Type 2 Diabetes Mellitus
Conditions
Brief summary
This study will examine the safety and efficacy of the addition of omarigliptin in participants with type 2 diabetes mellitus with inadequate glycemic control on metformin and glimepiride. The primary hypothesis is that after 24 weeks, the addition of treatment with omarigliptin provides a greater reduction in hemoglobin A1c (A1C) compared with the addition of placebo.
Interventions
DRUGOmarigliptin
Omarigliptin 25 mg capsule administered orally once a week
Matching placebo to omarigliptin capsule administered orally once a week
DRUGGlimepiride
Open-label glimepiride tablet(s) administered orally once daily for a total daily dose \>=4 mg. In the event of hypoglycemia, the glimepiride dose may be down-titrated to a minimum dose of 1 mg daily.
DRUGMetformin
Open-label metformin tablet(s) administered orally once or twice daily for a total daily dose \>=1500 mg
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with type 2 diabetes mellitus * Currently taking stable doses of metformin (\>=1500 mg/day) and sulfonylurea * Male, or female not of reproductive potential or female of reproductive potential who agrees to remain abstinent or use (or have their partner use) 2 methods of 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 * Treated with any antihyperglycemic agent therapies other than the protocol-required sulfonylurea and metformin within 12 weeks prior to study participation or with omarigliptin at any time prior to study participation. * History of hypersensitivity to a dipeptidyl peptidase IV (DPP-4) inhibitor * 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. * Is on or likely to require treatment for \>=2 consecutive weeks or repeated courses of corticosteroids (inhaled, nasal or topical corticosteroids are permitted) * Currently being treated for hyperthyroidism or is on thyroid replacement therapy and has not been on a stable dose for at least 6 weeks * 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 * 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 * 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 * Current user of recreational or illicit drugs or has had a recent history of drug abuse or routinely consumes \>2 alcoholic drinks per day or \>14 drinks per week, or engages in binge drinking * Donated blood products within 8 weeks of study participation, or intends to donate blood products during the study or has received or anticipates receiving blood products within 12 weeks prior to study participation or during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | Baseline and Week 24 | A1C is blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%). Thus, this change from baseline reflects the Week 24 A1C minus the Week 0 A1C. |
| Percentage of Participants Who Experienced at Least One Adverse Event (AE) | Up to Week 27 | 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 AE | Up to Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline and Week 24 | Blood glucose was measured on a fasting basis. FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 24 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 24 minus FPG at baseline). |
| Percentage of Participants Attaining A1C Glycemic Goals of <7% and <6.5% at Week 24 | 24 weeks | The percentage of participants who achieved A1C values \<6.5% (48 mmol/mol) or \<7.0% (53 mmol/mol) in the FAS population at Week 24. |
Participant flow
Recruitment details
Fifty-one sites received IEC/IRB approval and were shipped clinical supplies.
Pre-assignment details
In total, 583 participants were screened and 276 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 not meeting the metformin and glimepiride dose requirements inclusion criterion or meeting exclusionary laboratory values.
Participants by arm
| Arm | Count |
|---|---|
| Omarigliptin Omarigliptin 25 mg capsule administered orally once a week for 24 weeks. Participants continue pre-study concomitant therapy of open-label glimepiride tablet(s) orally once daily (total daily dose \>=4 mg per day) and metformin tablet(s) orally once or twice daily (total daily dose \>=1500 mg per day). | 154 |
| Placebo Matching placebo to omarigliptin capsule administered orally once a week for 24 weeks. Participants continue pre-study concomitant therapy of open-label glimepiride tablet(s) orally once daily (total daily dose \>=4 mg per day) and metformin tablet(s) orally once or twice daily (total daily dose \>=1500 mg per day). | 153 |
| Total | 307 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 12 | 15 |
Baseline characteristics
| Characteristic | Omarigliptin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 57.2 Years STANDARD_DEVIATION 8.4 | 58.4 Years STANDARD_DEVIATION 9.4 | 57.8 Years STANDARD_DEVIATION 8.9 |
| Sex: Female, Male Female | 81 Participants | 79 Participants | 160 Participants |
| Sex: Female, Male Male | 73 Participants | 74 Participants | 147 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 153 | 23 / 153 |
| serious Total, serious adverse events | 3 / 153 | 5 / 153 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (A1C) at Week 24
A1C is blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%). Thus, this change from baseline reflects the Week 24 A1C minus the Week 0 A1C.
Time frame: Baseline and Week 24
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. One participant was in 2 clinical trials in parallel and was excluded from all efficacy and safety analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin | Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | -0.67 %A1C |
| Placebo | Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | -0.06 %A1C |
p-value: <0.00195% CI: [-0.85, -0.38]Difference in the least squares means
Primary
Percentage of Participants Who Discontinued From the Study Due to an AE
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 24
Population: The ASaT Population was 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. One participant was in 2 clinical trials and was excluded from all efficacy and safety analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin | Percentage of Participants Who Discontinued From the Study Due to an AE | 2.6 Percentage of participants |
| Placebo | Percentage of Participants Who Discontinued From the Study Due to an AE | 2.6 Percentage of participants |
95% CI: [-4.3, 4.3]
Primary
Percentage of Participants Who Experienced at Least One Adverse Event (AE)
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 27
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. One participant was in 2 clinical trials and was excluded from all efficacy and safety analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin | Percentage of Participants Who Experienced at Least One Adverse Event (AE) | 57.5 Percentage of participants |
| Placebo | Percentage of Participants Who Experienced at Least One Adverse Event (AE) | 47.7 Percentage of participants |
95% CI: [-1.4, 20.8]
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Blood glucose was measured on a fasting basis. FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 24 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 24 minus FPG at baseline).
Time frame: Baseline and Week 24
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. One participant was in 2 clinical trials in parallel and was excluded from all efficacy and safety analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | -19.6 mg/dL |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | -3.0 mg/dL |
p-value: <0.00195% CI: [-25.5, -7.8]Difference in the least squares means
Secondary
Percentage of Participants Attaining A1C Glycemic Goals of <7% and <6.5% at Week 24
The percentage of participants who achieved A1C values \<6.5% (48 mmol/mol) or \<7.0% (53 mmol/mol) in the FAS population at Week 24.
Time frame: 24 weeks
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. One participant was in 2 clinical trials in parallel and was excluded from all efficacy and safety analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omarigliptin | Percentage of Participants Attaining A1C Glycemic Goals of <7% and <6.5% at Week 24 | <7.0% | 23.8 Percentage of participants |
| Omarigliptin | Percentage of Participants Attaining A1C Glycemic Goals of <7% and <6.5% at Week 24 | <6.5% | 10.1 Percentage of participants |
| Placebo | Percentage of Participants Attaining A1C Glycemic Goals of <7% and <6.5% at Week 24 | <7.0% | 4.4 Percentage of participants |
| Placebo | Percentage of Participants Attaining A1C Glycemic Goals of <7% and <6.5% at Week 24 | <6.5% | 2.1 Percentage of participants |
p-value: <0.00195% CI: [11.7, 27.6]Miettinen & Nurminen method
p-value: 0.00595% CI: [2.7, 14.5]Miettinen & Nurminen method