Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to evaluate the cardiovascular (CV) safety profile of omarigliptin in participants with type 2 diabetes mellitus (T2DM). The primary hypothesis is that treatment with omarigliptin 25 mg once weekly is non-inferior to treatment with placebo and active comparators across the omarigliptin program with regard to the risk of developing a confirmed event in the primary CV composite endpoint.
Detailed description
The trial was amended to extend the length of the trial in order to meet FDA requirements for the post-approval assessment of cardiovascular (CV) safety. The trial now contains 2 time intervals: Period 1 and Period 2. Period 1 refers to the time interval up to this recent protocol amendment and Period 2, the time interval from this protocol amendment until the end of the study. Participants in Period 1 will be re-consented and continue into Period 2. If required, additional participants will be enrolled in Period 2. Stage 1 refers to the prefiling United States Food and Drug Administration (US FDA) requirement to rule out a 80% increased CV risk. Stage 2 refers to the US FDA post-marketing requirement to rule out a 30% increased CV risk. The Stage 1 assessment of CV risk occurred during Period 1 and was based on a meta-analysis of major adverse CV events (MACE) and unstable angina across the omarigliptin Phase 2/Phase 3 program. The Stage 2 assessment will be based on MACE in P018 alone including CV events from both Period 1 and Period 2.
Interventions
DRUGOmarigliptin
Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly
DRUGPlacebo
Matching placebo to omarigliptin capsule or tablet administered orally once weekly
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
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with type 2 diabetes mellitus * Is on one of the following diabetes treatment regimens that is stable for at least 12 weeks (except for pioglitazone for at least 16 weeks) and is within the associated A1C range for that treatment regimen: 1. A1C \>= 6.5% and \<= 10.0% (\>=48 mmol/mol and \<=86 mmol/mol) on: (a) diet or exercise alone (not on antihyperglycemic agent \[AHA\] for \>= 12 weeks) OR (b) monotherapy with metformin (MF), pioglitazone (PIO) or an alpha-glucosidase inhibitor (AGI) or a sodium-glucose cotransporter inhibitor (SGLT2i) OR (c) dual combination therapy with MF, PIO, AGI or SGLT2i OR 2. A1C \>= 7.0% and \<=10.0% (\>=53 mmol/mol and \<=86 mmol/mol) on (a) monotherapy with a sulfonylurea or meglitinide OR (b) dual combination therapy with a sulfonylurea or a meglitinide and MF, PIO, AGI, or SGLT2i OR 3. A1C \>=7.0% and \<=10.0% (\>=53 mmol/mol and \<=86 mmol/mol) on one of the following insulin regimens (with or without metformin): (a) basal insulin (e.g.; insulin glargine, insulin detemir, NPH insulin, degludec) OR (b) prandial insulin (e.g. regular, aspart, lispro, glulisine) OR (c) basal/prandial insulin regimen consisting of multiple dose insulin injections of basal and prandial insulin or the use of pre-mixed insulin (e.g., Novolog 70/30®, Novolin 70/30®, Humalog 75/25®, or Humulin 70/30® * Pre-existing vascular disease (coronary artery disease, ischemic cerebrovascular disease, atherosclerotic peripheral artery disease) * (1) Male; (2) female not of reproductive potential; or (3) female of reproductive potential who agrees to remain abstinent or use alone or in conjunction with their partner 2 methods of 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 rosiglitazone, a dipeptidyl peptidase-IV (DPP-4) inhibitor, or a glucagon-like peptide-1 (GLP-1) receptor agonist within 12 weeks prior to study participation or previously treated with omarigliptin * 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 * 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) as assessed by medical history * 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 |
|---|---|---|
| Percentage of Participants Who Experienced at Least One Adverse Event in a Sub-study of Participants Taking Insulin Excluding Data After Background Antihyperglycemic Agent (AHA) Change | Up to Week 18 | 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 Study Drug Due to an Adverse Event in a Sub-Study of Participants Taking Insulin Excluding Data After Background AHA Change | Up to Week 18 | 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. |
| Number of Participants With MACE-plus (Confirmed Cardiovascular [CV]-Related Death, Nonfatal Myocardial Infarction [MI], Nonfatal Stroke, or Hospitalization Due to Unstable Angina) | Up to 156 weeks | Participants with confirmed MACE-plus events (confirmed cardiovascular, CV-related death, nonfatal myocardial infarction \[MI\], nonfatal stroke, or hospitalization due to unstable angina). In the MK-3102-018 study, MACE plus events had a data cut-off date of April 15, 2015. |
| Number of Participants With an Event of MACE (Confirmed CV-Related Death, Fatal and Nonfatal MI, and Fatal and Nonfatal Stroke) | Up to 179 weeks | Participants with an Event of MACE (confirmed cardiovascular, CV-related death, fatal and nonfatal myocardial infarction \[MI\], and fatal and nonfatal stroke). |
| Number of Participants With an Event Per 100 Person-Years for First Event of MACE (Confirmed CV-Related Death, Fatal and Nonfatal MI, and Fatal and Nonfatal Stroke) | Up to 179 weeks | Participants with an event of MACE (confirmed cardiovascular, CV-related death, fatal and nonfatal myocardial infarction \[MI\], and fatal and nonfatal stroke). Person-years were calculated as the sum of all participants' follow-up time to first event. |
| Change From Baseline in Hemoglobin A1C (A1C) at Week 18 | Baseline and Week 18 | A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 18 A1C minus the Week 0 A1C. |
| Change From Baseline in A1C at Week 18 in a Sub-Study of Participants Taking Insulin (With or Without Metformin) | Baseline and Week 18 | A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 18 A1C minus the Week 0 A1C. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an Event of All-Cause Death | Up to 179 weeks | All-cause death was death from any cause. |
| Number of Participants With an Event Per 100 Person-Years of the Event of All-Cause Death | Up to 179 weeks | All-cause death was death for any cause. Person-years were calculated as the sum of all participants' follow-up time to event. |
| Change From Baseline in A1C at Week 142 | Baseline and Week 142 | A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 142 A1C minus the Week 0 A1C. |
| Percentage of Participants Achieving a Target A1C <7.0 % (53 mmol/Mol) at 4 Months | 4 months | A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). |
| Time to Initiation of Long-Term Insulin Therapy in Participants Not Receiving Insulin at Baseline | Up to 179 weeks | Long-term insulin therapy was defined as a continuous period of insulin use of more than 3 months. |
| Percentage of Participants Who Experienced at Least One Adverse Event | Up to 234 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 Study Drug Due to an Adverse Event | Up to 212 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. |
| Change From Baseline in FPG at Week 18 in a Sub-Study of Participants Taking Insulin | Baseline and Week 18 | This change from baseline reflects the Week 18 FPG minus the Week 0 FPG. |
| Percentage of Participants Achieving a Target A1C <7.0 % (53 mmol/Mol) at Week 18 in a Sub-Study of Participants Taking Insulin | 18 weeks | A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Analysis was performed with multiple data imputation. |
| Change From Baseline in Fasting Plasma Glucose (FPG) at 4 Months | Baseline and 4 months | This change from baseline reflects the Month 4 FPG minus the Week 0 FPG. |
| Number of Participants With an Event of CV-Related Death | Up to 179 weeks | Participants with adjudicated and confirmed AEs of cardiovascular-related death. |
| Number of Participants With an Event Per 100 Person-Years of CV-Related Death | Up to 179 weeks | Participants with adjudicated and confirmed AEs of cardiovascular-related death. Person-years were calculated as the sum of all participants' follow-up time to event. |
| Number of Participants With an Event of First MI (Fatal and Non-fatal) | Up to 179 weeks | Participants with adjudicated and confirmed AEs of fatal and non-fatal MI. |
| Number of Participants With an Event Per 100 Person-Years of First MI (Fatal and Non-fatal) | Up to 179 weeks | Participants with adjudicated and confirmed AEs of fatal and non-fatal MI. Person-years were calculated as the sum of all participants' follow-up time to first event. |
| Number of Participants With an Event of Stroke (Fatal and Non-fatal) | Up to 179 weeks | Participants with adjudicated and confirmed AEs fatal and non-fatal stroke. |
| Number of Participants With an Event Per 100 Person-Years of First Stroke (Fatal and Non-fatal) | Up to 179 weeks | Participants with adjudicated and confirmed AEs fatal and non-fatal stroke. Person-years were calculated as the sum of all participants' follow-up time to event. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an Event of First Hospitalization for Heart Failure (Exploratory) | Up to 179 weeks | Participants with adjudicated and confirmed events of first hospitalization for heart failure. |
| Number of Participants With an Event Per 100 Person-years of the Event of the First Hospitalization for Heart Failure (Exploratory) | Up to 179 weeks | Participants with adjudicated and confirmed events of first hospitalization for heart failure. Person-years were calculated as the sum of all participants' follow-up time to event. |
Participant flow
Recruitment details
A total of 559 sites received IEC/IRB approval in 40 countries and 547 were shipped clinical supplies. Of the 559 sites, 525 screened at least 1 participant. An insulin sub-study of MK-3102-018 was performed and included the sub-population of participants receiving ≥20 units/day of background insulin with or without metformin.
Pre-assignment details
On April 8, 2016, Merck & Co. Inc. announced that it would not submit marketing applications for omarigliptin (MK-3102) in the US and Europe for business reasons only. Because of this decision, the MK-3102-018 study was terminated early on May 13, 2016. Due to delays in study close-out the Last-Participant-Last-Visit occurred on March 22, 2017.
Participants by arm
| Arm | Count |
|---|---|
| Omarigliptin 25 mg Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly | 2,100 |
| Placebo Matching placebo to omarigliptin capsule or tablet administered once weekly. | 2,102 |
| Total | 4,202 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 14 | 19 |
| Overall Study | Death | 61 | 48 |
| Overall Study | Excluded Medication | 1 | 2 |
| Overall Study | Lack of Efficacy | 1 | 2 |
| Overall Study | Lost to Follow-up | 68 | 62 |
| Overall Study | Non-Compliance with Study Drug | 1 | 0 |
| Overall Study | Physician Decision | 11 | 13 |
| Overall Study | Progressive disease | 2 | 2 |
| Overall Study | Protocol Deviation | 2 | 0 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Site Discontinued Study Participation | 23 | 27 |
| Overall Study | Study Terminated by Sponsor | 1,710 | 1,716 |
| Overall Study | Technical Problems | 0 | 1 |
| Overall Study | Withdrawal by Subject | 205 | 209 |
Baseline characteristics
| Characteristic | Omarigliptin 25 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 63.7 Years STANDARD_DEVIATION 8.5 | 63.6 Years STANDARD_DEVIATION 8.5 | 63.6 Years STANDARD_DEVIATION 8.5 |
| Fasting Plasma Glucose (FPG) | 184.1 mg/dL STANDARD_DEVIATION 52.2 | 179.5 mg/dL STANDARD_DEVIATION 45.7 | 180.4 mg/dL STANDARD_DEVIATION 47.8 |
| Hemoglobin A1C % | 7.99 Percent STANDARD_DEVIATION 0.86 | 8.03 Percent STANDARD_DEVIATION 0.89 | 8.01 Percent STANDARD_DEVIATION 0.87 |
| Sex: Female, Male Female | 639 Participants | 615 Participants | 1254 Participants |
| Sex: Female, Male Male | 1461 Participants | 1487 Participants | 2948 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 788 / 2,092 | 794 / 2,100 |
| serious Total, serious adverse events | 512 / 2,092 | 503 / 2,100 |
Outcome results
Primary
Change From Baseline in A1C at Week 18 in a Sub-Study of Participants Taking Insulin (With or Without Metformin)
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 18 A1C minus the Week 0 A1C.
Time frame: Baseline and Week 18
Population: The analysis population consists of all randomized participants in a sub-study of participants taking insulin who received at least one dose of blinded study medication and had a baseline or a post-randomization measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin 25 mg | Change From Baseline in A1C at Week 18 in a Sub-Study of Participants Taking Insulin (With or Without Metformin) | -0.50 Percentage |
| Placebo | Change From Baseline in A1C at Week 18 in a Sub-Study of Participants Taking Insulin (With or Without Metformin) | -0.11 Percentage |
p-value: <0.00195% CI: [-0.5, -0.27]Longitudinal data analysis
Primary
Change From Baseline in Hemoglobin A1C (A1C) at Week 18
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 18 A1C minus the Week 0 A1C.
Time frame: Baseline and Week 18
Population: The analysis population consisted of all randomized participants who received at least one dose of blinded study medication and had a baseline or a post-randomization measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Omarigliptin 25 mg | Change From Baseline in Hemoglobin A1C (A1C) at Week 18 | -0.58 Percent | 95% Confidence Interval 0.82 |
| Placebo | Change From Baseline in Hemoglobin A1C (A1C) at Week 18 | -0.16 Percent | 95% Confidence Interval 0.88 |
95% CI: [-0.48, -0.37]
Primary
Number of Participants With an Event of MACE (Confirmed CV-Related Death, Fatal and Nonfatal MI, and Fatal and Nonfatal Stroke)
Participants with an Event of MACE (confirmed cardiovascular, CV-related death, fatal and nonfatal myocardial infarction \[MI\], and fatal and nonfatal stroke).
Time frame: Up to 179 weeks
Population: The analysis population included all randomized participants who took at least one dose of blinded trial medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Number of Participants With an Event of MACE (Confirmed CV-Related Death, Fatal and Nonfatal MI, and Fatal and Nonfatal Stroke) | 114 Participants |
| Placebo | Number of Participants With an Event of MACE (Confirmed CV-Related Death, Fatal and Nonfatal MI, and Fatal and Nonfatal Stroke) | 114 Participants |
Primary
Number of Participants With an Event Per 100 Person-Years for First Event of MACE (Confirmed CV-Related Death, Fatal and Nonfatal MI, and Fatal and Nonfatal Stroke)
Participants with an event of MACE (confirmed cardiovascular, CV-related death, fatal and nonfatal myocardial infarction \[MI\], and fatal and nonfatal stroke). Person-years were calculated as the sum of all participants' follow-up time to first event.
Time frame: Up to 179 weeks
Population: The analysis population included all randomized participants who took at least one dose of blinded trial medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Number of Participants With an Event Per 100 Person-Years for First Event of MACE (Confirmed CV-Related Death, Fatal and Nonfatal MI, and Fatal and Nonfatal Stroke) | 2.96 Participants/100 Person-years |
| Placebo | Number of Participants With an Event Per 100 Person-Years for First Event of MACE (Confirmed CV-Related Death, Fatal and Nonfatal MI, and Fatal and Nonfatal Stroke) | 2.97 Participants/100 Person-years |
95% CI: [0.77, 1.29]
Primary
Number of Participants With MACE-plus (Confirmed Cardiovascular [CV]-Related Death, Nonfatal Myocardial Infarction [MI], Nonfatal Stroke, or Hospitalization Due to Unstable Angina)
Participants with confirmed MACE-plus events (confirmed cardiovascular, CV-related death, nonfatal myocardial infarction \[MI\], nonfatal stroke, or hospitalization due to unstable angina). In the MK-3102-018 study, MACE plus events had a data cut-off date of April 15, 2015.
Time frame: Up to 156 weeks
Population: The analysis population included all randomized participants who took at least one dose of blinded study medication and were evaluated for MACE-plus events.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Number of Participants With MACE-plus (Confirmed Cardiovascular [CV]-Related Death, Nonfatal Myocardial Infarction [MI], Nonfatal Stroke, or Hospitalization Due to Unstable Angina) | 66 Participants |
| Placebo | Number of Participants With MACE-plus (Confirmed Cardiovascular [CV]-Related Death, Nonfatal Myocardial Infarction [MI], Nonfatal Stroke, or Hospitalization Due to Unstable Angina) | 70 Participants |
Primary
Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event in a Sub-Study of Participants Taking Insulin Excluding Data After Background AHA Change
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 Week 18
Population: The analysis population included all randomized participants in a sub-study of participants taking insulin who received at least one dose of blinded study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event in a Sub-Study of Participants Taking Insulin Excluding Data After Background AHA Change | 1.1 Percentage of participants |
| Placebo | Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event in a Sub-Study of Participants Taking Insulin Excluding Data After Background AHA Change | 0.8 Percentage of participants |
95% CI: [-1, 1.7]
Primary
Percentage of Participants Who Experienced at Least One Adverse Event in a Sub-study of Participants Taking Insulin Excluding Data After Background Antihyperglycemic Agent (AHA) Change
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 Week 18
Population: The analysis population included all randomized participants in a sub-study of participants taking insulin who received at least one dose of blinded study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Percentage of Participants Who Experienced at Least One Adverse Event in a Sub-study of Participants Taking Insulin Excluding Data After Background Antihyperglycemic Agent (AHA) Change | 48.8 Percentage of participants |
| Placebo | Percentage of Participants Who Experienced at Least One Adverse Event in a Sub-study of Participants Taking Insulin Excluding Data After Background Antihyperglycemic Agent (AHA) Change | 49.9 Percentage of participants |
95% CI: [-7.2, 4.9]
Secondary
Change From Baseline in A1C at Week 142
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 142 A1C minus the Week 0 A1C.
Time frame: Baseline and Week 142
Population: The analysis population consisted of all randomized participants who received at least one dose of blinded study medication and had a baseline or a post-randomization measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Omarigliptin 25 mg | Change From Baseline in A1C at Week 142 | -0.36 Percent | 95% Confidence Interval 0.06 |
| Placebo | Change From Baseline in A1C at Week 142 | -0.06 Percent | 95% Confidence Interval 1.12 |
95% CI: [-0.46, -0.14]
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at 4 Months
This change from baseline reflects the Month 4 FPG minus the Week 0 FPG.
Time frame: Baseline and 4 months
Population: Data for this efficacy endpoint was not collected, analyzed or summarized.
Secondary
Change From Baseline in FPG at Week 18 in a Sub-Study of Participants Taking Insulin
This change from baseline reflects the Week 18 FPG minus the Week 0 FPG.
Time frame: Baseline and Week 18
Population: The analysis population consisted of all randomized participants in a sub-study of participants taking insulin who received at least one dose of blinded study medication and had a baseline or a post-randomization measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin 25 mg | Change From Baseline in FPG at Week 18 in a Sub-Study of Participants Taking Insulin | -6.8 mg/dL |
| Placebo | Change From Baseline in FPG at Week 18 in a Sub-Study of Participants Taking Insulin | -3.6 mg/dL |
p-value: 0.42195% CI: [-10.8, 4.5]Longitudinal constrained data analysis
Secondary
Number of Participants With an Event of All-Cause Death
All-cause death was death from any cause.
Time frame: Up to 179 weeks
Population: The analysis population included all randomized participants who took at least one dose of blinded trial medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Number of Participants With an Event of All-Cause Death | 64 Participants |
| Placebo | Number of Participants With an Event of All-Cause Death | 50 Participants |
Secondary
Number of Participants With an Event of CV-Related Death
Participants with adjudicated and confirmed AEs of cardiovascular-related death.
Time frame: Up to 179 weeks
Population: The analysis population consisted of all randomized participants who received at least one dose of blinded study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Number of Participants With an Event of CV-Related Death | 37 Participants |
| Placebo | Number of Participants With an Event of CV-Related Death | 35 Participants |
Secondary
Number of Participants With an Event of First MI (Fatal and Non-fatal)
Participants with adjudicated and confirmed AEs of fatal and non-fatal MI.
Time frame: Up to 179 weeks
Population: The analysis population consisted of all participants who took at least one dose of blinded study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Number of Participants With an Event of First MI (Fatal and Non-fatal) | 52 Participants |
| Placebo | Number of Participants With an Event of First MI (Fatal and Non-fatal) | 60 Participants |
Secondary
Number of Participants With an Event of Stroke (Fatal and Non-fatal)
Participants with adjudicated and confirmed AEs fatal and non-fatal stroke.
Time frame: Up to 179 weeks
Population: The analysis population consisted of all participants who took at least one dose of blinded study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Number of Participants With an Event of Stroke (Fatal and Non-fatal) | 32 Participants |
| Placebo | Number of Participants With an Event of Stroke (Fatal and Non-fatal) | 34 Participants |
Secondary
Number of Participants With an Event Per 100 Person-Years of CV-Related Death
Participants with adjudicated and confirmed AEs of cardiovascular-related death. Person-years were calculated as the sum of all participants' follow-up time to event.
Time frame: Up to 179 weeks
Population: The analysis population consisted of all participants who took at least one dose of blinded study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Number of Participants With an Event Per 100 Person-Years of CV-Related Death | 0.94 Participants/100 person-years |
| Placebo | Number of Participants With an Event Per 100 Person-Years of CV-Related Death | 0.89 Participants/100 person-years |
95% CI: [0.66, 1.68]
Secondary
Number of Participants With an Event Per 100 Person-Years of First MI (Fatal and Non-fatal)
Participants with adjudicated and confirmed AEs of fatal and non-fatal MI. Person-years were calculated as the sum of all participants' follow-up time to first event.
Time frame: Up to 179 weeks
Population: The analysis population consisted of all participants who took at least one dose of blinded study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Number of Participants With an Event Per 100 Person-Years of First MI (Fatal and Non-fatal) | 1.34 Participants/100 person-years |
| Placebo | Number of Participants With an Event Per 100 Person-Years of First MI (Fatal and Non-fatal) | 1.55 Participants/100 person-years |
95% CI: [0.6, 1.26]
Secondary
Number of Participants With an Event Per 100 Person-Years of First Stroke (Fatal and Non-fatal)
Participants with adjudicated and confirmed AEs fatal and non-fatal stroke. Person-years were calculated as the sum of all participants' follow-up time to event.
Time frame: Up to 179 weeks
Population: The analysis population consisted of all participants who took at least one dose of blinded study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Number of Participants With an Event Per 100 Person-Years of First Stroke (Fatal and Non-fatal) | 0.82 Participants/100 person-years |
| Placebo | Number of Participants With an Event Per 100 Person-Years of First Stroke (Fatal and Non-fatal) | 0.88 Participants/100 person-years |
95% CI: [0.58, 1.52]
Secondary
Number of Participants With an Event Per 100 Person-Years of the Event of All-Cause Death
All-cause death was death for any cause. Person-years were calculated as the sum of all participants' follow-up time to event.
Time frame: Up to 179 weeks
Population: The analysis population included all randomized participants who took at least one dose of blinded study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Number of Participants With an Event Per 100 Person-Years of the Event of All-Cause Death | 1.63 Participants/100 Person-years |
| Placebo | Number of Participants With an Event Per 100 Person-Years of the Event of All-Cause Death | 1.28 Participants/100 Person-years |
95% CI: [0.88, 1.85]
Secondary
Percentage of Participants Achieving a Target A1C <7.0 % (53 mmol/Mol) at 4 Months
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%).
Time frame: 4 months
Population: Data for this efficacy endpoint was not collected, analyzed or summarized.
Secondary
Percentage of Participants Achieving a Target A1C <7.0 % (53 mmol/Mol) at Week 18 in a Sub-Study of Participants Taking Insulin
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Analysis was performed with multiple data imputation.
Time frame: 18 weeks
Population: The analysis population consisted of all randomized participants in a sub-study of participants taking insulin who received at least one dose of blinded study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Percentage of Participants Achieving a Target A1C <7.0 % (53 mmol/Mol) at Week 18 in a Sub-Study of Participants Taking Insulin | 22.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving a Target A1C <7.0 % (53 mmol/Mol) at Week 18 in a Sub-Study of Participants Taking Insulin | 10.2 Percentage of participants |
p-value: <0.00195% CI: [6.9, 16.8]Miettinen & Nurminen method
Secondary
Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event
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 212 weeks
Population: The analysis population included all randomized participants who took at least one dose of blinded study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event | 4.1 Percentage of participants |
| Placebo | Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event | 3.6 Percentage of participants |
Secondary
Percentage of Participants Who Experienced at Least One Adverse Event
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 234 weeks
Population: The analysis population included all randomized participants who took at least one dose of blinded study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Percentage of Participants Who Experienced at Least One Adverse Event | 78.3 Percentage of participants |
| Placebo | Percentage of Participants Who Experienced at Least One Adverse Event | 76.8 Percentage of participants |
Secondary
Time to Initiation of Long-Term Insulin Therapy in Participants Not Receiving Insulin at Baseline
Long-term insulin therapy was defined as a continuous period of insulin use of more than 3 months.
Time frame: Up to 179 weeks
Population: Data for this efficacy endpoint was not collected, analyzed or summarized.
Other Pre-specified
Number of Participants With an Event of First Hospitalization for Heart Failure (Exploratory)
Participants with adjudicated and confirmed events of first hospitalization for heart failure.
Time frame: Up to 179 weeks
Population: The analysis population consisted of all participants who took at least one dose of blinded study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Number of Participants With an Event of First Hospitalization for Heart Failure (Exploratory) | 20 Participants |
| Placebo | Number of Participants With an Event of First Hospitalization for Heart Failure (Exploratory) | 33 Participants |
Other Pre-specified
Number of Participants With an Event Per 100 Person-years of the Event of the First Hospitalization for Heart Failure (Exploratory)
Participants with adjudicated and confirmed events of first hospitalization for heart failure. Person-years were calculated as the sum of all participants' follow-up time to event.
Time frame: Up to 179 weeks
Population: The analysis population consisted of all participants who took at least one dose of blinded study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Number of Participants With an Event Per 100 Person-years of the Event of the First Hospitalization for Heart Failure (Exploratory) | 0.51 Participants/100 Person-years |
| Placebo | Number of Participants With an Event Per 100 Person-years of the Event of the First Hospitalization for Heart Failure (Exploratory) | 0.85 Participants/100 Person-years |
95% CI: [0.35, 1.05]