Type 2 Diabetes Mellitus
Conditions
Keywords
diabetes
Brief summary
This trial will assess the safety and efficacy of omarigliptin (MK-3102) compared with the sulfonylurea, glimepiride, in Type 2 diabetes mellitus participants with inadequate glycemic control on metformin monotherapy. The primay hypothesis of the study is that after 54 weeks, the mean change from baseline in hemoglobin A1C (A1C) in participants treated with omarigliptin is non-inferior compared with that in participants treated with glimepiride.
Interventions
DRUGOmarigliptin
DRUGGlimepiride
Glimepiride (1 mg and/or 2 mg tablets). During the 54-week double-blind treatment period, glimepiride can be up-titrated, as appropriate, to a maximum total daily dose of 6 mg/day. Throughout the trial, down-titration of glimepiride may also occur based upon the participant's glucose measurements and clinical symptoms of hypoglycemia.
DRUGMetformin
Participants will continue on their stable dose (\>=1500 mg/day) of open-label metformin throughout the trial.
DRUGInsulin Glargine
Insulin glargine can be used for rescue therapy, if glycemic control is not maintained. Insulin therapy should be initiated as per local country insulin glargine label.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with Type 2 diabetes mellitus * On a stable dose of metformin (≥1500 mg/day) for at least 12 weeks with inadequate glycemic control * Females of reproductive potential agree to remain abstinent or use or have their partner use acceptable methods of birth control
Exclusion criteria
* History of type 1 diabetes mellitus or a history of ketoacidosis * Treated with any antihyperglycemic agents (AHA) therapies other than the protocol-required metformin within the prior 12 weeks of study participation or with omarigliptin at any time prior to signing informed consent * On a weight loss program and is not in the maintenance phase or has started a weight loss medication in the past 6 months or has undergone bariatric surgery within 12 months prior to study participation * Medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease * Human immunodeficiency virus * New or worsening coronary heart disease, congestive heart failure, myocardial infarction, unstable angina, coronary artery intervention, stroke or transient ischemic neurological disorder within the past 3 months * 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 * Clinically important hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia) * Pregnant or breast-feeding, or is expecting to conceive or donate eggs during the trial, including 21 days following the last dose of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1C at Week 54 | Baseline and Week 54 | Hemoglobin A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Thus, this change from baseline reflects the Week 54 A1C minus the Week 0 A1C. |
| Percentage of Participants Who Experienced at Least One Adverse Event Excluding Data After Glycemic Rescue | Up to Week 57 | 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. |
| Percentage of Participants Who Discontinued From the Study Due to an Adverse Event Excluding Data After Glycemic Rescue | Up to Week 54 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Body Weight at Week 54 Excluding Data After Gylcemic Rescue | Baseline and Week 54 | — |
| Change From Baseline in Fasting Plasma Glucose at Week 54 | Baseline and Week 54 | Blood glucose was measured on a fasting basis. FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 54 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 54 minus FPG at baseline). |
| Percentage of Participants Achieving a Hemoglobin A1C of <7.0% at Week 54 | Week 54 | The percentage of participants who achieved A1C values \<7.0% (53 mmol/mol) in the FAS Population at Week 54. |
| Percentage of Participants Achieving a Hemoglobin A1C of <6.5% at Week 54 | Week 54 | The percentage of participants who achieved A1C values \<6.5% (48 mmol/mol) in the FAS Population at Week 54. |
| Percentage of Participants With an Adverse Event of Symptomatic Hypoglycemia Excluding Data After Glycemic Rescue | Up to Week 54 | Symptomatic episode of hypoglycemia was an episode with clinical symptoms reported by the investigator as hypoglycemia (concurrent fingerstick glucose not required). |
Participant flow
Recruitment details
In total, 1197 participants at 115 clinical sites were screened and 446 participants were excluded during screening. The most common reason for participants not being randomized was screen failure. The most common reasons for screen failure were participants not meeting the metformin inclusion criteria or meeting exclusionary laboratory values.
Participants by arm
| Arm | Count |
|---|---|
| Omarigliptin Participants will receive omarigliptin, 25 mg once weekly and placebo matching glimepiride once daily for up to 54 weeks. | 376 |
| Glimepiride Participants will receive glimepiride titrated to a maximum of 6 mg, once daily, and placebo to omarigliptin, once weekly for up to 54 weeks. | 375 |
| Total | 751 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 1 |
| Overall Study | Lost to Follow-up | 10 | 13 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Withdrawal by Subject | 56 | 55 |
Baseline characteristics
| Characteristic | Omarigliptin | Glimepiride | Total |
|---|---|---|---|
| Age, Continuous | 57.9 years STANDARD_DEVIATION 9.6 | 57.6 years STANDARD_DEVIATION 9.3 | 57.7 years STANDARD_DEVIATION 9.5 |
| Body Weight | 87.5 kg STANDARD_DEVIATION 18.1 | 88.7 kg STANDARD_DEVIATION 18.7 | 88.1 kg STANDARD_DEVIATION 18.4 |
| Fasting Plamsa Glucose (FPG) | 155.3 mg/dL STANDARD_DEVIATION 31.4 | 152.7 mg/dL STANDARD_DEVIATION 30 | 154.0 mg/dL STANDARD_DEVIATION 30.7 |
| Hemoglobin A1C | 7.49 A1C (%) STANDARD_DEVIATION 0.75 | 7.43 A1C (%) STANDARD_DEVIATION 0.72 | 7.46 A1C (%) STANDARD_DEVIATION 0.73 |
| Sex: Female, Male Female | 173 Participants | 164 Participants | 337 Participants |
| Sex: Female, Male Male | 203 Participants | 211 Participants | 414 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 43 / 375 | 125 / 375 |
| serious Total, serious adverse events | 24 / 375 | 18 / 375 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1C at Week 54
Hemoglobin A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Thus, this change from baseline reflects the Week 54 A1C minus the Week 0 A1C.
Time frame: Baseline and Week 54
Population: The Full Analysis Set (FAS) population consisted of all randomized participants who received at least 1 dose of study medication and had a baseline measurement or a measurement for the analysis endpoint after receiving study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin | Change From Baseline in Hemoglobin A1C at Week 54 | -0.30 A1C (%) |
| Glimepiride | Change From Baseline in Hemoglobin A1C at Week 54 | -0.48 A1C (%) |
95% CI: [0.06, 0.3]
Primary
Percentage of Participants Who Discontinued From the Study Due to an Adverse Event Excluding Data After Glycemic Rescue
Time frame: Up to Week 54
Population: The ASaT Population is defined as all randomized participants who received at least 1 dose of study medication. Participants were included in the treatment group corresponding to the study treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin | Percentage of Participants Who Discontinued From the Study Due to an Adverse Event Excluding Data After Glycemic Rescue | 3.7 Percentage of participants |
| Glimepiride | Percentage of Participants Who Discontinued From the Study Due to an Adverse Event Excluding Data After Glycemic Rescue | 2.7 Percentage of participants |
95% CI: [-1.6, 3.8]
Primary
Percentage of Participants Who Experienced at Least One Adverse Event Excluding Data After Glycemic Rescue
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.
Time frame: Up to Week 57
Population: All Subjects as Treated (ASaT) population, defined as all randomized participants who received at least 1 dose of study medication. Participants were included in the treatment group corresponding to the study treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin | Percentage of Participants Who Experienced at Least One Adverse Event Excluding Data After Glycemic Rescue | 54.7 Percentage of participants |
| Glimepiride | Percentage of Participants Who Experienced at Least One Adverse Event Excluding Data After Glycemic Rescue | 61.6 Percentage of participants |
95% CI: [-13.9, 0.1]
Secondary
Change From Baseline in Body Weight at Week 54 Excluding Data After Gylcemic Rescue
Time frame: Baseline and Week 54
Population: The ASaT Population is defined as all randomized participants who received at least 1 dose of study medication. Participants were included in the treatment group corresponding to the study treatment they actually received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin | Change From Baseline in Body Weight at Week 54 Excluding Data After Gylcemic Rescue | -0.4 kg |
| Glimepiride | Change From Baseline in Body Weight at Week 54 Excluding Data After Gylcemic Rescue | 1.5 kg |
p-value: <0.00195% CI: [-2.5, -1.4]Difference in the least squares means
Secondary
Change From Baseline in Fasting Plasma Glucose at Week 54
Blood glucose was measured on a fasting basis. FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 54 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 54 minus FPG at baseline).
Time frame: Baseline and Week 54
Population: The FAS population consisted of all randomized participants who received at least 1 dose of study medication and had a baseline measurement or a measurement for the analysis endpoint after receiving study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin | Change From Baseline in Fasting Plasma Glucose at Week 54 | -2.7 mg/dL |
| Glimepiride | Change From Baseline in Fasting Plasma Glucose at Week 54 | -8.3 mg/dL |
95% CI: [0.1, 11.2]
Secondary
Percentage of Participants Achieving a Hemoglobin A1C of <6.5% at Week 54
The percentage of participants who achieved A1C values \<6.5% (48 mmol/mol) in the FAS Population at Week 54.
Time frame: Week 54
Population: The FAS Population (with multiple imputation) consisted of all randomized participants who received at least 1 dose of study medication and had a baseline measurement or a measurement for the analysis endpoint after receiving study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin | Percentage of Participants Achieving a Hemoglobin A1C of <6.5% at Week 54 | 25.1 Percentage of participants |
| Glimepiride | Percentage of Participants Achieving a Hemoglobin A1C of <6.5% at Week 54 | 28.8 Percentage of participants |
Comparison: A1C \<6.5%95% CI: [-10.6, 3.3]
Secondary
Percentage of Participants Achieving a Hemoglobin A1C of <7.0% at Week 54
The percentage of participants who achieved A1C values \<7.0% (53 mmol/mol) in the FAS Population at Week 54.
Time frame: Week 54
Population: The FAS Population (with multiple imputation) consisted of all randomized participants who received at least 1 dose of study medication and had a baseline measurement or a measurement for the analysis endpoint after receiving study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin | Percentage of Participants Achieving a Hemoglobin A1C of <7.0% at Week 54 | 47.7 Percentage of participants |
| Glimepiride | Percentage of Participants Achieving a Hemoglobin A1C of <7.0% at Week 54 | 58.0 Percentage of participants |
Comparison: A1C \< 7.0%95% CI: [-17.8, -2.8]
Secondary
Percentage of Participants With an Adverse Event of Symptomatic Hypoglycemia Excluding Data After Glycemic Rescue
Symptomatic episode of hypoglycemia was an episode with clinical symptoms reported by the investigator as hypoglycemia (concurrent fingerstick glucose not required).
Time frame: Up to Week 54
Population: The ASaT Population is defined as all randomized participants who received at least 1 dose of study medication. Participants were included in the treatment group corresponding to the study treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin | Percentage of Participants With an Adverse Event of Symptomatic Hypoglycemia Excluding Data After Glycemic Rescue | 5.3 Percentage of participants |
| Glimepiride | Percentage of Participants With an Adverse Event of Symptomatic Hypoglycemia Excluding Data After Glycemic Rescue | 26.7 Percentage of participants |
p-value: <0.00195% CI: [-26.5, -16.4]Difference in percentages