Categories

Title	Measurements
	OG000-0.54(-0.69 to -0.40) OG0010.00(-0.14 to 0.15)

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		cLDA	Based on a cLDA method with a restriction of the same baseline mean.	<0.001		Difference in least squares means	-0.55			2-Sided	95	-0.75	-0.34					Superiority or Other

Primary

Percentage of Participants Who Experienced at Least One Adverse Event (Phase A+B)

An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Presented data exclude data after glycemic rescue.

All participants as treated population included all participants who received at least one dose of study medication.

Posted

Number

Percentage of participants

Up to 107 weeks

ID	Title	Description
OG000	Omarigliptin (Phase A) → Omarigliptin (Phase B)	Phase A: Omarigliptin 25 mg capsule administered orally once weekly for 24 weeks. Phase B: Omarigliptin 25 mg capsule administered orally once weekly and matching placebo to glimepiride tablet/capsule administered orally once daily for 80 weeks.
OG001	Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)	Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: Matching placebo to omarigliptin capsule administered orally once weekly and glimepiride 1 or 2 mg tablet/capsule administered orally once daily (titrated up to 6 mg daily) for 80 weeks.

Units	Counts

Primary

Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (Phase A+B)

All participants as treated population included all participants who received at least one dose of study medication.

Posted

Number

Percentage of participants

Up to 104 weeks

ID	Title	Description
OG000	Omarigliptin (Phase A) → Omarigliptin (Phase B)	Phase A: Omarigliptin 25 mg capsule administered orally once weekly for 24 weeks. Phase B: Omarigliptin 25 mg capsule administered orally once weekly and matching placebo to glimepiride tablet/capsule administered orally once daily for 80 weeks.
OG001	Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)	Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: Matching placebo to omarigliptin capsule administered orally once weekly and glimepiride 1 or 2 mg tablet/capsule administered orally once daily (titrated up to 6 mg daily) for 80 weeks.

Units

Primary

Percentage of Participants Who Experienced an Adverse Event Which Were Included Under the System Order Class of Investigations (Phase A+B)

The following laboratory parameters were included: blood chemistry, hematology, electrocardiograms, lipids, body weight, and vital signs.

All participants as treated population included all participants who received at least one dose of study medication.

Posted

Number

Percentage of participants

Up to 104 weeks

ID	Title	Description
OG000	Omarigliptin (Phase A) → Omarigliptin (Phase B)	Phase A: Omarigliptin 25 mg capsule administered orally once weekly for 24 weeks. Phase B: Omarigliptin 25 mg capsule administered orally once weekly and matching placebo to glimepiride tablet/capsule administered orally once daily for 80 weeks.
OG001	Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)	Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: Matching placebo to omarigliptin capsule administered orally once weekly and glimepiride 1 or 2 mg tablet/capsule administered orally once daily (titrated up to 6 mg daily) for 80 weeks.

Units	Counts

Secondary

Change From Baseline in 2-hour Post-meal Glucose (PMG) at Week 24 (Phase A)

Change from baseline in 2-hour PMG at Week 24 was analyzed using cLDA method with a restriction of the same baseline mean across treatment groups. The cLDA model included terms for treatment, time, and the interaction of time by treatment.

Full analysis set population included all randomized participants who received at least 1 dose of study medication and had a baseline measurement or a post-randomization measurement.

Posted

Least Squares Mean

95% Confidence Interval

mg/dL

Baseline and Week 24

ID	Title	Description
OG000	Omarigliptin (Phase A)	Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.
OG001	Placebo to Omarigliptin (Phase A)	Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks

Units	Counts
Participants	OG000

Secondary

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

Change from baseline in FPG at Week 24 was analyzed using cLDA method with a restriction of the same baseline mean across treatment groups. The cLDA model included terms for treatment, time, and the interaction of time by treatment.

Full analysis set population included all randomized participants who received at least 1 dose of study medication and had a baseline measurement or a post-randomization measurement.

Posted

Least Squares Mean

95% Confidence Interval

mg/dL

Baseline and Week 24

ID	Title	Description
OG000	Omarigliptin (Phase A)	Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.
OG001	Placebo to Omarigliptin (Phase A)	Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks

Units	Counts
Participants	OG000

Secondary

Change From Baseline in A1C at Week 104 (Phase A+B)

A1C is measured as a percent. Change from baseline in A1C at Week 104 was analyzed using cLDA method with a restriction of the same baseline mean across treatment groups. The cLDA model included terms for treatment, time, and the interaction of time by treatment.

Full analysis set population included all randomized participants who received at least one dose of study medication and had a baseline measurement or a post-randomization measurement.

Posted

Least Squares Mean

95% Confidence Interval

Percent

Baseline and Week 104

ID	Title	Description
OG000	Omarigliptin (Phase A) → Omarigliptin (Phase B)	Phase A: Omarigliptin 25 mg capsule administered orally once weekly for 24 weeks. Phase B: Omarigliptin 25 mg capsule administered orally once weekly and matching placebo to glimepiride tablet/capsule administered orally once daily for 80 weeks.
OG001	Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)	Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: Matching placebo to omarigliptin capsule administered orally once weekly and glimepiride 1 or 2 mg tablet/capsule administered orally once daily (titrated up to 6 mg daily) for 80 weeks.

Secondary

Change From Baseline in FPG at Week 104 (Phase A+B)

Change from baseline in FPG at Week 104 was analyzed using cLDA method with a restriction of the same baseline mean across treatment groups. The cLDA model included terms for treatment, time, and the interaction of time by treatment.

Full analysis set population included all randomized participants who received at least one dose of study medication and had a baseline measurement or a post-randomization measurement.

Posted

Least Squares Mean

95% Confidence Interval

mg/dL

Baseline and Week 104

ID	Title	Description
OG000	Omarigliptin (Phase A) → Omarigliptin (Phase B)	Phase A: Omarigliptin 25 mg capsule administered orally once weekly for 24 weeks. Phase B: Omarigliptin 25 mg capsule administered orally once weekly and matching placebo to glimepiride tablet/capsule administered orally once daily for 80 weeks.
OG001	Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)	Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: Matching placebo to omarigliptin capsule administered orally once weekly and glimepiride 1 or 2 mg tablet/capsule administered orally once daily (titrated up to 6 mg daily) for 80 weeks.

Secondary

Percentage of Participants Attaining A1C Glycemic Goals of <7.0% After 24 Weeks of Treatment (Phase A)

Percentage of participants attaining A1C glycemic goals of <7.0% (53 mmol/mol) after 24 weeks of treatment estimated using standard multiple imputation techniques.

Full analysis set population included all randomized participants who received at least 1 dose of study medication and had a baseline measurement or a post-randomization measurement.

Posted

Number

95% Confidence Interval

Percentage of participants

24 weeks

ID	Title	Description
OG000	Omarigliptin (Phase A)	Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.
OG001	Placebo to Omarigliptin (Phase A)	Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Attaining A1C Glycemic Goals of <6.5% After 24 Weeks of Treatment (Phase A)

Percentage of participants attaining A1C glycemic goals of <6.5% (48 mmol/mol) after 24 weeks of treatment estimated using standard multiple imputation techniques.

Full analysis set population included all randomized participants who received at least 1 dose of study medication and had a baseline measurement or a post-randomization measurement.

Posted

Number

95% Confidence Interval

Percentage of participants

24 weeks

ID	Title	Description
OG000	Omarigliptin (Phase A)	Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.
OG001	Placebo to Omarigliptin (Phase A)	Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Attaining A1C Glycemic Goals of <7% After 104 Weeks of Treatment (Phase A+B)

Percentage of participants attaining A1C glycemic goals of <7.0% (53 mmol/mol) after 104 weeks of treatment estimated using standard multiple imputation techniques.

Full analysis set population included all randomized participants who received at least one dose of study medication and had a baseline measurement or a post-randomization measurement.

Posted

Least Squares Mean

95% Confidence Interval

Percentage of participants

104 weeks

ID	Title	Description
OG000	Omarigliptin (Phase A) → Omarigliptin (Phase B)	Phase A: Omarigliptin 25 mg capsule administered orally once weekly for 24 weeks. Phase B: Omarigliptin 25 mg capsule administered orally once weekly and matching placebo to glimepiride tablet/capsule administered orally once daily for 80 weeks.
OG001	Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)	Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: Matching placebo to omarigliptin capsule administered orally once weekly and glimepiride 1 or 2 mg tablet/capsule administered orally once daily (titrated up to 6 mg daily) for 80 weeks.

Secondary

Percentage of Participants Attaining A1C Glycemic Goals of <6.5% After 104 Weeks of Treatment (Phase A+B)

Percentage of participants attaining A1C glycemic goals of <6.5% (48 mmol/mol) after 104 weeks of treatment estimated using standard multiple imputation techniques.

Full analysis set population included all randomized participants who received at least one dose of study medication and had a baseline measurement or a post-randomization measurement.

Posted

Least Squares Mean

95% Confidence Interval

Percentage of participants

104 weeks

ID	Title	Description
OG000	Omarigliptin (Phase A) → Omarigliptin (Phase B)	Phase A: Omarigliptin 25 mg capsule administered orally once weekly for 24 weeks. Phase B: Omarigliptin 25 mg capsule administered orally once weekly and matching placebo to glimepiride tablet/capsule administered orally once daily for 80 weeks.
OG001	Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)	Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: Matching placebo to omarigliptin capsule administered orally once weekly and glimepiride 1 or 2 mg tablet/capsule administered orally once daily (titrated up to 6 mg daily) for 80 weeks.

Secondary

Change From Baseline in PMG Total Area Under the Plasma Concentration Time Curve (AUC) at Week 24 (Phase A)

Change from baseline in PMG total AUC at Week 24 based on a cLDA model including terms for treatment, time, and the interaction of time by treatment. Plasma glucose levels were measured before the meal (0 minutes), and at 60 and 120 minutes after the meal.

Full analysis set population included all randomized participants who received at least 1 dose of study medication and had a baseline measurement or a post-randomization measurement.

Posted

Least Squares Mean

95% Confidence Interval

mg*h/dL

Baseline and Week 24

ID	Title	Description
OG000	Omarigliptin (Phase A)	Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.
OG001	Placebo to Omarigliptin (Phase A)	Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Fasting Insulin at Week 24 (Phase A)

Change from baseline in fasting insulin at Week 24 based on a cLDA model including terms for treatment, time, and the interaction of time by treatment.

Full analysis set population included all randomized participants who received at least 1 dose of study medication and had a baseline measurement or a post-randomization measurement.

Posted

Least Squares Mean

95% Confidence Interval

micro International Unit (μIU)/mL

Baseline and Week 24

ID	Title	Description
OG000	Omarigliptin (Phase A)	Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.
OG001	Placebo to Omarigliptin (Phase A)	Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Fasting Insulin at Week 104 (Phase A+B)

Change from baseline in fasting insulin at Week 104 based on a cLDA model including terms for treatment, time, and the interaction of time by treatment.

Full analysis set population included all randomized participants who received at least one dose of study medication and had a baseline measurement or a post-randomization measurement.

Posted

Least Squares Mean

95% Confidence Interval

μIU/mL

Baseline and Week 104

ID	Title	Description
OG000	Omarigliptin (Phase A) → Omarigliptin (Phase B)	Phase A: Omarigliptin 25 mg capsule administered orally once weekly for 24 weeks. Phase B: Omarigliptin 25 mg capsule administered orally once weekly and matching placebo to glimepiride tablet/capsule administered orally once daily for 80 weeks.
OG001	Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)	Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: Matching placebo to omarigliptin capsule administered orally once weekly and glimepiride 1 or 2 mg tablet/capsule administered orally once daily (titrated up to 6 mg daily) for 80 weeks.

Units	Counts

Secondary

Kaplan-Meier Estimate of Cumulative Incidence of Participants Requiring Glycemic Rescue Therapy by 24 Weeks (Phase A)

Participants who did not meet progressively stricter glycemic criteria in Phase A had rescue initiated with open-label glimepiride.

All participants randomized population.

Posted

Number

95% Confidence Interval

Percentage of participants

Up to 24 weeks

ID	Title	Description
OG000	Omarigliptin (Phase A)	Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.
OG001	Placebo to Omarigliptin (Phase A)	Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks

Units	Counts
Participants	OG000

Secondary

Kaplan-Meier Estimate of Cumulative Incidence of Participants Requiring Glycemic Rescue Therapy by 104 Weeks (Phase A+B)

Participants who did not meet progressively stricter glycemic criteria in Phase A had rescue initiated with open-label glimepiride. If during Phase B participants on open-label glimepiride or blinded glimepiride/glimepiride matching placebo needed rescue after maximum up-titration, then insulin glargine was initiated and the dose of open-label glimepiride or blinded glimepiride/glimepiride-matching placebo was discontinued.

All participants randomized population.

Posted

Number

95% Confidence Interval

Percentage of participants

Up to 104 weeks

ID	Title	Description
OG000	Omarigliptin (Phase A) → Omarigliptin (Phase B)	Phase A: Omarigliptin 25 mg capsule administered orally once weekly for 24 weeks. Phase B: Omarigliptin 25 mg capsule administered orally once weekly and matching placebo to glimepiride tablet/capsule administered orally once daily for 80 weeks.
OG001	Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)	Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: Matching placebo to omarigliptin capsule administered orally once weekly and glimepiride 1 or 2 mg tablet/capsule administered orally once daily (titrated up to 6 mg daily) for 80 weeks.

Secondary

Percentage of Participants Requiring Glycemic Rescue Therapy at or Before Week 24 (Phase A)

Data presented are a cumulative incidence of participants with glycemic rescue by Week 24.

All participants randomized population.

Posted

Number

Percentage of participants

Up to 24 weeks

ID	Title	Description
OG000	Omarigliptin (Phase A)	Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.
OG001	Placebo to Omarigliptin (Phase A)	Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Requiring Glycemic Rescue Therapy at or Before Week 104 (Phase A+B)

Data presented are a cumulative incidence of participants with glycemic rescue by Week 104.

All participants randomized population.

Posted

Number

Percentage of participants

Up to 104 weeks

ID	Title	Description
OG000	Omarigliptin (Phase A) → Omarigliptin (Phase B)	Phase A: Omarigliptin 25 mg capsule administered orally once weekly for 24 weeks. Phase B: Omarigliptin 25 mg capsule administered orally once weekly and matching placebo to glimepiride tablet/capsule administered orally once daily for 80 weeks.
OG001	Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)	Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: Matching placebo to omarigliptin capsule administered orally once weekly and glimepiride 1 or 2 mg tablet/capsule administered orally once daily (titrated up to 6 mg daily) for 80 weeks.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Omarigliptin (Phase A)	Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.	5	201	27	201
EG001	Placebo to Omarigliptin (Phase A)	Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks.	10	201	17	201
EG002	Omarigliptin (Phase A) → Omarigliptin (Phase B)	Phase A: Omarigliptin 25 mg capsule administered orally once weekly for 24 weeks. Phase B: Omarigliptin 25 mg capsule administered orally once weekly and matching placebo to glimepiride tablet/capsule administered orally once daily for 80 weeks.	12	201	53	201
EG003	Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)	Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: Matching placebo to omarigliptin capsule administered orally once weekly and glimepiride 1 or 2 mg tablet/capsule administered orally once daily (titrated up to 6 mg daily) for 80 weeks.	18	201	58	201

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute coronary syndrome	Cardiac disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0011 events1 affected201 at risk EG0020 events0 affected201 at risk EG0031 events1 affected201 at risk
Atrioventricular block second degree	Cardiac disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected201 at risk EG0020 events0 affected201 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected201 at risk EG0021 events1 affected201 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected201 at risk EG0020 events0 affected201 at risk EG003
Myocardial ischaemia	Cardiac disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected201 at risk EG0020 events0 affected201 at risk EG003
Supraventricular tachycardia	Cardiac disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0001 events1 affected201 at risk EG0010 events0 affected201 at risk EG0021 events1 affected201 at risk EG003
Gastric polyps	Gastrointestinal disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0001 events1 affected201 at risk EG0010 events0 affected201 at risk EG0021 events1 affected201 at risk EG003
Pancreatic cyst	Gastrointestinal disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected201 at risk EG0020 events0 affected201 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected201 at risk EG0020 events0 affected201 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0011 events1 affected201 at risk EG0020 events0 affected201 at risk EG003
Chest pain	General disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0011 events1 affected201 at risk EG0020 events0 affected201 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0011 events1 affected201 at risk EG0020 events0 affected201 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected201 at risk EG0021 events1 affected201 at risk EG003
Bronchitis	Infections and infestations	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected201 at risk EG0020 events0 affected201 at risk EG003
Pneumonia	Infections and infestations	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0011 events1 affected201 at risk EG0020 events0 affected201 at risk EG003
Femur fracture	Injury, poisoning and procedural complications	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected201 at risk EG0021 events1 affected201 at risk EG003
Seroma	Injury, poisoning and procedural complications	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0011 events1 affected201 at risk EG0020 events0 affected201 at risk EG003
Tendon injury	Injury, poisoning and procedural complications	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected201 at risk EG0021 events1 affected201 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0001 events1 affected201 at risk EG0011 events1 affected201 at risk EG0022 events2 affected201 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected201 at risk EG0021 events1 affected201 at risk EG003
Osteochondrosis	Musculoskeletal and connective tissue disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0011 events1 affected201 at risk EG0020 events0 affected201 at risk EG003
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0011 events1 affected201 at risk EG0020 events0 affected201 at risk EG003
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected201 at risk EG0021 events1 affected201 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected201 at risk EG0021 events1 affected201 at risk EG003
Hepatocellular carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected201 at risk EG0020 events0 affected201 at risk EG003
Invasive ductal breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1, 18.1	Systematic Assessment	EG0001 events1 affected201 at risk EG0010 events0 affected201 at risk EG0021 events1 affected201 at risk EG003
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0011 events1 affected201 at risk EG0020 events0 affected201 at risk EG003
Uterine haemorrhage	Reproductive system and breast disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0001 events1 affected201 at risk EG0010 events0 affected201 at risk EG0021 events1 affected201 at risk EG003
Hypertension	Vascular disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0011 events1 affected201 at risk EG0020 events0 affected201 at risk EG003
Peripheral venous disease	Vascular disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected201 at risk EG0021 events1 affected201 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 17.1, 18.1	Systematic Assessment	EG0005 events5 affected201 at risk EG0011 events1 affected201 at risk EG00212 events11 affected201 at risk EG0037 events7 affected201 at risk
Blood glucose increased	Investigations	MedDRA 17.1, 18.1	Systematic Assessment	EG0009 events9 affected201 at risk EG00110 events7 affected201 at risk EG00216 events14 affected201 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG00013 events7 affected201 at risk EG0018 events5 affected201 at risk EG00243 events17 affected201 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0003 events2 affected201 at risk EG0010 events0 affected201 at risk EG00212 events11 affected201 at risk EG003
Headache	Nervous system disorders	MedDRA 17.1, 18.1	Systematic Assessment	EG0005 events5 affected201 at risk EG0015 events5 affected201 at risk EG0028 events8 affected201 at risk EG003

ID	Term
D003924	Diabetes Mellitus, Type 2

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
D000069036	Insulin Glargine
D008687	Metformin

Ancestor Terms

ID	Term
D049528	Insulin, Long-Acting
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals

Units	Counts
Participants	OG000201 OG001201

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