Type 2 Diabetes
Conditions
Keywords
Diabetes Mellitus, Diabetes Mellitus, Type 2, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Glimepiride, Metformin, Hypoglycemic Agents, Physiological Effects of Drugs, Pharmacologic Actions
Brief summary
This is a non-inferiority study comparing omarigliptin with sitagliptin in participants with type 2 diabetes mellitus (T2DM) with inadequate glycemic control on metformin therapy. The primary hypothesis is that after 24 weeks, the mean change from baseline in hemoglobin A1c (A1C) in participants treated with omarigliptin is non-inferior to that in participants treated with sitagliptin. There will be a 2-week run-in period with placebo + metformin prior to the double-blind treatment period.
Interventions
DRUGOmarigliptin
Omarigliptin (MK-3102) 25 mg oral capsule once a week for 24 weeks
DRUGSitagliptin
Sitagliptin 100 mg oral tablet once a day for 24 weeks
Placebo to omarigliptin 25 mg oral capsule once a week for 24 weeks
Placebo to sitagliptin 100 mg oral tablet once a day for 24 weeks
Metformin oral tablet(s) - total daily dose of ≥1500 mg, once or twice a day
DRUGOpen-label Glimepiride
Glimepiride oral tablet(s) - total daily dose of 1 to 6 mg once a day as rescue therapy
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
* Type 2 diabetes mellitus * Currently on a stable dose of metformin monotherapy (≥1500 mg per day) for at least 12 weeks prior to study participation * Male, or female who is not of reproductive potential or if of reproductive potential agrees to abstain from heterosexual activity or use (or have their partner use) acceptable contraception to prevent pregnancy during the study and for 21 days after the last dose of study drug
Exclusion criteria
* History of type 1 diabetes mellitus or a history of ketoacidosis * Has been treated with any antihyperglycemic agent (AHA) other than the protocol-required metformin within 12 weeks prior to study participation or with omarigliptin at any time prior to signing informed consent * History of hypersensitivity to a dipeptidyl peptidase IV (DPP-4) inhibitor * Is currently participating in, or has participated in, a trial in which the participant received an investigational compound or used an investigational device within the prior 12 weeks of signing the informed consent or is not willing to refrain from participating in any other trial * History of intolerance, hypersensitivity, or any other contraindication to metformin or sitagliptin * Is on a weight loss program and is not in the maintenance phase or has been on a weight loss medication in the past 6 months or has undergone bariatric surgery within 12 months prior to study participation * Has undergone a surgical procedure within 4 weeks of study participation or has planned major surgery during the study * Is on or likely to require treatment ≥14 consecutive days or repeated courses of corticosteroids (inhaled, nasal and topical corticosteroids are permitted) * Currently being treated for hyperthyroidism or is on thyroid hormone replacement therapy and has not been on a stable dose for at least 6 weeks * Is expecting to undergo hormonal therapy in preparation to donate eggs during the period of the trial, including 21 days after the last dose of trial medication * History of active liver disease (other than non-alcoholic steatosis) including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gall bladder disease * Human immunodeficiency virus (HIV) * New or worsening signs or symptoms of coronary heart disease or congestive heart failure within the past 3 months, or myocardial infarction, unstable angina, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, stroke, or transient ischemic attacks in the past 3 months * Poorly controlled hypertension * History of malignancy ≤5 years prior to study participation, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer * Hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia) * Positive urine pregnancy test * Pregnant or breastfeeding, or is expecting to conceive during the study including 21 days following the last dose of blinded study drug * User of recreational or illicit drugs or has had a recent history of drug abuse * Routinely consumes \>2 alcoholic drinks per day or \>14 alcoholic drinks per week, or engages in binge drinking * Has donated blood products or has had phlebotomy of \>300 mL within 8 weeks of study participation, or intends to donate blood products within the projected duration of the trial or has received, or is anticipated to receive, blood products within 12 weeks of study participation or within the projected duration of the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in A1C at Week 24 | Baseline and Week 24 | A1C is a measure of the percentage of glycated hemoglobin in the blood. Participant whole blood samples were collected at baseline and Week 24 to determine the least squares mean A1C change from baseline. |
| Percentage of Participants Who Experienced at Least One Adverse Event | Up to 27 weeks (including 3-week follow-up) | An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after initiation of glycemic rescue therapy. |
| Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event | Up to 24 weeks | An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after initiation of glycemic rescue therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in FPG at Week 24 | Baseline and Week 24 | Participant whole blood samples were collected after an overnight fast at baseline and Week 24 to determine the least squares mean change from baseline in participant FPG. |
| Percentage of Participants Achieving an A1C Goal <7.0% After 24 Weeks of Treatment | Week 24 | Participant whole blood samples were collected at Week 24 to determine the number of participants achieving A1C \<7.0% at Week 24. |
| Percentage of Participants Achieving an A1C Goal <6.5% After 24 Weeks of Treatment | Week 24 | Participant whole blood samples were collected at Week 24 to determine the percentage of participants achieving A1C \<6.5% at Week 24. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omarigliptin 25 mg Once Weekly Participants received omarigliptin 25 mg once a week plus placebo to sitagliptin once daily for 24 weeks. Participants continued pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may have received glimepiride (total daily dose of 1-6 mg) as rescue therapy. | 322 |
| Sitagliptin 100 mg Once Daily Participants received sitagliptin 100 mg once daily plus placebo to omarigliptin once a week for 24 weeks. Participants continued pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may have received glimepiride (total daily dose of 1-6 mg) as rescue therapy. | 320 |
| Total | 642 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 4 | 1 |
| Overall Study | Withdrawal by Subject | 16 | 16 |
Baseline characteristics
| Characteristic | Omarigliptin 25 mg Once Weekly | Sitagliptin 100 mg Once Daily | Total |
|---|---|---|---|
| Age, Continuous | 57.0 Years STANDARD_DEVIATION 9.8 | 57.6 Years STANDARD_DEVIATION 9.8 | 57.3 Years STANDARD_DEVIATION 9.8 |
| Fasting plasma glucose (FPG) | 160.1 mg/dL STANDARD_DEVIATION 35.7 | 153.9 mg/dL STANDARD_DEVIATION 32.8 | 157.0 mg/dL STANDARD_DEVIATION 34.4 |
| Hemoglobin A1c (A1C) | 7.52 Percent STANDARD_DEVIATION 0.77 | 7.49 Percent STANDARD_DEVIATION 0.74 | 7.50 Percent STANDARD_DEVIATION 0.76 |
| Sex: Female, Male Female | 171 Participants | 145 Participants | 316 Participants |
| Sex: Female, Male Male | 151 Participants | 175 Participants | 326 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 322 | 0 / 320 |
| serious Total, serious adverse events | 11 / 322 | 9 / 320 |
Outcome results
Primary
Change From Baseline in A1C at Week 24
A1C is a measure of the percentage of glycated hemoglobin in the blood. Participant whole blood samples were collected at baseline and Week 24 to determine the least squares mean A1C change from baseline.
Time frame: Baseline and Week 24
Population: Full analysis set population consists of all randomized participants who received at least one dose of study treatment and have a baseline measurement or a post-randomization measurement for the analysis endpoint subsequent to at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin 25 mg Once Weekly | Change From Baseline in A1C at Week 24 | -0.47 Percent |
| Sitagliptin 100 mg Once Daily | Change From Baseline in A1C at Week 24 | -0.43 Percent |
Comparison: Constrained longitudinal data analysis95% CI: [-0.15, 0.08]
Primary
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event
An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after initiation of glycemic rescue therapy.
Time frame: Up to 24 weeks
Population: All participants as treated population consists of all randomized participants who received at least one dose of trial treatment. Participants are included in the treatment group corresponding to the trial treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg Once Weekly | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event | 0.9 Percentage of participants |
| Sitagliptin 100 mg Once Daily | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event | 2.2 Percentage of participants |
95% CI: [-3.6, 0.8]
Primary
Percentage of Participants Who Experienced at Least One Adverse Event
An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after initiation of glycemic rescue therapy.
Time frame: Up to 27 weeks (including 3-week follow-up)
Population: All participants as treated population consists of all randomized participants who received at least one dose of trial treatment. Participants are included in the treatment group corresponding to the trial treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg Once Weekly | Percentage of Participants Who Experienced at Least One Adverse Event | 36.3 Percentage of participants |
| Sitagliptin 100 mg Once Daily | Percentage of Participants Who Experienced at Least One Adverse Event | 40.6 Percentage of participants |
95% CI: [-11.8, 3.2]
Secondary
Change From Baseline in FPG at Week 24
Participant whole blood samples were collected after an overnight fast at baseline and Week 24 to determine the least squares mean change from baseline in participant FPG.
Time frame: Baseline and Week 24
Population: Full analysis set population consists of all randomized participants who received at least one dose of study treatment and have a baseline measurement or a post-randomization measurement for the analysis endpoint subsequent to at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin 25 mg Once Weekly | Change From Baseline in FPG at Week 24 | -13.7 mg/dL |
| Sitagliptin 100 mg Once Daily | Change From Baseline in FPG at Week 24 | -9.5 mg/dL |
p-value: 0.08995% CI: [-9, 0.6]Constrained logitudinal data analysis
Secondary
Percentage of Participants Achieving an A1C Goal <6.5% After 24 Weeks of Treatment
Participant whole blood samples were collected at Week 24 to determine the percentage of participants achieving A1C \<6.5% at Week 24.
Time frame: Week 24
Population: Full analysis set population consists of all randomized participants who received at least one dose of study treatment and have a baseline measurement or a post-randomization measurement for the analysis endpoint subsequent to at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg Once Weekly | Percentage of Participants Achieving an A1C Goal <6.5% After 24 Weeks of Treatment | 27.0 Percentage of participants |
| Sitagliptin 100 mg Once Daily | Percentage of Participants Achieving an A1C Goal <6.5% After 24 Weeks of Treatment | 22.8 Percentage of participants |
Comparison: Proportion (rate) for each group was estimated using standard multiple imputation techniques. Between-group difference in proportion is omarigliptin minus sitagliptin.p-value: 0.21295% CI: [-2.5, 11.4]Miettinen & Nurminen method
Secondary
Percentage of Participants Achieving an A1C Goal <7.0% After 24 Weeks of Treatment
Participant whole blood samples were collected at Week 24 to determine the number of participants achieving A1C \<7.0% at Week 24.
Time frame: Week 24
Population: Full analysis set population consists of all randomized participants who received at least one dose of study treatment and have a baseline measurement or a post-randomization measurement for the analysis endpoint subsequent to at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg Once Weekly | Percentage of Participants Achieving an A1C Goal <7.0% After 24 Weeks of Treatment | 50.9 Percentage of participants |
| Sitagliptin 100 mg Once Daily | Percentage of Participants Achieving an A1C Goal <7.0% After 24 Weeks of Treatment | 49.1 Percentage of participants |
Comparison: Proportion (rate) for each group was estimated using standard multiple imputation techniques. Between-group difference in proportion is omarigliptin minus sitagliptin.p-value: 0.61995% CI: [-5.9, 9.9]Miettinen & Nurminen method