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A Study of the Safety and Efficacy of Omarigliptin (MK-3102) in ≥18 and <45 Year-Old Participants With Type 2 Diabetes Mellitus and Inadequate Glycemic Control (MK-3102-028)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01814748
Recruitment Status : Completed
First Posted : March 20, 2013
Results First Posted : July 18, 2016
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: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Diabetes Mellitus
Interventions Drug: Omarigliptin
Drug: Placebo to omarigliptin
Drug: Metformin
Enrollment 203
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Omarigliptin 25 mg Placebo
Hide Arm/Group Description Omarigliptin 25 mg, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited. Placebo to omarigliptin, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Period Title: Overall Study
Started 102 101
Completed 94 94
Not Completed 8 7
Reason Not Completed
Lost to Follow-up             1             2
Study site terminated by sponsor             1             1
Withdrawal by Subject             6             4
Arm/Group Title Omarigliptin 25 mg Placebo Total
Hide Arm/Group Description Omarigliptin 25 mg, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited. Placebo to omarigliptin, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited. Total of all reporting groups
Overall Number of Baseline Participants 102 101 203
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 102 participants 101 participants 203 participants
38.8  (4.7) 39.5  (4.5) 39.2  (4.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 102 participants 101 participants 203 participants
Female
35
  34.3%
41
  40.6%
76
  37.4%
Male
67
  65.7%
60
  59.4%
127
  62.6%
Hemoglobin A1c (A1C)  
Mean (Standard Deviation)
Unit of measure:  Percent
Number Analyzed 102 participants 101 participants 203 participants
7.9  (0.8) 8.1  (0.9) 8.0  (0.8)
2-hour post-meal glucose (2-hr PMG)   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 102 participants 101 participants 203 participants
204.9  (55.1) 217.3  (67.7) 211.2  (62.0)
[1]
Measure Description: Participants with available data at baseline: Omarigliptin, n=98; Placebo, n=101; Total, n=199
Fasting plasma glucose (FPG)  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 102 participants 101 participants 203 participants
164.0  (38.9) 167.8  (40.6) 165.9  (39.7)
1.Primary Outcome
Title Change From Baseline in A1C at Week 24
Hide Description

A1C (%) is used to report average blood glucose levels over prolonged periods of time.

The unexpected absence of a treatment effect in this study led to investigations that included measurement of metformin levels in available samples collected for future research during the study. Of the 92 participants with samples who had not been rescued with metformin, 57% (25/44) in the placebo group and 29% (14/48) in the omarigliptin group had detectable metformin, indicating the use of metformin that was prohibited by the protocol. The use of metformin prohibited by the protocol was without investigator knowledge and is a confounding factor impacting the ability to draw any conclusions regarding the efficacy results from this study.

Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) population comprised all participants who received at least one dose of study treatment and had a baseline measurement or a post-randomization measurement for the analysis endpoint.
Arm/Group Title Omarigliptin 25 mg Placebo
Hide Arm/Group Description:
Omarigliptin 25 mg, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Placebo to omarigliptin, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Overall Number of Participants Analyzed 102 101
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent
-0.33
(-0.60 to -0.06)
-0.45
(-0.72 to -0.18)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omarigliptin 25 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.535
Comments [Not Specified]
Method Constrained longitudinal data analysis
Comments Terms for treatment, time, and the interaction of time by treatment, with the constraint that the mean baseline is the same for all treatment groups.
Method of Estimation Estimation Parameter Difference in least squares means
Estimated Value 0.12
Confidence Interval (2-Sided) 95%
-0.26 to 0.49
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants Who Experienced at Least One Adverse Event (AE)
Hide Description

An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Data presented exclude data following the initiation of glycemic rescue.

The safety database was analyzed in a standard fashion in the all participants as treated (APaT) population for all participants who took at least one dose of study medication. This analysis may have been confounded by the use of metformin prohibited by the protocol (see efficacy results description above).

Time Frame Up to Week 27
Hide Outcome Measure Data
Hide Analysis Population Description
APaT population included all randomized participants who received at least one dose of study medication.
Arm/Group Title Omarigliptin 25 mg Placebo
Hide Arm/Group Description:
Omarigliptin 25 mg, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Placebo to omarigliptin, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Overall Number of Participants Analyzed 102 101
Measure Type: Number
Unit of Measure: Percentage of participants
39.2 39.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omarigliptin 25 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percent
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-13.8 to 13.0
Estimation Comments [Not Specified]
3.Primary Outcome
Title Percentage of Participants Who Discontinued Study Drug Due to an AE
Hide Description

An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Data presented exclude data following the initiation of glycemic rescue.

The safety database was analyzed in a standard fashion in the APaT population for all participants who took at least one dose of study medication. This analysis may have been confounded by the use of metformin prohibited by the protocol (see efficacy results description above).

Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
APaT population included all randomized participants who received at least one dose of study medication.
Arm/Group Title Omarigliptin 25 mg Placebo
Hide Arm/Group Description:
Omarigliptin 25 mg, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Placebo to omarigliptin, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Overall Number of Participants Analyzed 102 101
Measure Type: Number
Unit of Measure: Percentage of participants
0.0 2.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omarigliptin 25 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percent
Estimated Value -2.0
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in 2-hr PMG at Week 24
Hide Description

Blood glucose was measured 120 minutes from start of meal.

The unexpected absence of a treatment effect in this study led to investigations that included measurement of metformin levels in available samples collected for future research during the study. Of the 92 participants with samples who had not been rescued with metformin, 57% (25/44) in the placebo group and 29% (14/48) in the omarigliptin group had detectable metformin, indicating the use of metformin that was prohibited by the protocol. The use of metformin prohibited by the protocol was without investigator knowledge and is a confounding factor impacting the ability to draw any conclusions regarding the efficacy results from this study.

Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population comprised all participants who received at least one dose of study treatment and had a baseline measurement or a post-randomization measurement for the analysis endpoint.
Arm/Group Title Omarigliptin 25 mg Placebo
Hide Arm/Group Description:
Omarigliptin 25 mg, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Placebo to omarigliptin, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Overall Number of Participants Analyzed 100 101
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mg/dL
-11.3
(-26.1 to 3.5)
-15.5
(-30.6 to -0.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omarigliptin 25 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.685
Comments [Not Specified]
Method Constrained longitudinal data analysis
Comments Terms for treatment, time, and the interaction of time by treatment, with the constraint that the mean baseline is the same for all treatment groups.
Method of Estimation Estimation Parameter Difference in least squares means
Estimated Value 4.2
Confidence Interval (2-Sided) 95%
-16.1 to 24.4
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change in Baseline in FPG at Week 24
Hide Description

Blood glucose was measured on a fasting basis.

The unexpected absence of a treatment effect in this study led to investigations that included measurement of metformin levels in available samples collected for future research during the study. Of the 92 participants with samples who had not been rescued with metformin, 57% (25/44) in the placebo group and 29% (14/48) in the omarigliptin group had detectable metformin, indicating the use of metformin that was prohibited by the protocol. The use of metformin prohibited by the protocol was without investigator knowledge and is a confounding factor impacting the ability to draw any conclusions regarding the efficacy results from this study.

Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population comprised all participants who received at least one dose of study treatment and had a baseline measurement or a post-randomization measurement for the analysis endpoint.
Arm/Group Title Omarigliptin 25 mg Placebo
Hide Arm/Group Description:
Omarigliptin 25 mg, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Placebo to omarigliptin, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Overall Number of Participants Analyzed 102 101
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mg/dL
-5.0
(-14.6 to 4.6)
-1.3
(-11.2 to 8.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omarigliptin 25 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.586
Comments [Not Specified]
Method Constrained longitudinal data analysis
Comments Terms for treatment, time, and the interaction of time by treatment, with the constraint that the mean baseline is the same for all treatment groups.
Method of Estimation Estimation Parameter Difference in least squares means
Estimated Value -3.7
Confidence Interval (2-Sided) 95%
-17.1 to 9.7
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants Attaining A1C Glycemic Goals of <7.0% at Week 24
Hide Description

Percentage of participants was estimated using standard multiple imputation techniques (constrained longitudinal data analysis [cLDA] model). Within-group confidence intervals (CIs) were calculated via the Wilson score method.

The unexpected absence of a treatment effect in this study led to investigations that included measurement of metformin levels in available samples collected for future research during the study. Of the 92 participants with samples who had not been rescued with metformin, 57% (25/44) in the placebo group and 29% (14/48) in the omarigliptin group had detectable metformin, indicating the use of metformin that was prohibited by the protocol. The use of metformin prohibited by the protocol was without investigator knowledge and is a confounding factor impacting the ability to draw any conclusions regarding the efficacy results from this study.

Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population comprised all participants who received at least one dose of study treatment and had a baseline measurement or a post-randomization measurement for the analysis endpoint.
Arm/Group Title Omarigliptin 25 mg Placebo
Hide Arm/Group Description:
Omarigliptin 25 mg, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Placebo to omarigliptin, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Overall Number of Participants Analyzed 102 101
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
33.5
(24.7 to 43.7)
34.0
(25.1 to 44.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omarigliptin 25 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mietinnen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Between-group rate difference
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-14.0 to 13.1
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants Attaining A1C Glycemic Goals of <6.5% (48 mmol/Mol) at Week 24
Hide Description

Percentage of participants was estimated using standard multiple imputation techniques (cLDA). Within-group CIs were calculated via the Wilson score method.

The unexpected absence of a treatment effect in this study led to investigations that included measurement of metformin levels in available samples collected for future research during the study. Of the 92 participants with samples who had not been rescued with metformin, 57% (25/44) in the placebo group and 29% (14/48) in the omarigliptin group had detectable metformin, indicating the use of metformin that was prohibited by the protocol. The use of metformin prohibited by the protocol was without investigator knowledge and is a confounding factor impacting the ability to draw any conclusions regarding the efficacy results from this study.

Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population comprised all participants who received at least one dose of study treatment and had a baseline measurement or a post-randomization measurement for the analysis endpoint.
Arm/Group Title Omarigliptin 25 mg Placebo
Hide Arm/Group Description:
Omarigliptin 25 mg, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Placebo to omarigliptin, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Overall Number of Participants Analyzed 102 101
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
21.7
(14.5 to 31.1)
17.6
(11.3 to 26.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omarigliptin 25 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mietinnen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Between-group rate difference
Estimated Value 4.0
Confidence Interval (2-Sided) 95%
-7.4 to 15.5
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percentage of Participants Who Required Glycemic Rescue by Week 24
Hide Description

Participants exceeding pre-specified glycemic thresholds after starting the double-blind treatment period may have received rescue therapy (per protocol) with open-label metformin initiated by the investigator.

This analysis may have been confounded by the use of metformin prohibited by the protocol (see efficacy results description above).

Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Omarigliptin 25 mg Placebo
Hide Arm/Group Description:
Omarigliptin 25 mg, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Placebo to omarigliptin, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Overall Number of Participants Analyzed 102 101
Measure Type: Number
Unit of Measure: Percentage of participants
10.8 12.9
Time Frame Up to 27 weeks; Serious adverse events (SAEs) were collected up to 24 weeks during treatment + 3 week follow-up, non-serious adverse events (NSAEs) were collected up to 24 weeks during treatment
Adverse Event Reporting Description SAEs include data after glycemic rescue; NSAEs exclude data after glycemic rescue. Investigations performed by the Sponsor revealed that many participants had used a prohibited antihyperglycemic agent-metformin (i.e., not as rescue medication; see efficacy results description above).
 
Arm/Group Title Omarigliptin 25 mg Placebo
Hide Arm/Group Description Omarigliptin 25 mg, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited. Placebo to omarigliptin, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
All-Cause Mortality
Omarigliptin 25 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Omarigliptin 25 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/102 (0.98%)      3/101 (2.97%)    
Infections and infestations     
Pneumonia  1  0/102 (0.00%)  0 1/101 (0.99%)  1
Pyelonephritis acute  1  0/102 (0.00%)  0 1/101 (0.99%)  1
Vulvovaginal candidiasis  1  0/102 (0.00%)  0 1/101 (0.99%)  1
Metabolism and nutrition disorders     
Diabetes mellitus  1  1/102 (0.98%)  1 0/101 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Omarigliptin 25 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/102 (9.80%)      7/101 (6.93%)    
Gastrointestinal disorders     
Nausea  1  6/102 (5.88%)  6 2/101 (1.98%)  2
Nervous system disorders     
Headache  1  6/102 (5.88%)  6 6/101 (5.94%)  6
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Investigations indicate that the presence of metformin in future biomedical research (FBR) samples from non-rescued participants was due to participant self-administration of metformin outside of the protocol and without investigator knowledge.
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 trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01814748    
Other Study ID Numbers: 3102-028
2012-004303-12 ( EudraCT Number )
First Submitted: March 18, 2013
First Posted: March 20, 2013
Results First Submitted: June 7, 2016
Results First Posted: July 18, 2016
Last Update Posted: September 10, 2018