Trial Outcomes & Findings for 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) (NCT NCT01814748)
NCT ID: NCT01814748
Last Updated: 2018-09-10
Results Overview
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.
COMPLETED
PHASE3
203 participants
Baseline and Week 24
2018-09-10
Participant Flow
Participant milestones
| Measure |
Omarigliptin 25 mg
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
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 Study
STARTED
|
102
|
101
|
|
Overall Study
COMPLETED
|
94
|
94
|
|
Overall Study
NOT COMPLETED
|
8
|
7
|
Reasons for withdrawal
| Measure |
Omarigliptin 25 mg
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
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 Study
Lost to Follow-up
|
1
|
2
|
|
Overall Study
Study site terminated by sponsor
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
6
|
4
|
Baseline Characteristics
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)
Baseline characteristics by cohort
| Measure |
Omarigliptin 25 mg
n=102 Participants
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
n=101 Participants
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
n=203 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.8 Years
STANDARD_DEVIATION 4.7 • n=5 Participants
|
39.5 Years
STANDARD_DEVIATION 4.5 • n=7 Participants
|
39.2 Years
STANDARD_DEVIATION 4.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
35 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
76 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
67 Participants
n=5 Participants
|
60 Participants
n=7 Participants
|
127 Participants
n=5 Participants
|
|
Hemoglobin A1c (A1C)
|
7.9 Percent
STANDARD_DEVIATION 0.8 • n=5 Participants
|
8.1 Percent
STANDARD_DEVIATION 0.9 • n=7 Participants
|
8.0 Percent
STANDARD_DEVIATION 0.8 • n=5 Participants
|
|
2-hour post-meal glucose (2-hr PMG)
|
204.9 mg/dL
STANDARD_DEVIATION 55.1 • n=5 Participants
|
217.3 mg/dL
STANDARD_DEVIATION 67.7 • n=7 Participants
|
211.2 mg/dL
STANDARD_DEVIATION 62.0 • n=5 Participants
|
|
Fasting plasma glucose (FPG)
|
164.0 mg/dL
STANDARD_DEVIATION 38.9 • n=5 Participants
|
167.8 mg/dL
STANDARD_DEVIATION 40.6 • n=7 Participants
|
165.9 mg/dL
STANDARD_DEVIATION 39.7 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 24Population: 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.
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.
Outcome measures
| Measure |
Omarigliptin 25 mg
n=102 Participants
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
n=101 Participants
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.
|
|---|---|---|
|
Change From Baseline in A1C at Week 24
|
-0.33 Percent
Interval -0.6 to -0.06
|
-0.45 Percent
Interval -0.72 to -0.18
|
PRIMARY outcome
Timeframe: Up to Week 27Population: APaT population included all randomized participants who received at least one dose of study medication.
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).
Outcome measures
| Measure |
Omarigliptin 25 mg
n=102 Participants
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
n=101 Participants
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.
|
|---|---|---|
|
Percentage of Participants Who Experienced at Least One Adverse Event (AE)
|
39.2 Percentage of participants
|
39.6 Percentage of participants
|
PRIMARY outcome
Timeframe: Up to Week 24Population: APaT population included all randomized participants who received at least one dose of study medication.
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).
Outcome measures
| Measure |
Omarigliptin 25 mg
n=102 Participants
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
n=101 Participants
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.
|
|---|---|---|
|
Percentage of Participants Who Discontinued Study Drug Due to an AE
|
0.0 Percentage of participants
|
2.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: 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.
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.
Outcome measures
| Measure |
Omarigliptin 25 mg
n=100 Participants
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
n=101 Participants
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.
|
|---|---|---|
|
Change From Baseline in 2-hr PMG at Week 24
|
-11.3 mg/dL
Interval -26.1 to 3.5
|
-15.5 mg/dL
Interval -30.6 to -0.3
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: 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.
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.
Outcome measures
| Measure |
Omarigliptin 25 mg
n=102 Participants
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
n=101 Participants
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.
|
|---|---|---|
|
Change in Baseline in FPG at Week 24
|
-5.0 mg/dL
Interval -14.6 to 4.6
|
-1.3 mg/dL
Interval -11.2 to 8.5
|
SECONDARY outcome
Timeframe: Week 24Population: 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.
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.
Outcome measures
| Measure |
Omarigliptin 25 mg
n=102 Participants
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
n=101 Participants
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.
|
|---|---|---|
|
Percentage of Participants Attaining A1C Glycemic Goals of <7.0% at Week 24
|
33.5 Percentage of participants
Interval 24.7 to 43.7
|
34.0 Percentage of participants
Interval 25.1 to 44.1
|
SECONDARY outcome
Timeframe: Week 24Population: 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.
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.
Outcome measures
| Measure |
Omarigliptin 25 mg
n=102 Participants
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
n=101 Participants
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.
|
|---|---|---|
|
Percentage of Participants Attaining A1C Glycemic Goals of <6.5% (48 mmol/Mol) at Week 24
|
21.7 Percentage of participants
Interval 14.5 to 31.1
|
17.6 Percentage of participants
Interval 11.3 to 26.5
|
SECONDARY outcome
Timeframe: Up to Week 24Population: All randomized participants.
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).
Outcome measures
| Measure |
Omarigliptin 25 mg
n=102 Participants
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
n=101 Participants
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.
|
|---|---|---|
|
Percentage of Participants Who Required Glycemic Rescue by Week 24
|
10.8 Percentage of participants
|
12.9 Percentage of participants
|
Adverse Events
Omarigliptin 25 mg
Placebo
Serious adverse events
| Measure |
Omarigliptin 25 mg
n=102 participants at risk
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
n=101 participants at risk
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.
|
|---|---|---|
|
Infections and infestations
Pneumonia
|
0.00%
0/102 • 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
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).
|
0.99%
1/101 • Number of events 1 • 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
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).
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/102 • 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
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).
|
0.99%
1/101 • Number of events 1 • 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
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).
|
|
Infections and infestations
Vulvovaginal candidiasis
|
0.00%
0/102 • 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
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).
|
0.99%
1/101 • Number of events 1 • 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
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).
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.98%
1/102 • Number of events 1 • 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
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).
|
0.00%
0/101 • 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
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).
|
Other adverse events
| Measure |
Omarigliptin 25 mg
n=102 participants at risk
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
n=101 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
5.9%
6/102 • Number of events 6 • 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
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).
|
2.0%
2/101 • Number of events 2 • 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
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).
|
|
Nervous system disorders
Headache
|
5.9%
6/102 • Number of events 6 • 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
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).
|
5.9%
6/101 • Number of events 6 • 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
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).
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER