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A Study to Evaluate the Safety, Tolerability, and Efficacy of the Addition of Omarigliptin (MK-3102) to Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin Therapy (MK-3102-024)

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ClinicalTrials.gov Identifier: NCT01755156
Recruitment Status : Completed
First Posted : December 24, 2012
Results First Posted : March 20, 2017
Last Update Posted : September 10, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Type 2 Diabetes Mellitus
Interventions Drug: Omarigliptin
Drug: Matching placebo to omarigliptin
Drug: Glimepiride
Drug: Matching placebo to glimepiride
Drug: Insulin glargine
Drug: Metformin
Enrollment 402

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Omarigliptin (Phase A) → Omarigliptin (Phase B) Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)
Hide Arm/Group Description 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. 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.
Period Title: Phase A (Weeks 0-24)
Started 201 201
Completed 184 177
Not Completed 17 24
Reason Not Completed
Adverse Event             2             3
Lack of Efficacy             1             0
Lost to Follow-up             5             3
Non-compliance with study drug             1             0
Physician Decision             0             1
Protocol Violation             1             1
Withdrawal by Subject             6             13
Creatinine or eGFR Discon. Criteria             0             2
Need for Excluded Med. Discon. Criteria             1             1
Period Title: Phase B (Weeks 24-104)
Started 183 [1] 177
Completed 144 141
Not Completed 39 36
Reason Not Completed
Lost to Follow-up             12             5
Withdrawal by Subject             27             31
[1]
1 participant who completed Phase A did not continue to Phase B.
Arm/Group Title Omarigliptin (Phase A) Placebo to Omarigliptin (Phase A) Total
Hide Arm/Group Description Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks. Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks Total of all reporting groups
Overall Number of Baseline Participants 201 201 402
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 201 participants 201 participants 402 participants
57.5  (8.1) 56.8  (9.1) 57.2  (8.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 201 participants 402 participants
Female
100
  49.8%
99
  49.3%
199
  49.5%
Male
101
  50.2%
102
  50.7%
203
  50.5%
Hemoglobin A1C (A1C)  
Mean (Standard Deviation)
Unit of measure:  Percent
Number Analyzed 201 participants 201 participants 402 participants
8.06  (0.87) 8.02  (0.89) 8.04  (0.88)
2-hour post-meal glucose (2-hr PMG)   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 201 participants 201 participants 402 participants
240.2  (60.5) 236.0  (59.9) 238.1  (60.2)
[1]
Measure Description: Omarigliptin (Phase A), n=192; Placebo to omarigliptin (Phase A), n=193; Total, n=385
Fasting plasma glucose (FPG)  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 201 participants 201 participants 402 participants
168.8  (37.6) 168.6  (37.2) 168.7  (37.4)
1.Primary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (A1C) at Week 24 (Phase A)
Hide Description 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.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omarigliptin (Phase A) Placebo to Omarigliptin (Phase A)
Hide Arm/Group Description:
Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.
Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks
Overall Number of Participants Analyzed 201 201
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent
-0.54
(-0.69 to -0.40)
0.00
(-0.14 to 0.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omarigliptin (Phase A), Placebo to Omarigliptin (Phase A)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method cLDA
Comments Based on a cLDA method with a restriction of the same baseline mean.
Method of Estimation Estimation Parameter Difference in least squares means
Estimated Value -0.55
Confidence Interval (2-Sided) 95%
-0.75 to -0.34
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants Who Experienced at Least One Adverse Event (Phase A+B)
Hide Description 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.
Time Frame Up to 107 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants as treated population included all participants who received at least one dose of study medication.
Arm/Group Title Omarigliptin (Phase A) → Omarigliptin (Phase B) Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 201 201
Measure Type: Number
Unit of Measure: Percentage of participants
65.7 65.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omarigliptin (Phase A) → Omarigliptin (Phase B), Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in %
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-8.8 to 9.8
Estimation Comments Based on Miettinen & Nurminen method. The 95% CI was computed only for those endpoints with at least 4 participants having events in 1 or more treatment groups.
3.Primary Outcome
Title Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (Phase A+B)
Hide Description 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.
Time Frame Up to 104 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants as treated population included all participants who received at least one dose of study medication.
Arm/Group Title Omarigliptin (Phase A) → Omarigliptin (Phase B) Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 201 201
Measure Type: Number
Unit of Measure: Percentage of participants
2.0 4.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omarigliptin (Phase A) → Omarigliptin (Phase B), Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in %
Estimated Value -2.5
Confidence Interval (2-Sided) 95%
-6.6 to 1.1
Estimation Comments Based on Miettinen & Nurminen method. The 95% CI was computed only for those endpoints with at least 4 participants having events in 1 or more treatment groups.
4.Primary Outcome
Title Percentage of Participants Who Experienced an Adverse Event Which Were Included Under the System Order Class of Investigations (Phase A+B)
Hide Description The following laboratory parameters were included: blood chemistry, hematology, electrocardiograms, lipids, body weight, and vital signs.
Time Frame Up to 104 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants as treated population included all participants who received at least one dose of study medication.
Arm/Group Title Omarigliptin (Phase A) → Omarigliptin (Phase B) Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 201 201
Measure Type: Number
Unit of Measure: Percentage of participants
21.9 17.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omarigliptin (Phase A) → Omarigliptin (Phase B), Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in %
Estimated Value 4.5
Confidence Interval (2-Sided) 95%
-3.3 to 12.3
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in 2-hour Post-meal Glucose (PMG) at Week 24 (Phase A)
Hide Description 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.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omarigliptin (Phase A) Placebo to Omarigliptin (Phase A)
Hide Arm/Group Description:
Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.
Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks
Overall Number of Participants Analyzed 195 199
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mg/dL
-26.8
(-34.8 to -18.7)
-12.2
(-20.7 to -3.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omarigliptin (Phase A), Placebo to Omarigliptin (Phase A)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method cLDA
Comments Based on a cLDA method with a restriction of the same baseline mean.
Method of Estimation Estimation Parameter Difference in %
Estimated Value -14.5
Confidence Interval (2-Sided) 95%
-25.6 to -3.4
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Phase A)
Hide Description 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.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omarigliptin (Phase A) Placebo to Omarigliptin (Phase A)
Hide Arm/Group Description:
Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.
Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks
Overall Number of Participants Analyzed 201 201
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mg/dL
-10.7
(-16.0 to -5.5)
-1.2
(-6.6 to 4.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omarigliptin (Phase A), Placebo to Omarigliptin (Phase A)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments [Not Specified]
Method cLDA
Comments Based on a cLDA method with a restriction of the same baseline mean.
Method of Estimation Estimation Parameter Difference in least squares means
Estimated Value -9.5
Confidence Interval (2-Sided) 95%
-16.7 to -2.3
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in A1C at Week 104 (Phase A+B)
Hide Description 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.
Time Frame Baseline and Week 104
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omarigliptin (Phase A) → Omarigliptin (Phase B) Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 201 201
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent
-0.42
(-0.59 to -0.25)
-0.51
(-0.68 to -0.34)
8.Secondary Outcome
Title Change From Baseline in FPG at Week 104 (Phase A+B)
Hide Description 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.
Time Frame Baseline and Week 104
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omarigliptin (Phase A) → Omarigliptin (Phase B) Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 201 201
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mg/dL
-7.8
(-14.4 to -1.3)
-18.2
(-24.7 to -11.7)
9.Secondary Outcome
Title Percentage of Participants Attaining A1C Glycemic Goals of <7.0% After 24 Weeks of Treatment (Phase A)
Hide Description Percentage of participants attaining A1C glycemic goals of <7.0% (53 mmol/mol) after 24 weeks of treatment estimated using standard multiple imputation techniques.
Time Frame 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omarigliptin (Phase A) Placebo to Omarigliptin (Phase A)
Hide Arm/Group Description:
Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.
Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks
Overall Number of Participants Analyzed 201 201
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
38.0
(31.3 to 45.1)
18.8
(13.9 to 25.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omarigliptin (Phase A), Placebo to Omarigliptin (Phase A)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Miettinen & Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Between-group rate difference (%)
Estimated Value 19.2
Confidence Interval (2-Sided) 95%
10.1 to 28.0
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percentage of Participants Attaining A1C Glycemic Goals of <6.5% After 24 Weeks of Treatment (Phase A)
Hide Description Percentage of participants attaining A1C glycemic goals of <6.5% (48 mmol/mol) after 24 weeks of treatment estimated using standard multiple imputation techniques.
Time Frame 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omarigliptin (Phase A) Placebo to Omarigliptin (Phase A)
Hide Arm/Group Description:
Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.
Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks
Overall Number of Participants Analyzed 201 201
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
10.6
(6.8 to 16.2)
6.4
(3.6 to 11.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omarigliptin (Phase A), Placebo to Omarigliptin (Phase A)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.164
Comments [Not Specified]
Method Miettinen & Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Between-group rate difference (%)
Estimated Value 4.2
Confidence Interval (2-Sided) 95%
-1.8 to 10.5
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Percentage of Participants Attaining A1C Glycemic Goals of <7% After 104 Weeks of Treatment (Phase A+B)
Hide Description Percentage of participants attaining A1C glycemic goals of <7.0% (53 mmol/mol) after 104 weeks of treatment estimated using standard multiple imputation techniques.
Time Frame 104 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omarigliptin (Phase A) → Omarigliptin (Phase B) Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 201 201
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percentage of participants
32.2
(25.7 to 39.5)
39.0
(31.7 to 46.8)
12.Secondary Outcome
Title Percentage of Participants Attaining A1C Glycemic Goals of <6.5% After 104 Weeks of Treatment (Phase A+B)
Hide Description Percentage of participants attaining A1C glycemic goals of <6.5% (48 mmol/mol) after 104 weeks of treatment estimated using standard multiple imputation techniques.
Time Frame 104 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omarigliptin (Phase A) → Omarigliptin (Phase B) Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 201 201
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percentage of participants
13.7
(9.4 to 19.6)
17.9
(12.5 to 24.8)
13.Secondary Outcome
Title Change From Baseline in PMG Total Area Under the Plasma Concentration Time Curve (AUC) at Week 24 (Phase A)
Hide Description 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.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omarigliptin (Phase A) Placebo to Omarigliptin (Phase A)
Hide Arm/Group Description:
Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.
Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks
Overall Number of Participants Analyzed 195 198
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mg*h/dL
-46.4
(-58.7 to -34.1)
-18.6
(-31.5 to -5.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omarigliptin (Phase A), Placebo to Omarigliptin (Phase A)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method cLDA
Comments Based on a cLDA method with a restriction of the same baseline mean.
Method of Estimation Estimation Parameter Difference in least squares means
Estimated Value -27.8
Confidence Interval (2-Sided) 95%
-44.8 to -10.8
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline in Fasting Insulin at Week 24 (Phase A)
Hide Description 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.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omarigliptin (Phase A) Placebo to Omarigliptin (Phase A)
Hide Arm/Group Description:
Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.
Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks
Overall Number of Participants Analyzed 200 200
Least Squares Mean (95% Confidence Interval)
Unit of Measure: micro International Unit (μIU)/mL
1.8
(-0.6 to 4.2)
-1.9
(-4.3 to 0.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omarigliptin (Phase A), Placebo to Omarigliptin (Phase A)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.025
Comments [Not Specified]
Method cLDA
Comments Based on a cLDA method with a restriction of the same baseline mean.
Method of Estimation Estimation Parameter Difference in least squares means
Estimated Value 3.7
Confidence Interval (2-Sided) 95%
0.5 to 6.9
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Change From Baseline in Fasting Insulin at Week 104 (Phase A+B)
Hide Description 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.
Time Frame Baseline and Week 104
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omarigliptin (Phase A) → Omarigliptin (Phase B) Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 201 200
Least Squares Mean (95% Confidence Interval)
Unit of Measure: μIU/mL
1.2
(-1.9 to 4.2)
1.8
(-1.2 to 4.8)
16.Secondary Outcome
Title Kaplan-Meier Estimate of Cumulative Incidence of Participants Requiring Glycemic Rescue Therapy by 24 Weeks (Phase A)
Hide Description Participants who did not meet progressively stricter glycemic criteria in Phase A had rescue initiated with open-label glimepiride.
Time Frame Up to 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants randomized population.
Arm/Group Title Omarigliptin (Phase A) Placebo to Omarigliptin (Phase A)
Hide Arm/Group Description:
Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.
Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks
Overall Number of Participants Analyzed 201 201
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
8.5
(5.3 to 13.6)
9.7
(6.2 to 15.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omarigliptin (Phase A), Placebo to Omarigliptin (Phase A)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.654
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Kaplan-Meier difference %
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-7.0 to 4.7
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Kaplan-Meier Estimate of Cumulative Incidence of Participants Requiring Glycemic Rescue Therapy by 104 Weeks (Phase A+B)
Hide Description 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.
Time Frame Up to 104 weeks
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Hide Analysis Population Description
All participants randomized population.
Arm/Group Title Omarigliptin (Phase A) → Omarigliptin (Phase B) Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 201 201
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
20.2
(14.9 to 27.1)
16.2
(11.5 to 22.7)
18.Secondary Outcome
Title Percentage of Participants Requiring Glycemic Rescue Therapy at or Before Week 24 (Phase A)
Hide Description Data presented are a cumulative incidence of participants with glycemic rescue by Week 24.
Time Frame Up to 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants randomized population.
Arm/Group Title Omarigliptin (Phase A) Placebo to Omarigliptin (Phase A)
Hide Arm/Group Description:
Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks.
Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks
Overall Number of Participants Analyzed 201 201
Measure Type: Number
Unit of Measure: Percentage of participants
8.0 9.0
19.Secondary Outcome
Title Percentage of Participants Requiring Glycemic Rescue Therapy at or Before Week 104 (Phase A+B)
Hide Description Data presented are a cumulative incidence of participants with glycemic rescue by Week 104.
Time Frame Up to 104 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants randomized population.
Arm/Group Title Omarigliptin (Phase A) → Omarigliptin (Phase B) Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 201 201
Measure Type: Number
Unit of Measure: Percentage of participants
17.4 13.9
Time Frame Up to 107 weeks (treatment period + 21-day follow-up)
Adverse Event Reporting Description APaT population consists of all randomized participants who took at least 1 dose of study drug. Serious adverse events (SAEs) include data after glycemic rescue; non-serious adverse events exclude data after glycemic rescue. The AEs reported in the (Phase A) → (Phase B) columns are a total of the AEs (SAEs) that occurred in Phases A and B.
 
Arm/Group Title Omarigliptin (Phase A) Placebo to Omarigliptin (Phase A) Omarigliptin (Phase A) → Omarigliptin (Phase B) Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)
Hide Arm/Group Description Phase A: Omarigliptin 25 mg capsule orally once a week for 24 weeks. Phase A: Matching placebo to omarigliptin capsule administered orally once weekly for 24 weeks. 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. 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.
All-Cause Mortality
Omarigliptin (Phase A) Placebo to Omarigliptin (Phase A) Omarigliptin (Phase A) → Omarigliptin (Phase B) Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Omarigliptin (Phase A) Placebo to Omarigliptin (Phase A) Omarigliptin (Phase A) → Omarigliptin (Phase B) Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/201 (2.49%)      10/201 (4.98%)      12/201 (5.97%)      18/201 (8.96%)    
Cardiac disorders         
Acute coronary syndrome  1  0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0 1/201 (0.50%)  1
Atrioventricular block second degree  1  0/201 (0.00%)  0 0/201 (0.00%)  0 0/201 (0.00%)  0 1/201 (0.50%)  1
Coronary artery disease  1  0/201 (0.00%)  0 0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0
Myocardial infarction  1  0/201 (0.00%)  0 0/201 (0.00%)  0 0/201 (0.00%)  0 1/201 (0.50%)  1
Myocardial ischaemia  1  0/201 (0.00%)  0 0/201 (0.00%)  0 0/201 (0.00%)  0 1/201 (0.50%)  1
Supraventricular tachycardia  1  1/201 (0.50%)  1 0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0
Gastrointestinal disorders         
Gastric polyps  1  1/201 (0.50%)  1 0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0
Pancreatic cyst  1  0/201 (0.00%)  0 0/201 (0.00%)  0 0/201 (0.00%)  0 1/201 (0.50%)  1
Pancreatitis  1  0/201 (0.00%)  0 0/201 (0.00%)  0 0/201 (0.00%)  0 1/201 (0.50%)  1
Pancreatitis acute  1  0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0 2/201 (1.00%)  2
General disorders         
Chest pain  1  0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0 1/201 (0.50%)  1
Non-cardiac chest pain  1  0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0 1/201 (0.50%)  1
Hepatobiliary disorders         
Cholelithiasis  1  0/201 (0.00%)  0 0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0
Infections and infestations         
Bronchitis  1  0/201 (0.00%)  0 0/201 (0.00%)  0 0/201 (0.00%)  0 1/201 (0.50%)  1
Pneumonia  1  0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0 2/201 (1.00%)  2
Injury, poisoning and procedural complications         
Femur fracture  1  0/201 (0.00%)  0 0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0
Seroma  1  0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0 1/201 (0.50%)  1
Tendon injury  1  0/201 (0.00%)  0 0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Intervertebral disc protrusion  1  1/201 (0.50%)  1 1/201 (0.50%)  1 2/201 (1.00%)  2 1/201 (0.50%)  1
Osteoarthritis  1  0/201 (0.00%)  0 0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0
Osteochondrosis  1  0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0 1/201 (0.50%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Adenocarcinoma of colon  1  0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0 1/201 (0.50%)  1
Bladder neoplasm  1  0/201 (0.00%)  0 0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0
Breast cancer  1  0/201 (0.00%)  0 0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0
Hepatocellular carcinoma  1  0/201 (0.00%)  0 0/201 (0.00%)  0 0/201 (0.00%)  0 1/201 (0.50%)  1
Invasive ductal breast carcinoma  1  1/201 (0.50%)  1 0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0
Lung neoplasm malignant  1  0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0 2/201 (1.00%)  2
Reproductive system and breast disorders         
Uterine haemorrhage  1  1/201 (0.50%)  1 0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0
Vascular disorders         
Hypertension  1  0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0 1/201 (0.50%)  1
Peripheral venous disease  1  0/201 (0.00%)  0 0/201 (0.00%)  0 1/201 (0.50%)  1 0/201 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1, 18.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Omarigliptin (Phase A) Placebo to Omarigliptin (Phase A) Omarigliptin (Phase A) → Omarigliptin (Phase B) Placebo to Omarigliptin (Phase A) → Glimepiride (Phase B)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   27/201 (13.43%)      17/201 (8.46%)      53/201 (26.37%)      58/201 (28.86%)    
Infections and infestations         
Nasopharyngitis  1  5/201 (2.49%)  5 1/201 (0.50%)  1 11/201 (5.47%)  12 7/201 (3.48%)  7
Investigations         
Blood glucose increased  1  9/201 (4.48%)  9 7/201 (3.48%)  10 14/201 (6.97%)  16 10/201 (4.98%)  14
Metabolism and nutrition disorders         
Hypoglycaemia  1  7/201 (3.48%)  13 5/201 (2.49%)  8 17/201 (8.46%)  43 32/201 (15.92%)  112
Musculoskeletal and connective tissue disorders         
Arthralgia  1  2/201 (1.00%)  3 0/201 (0.00%)  0 11/201 (5.47%)  12 8/201 (3.98%)  9
Nervous system disorders         
Headache  1  5/201 (2.49%)  5 5/201 (2.49%)  5 8/201 (3.98%)  8 11/201 (5.47%)  11
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1, 18.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission.
Results Point of Contact
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01755156     History of Changes
Other Study ID Numbers: 3102-024
2012-003670-11 ( EudraCT Number )
First Submitted: December 18, 2012
First Posted: December 24, 2012
Results First Submitted: January 30, 2017
Results First Posted: March 20, 2017
Last Update Posted: September 10, 2018