Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to assess the efficacy of omarigliptin 25 mg weekly (as monotherapy) compared with sitagliptin 50 mg daily and placebo, and the long term safety (up to 52 weeks) of omarigliptin 25 mg weekly. The primary hypotheses are that after 24 weeks: 1) Omarigliptin 25 mg weekly provides a greater reduction from baseline in glycosylated hemoglobin (HbA1c) compared with placebo, and 2) The mean change from baseline in HbA1c in participants treated with omarigliptin 25 mg weekly is non-inferior compared with that in participants treated with sitagliptin 50 mg daily.
Detailed description
The treatment period is composed of a 24-week double-blind period (Phase A) and a 28-week open-label period (Phase B). Participants will receive in Phase A: omarigliptin 25 mg once weekly, sitagliptin 50 mg once daily or placebo and in Phase B: omarigliptin 25 mg once weekly.
Interventions
DRUGOmarigliptin
Omarigliptin (MK-3102) 25 mg capsule administered orally once weekly
DRUGSitagliptin
Sitagliptin 50 mg tablet administered orally once daily
Placebo to omarigliptin 25 mg capsule administered orally once weekly
Placebo to sitagliptin 50 mg tablet administered orally once daily
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
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has type 2 diabetes mellitus
Exclusion criteria
* History of type 1 diabetes mellitus or a history of ketoacidosis * History of any of the following medications: thiazolidinediones and/or insulin within 12 weeks prior to study participation, omarigliptin and/or sitagliptin anytime
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced at Least One Adverse Event During Phase A | Up to 24 weeks | An adverse event (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. |
| Percentage of Participants Who Discontinued From the Study Due to an Adverse Event During Phase A | Up to 24 weeks | 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. |
| Percentage of Participants Who Discontinued From the Study Due to an Adverse Event During the Overall Study | Up to 52 weeks | 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. These results represent the accrual of events over different treatment intervals: 52 weeks, omarigliptin (Phase A+B) defined as the double-blind period and open label extension period versus 28 weeks for the Sitagliptin (Phase A)→Omarigliptin (Phase B) and placebo (Phase A)→Omarigliptin (Phase B) group defined as the open-label extension period only. |
| Change From Baseline for Hemoglobin A1c (HbA1c) at Week 24 | Baseline and Week 24 | HbA1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Change in A1C following 24 weeks of therapy (i.e., A1C at Week 24 minus A1C at baseline). |
| Percentage of Participants Who Experienced at Least One Adverse Event During the Overall Study | Up to 52 weeks | 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. These results represent the accrual of events over different treatment intervals: 52 weeks, omarigliptin (Phase A+B) defined as the double-blind period and open label extension period versus 28 weeks for the Sitagliptin (Phase A)→Omarigliptin (Phase B) and placebo (Phase A)→Omarigliptin (Phase B) group defined as the open-label extension period only. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline for 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). |
| Change From Baseline for 2-hour Post Meal Glucose (PMG) at Week 24 | Baseline and Week 24 | Change from baseline at Week 24 is defined as PMG at Week 24 minus PMG at Week 0. |
Participant flow
Recruitment details
Forty-eight sites in Japan received IRB approval and were shipped clinical supplies in this study and randomized at least one participant. One hundred and seventeen participants were not randomized; the most common reason for participants not being randomized was screen failure.
Pre-assignment details
In Phase A, participants were randomized to receive either omarigliptin 25 mg once weekly, sitagliptin 50 mg once daily or placebo for 24 weeks in a blinded manner. In Phase B, all participants received open-label omarigliptin 25 mg once weekly for 28 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Omarigliptin (Phase A+B) Omarigliptin 25 mg once weekly for 52 weeks (Phase A + B) | 166 |
| Sitagliptin (Phase A) Switching to Omarigliptin (Phase B) Sitagliptin 50 mg once daily for 24 weeks (Phase A) switching to omarigliptin 25 mg once weekly for 28 weeks (Phase B) | 165 |
| Placebo (Phase A) Switching to Omarigliptin (Phase B) Placebo for 24 weeks (Phase A) switching to omarigliptin 25 mg once weekly for 28 weeks (Phase B) | 83 |
| Total | 414 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Phase A (Up to 24 Weeks) | Adverse Event | 2 | 4 | 0 |
| Phase A (Up to 24 Weeks) | Lack of Efficacy | 2 | 0 | 1 |
| Phase A (Up to 24 Weeks) | Physician Decision | 1 | 0 | 0 |
| Phase A (Up to 24 Weeks) | Protocol Violation | 0 | 0 | 1 |
| Phase A (Up to 24 Weeks) | Withdrawal by Subject | 2 | 0 | 1 |
| Phase B - (Week 25 to 52) | Adverse Event | 2 | 3 | 2 |
| Phase B - (Week 25 to 52) | Lack of Efficacy | 12 | 10 | 3 |
| Phase B - (Week 25 to 52) | Withdrawal by Subject | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Omarigliptin (Phase A+B) | Sitagliptin (Phase A) Switching to Omarigliptin (Phase B) | Placebo (Phase A) Switching to Omarigliptin (Phase B) | Total |
|---|---|---|---|---|
| Age, Continuous | 60 Years STANDARD_DEVIATION 11 | 60 Years STANDARD_DEVIATION 9 | 61 Years STANDARD_DEVIATION 9 | 60 Years STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 62 Participants | 50 Participants | 26 Participants | 138 Participants |
| Sex: Female, Male Male | 104 Participants | 115 Participants | 57 Participants | 276 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 21 / 166 | 18 / 164 | 25 / 82 | 45 / 166 | 22 / 161 | 17 / 80 |
| serious Total, serious adverse events | 3 / 166 | 3 / 164 | 0 / 82 | 6 / 166 | 2 / 161 | 0 / 80 |
Outcome results
Primary
Change From Baseline for Hemoglobin A1c (HbA1c) at Week 24
HbA1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Change in A1C following 24 weeks of therapy (i.e., A1C at Week 24 minus A1C at baseline).
Time frame: Baseline and Week 24
Population: The Full Analysis Set (FAS) consisted of all randomized participants who had at least one study drug and had a baseline or post-randomization measurement for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin (Phase A) | Change From Baseline for Hemoglobin A1c (HbA1c) at Week 24 | -0.66 Percent HbA1c |
| Sitagliptin (Phase A) | Change From Baseline for Hemoglobin A1c (HbA1c) at Week 24 | -0.65 Percent HbA1c |
| Placebo (Phase A) | Change From Baseline for Hemoglobin A1c (HbA1c) at Week 24 | 0.13 Percent HbA1c |
p-value: <0.00195% CI: [-0.96, -0.63]Constrained longitudinal analysis
p-value: <0.00195% CI: [-0.94, -0.61]Constrained longitudinal analysis
p-value: 0.79295% CI: [-0.15, 0.12]Constrained longitudinal analysis
Primary
Percentage of Participants Who Discontinued From the Study Due to an Adverse Event During Phase A
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.
Time frame: Up to 24 weeks
Population: The ASaT Population consisted of all randomized participants who received at least one study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin (Phase A) | Percentage of Participants Who Discontinued From the Study Due to an Adverse Event During Phase A | 0.6 Percentage of participants |
| Sitagliptin (Phase A) | Percentage of Participants Who Discontinued From the Study Due to an Adverse Event During Phase A | 1.2 Percentage of participants |
| Placebo (Phase A) | Percentage of Participants Who Discontinued From the Study Due to an Adverse Event During Phase A | 0 Percentage of participants |
Primary
Percentage of Participants Who Discontinued From the Study Due to an Adverse Event During the Overall Study
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. These results represent the accrual of events over different treatment intervals: 52 weeks, omarigliptin (Phase A+B) defined as the double-blind period and open label extension period versus 28 weeks for the Sitagliptin (Phase A)→Omarigliptin (Phase B) and placebo (Phase A)→Omarigliptin (Phase B) group defined as the open-label extension period only.
Time frame: Up to 52 weeks
Population: The ASaT Population consisted of all randomized participants who received at least one study drug. Data was unavailable for 7 participants who discontinued the study in sitagliptin and placebo arms in Phase A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin (Phase A) | Percentage of Participants Who Discontinued From the Study Due to an Adverse Event During the Overall Study | 2.4 Percentage of participants |
| Sitagliptin (Phase A) | Percentage of Participants Who Discontinued From the Study Due to an Adverse Event During the Overall Study | 1.2 Percentage of participants |
| Placebo (Phase A) | Percentage of Participants Who Discontinued From the Study Due to an Adverse Event During the Overall Study | 1.3 Percentage of participants |
Primary
Percentage of Participants Who Experienced at Least One Adverse Event During Phase A
An adverse event (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.
Time frame: Up to 24 weeks
Population: All Subjects as Treated (ASaT) population consisted of all randomized participants who received at least one study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin (Phase A) | Percentage of Participants Who Experienced at Least One Adverse Event During Phase A | 50.0 Percentage of participants |
| Sitagliptin (Phase A) | Percentage of Participants Who Experienced at Least One Adverse Event During Phase A | 49.4 Percentage of participants |
| Placebo (Phase A) | Percentage of Participants Who Experienced at Least One Adverse Event During Phase A | 65.9 Percentage of participants |
Primary
Percentage of Participants Who Experienced at Least One Adverse Event During the Overall Study
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. These results represent the accrual of events over different treatment intervals: 52 weeks, omarigliptin (Phase A+B) defined as the double-blind period and open label extension period versus 28 weeks for the Sitagliptin (Phase A)→Omarigliptin (Phase B) and placebo (Phase A)→Omarigliptin (Phase B) group defined as the open-label extension period only.
Time frame: Up to 52 weeks
Population: The ASaT Population included all randomized participants who received at least one study drug. Data was unavailable for 7 participants who discontinued the study in sitagliptin and placebo arms in Phase A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin (Phase A) | Percentage of Participants Who Experienced at Least One Adverse Event During the Overall Study | 69.9 Percentage of Participants |
| Sitagliptin (Phase A) | Percentage of Participants Who Experienced at Least One Adverse Event During the Overall Study | 47.2 Percentage of Participants |
| Placebo (Phase A) | Percentage of Participants Who Experienced at Least One Adverse Event During the Overall Study | 56.3 Percentage of Participants |
Secondary
Change From Baseline for 2-hour Post Meal Glucose (PMG) at Week 24
Change from baseline at Week 24 is defined as PMG at Week 24 minus PMG at Week 0.
Time frame: Baseline and Week 24
Population: The FAS Population consisted of all randomized participants who had at least one study drug and had a baseline or post-randomization measurement for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin (Phase A) | Change From Baseline for 2-hour Post Meal Glucose (PMG) at Week 24 | -42.38 mg/dL |
| Sitagliptin (Phase A) | Change From Baseline for 2-hour Post Meal Glucose (PMG) at Week 24 | -45.24 mg/dL |
| Placebo (Phase A) | Change From Baseline for 2-hour Post Meal Glucose (PMG) at Week 24 | -5.48 mg/dL |
p-value: <0.00195% CI: [-48.46, -25.33]Constrained longitudinal analysis
p-value: <0.00195% CI: [-51.28, -28.23]Constrained longitudinal analysis
p-value: 0.55595% CI: [-6.67, 12.39]Constrained longitudinal analysis
Secondary
Change From Baseline for 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 had at least one study drug and had a baseline or post-randomization measurement for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin (Phase A) | Change From Baseline for Fasting Plasma Glucose (FPG) at Week 24 | -18.52 mg/dL |
| Sitagliptin (Phase A) | Change From Baseline for Fasting Plasma Glucose (FPG) at Week 24 | -20.75 mg/dL |
| Placebo (Phase A) | Change From Baseline for Fasting Plasma Glucose (FPG) at Week 24 | -6.23 mg/dL |
p-value: <0.00195% CI: [-17.78, -6.78]Constrained longitudinal analysis
p-value: <0.00195% CI: [-20.04, -8.98]Constrained longitudinal analysis
p-value: 0.3395% CI: [-2.27, 6.73]Constrained longitudinal analysis