Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to assess the hypothesis that treatment with study medication (omarigliptin; MK-3102) provides greater reduction in A1C Hemoglobin (a marker of diabetic severity) compared with placebo, after 12 weeks of treatment. The study will evaluate 5 different doses of omarigliptin to identify which dose is the most effective in the treatment of type 2 diabetes.
Detailed description
MK-3102-006-Ext 1 added a 66-week extension to the base study (MK-3102 P006) to assess the long-term safety and tolerability of omarigliptin. To be eligible for the extension, participants must complete the double-blind base study, must have had at least a 75% compliance with study drug during the base study and can not meet any of the criteria for discontinuation. Participants randomized to placebo in the base study will be switched in a blinded manner to pioglitazone 30 mg once daily, in the extension study prior to implementation of amendment P006-13. Once amendment P006-13 has been IRB/IEC approved and blinded metformin drug supply is available at the site, participants will be switched from pioglitazone to metformin, starting at 500 mg once daily and titrated up to 1000 mg twice daily. Participants with a contraindication to metformin will be discontinued from the study. Participants randomized to 0.25 mg, 1 mg, 3 mg, and 10 mg of omarigliptin in the base study will be switched to omarigliptin 25 mg; those randomized to 25 mg of omarigliptin in the base study will continue on the same dose in the extension study. After the clinical dose of omarigliptin selected for further development has been identified based upon the results of the base study, all participants randomized to omarigliptin will be switched to the identified clinical dose.
Interventions
DRUGOmarigliptin
Omarigliptin 0.25, 1, 1.5, 10 or 25 mg oral capsule administered once weekly. For omarigliptin 3 mg, participants received two omarigliptin 1.5 mg capsules.
Matching placebo to omarigliptin 0.25, 1, 1.5, 10 or 25 mg oral capsule administered once weekly. For matching placebo to omarigliptin 3 mg, participants received two matching placebo to omarigliptin 1.5 mg capsules.
DRUGPioglitazone
Pioglitazone 15 mg oral tablet or capsule administered once daily
DRUGMetformin
Metformin 500 mg oral tablet administered once or twice daily
Matching placebo to metformin oral tablet administered 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
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
The prospective participant must meet, at least, all of the criteria below (among others determined by the study staff) to be eligible for study participation. The participant: * Has type 2 diabetes mellitus and is between 18 and 70 years of age; for Japan, 20 to 70 years of age; * Has a body mass index (BMI) \> 20 kg/m\^2 and \< 43 kg/m\^2; for Japan: BMI \>18 kg/m\^2 and \<43 kg/m\^2; * Is currently not on an antihyperglycemic agent (AHA) medication (off for ≥ 14 weeks) or is on oral AHA therapy but has inadequate glycemic control; * Is a male, or a female who is highly unlikely to conceive.
Exclusion criteria
If the prospective participant meets any of the criteria below (among others determined by the study staff) they will NOT be eligible for study participation. The participant: * Has a history of type 1 diabetes mellitus or a history of ketoacidosis; * Is on a weight loss program or has started a weight loss medication within the prior 8 weeks; * Has required insulin therapy within 14 weeks prior to signing informed consent; * Has a medical history of active liver disease (other than nonalcoholic hepatic steatosis), including chronic active hepatitis B or C, cirrhosis, or symptomatic gallbladder disease; * Has congestive heart failure or has new or worsening signs or symptoms of coronary heart disease; * Had any of the following disorders within the past 3 months: acute coronary syndrome, coronary artery intervention, stroke or transient ischemic neurological disorder; * Has a history of malignancy or clinically important hematological disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma A1C Levels at Week 12 | Baseline (Week 0) and Week 12 | A1C levels were measured as a percent. Change from baseline was calculated by subtracting the baseline level from the Week 12 level. |
| Percentage of Participants Who Experienced at Least One Adverse Event During the Base Period | Up to 16 weeks (including 28 days following the last dose of study drug) | An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after the initiation of glycemic rescue. |
| Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During the 12-week Base Period | Up to 12 weeks | An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after the initiation of glycemic rescue. |
| Percentage of Participants Who Experienced at Least One Adverse Event During the 66-week Extension Period | Up to 70 Weeks (Weeks 12 to 78 plus 4-week follow-up period) | An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after the initiation of glycemic rescue. |
| Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event During the 66-week Extension Period | Up to 66 weeks (Weeks 12 to 78) | An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after the initiation of glycemic rescue. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 2h-PMG at Week 78 | Baseline (Week 0) and Week 78 | Change from baseline was calculated by subtracting the baseline level from the Week 78 level. |
| Change From Baseline in 2 Hour-post-meal Glucose (2h-PMG) Levels at Week 12 | Baseline (Week 0) and Week 12 | Change from baseline was calculated by subtracting the baseline level from the Week 12 level. |
| Change From Baseline in FPG Levels at Week 78 | Baseline (Week 0) and Week 78 | Change from baseline was calculated by subtracting the baseline level from the Week 78 level. |
| Mean FPG Level at Baseline of the Extension Period | Baseline (Week 0) | Plasma FPG levels were measured at baseline (Week 0) for particiapnts who entered the extension period. |
| Change From Baseline in Fasting Plasma Glucose (FPG) Levels at Week 12 | Baseline (Week 0) and Week 12 | Change from baseline was calculated by subtracting the baseline level from the Week 12 level. |
| Mean Plasma A1C Level at Baseline of the Extension Period | Baseline (Week 0) | A1C levels were measured as a percent at baseline (Week 0) for participants who entered the extension period. |
| Change From Baseline in Plasma A1C Levels at Week 78 | Baseline (Week 0) and Week 78 | A1C levels were measured as a percent. Change from baseline was calculated by subtracting the baseline level from the Week 78 level. |
| Mean 2h-PMG Level at Baseline of the Extension Period | Baseline (Week 0) | Plasma 2h-PMG levels were measured at baseline (Week 0) for participants who entered the extension period. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omarigliptin 0.25 mg (Base) Omarigliptin 0.25 mg administered once weekly for 12 weeks (base period) | 113 |
| Omarigliptin 1 mg (Base) Omarigliptin 1 mg administered once weekly for 12 weeks (base period) | 115 |
| Omarigliptin 3 mg (Base) Omarigliptin 3 mg administered once weekly for 12 weeks (base period) | 114 |
| Omarigliptin 10 mg (Base) Omarigliptin 10 mg administered once weekly for 12 weeks (base period) | 115 |
| Omarigliptin 25 mg (Base) Omarigliptin 25 mg administered once weekly for 12 weeks (base period) | 114 |
| Placebo (Base) Matching placebo to omarigliptin administered once weekly for 12 weeks (base period) | 114 |
| Total | 685 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Base Period | Adverse Event | 1 | 0 | 1 | 0 | 4 | 1 | 0 | 0 |
| Base Period | Alanine aminotransferase (ALT)/AST | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Base Period | Excluded medication | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Base Period | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Base Period | Lost to Follow-up | 0 | 0 | 1 | 1 | 3 | 0 | 0 | 0 |
| Base Period | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Base Period | Protocol Violation | 1 | 0 | 0 | 0 | 1 | 2 | 0 | 0 |
| Base Period | Withdrawal by Subject | 4 | 5 | 5 | 1 | 5 | 5 | 0 | 0 |
| Extension Period | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 19 | 5 |
| Extension Period | ALT/AST | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Extension Period | Contraindication to study medication | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Extension Period | Creatinine/eGFR | 0 | 0 | 0 | 0 | 0 | 0 | 11 | 1 |
| Extension Period | Death | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Extension Period | Excluded medication | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Extension Period | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 |
| Extension Period | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 9 | 1 |
| Extension Period | Non-compliance with study drug | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Extension Period | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 1 |
| Extension Period | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 |
| Extension Period | Site discontinued study participation | 0 | 0 | 0 | 0 | 0 | 0 | 7 | 2 |
| Extension Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 30 | 8 |
Baseline characteristics
| Characteristic | Omarigliptin 0.25 mg (Base) | Total | Placebo (Base) | Omarigliptin 25 mg (Base) | Omarigliptin 10 mg (Base) | Omarigliptin 3 mg (Base) | Omarigliptin 1 mg (Base) |
|---|---|---|---|---|---|---|---|
| 2-hour post meal glucose (2-hr PMG) | 229.4 mg/dL STANDARD_DEVIATION 63.7 | 235.2 mg/dL STANDARD_DEVIATION 73.2 | 241.4 mg/dL STANDARD_DEVIATION 72.2 | 245.3 mg/dL STANDARD_DEVIATION 82.7 | 231.6 mg/dL STANDARD_DEVIATION 72.3 | 234.7 mg/dL STANDARD_DEVIATION 81.7 | 229.3 mg/dL STANDARD_DEVIATION 64.5 |
| Age, Continuous | 54.3 Years STANDARD_DEVIATION 8.9 | 55.1 Years STANDARD_DEVIATION 8.8 | 55.9 Years STANDARD_DEVIATION 8.4 | 55.1 Years STANDARD_DEVIATION 8.5 | 54.4 Years STANDARD_DEVIATION 10 | 55.3 Years STANDARD_DEVIATION 8.5 | 55.7 Years STANDARD_DEVIATION 8.5 |
| Fasting plasma glucose (FPG) | 170.3 mg/dL STANDARD_DEVIATION 45.3 | 170.2 mg/dL STANDARD_DEVIATION 43 | 171.9 mg/dL STANDARD_DEVIATION 42.8 | 173.9 mg/dL STANDARD_DEVIATION 47.6 | 166.8 mg/dL STANDARD_DEVIATION 37.6 | 169.0 mg/dL STANDARD_DEVIATION 42.6 | 169.4 mg/dL STANDARD_DEVIATION 42.4 |
| Hemoglobin A1c (A1C) | 8.1 Percent STANDARD_DEVIATION 0.9 | 8.1 Percent STANDARD_DEVIATION 0.9 | 8.1 Percent STANDARD_DEVIATION 0.9 | 8.1 Percent STANDARD_DEVIATION 1 | 8.0 Percent STANDARD_DEVIATION 0.9 | 7.9 Percent STANDARD_DEVIATION 0.9 | 8.0 Percent STANDARD_DEVIATION 0.9 |
| Sex: Female, Male Female | 48 Participants | 298 Participants | 49 Participants | 45 Participants | 59 Participants | 49 Participants | 48 Participants |
| Sex: Female, Male Male | 65 Participants | 387 Participants | 65 Participants | 69 Participants | 56 Participants | 65 Participants | 67 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 | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 113 | 7 / 115 | 4 / 114 | 5 / 115 | 7 / 114 | 6 / 113 | 76 / 392 | 10 / 76 |
| serious Total, serious adverse events | 0 / 113 | 1 / 115 | 0 / 114 | 2 / 115 | 3 / 114 | 0 / 113 | 28 / 405 | 3 / 80 |
Outcome results
Primary
Change From Baseline in Plasma A1C Levels at Week 12
A1C levels were measured as a percent. Change from baseline was calculated by subtracting the baseline level from the Week 12 level.
Time frame: Baseline (Week 0) and Week 12
Population: Full analysis set defined as all randomized participants who received at least one dose of study treatment and had a baseline measurement or a post-randomization measurement for the analysis endpoint subsequent to at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin 0.25 mg (Base) | Change From Baseline in Plasma A1C Levels at Week 12 | -0.14 Percent |
| Omarigliptin 1 mg (Base) | Change From Baseline in Plasma A1C Levels at Week 12 | -0.36 Percent |
| Omarigliptin 3 mg (Base) | Change From Baseline in Plasma A1C Levels at Week 12 | -0.35 Percent |
| Omarigliptin 10 mg (Base) | Change From Baseline in Plasma A1C Levels at Week 12 | -0.53 Percent |
| Omarigliptin 25 mg (Base) | Change From Baseline in Plasma A1C Levels at Week 12 | -0.57 Percent |
| Placebo (Base) | Change From Baseline in Plasma A1C Levels at Week 12 | 0.14 Percent |
p-value: <0.00195% CI: [-0.93, -0.5]Constrained longitudinal data analysis
p-value: <0.00195% CI: [-0.88, -0.45]Constrained longitudinal data analysis
p-value: <0.00195% CI: [-0.7, -0.27]Constrained longitudinal data analysis
p-value: <0.00195% CI: [-0.71, -0.28]Constrained longitudinal data analysis
p-value: 0.01295% CI: [-0.5, -0.06]Constrained longitudinal data analysis
Primary
Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event During the 66-week Extension Period
An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after the initiation of glycemic rescue.
Time frame: Up to 66 weeks (Weeks 12 to 78)
Population: Analysis population defined as all randomized participants who received at least one dose of extension study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received. Participants who received glycemic rescue during the base period were excluded from this analysis population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 0.25 mg (Base) | Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event During the 66-week Extension Period | 3.8 Percentage of participants |
| Omarigliptin 1 mg (Base) | Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event During the 66-week Extension Period | 5.3 Percentage of participants |
95% CI: [-9.1, 2.6]
Primary
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During the 12-week Base Period
An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after the initiation of glycemic rescue.
Time frame: Up to 12 weeks
Population: The all participants as treated population defined as all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received during the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 0.25 mg (Base) | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During the 12-week Base Period | 0.9 Percentage of participants |
| Omarigliptin 1 mg (Base) | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During the 12-week Base Period | 0 Percentage of participants |
| Omarigliptin 3 mg (Base) | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During the 12-week Base Period | 0.9 Percentage of participants |
| Omarigliptin 10 mg (Base) | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During the 12-week Base Period | 0 Percentage of participants |
| Omarigliptin 25 mg (Base) | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During the 12-week Base Period | 3.5 Percentage of participants |
| Placebo (Base) | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During the 12-week Base Period | 0.9 Percentage of participants |
95% CI: [-4.1, 4.1]
95% CI: [-4.9, 2.4]
95% CI: [-4.1, 4]
95% CI: [-4.9, 2.4]
95% CI: [-1.7, 7.9]
Primary
Percentage of Participants Who Experienced at Least One Adverse Event During the 66-week Extension Period
An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after the initiation of glycemic rescue.
Time frame: Up to 70 Weeks (Weeks 12 to 78 plus 4-week follow-up period)
Population: Analysis population defined as all randomized participamts who received at least one dose of extension study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received. Participants who received glycemic rescue during the base period were excluded from this analysis population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 0.25 mg (Base) | Percentage of Participants Who Experienced at Least One Adverse Event During the 66-week Extension Period | 66.8 Percentage of participants |
| Omarigliptin 1 mg (Base) | Percentage of Participants Who Experienced at Least One Adverse Event During the 66-week Extension Period | 65.8 Percentage of participants |
95% CI: [-9.8, 13.1]
Primary
Percentage of Participants Who Experienced at Least One Adverse Event During the Base Period
An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after the initiation of glycemic rescue.
Time frame: Up to 16 weeks (including 28 days following the last dose of study drug)
Population: The all participants as treated population defined as all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received during the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omarigliptin 0.25 mg (Base) | Percentage of Participants Who Experienced at Least One Adverse Event During the Base Period | 37.2 Percentage of participants |
| Omarigliptin 1 mg (Base) | Percentage of Participants Who Experienced at Least One Adverse Event During the Base Period | 43.5 Percentage of participants |
| Omarigliptin 3 mg (Base) | Percentage of Participants Who Experienced at Least One Adverse Event During the Base Period | 36.8 Percentage of participants |
| Omarigliptin 10 mg (Base) | Percentage of Participants Who Experienced at Least One Adverse Event During the Base Period | 36.5 Percentage of participants |
| Omarigliptin 25 mg (Base) | Percentage of Participants Who Experienced at Least One Adverse Event During the Base Period | 33.3 Percentage of participants |
| Placebo (Base) | Percentage of Participants Who Experienced at Least One Adverse Event During the Base Period | 31.0 Percentage of participants |
95% CI: [-6.2, 18.4]
95% CI: [-0.1, 24.7]
95% CI: [-6.5, 18]
95% CI: [-6.8, 17.7]
95% CI: [-9.8, 14.5]
Secondary
Change From Baseline in 2 Hour-post-meal Glucose (2h-PMG) Levels at Week 12
Change from baseline was calculated by subtracting the baseline level from the Week 12 level.
Time frame: Baseline (Week 0) and Week 12
Population: Full analysis set defined as all randomized participants who received at least one dose of study treatment and had a baseline measurement or a post-randomization measurement for the analysis endpoint subsequent to at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin 0.25 mg (Base) | Change From Baseline in 2 Hour-post-meal Glucose (2h-PMG) Levels at Week 12 | -11.3 mg/dL |
| Omarigliptin 1 mg (Base) | Change From Baseline in 2 Hour-post-meal Glucose (2h-PMG) Levels at Week 12 | -26.0 mg/dL |
| Omarigliptin 3 mg (Base) | Change From Baseline in 2 Hour-post-meal Glucose (2h-PMG) Levels at Week 12 | -27.5 mg/dL |
| Omarigliptin 10 mg (Base) | Change From Baseline in 2 Hour-post-meal Glucose (2h-PMG) Levels at Week 12 | -34.0 mg/dL |
| Omarigliptin 25 mg (Base) | Change From Baseline in 2 Hour-post-meal Glucose (2h-PMG) Levels at Week 12 | -37.3 mg/dL |
| Placebo (Base) | Change From Baseline in 2 Hour-post-meal Glucose (2h-PMG) Levels at Week 12 | 7.5 mg/dL |
p-value: <0.00195% CI: [-59, -30.7]Constrained longitudinal data analysis
p-value: <0.00195% CI: [-55.3, -27.8]Constrained longitudinal data analysis
p-value: <0.00195% CI: [-48.9, -21.3]Constrained longitudinal data analysis
p-value: <0.00195% CI: [-47.3, -19.7]Constrained longitudinal data analysis
p-value: 0.00995% CI: [-32.9, -4.8]Constrained longitudinal data analysis
Secondary
Change From Baseline in 2h-PMG at Week 78
Change from baseline was calculated by subtracting the baseline level from the Week 78 level.
Time frame: Baseline (Week 0) and Week 78
Population: Extension full analysis set population defined as all randomized participants who received at least one dose of extension study treatment, have baseline and at least one post-randomization observation for the analysis endpoint subsequent to at least one dose of extension study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin 0.25 mg (Base) | Change From Baseline in 2h-PMG at Week 78 | -37.0 mg/dL |
| Omarigliptin 1 mg (Base) | Change From Baseline in 2h-PMG at Week 78 | -21.3 mg/dL |
| Omarigliptin 3 mg (Base) | Change From Baseline in 2h-PMG at Week 78 | -18.0 mg/dL |
| Omarigliptin 10 mg (Base) | Change From Baseline in 2h-PMG at Week 78 | -27.6 mg/dL |
| Omarigliptin 25 mg (Base) | Change From Baseline in 2h-PMG at Week 78 | -43.2 mg/dL |
| Placebo (Base) | Change From Baseline in 2h-PMG at Week 78 | -40.3 mg/dL |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) Levels at Week 12
Change from baseline was calculated by subtracting the baseline level from the Week 12 level.
Time frame: Baseline (Week 0) and Week 12
Population: Full analysis set defined as all randomized participants who received at least one dose of study treatment and had a baseline measurement or a post-randomization measurement for the analysis endpoint subsequent to at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin 0.25 mg (Base) | Change From Baseline in Fasting Plasma Glucose (FPG) Levels at Week 12 | 1.2 mg/dL |
| Omarigliptin 1 mg (Base) | Change From Baseline in Fasting Plasma Glucose (FPG) Levels at Week 12 | -15.3 mg/dL |
| Omarigliptin 3 mg (Base) | Change From Baseline in Fasting Plasma Glucose (FPG) Levels at Week 12 | -10.6 mg/dL |
| Omarigliptin 10 mg (Base) | Change From Baseline in Fasting Plasma Glucose (FPG) Levels at Week 12 | -9.8 mg/dL |
| Omarigliptin 25 mg (Base) | Change From Baseline in Fasting Plasma Glucose (FPG) Levels at Week 12 | -17.7 mg/dL |
| Placebo (Base) | Change From Baseline in Fasting Plasma Glucose (FPG) Levels at Week 12 | 3.7 mg/dL |
p-value: <0.00195% CI: [-29.4, -13.4]Constrained longitudinal data analysis
p-value: <0.00195% CI: [-21.3, -5.7]Constrained longitudinal data analysis
p-value: <0.00195% CI: [-22.2, -6.3]Constrained longitudinal data analysis
p-value: <0.00195% CI: [-26.9, -11.2]Constrained longitudinal data analysis
p-value: 0.53995% CI: [-10.4, 5.5]Constrained longitudinal data analysis
Secondary
Change From Baseline in FPG Levels at Week 78
Change from baseline was calculated by subtracting the baseline level from the Week 78 level.
Time frame: Baseline (Week 0) and Week 78
Population: Extension full analysis set population defined as all randomized participants who received at least one dose of extension study treatment, have baseline and at least one post-randomization observation for the analysis endpoint subsequent to at least one dose of extension study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin 0.25 mg (Base) | Change From Baseline in FPG Levels at Week 78 | -7.4 mg/dL |
| Omarigliptin 1 mg (Base) | Change From Baseline in FPG Levels at Week 78 | -11.3 mg/dL |
| Omarigliptin 3 mg (Base) | Change From Baseline in FPG Levels at Week 78 | -2.0 mg/dL |
| Omarigliptin 10 mg (Base) | Change From Baseline in FPG Levels at Week 78 | -10.0 mg/dL |
| Omarigliptin 25 mg (Base) | Change From Baseline in FPG Levels at Week 78 | -0.7 mg/dL |
| Placebo (Base) | Change From Baseline in FPG Levels at Week 78 | -19.6 mg/dL |
Secondary
Change From Baseline in Plasma A1C Levels at Week 78
A1C levels were measured as a percent. Change from baseline was calculated by subtracting the baseline level from the Week 78 level.
Time frame: Baseline (Week 0) and Week 78
Population: Extension full analysis set population defined as all randomized participants who received at least one dose of extension study treatment, have baseline and at least one post-randomization observation for the analysis endpoint subsequent to at least one dose of extension study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omarigliptin 0.25 mg (Base) | Change From Baseline in Plasma A1C Levels at Week 78 | -0.57 Percent |
| Omarigliptin 1 mg (Base) | Change From Baseline in Plasma A1C Levels at Week 78 | -0.55 Percent |
| Omarigliptin 3 mg (Base) | Change From Baseline in Plasma A1C Levels at Week 78 | -0.30 Percent |
| Omarigliptin 10 mg (Base) | Change From Baseline in Plasma A1C Levels at Week 78 | -0.60 Percent |
| Omarigliptin 25 mg (Base) | Change From Baseline in Plasma A1C Levels at Week 78 | -0.46 Percent |
| Placebo (Base) | Change From Baseline in Plasma A1C Levels at Week 78 | -0.88 Percent |
Secondary
Mean 2h-PMG Level at Baseline of the Extension Period
Plasma 2h-PMG levels were measured at baseline (Week 0) for participants who entered the extension period.
Time frame: Baseline (Week 0)
Population: All participants who entered the extension period of the study with available 2h-PMG baseline data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omarigliptin 0.25 mg (Base) | Mean 2h-PMG Level at Baseline of the Extension Period | 232.8 mg/dL | Standard Deviation 69.5 |
| Omarigliptin 1 mg (Base) | Mean 2h-PMG Level at Baseline of the Extension Period | 244.5 mg/dL | Standard Deviation 70.1 |
Secondary
Mean FPG Level at Baseline of the Extension Period
Plasma FPG levels were measured at baseline (Week 0) for particiapnts who entered the extension period.
Time frame: Baseline (Week 0)
Population: All participants who entered the extension period of the study with available FPG baseline data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omarigliptin 0.25 mg (Base) | Mean FPG Level at Baseline of the Extension Period | 169.4 mg/dL | Standard Deviation 41.7 |
| Omarigliptin 1 mg (Base) | Mean FPG Level at Baseline of the Extension Period | 172.9 mg/dL | Standard Deviation 43.5 |
Secondary
Mean Plasma A1C Level at Baseline of the Extension Period
A1C levels were measured as a percent at baseline (Week 0) for participants who entered the extension period.
Time frame: Baseline (Week 0)
Population: All participants who entered the extension period of the study with available A1C baseline data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omarigliptin 0.25 mg (Base) | Mean Plasma A1C Level at Baseline of the Extension Period | 8.0 Percent | Standard Deviation 0.9 |
| Omarigliptin 1 mg (Base) | Mean Plasma A1C Level at Baseline of the Extension Period | 8.2 Percent | Standard Deviation 0.9 |