Type 2 Diabetes Mellitus
Conditions
Brief summary
This study will examine the efficacy of omarigliptin 25 mg once weekly compared to placebo in Japanese patients with T2DM who have inadequate glycemic control on insulin monotherapy in addition to diet and exercise therapy. The primary hypothesis of the study is that omarigliptin 25 mg once weekly provides greater reduction in hemoglobin A1C (HbA1c) compared with placebo as assessed by change from baseline to Week 16 \[Phase A (double-blind period)\].
Detailed description
After a screening period of up to 2 weeks followed by a pretreatment period of 2 or 10 weeks, each participant will be receiving assigned double-blind treatment (omarigliptin 25 mg or placebo once weekly) for approximately 16 weeks (Phase A) followed by 36 weeks of open-label treatment (omarigliptin 25 mg once weekly, Phase B). After the end of treatment each participant will be followed for 21 days.
Interventions
DRUGOmarigliptin
Omarigliptin, 25 mg orally once weekly
DRUGPlacebo
Placebo to omarigliptin orally once weekly
BIOLOGICALInsulin
Insulin will be administered subcutaneously during the trial as monotherapy; dosage and administration following each package insert.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have T2DM * Meet all of following criteria at Week -2 of pre-randomization 1. On diet and exercise therapy for 6 weeks or longer, AND 2. Have been on a stable dosage and administration of insulin (8 to 40 units/day) for 10 weeks or longer, AND. 3. Have not been on any additional anti-hyperglycemic agent (AHAs, except for insulin monotherapy) for 8 weeks or longer, AND 4. HbA1c ≥7.5% and ≤10.0% 5. Fasting Plasma Glucose (FPG) ≥126 mg/dL and ≤230 mg/dL * Have a body mass index (BMI) \>18 kg/m\^2 and \<40 kg/m\^2 * A male or female not of reproductive potential or a female of reproductive potential and agrees to remain abstinent from heterosexual activity, or agrees to use acceptable contraception to prevent pregnancy.
Exclusion criteria
* Has type 1 diabetes mellitus or has a history of diabetic ketoacidosis. * Has a history of being administered any of the following AHAs including fixed dose combination (FDC) containing the following ingredients: 1. Thiazolidinediones within 12 weeks 2. Glucagon-like peptide 1 (GLP-1) receptor agonists within 12 weeks 3. Omarigliptin at any time * Has history of severe hypoglycemia with coma or loss of consciousness, or for whom hypoglycemia was observed greater or equal to two times per week within 8 weeks * Is currently participating in or has participated in another study with an investigational compound or device within the prior 12 weeks * Has undergone a surgical procedure within 8 weeks or has planned major surgery during the study. * Receives a lipid-lowering medication or thyroid replacement therapy at unstable dosage and administration * Has poorly controlled hypertension * Has a medical history of active liver disease, including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease. * Has human immunodeficiency virus (HIV). * Has had new or worsening signs or symptoms of coronary heart disease or congestive heart failure within the past 3 months, or has acute coronary syndrome, coronary artery intervention, or stroke or transient ischemic neurological disorder within the past 3 months * Has severe peripheral vascular disease. * Has a history of malignancy ≤ 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer: * Has a clinically important hematological disorder. * (For women of childbearing potential) has a positive urine pregnancy test. * Is pregnant or breast feeding * Is expected to conceive during the study * Is expected to undergo hormonal therapy in preparation to donate eggs during the study * Routinely consumes \>14 alcoholic drinks per week or engages in binge drinking * Has donated or plans to donate blood products of \>300 mL within 8 weeks or during the study * Has received or plans to receive blood products within 12 weeks or during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Constrained Longitudinal Data Analysis of Change From Baseline in Hemoglobin A1c (HbA1c) at Week 16 Excluding Data After Glycemic Rescue (Phase A) | Baseline (Day 1) and Week 16 | HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Participant whole blood samples were collected at baseline and Week 16 to determine the Constrained Longitudinal Data Analysis least squares mean HbA1c change from baseline (i.e., HbA1c at Week 16 minus HbA1c at baseline). Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis. Negative data values indicated a reduction in HbA1c levels. |
| Percentage of Participants Who Experienced One or More Adverse Events (AE) Excluding Data After Glycemic Rescue (Phase A) | Up to Week 16 | 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. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis. |
| Percentage of Participants Who Experienced One or More AE (Omarigliptin [Phase A+B]; Placebo→Omarigliptin [Phase B Only]) | Up to Week 52 | 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. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. The results for the Placebo→Omarigliptin group summarized data from the open label period only (36 weeks), which corresponds to the study interval in which those participants were exposed to omarigliptin. |
| Percentage of Participants Who Discontinued Study Drug Due to an AE Excluding Data After Glycemic Rescue (Phase A) | Up to Week 16 | 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. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis. |
| Percentage of Participants Who Discontinued Study Drug Due to an AE Including Data After Glycemic Rescue (Omarigliptin [Phase A+B]; Placebo→Omarigliptin [Phase B Only]) | Up to Week 52 | 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. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. The results for the Placebo→Omarigliptin group summarized data from the open label period only (36 weeks), which corresponds to the study interval in which those participants were exposed to omarigliptin. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 (Phase A+B) | Baseline (Day 1) and Week 52 | Blood glucose was measured on a fasting basis. FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 52 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 52 minus FPG at baseline). Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Negative data values indicated a reduction in FPG levels. |
| Constrained Longitudinal Data Analysis of Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16 Excluding Data After Glycemic Rescue (Phase A) | Baseline (Day 1) and Week 16 | Blood glucose was measured on a fasting basis. FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 16 weeks of treatment to determine Constrained Longitudinal Data Analysis change in plasma glucose levels (i.e., FPG at Week 16 minus FPG at baseline). Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis. Negative data values indicated a reduction in FPG levels. |
| Percentage of Participants Achieving Hemoglobin A1c Goals (<6.5%) at Week 52 (Phase A+B) | Week 52 | HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. For the HbA1c goals of \<6.5% at Week 52, the percentage of participants and the 95% confidence intervals were calculated using Wilson score method by treatment groups of the double-blind period. |
| Percentage of Participants Achieving Hemoglobin A1c Goals (<7.0%) at Week 52 (Phase A+B) | Week 52 | HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. For the HbA1c goals of \<7.0% at Week 52, the percentage of participants and the 95% confidence intervals were calculated using Wilson score method by treatment groups of the double-blind period. |
| Percentage of Participants Achieving Hemoglobin A1c Goals (<7.0%) at Week 16 Constrained Longitudinal Data Analysis Using Multiple Imputation Excluding Data After Glycemic Rescue (Phase A) | Week 16 | HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis. Each of the 10 imputed data sets was summarized to obtain the percentage of responders within each group and were combined using standard multiple imputation techniques to yield an overall estimate of response rate and associated variance for each group. A constrained longitudinal data analysis was used to analyze the data and Wilson score method by treatment groups used for the analysis of percentages of individuals at the HbA1c goals of \<7.0% at Week 16 and the 95% confidence intervals (CIs). Miettinen & Nurminen (M&N) method after imputations were used to calculate the treatment differences of the percentages of individuals and the 95% CIs. |
| Percentage of Participants Achieving HbA1c Goals (<6.5%) at Week 16 Constrained Longitudinal Data Analysis Using Multiple Imputation Excluding Data After Glycemic Rescue (Phase A) | Week 16 | HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis. Each of the 10 imputed data sets was summarized to obtain the percentage of responders within each group and were combined using standard multiple imputation techniques to yield an overall estimate of response rate and associated variance for each group. A constrained longitudinal data analysis was used to analyze the data and Wilson score method by treatment groups used for the analysis of percentages of individuals at the HbA1c goals of \<6.5% at Week 16 and the 95% confidence intervals (CIs). Miettinen & Nurminen (M&N) method after imputations were used to calculate the treatment differences of the percentages of individuals and the 95% CIs. |
| Constrained Longitudinal Data Analysis of Change From Baseline in 1,5-anhydroglucitol (1,5-AG) at Week 16 Excluding Data After Glycemic Rescue (Phase A) | Baseline (Day 1) and Week 16 | 1,5-anhydroglucitol (1,5-AG) is a marker of short-term glycemic control especially postprandial hyperglycemia. 1,5-AG accurately predicts rapid changes in glycemia and is tightly associated with glucose fluctuations and postprandial glucose. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis. Data (1,5-AG at Week 16 minus 1,5-AG at baseline) was analyzed by Constrained Longitudinal Data Analysis. Positive data values indicate an increase in 1,5-AG levels and correlate with an improvement in glycemia. |
| Change From Baseline in Hemoglobin A1c (HbA1c) at Week 52 (Phase A+B) | Baseline (Day 1) and Week 52 | HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Participant whole blood samples were collected at baseline and Week 52 to determine the mean HbA1c change from baseline (i.e., HbA1c at Week 52 minus HbA1c at baseline). Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Negative data values indicated a reduction in HbA1c levels. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omarigliptin 25 mg Omarigliptin 25 mg once weekly for 52 weeks (Phase A and B) | 123 |
| Placebo→Omarigliptin 25 mg Placebo once weekly for 16 weeks (Phase A) switching to Omarigliptin 25 mg once weekly for 36 weeks (Phase B) | 61 |
| Total | 184 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Phase A (Week 0 to Week 16) | Adverse Event | 1 | 2 |
| Phase A (Week 0 to Week 16) | Death | 0 | 1 |
| Phase B (Extension, Week 17 to Week 52) | Adverse Event | 3 | 0 |
| Phase B (Extension, Week 17 to Week 52) | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo→Omarigliptin 25 mg | Total | Omarigliptin 25 mg |
|---|---|---|---|
| Age, Continuous | 60.9 Years STANDARD_DEVIATION 11.7 | 61.0 Years STANDARD_DEVIATION 11.2 | 61.1 Years STANDARD_DEVIATION 11 |
| Baseline 1,5-anhydroglucitol (1,5-AG) Levels | 3.4 mg/L STANDARD_DEVIATION 2.1 | 3.5 mg/L STANDARD_DEVIATION 2.5 | 3.6 mg/L STANDARD_DEVIATION 2.7 |
| Fasting Plasma Glucose (FPG) | 152.2 mg/dL STANDARD_DEVIATION 26 | 156.8 mg/dL STANDARD_DEVIATION 30.2 | 159.1 mg/dL STANDARD_DEVIATION 31.9 |
| Hemoglobin A1C | 8.83 Percent A1C STANDARD_DEVIATION 0.78 | 8.82 Percent A1C STANDARD_DEVIATION 0.71 | 8.81 Percent A1C STANDARD_DEVIATION 0.68 |
| Prior Antihyperglycemic Therapy Status No | 39 Participants | 119 Participants | 80 Participants |
| Prior Antihyperglycemic Therapy Status Yes | 22 Participants | 65 Participants | 43 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 61 Participants | 184 Participants | 123 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 14 Participants | 51 Participants | 37 Participants |
| Sex: Female, Male Male | 47 Participants | 133 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 123 | 1 / 61 | 0 / 123 | 0 / 58 |
| other Total, other adverse events | 35 / 123 | 11 / 61 | 72 / 123 | 27 / 58 |
| serious Total, serious adverse events | 5 / 123 | 2 / 61 | 12 / 123 | 1 / 58 |
Outcome results
Primary
Constrained Longitudinal Data Analysis of Change From Baseline in Hemoglobin A1c (HbA1c) at Week 16 Excluding Data After Glycemic Rescue (Phase A)
HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Participant whole blood samples were collected at baseline and Week 16 to determine the Constrained Longitudinal Data Analysis least squares mean HbA1c change from baseline (i.e., HbA1c at Week 16 minus HbA1c at baseline). Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis. Negative data values indicated a reduction in HbA1c levels.
Time frame: Baseline (Day 1) and Week 16
Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one measurement (baseline or post randomization) for the outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin 25 mg | Constrained Longitudinal Data Analysis of Change From Baseline in Hemoglobin A1c (HbA1c) at Week 16 Excluding Data After Glycemic Rescue (Phase A) | -0.61 Percent HbA1c |
| Placebo | Constrained Longitudinal Data Analysis of Change From Baseline in Hemoglobin A1c (HbA1c) at Week 16 Excluding Data After Glycemic Rescue (Phase A) | 0.29 Percent HbA1c |
p-value: <0.00195% CI: [-1.15, -0.66]Constrained Longitudinal Data Analysis
Primary
Percentage of Participants Who Discontinued Study Drug Due to an AE Excluding Data After Glycemic Rescue (Phase A)
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. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis.
Time frame: Up to Week 16
Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment and had safety data for the specified measurement and timeframe.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Percentage of Participants Who Discontinued Study Drug Due to an AE Excluding Data After Glycemic Rescue (Phase A) | 0.8 Percentage of Participants |
| Placebo | Percentage of Participants Who Discontinued Study Drug Due to an AE Excluding Data After Glycemic Rescue (Phase A) | 4.9 Percentage of Participants |
95% CI: [-12.8, 0.4]
Primary
Percentage of Participants Who Discontinued Study Drug Due to an AE Including Data After Glycemic Rescue (Omarigliptin [Phase A+B]; Placebo→Omarigliptin [Phase B Only])
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. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. The results for the Placebo→Omarigliptin group summarized data from the open label period only (36 weeks), which corresponds to the study interval in which those participants were exposed to omarigliptin.
Time frame: Up to Week 52
Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment and had safety data for the specified measurement and timeframe.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Percentage of Participants Who Discontinued Study Drug Due to an AE Including Data After Glycemic Rescue (Omarigliptin [Phase A+B]; Placebo→Omarigliptin [Phase B Only]) | 3.3 Percentage of Participants |
| Placebo | Percentage of Participants Who Discontinued Study Drug Due to an AE Including Data After Glycemic Rescue (Omarigliptin [Phase A+B]; Placebo→Omarigliptin [Phase B Only]) | 0 Percentage of Participants |
Primary
Percentage of Participants Who Experienced One or More Adverse Events (AE) Excluding Data After Glycemic Rescue (Phase A)
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. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis.
Time frame: Up to Week 16
Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment and had safety data for the specified measurement and timeframe.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Percentage of Participants Who Experienced One or More Adverse Events (AE) Excluding Data After Glycemic Rescue (Phase A) | 51.2 Percentage of participants |
| Placebo | Percentage of Participants Who Experienced One or More Adverse Events (AE) Excluding Data After Glycemic Rescue (Phase A) | 44.3 Percentage of participants |
95% CI: [-8.4, 21.8]
Primary
Percentage of Participants Who Experienced One or More AE (Omarigliptin [Phase A+B]; Placebo→Omarigliptin [Phase B Only])
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. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. The results for the Placebo→Omarigliptin group summarized data from the open label period only (36 weeks), which corresponds to the study interval in which those participants were exposed to omarigliptin.
Time frame: Up to Week 52
Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment and had safety data for the specified measurement and timeframe.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Percentage of Participants Who Experienced One or More AE (Omarigliptin [Phase A+B]; Placebo→Omarigliptin [Phase B Only]) | 84.6 Percentage of Participants |
| Placebo | Percentage of Participants Who Experienced One or More AE (Omarigliptin [Phase A+B]; Placebo→Omarigliptin [Phase B Only]) | 67.2 Percentage of Participants |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 (Phase A+B)
Blood glucose was measured on a fasting basis. FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 52 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 52 minus FPG at baseline). Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Negative data values indicated a reduction in FPG levels.
Time frame: Baseline (Day 1) and Week 52
Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one measurement (baseline or post randomization) for the outcome measure. Three participants in the Placebo group did not have data to contribute to the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Omarigliptin 25 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 (Phase A+B) | -11.5 mg/dL |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 (Phase A+B) | -5.3 mg/dL |
Secondary
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 52 (Phase A+B)
HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Participant whole blood samples were collected at baseline and Week 52 to determine the mean HbA1c change from baseline (i.e., HbA1c at Week 52 minus HbA1c at baseline). Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Negative data values indicated a reduction in HbA1c levels.
Time frame: Baseline (Day 1) and Week 52
Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one measurement (baseline or post randomization) for the outcome measure. Three participants in the Placebo group did not have data to contribute to the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Omarigliptin 25 mg | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 52 (Phase A+B) | -0.57 Percent A1C |
| Placebo | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 52 (Phase A+B) | -0.57 Percent A1C |
Secondary
Constrained Longitudinal Data Analysis of Change From Baseline in 1,5-anhydroglucitol (1,5-AG) at Week 16 Excluding Data After Glycemic Rescue (Phase A)
1,5-anhydroglucitol (1,5-AG) is a marker of short-term glycemic control especially postprandial hyperglycemia. 1,5-AG accurately predicts rapid changes in glycemia and is tightly associated with glucose fluctuations and postprandial glucose. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis. Data (1,5-AG at Week 16 minus 1,5-AG at baseline) was analyzed by Constrained Longitudinal Data Analysis. Positive data values indicate an increase in 1,5-AG levels and correlate with an improvement in glycemia.
Time frame: Baseline (Day 1) and Week 16
Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one measurement (baseline or post randomization) for the outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin 25 mg | Constrained Longitudinal Data Analysis of Change From Baseline in 1,5-anhydroglucitol (1,5-AG) at Week 16 Excluding Data After Glycemic Rescue (Phase A) | 2.9 mg/L |
| Placebo | Constrained Longitudinal Data Analysis of Change From Baseline in 1,5-anhydroglucitol (1,5-AG) at Week 16 Excluding Data After Glycemic Rescue (Phase A) | -0.2 mg/L |
p-value: <0.00195% CI: [2.3, 4]Constrained Longitudinal Data Analysis
Secondary
Constrained Longitudinal Data Analysis of Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16 Excluding Data After Glycemic Rescue (Phase A)
Blood glucose was measured on a fasting basis. FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 16 weeks of treatment to determine Constrained Longitudinal Data Analysis change in plasma glucose levels (i.e., FPG at Week 16 minus FPG at baseline). Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis. Negative data values indicated a reduction in FPG levels.
Time frame: Baseline (Day 1) and Week 16
Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one measurement (baseline or post randomization) for the outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin 25 mg | Constrained Longitudinal Data Analysis of Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16 Excluding Data After Glycemic Rescue (Phase A) | -11.6 mg/dL |
| Placebo | Constrained Longitudinal Data Analysis of Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16 Excluding Data After Glycemic Rescue (Phase A) | 3.4 mg/dL |
p-value: 0.00295% CI: [-24.5, -5.4]Constrained Longitudinal Data Analysis
Secondary
Percentage of Participants Achieving HbA1c Goals (<6.5%) at Week 16 Constrained Longitudinal Data Analysis Using Multiple Imputation Excluding Data After Glycemic Rescue (Phase A)
HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis. Each of the 10 imputed data sets was summarized to obtain the percentage of responders within each group and were combined using standard multiple imputation techniques to yield an overall estimate of response rate and associated variance for each group. A constrained longitudinal data analysis was used to analyze the data and Wilson score method by treatment groups used for the analysis of percentages of individuals at the HbA1c goals of \<6.5% at Week 16 and the 95% confidence intervals (CIs). Miettinen & Nurminen (M&N) method after imputations were used to calculate the treatment differences of the percentages of individuals and the 95% CIs.
Time frame: Week 16
Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one measurement (baseline or post randomization) for the outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Percentage of Participants Achieving HbA1c Goals (<6.5%) at Week 16 Constrained Longitudinal Data Analysis Using Multiple Imputation Excluding Data After Glycemic Rescue (Phase A) | 1.7 Percentage of Participants |
| Placebo | Percentage of Participants Achieving HbA1c Goals (<6.5%) at Week 16 Constrained Longitudinal Data Analysis Using Multiple Imputation Excluding Data After Glycemic Rescue (Phase A) | 0.0 Percentage of Participants |
p-value: 0.33495% CI: [-4.7, 5.8]Miettinen & Nurminen method
Secondary
Percentage of Participants Achieving Hemoglobin A1c Goals (<6.5%) at Week 52 (Phase A+B)
HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. For the HbA1c goals of \<6.5% at Week 52, the percentage of participants and the 95% confidence intervals were calculated using Wilson score method by treatment groups of the double-blind period.
Time frame: Week 52
Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one measurement (baseline or post randomization). Three participants in the Placebo group did not have data to contribute to the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Percentage of Participants Achieving Hemoglobin A1c Goals (<6.5%) at Week 52 (Phase A+B) | 1.6 Percentage of Participants |
| Placebo | Percentage of Participants Achieving Hemoglobin A1c Goals (<6.5%) at Week 52 (Phase A+B) | 0.0 Percentage of Participants |
Secondary
Percentage of Participants Achieving Hemoglobin A1c Goals (<7.0%) at Week 16 Constrained Longitudinal Data Analysis Using Multiple Imputation Excluding Data After Glycemic Rescue (Phase A)
HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis. Each of the 10 imputed data sets was summarized to obtain the percentage of responders within each group and were combined using standard multiple imputation techniques to yield an overall estimate of response rate and associated variance for each group. A constrained longitudinal data analysis was used to analyze the data and Wilson score method by treatment groups used for the analysis of percentages of individuals at the HbA1c goals of \<7.0% at Week 16 and the 95% confidence intervals (CIs). Miettinen & Nurminen (M&N) method after imputations were used to calculate the treatment differences of the percentages of individuals and the 95% CIs.
Time frame: Week 16
Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one measurement (baseline or post randomization) for the outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Percentage of Participants Achieving Hemoglobin A1c Goals (<7.0%) at Week 16 Constrained Longitudinal Data Analysis Using Multiple Imputation Excluding Data After Glycemic Rescue (Phase A) | 5.8 Percentage of Participants |
| Placebo | Percentage of Participants Achieving Hemoglobin A1c Goals (<7.0%) at Week 16 Constrained Longitudinal Data Analysis Using Multiple Imputation Excluding Data After Glycemic Rescue (Phase A) | 0.0 Percentage of Participants |
p-value: 0.06595% CI: [-0.7, 11.5]Miettinen & Nurminen method
Secondary
Percentage of Participants Achieving Hemoglobin A1c Goals (<7.0%) at Week 52 (Phase A+B)
HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. For the HbA1c goals of \<7.0% at Week 52, the percentage of participants and the 95% confidence intervals were calculated using Wilson score method by treatment groups of the double-blind period.
Time frame: Week 52
Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one measurement (baseline or post randomization). Three participants in the Placebo group did not have data to contribute to the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 25 mg | Percentage of Participants Achieving Hemoglobin A1c Goals (<7.0%) at Week 52 (Phase A+B) | 7.3 Percentage of Participants |
| Placebo | Percentage of Participants Achieving Hemoglobin A1c Goals (<7.0%) at Week 52 (Phase A+B) | 8.6 Percentage of Participants |