Type 2 Diabetes Mellitus
Conditions
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 who are metformin intolerant or who have a contraindication to the use of metformin. The primary hypothesis 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
Omarigliptin (MK-3102) 25 mg capsule administered orally once weekly
DRUGGlimepiride
Glimepiride tablet 1 mg and/or 2 mg (uptitrated to a maximum dose 6 mg/day) administered orally once daily with breakfast or the first main meal
DRUGOmarigliptin Placebo
Matching placebo to omarigliptin capsule administered orally once weekly
Matching placebo to glimepiride tablet administered orally once daily with breakfast or the first main meal
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 * Have intolerability to metformin ≥1000 mg/day or have a contraindication to the use of metformin * Females of reproductive potential agree to remain abstinent or use or have their partner use 2 acceptable methods of birth control
Exclusion criteria
* History of type 1 diabetes mellitus or a history of ketoacidosis or assessed by the investigator as possibly having type 1 diabetes * Has been treated with: 1. A thiazolidinedione (TZD) within 4 months of study participation, or 2. A glucagon-like peptide-1 (GLP-1) receptor mimetic or agonist (such as exenatide or liraglutide) within 6 months of study participation, or 3. Insulin within 12 weeks prior to study participation, or 4. Dual antihyperglycemic agent (AHA) therapy within 12 weeks of study participation (4 months if a component of the dual AHA therapy was a TZD) 5. Omarigliptin (MK-3102) at any time prior to study participation * On a weight loss program and is not in the maintenance phase; 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 (HIV) * 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 (A1C) at Week 54 | Baseline and Week 54 | A1C is measured as a percent. Thus, this change from baseline reflects the Week 54 A1C percent minus the Week 0 A1C percent. |
| Percentage of Participants Who Experienced at Least One Adverse Event | Up to 57 weeks (including 3 weeks following the last dose of study drug) | An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of pre-existing conditions. |
| Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event | Up to 54 weeks | An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of pre-existing conditions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an Adverse Event of Symptomatic Hypoglycemia | Up to 54 weeks | An adverse event (AE) is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. AEs may include the onset of new illness and the exacerbation of pre-existing conditions. Per protocol, an adverse event was defined as symptomatic hypoglycemia if hypoglycemia was an adverse event collected on the AE form AND the symptoms associated with it were collected on the hypoglycemia assessment (HA) form. Due to the early termination of the study, the HA form information was not assessed; therefore, this endpoint cannot be reported. |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 54 | Baseline and Week 54 | This change from baseline reflects the FPG level at Week 54 minus the FPG level at Week 0. |
| Change From Baseline in Body Weight at Week 54 | Baseline and Week 54 | Body weight was to be measured (in duplicate) using a calibrated digital scale. |
| Percentage of Participants Achieving an A1C Goal <7.0% or <6.5% After 54 Weeks of Treatment | 54 weeks | Percentage of participants achieving glycemic goal (A1C \<7% or \<6.5%) after 54 weeks of treatment. |
| Percentage of Participants Meeting the Composite Endpoint of an A1C Decrease >0.5%, No Symptomatic Hypoglycemia, and No Body Weight Gain After 54 Weeks of Treatment | 54 weeks | Percentage of Participants who had an A1C decrease \>0.5%, no symptomatic hypoglycemia, and no body weight gain after 54 weeks of treatment |
Participant flow
Pre-assignment details
The study had a 1-week Screening Period; an oral antihyperglycemic agent (AHA) wash-off period of 8 weeks for participants on oral AHAs; a 2-week single-blind placebo run-in period; and a 54-week double-blind treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Omarigliptin Participants received an omarigliptin (MK-3102) 25 mg capsule once weekly and glimepiride placebo tablet(s) once daily, for 54 weeks. | 33 |
| Glimepiride Participants received glimepiride 1 mg and/or 2 mg tablet(s) (maximum dose 6 mg/day) once daily and an omarigliptin placebo capsule once weekly, for 54 weeks. | 32 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Study terminated by Sponsor | 30 | 30 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Omarigliptin | Glimepiride | Total |
|---|---|---|---|
| Age, Continuous | 58.0 Years STANDARD_DEVIATION 14.1 | 56.8 Years STANDARD_DEVIATION 9.9 | 57.4 Years STANDARD_DEVIATION 12.1 |
| Sex: Female, Male Female | 19 Participants | 16 Participants | 35 Participants |
| Sex: Female, Male Male | 14 Participants | 16 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 33 | 0 / 32 |
| serious Total, serious adverse events | 1 / 33 | 0 / 32 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1C (A1C) at Week 54
A1C is measured as a percent. Thus, this change from baseline reflects the Week 54 A1C percent minus the Week 0 A1C percent.
Time frame: Baseline and Week 54
Population: Full Analysis Set defined as all participants who received at least one dose of study drug and had a baseline measurement or a post-randomization measurement. Due to the early termination of the study, no participants completed Week 54.
Primary
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event
An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of pre-existing conditions.
Time frame: Up to 54 weeks
Population: All participants as treated defined as all randomized participants who received at least one dose of study drug and were included in the treatment group corresponding to the study drug they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event | 3 Percentage of participants |
| Glimepiride | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Percentage of participants |
Primary
Percentage of Participants Who Experienced at Least One Adverse Event
An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of pre-existing conditions.
Time frame: Up to 57 weeks (including 3 weeks following the last dose of study drug)
Population: All participants as treated defined as all randomized participants who received at least one dose of study drug and were included in the treatment group corresponding to the study drug they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin | Percentage of Participants Who Experienced at Least One Adverse Event | 9.1 Percentage of participants |
| Glimepiride | Percentage of Participants Who Experienced at Least One Adverse Event | 15.6 Percentage of participants |
Secondary
Change From Baseline in Body Weight at Week 54
Body weight was to be measured (in duplicate) using a calibrated digital scale.
Time frame: Baseline and Week 54
Population: All participants as treated defined as all randomized participants who received at least one dose of study drug and were included in the treatment group corresponding to the study drug they actually received. Due to the early termination of the study, no participants completed Week 54.
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 54
This change from baseline reflects the FPG level at Week 54 minus the FPG level at Week 0.
Time frame: Baseline and Week 54
Population: Full Analysis Set defined as all participants who received at least one dose of study drug and had a baseline measurement or a post-randomization measurement. Due to the early termination of the study, no participants completed Week 54.
Secondary
Percentage of Participants Achieving an A1C Goal <7.0% or <6.5% After 54 Weeks of Treatment
Percentage of participants achieving glycemic goal (A1C \<7% or \<6.5%) after 54 weeks of treatment.
Time frame: 54 weeks
Population: Full Analysis Set defined as all participants who received at least one dose of study drug and had a baseline measurement or a post-randomization measurement. Due to the early termination of the study, no participants completed Week 54.
Secondary
Percentage of Participants Meeting the Composite Endpoint of an A1C Decrease >0.5%, No Symptomatic Hypoglycemia, and No Body Weight Gain After 54 Weeks of Treatment
Percentage of Participants who had an A1C decrease \>0.5%, no symptomatic hypoglycemia, and no body weight gain after 54 weeks of treatment
Time frame: 54 weeks
Population: Full Analysis Set defined as all participants who received at least one dose of study drug and had a baseline measurement or a post-randomization measurement. Due to the early termination of the study, no participants completed Week 54.
Secondary
Percentage of Participants With an Adverse Event of Symptomatic Hypoglycemia
An adverse event (AE) is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. AEs may include the onset of new illness and the exacerbation of pre-existing conditions. Per protocol, an adverse event was defined as symptomatic hypoglycemia if hypoglycemia was an adverse event collected on the AE form AND the symptoms associated with it were collected on the hypoglycemia assessment (HA) form. Due to the early termination of the study, the HA form information was not assessed; therefore, this endpoint cannot be reported.
Time frame: Up to 54 weeks
Population: All participants as treated defined as all randomized participants who received at least one dose of study drug and were included in the treatment group corresponding to the study drug they actually received.