Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT04029480 | Ertugliflozin Type 2 Diabetes Mellitus (T2DM) Pediatric Study (MK-8835/PF-04971729) (MK-8835-059) | PHASE3 | COMPLETED | 166 | — | — | Oct 8, 2019 | Apr 11, 2025 | Oct 31, 2025 | 104 | United States, Belgium +20 |
| NCT02630706 | A Study to Evaluate the Efficacy and Safety of Ertugliflozin in Asian Participants With Type 2 Diabetes and Inadequate Glycemic Control on Metformin Monotherapy (MK-8835-012) | PHASE3 | COMPLETED | 506 | — | — | Dec 16, 2015 | Dec 27, 2017 | Dec 7, 2018 | - | — |
| NCT02226003 | Efficacy and Safety of Ertugliflozin (MK-8835/PF-04971729) With Sitagliptin in the Treatment of Participants With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Diet and Exercise (MK-8835-017) | PHASE3 | COMPLETED | 291 | — | — | Sep 23, 2014 | Feb 23, 2016 | Sep 13, 2018 | - | — |
| NCT02099110 | Ertugliflozin and Sitagliptin Co-administration Factorial Study (VERTIS FACTORAL, MK-8835-005) | PHASE3 | COMPLETED | 1,233 | — | — | Apr 22, 2014 | May 26, 2016 | Sep 12, 2018 | - | — |
| NCT02036515 | Safety and Efficacy of Ertugliflozin in the Treatment of Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin (MK-8835-006; VERTIS SITA2) | PHASE3 | COMPLETED | 464 | — | — | Mar 12, 2014 | Jun 6, 2016 | Sep 13, 2018 | - | — |
| NCT01999218 | Ertugliflozin vs. Glimepiride in Type 2 Diabetes Mellitus (T2DM) Participants on Metformin (MK-8835-002) | PHASE3 | COMPLETED | 1,326 | — | — | Dec 16, 2013 | Apr 18, 2017 | Apr 2, 2019 | - | — |
| NCT02033889 | A Study To Evaluate The Efficacy And Safety Of Ertugliflozin In Participants With Type 2 Diabetes Mellitus And Inadequate Glycemic Control On Metformin Monotherapy (MK-8835-007). | PHASE3 | COMPLETED | 621 | — | — | Dec 13, 2013 | Aug 3, 2017 | Sep 10, 2018 | - | — |
| NCT01986855 | A Study of the Efficacy and Safety of Ertugliflozin in Participants With Type 2 Diabetes Mellitus With Stage 3 Chronic Kidney Disease Who Have Inadequate Glycemic Control on Antihyperglycemic Therapy (MK-8835-001) | PHASE3 | COMPLETED | 468 | — | — | Dec 2, 2013 | Sep 28, 2016 | Sep 10, 2018 | - | — |
| NCT01986881 | Cardiovascular Outcomes Following Ertugliflozin Treatment in Type 2 Diabetes Mellitus Participants With Vascular Disease, The VERTIS CV Study (MK-8835-004) | PHASE3 | COMPLETED | 8,246 | — | — | Nov 4, 2013 | Dec 27, 2019 | Sep 23, 2022 | - | — |
| NCT01958671 | A Study of the Efficacy and Safety of Ertugliflozin Monotherapy in the Treatment of Participants With Type 2 Diabetes Mellitus and Inadequate Glycemic Control Despite Diet and Exercise (MK-8835-003, VERTIS MONO) | PHASE3 | COMPLETED | 461 | — | — | Oct 9, 2013 | Jul 28, 2016 | Sep 29, 2017 | - | — |
| NCT02115347 | Pharmacokinetics, Safety, and Tolerability of Ertugliflozin (MK-8835/PF-04971729) in Participants With Hepatic Impairment and in Healthy Participants (MK-8835-014) | PHASE1 | COMPLETED | 16 | — | — | Sep 19, 2014 | Jan 19, 2015 | Aug 20, 2018 | - | — |
| NCT00989079 | A Single Escalating Dose Study Of Ertugliflozin (PF-04971729, MK-8835) Under Fed and Fasted Conditons In Healthy Volunteers (MK-8835-036) | PHASE1 | COMPLETED | 24 | — | — | Oct 16, 2009 | Dec 11, 2009 | May 29, 2020 | - | — |
Hemoglobin A1C is a measure of the percentage of glycated HbA1C in the blood. Participant whole blood samples were collected at baseline and Week 24 to determine the A1C change from baseline (i.e., % A1C at Week 24 minus % A1C at baseline). A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. The Bayesian mean change from baseline for each combined ertugliflozin and placebo are reported. Per protocol, the ertugliflozin arms are combined for this analysis.
An adverse event -- Select --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. Per protocol, the ertugliflozin arms are combined for this analysis.
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. Per protocol, the ertugliflozin arms are combined for this analysis.
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. Per protocol, the ertugliflozin arms are combined for this analysis.
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. Per protocol, the ertugliflozin arms are combined for this analysis.
A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 26 A1C minus the Week 0 A1C (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 26 A1C minus the Week 0 A1C (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
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.
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.
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.
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.
HbA1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). HbA1C represents the percentage of glycated hemoglobin. A negative number indicates a reduction in HbA1C level. Excluding rescue approach excludes all data following the initiation of rescue, in order to avoid the confounding influence of the rescue therapy with open-label glimepiride.
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Excluding rescue approach excludes all data following the initiation of rescue, in order to avoid the confounding influence of the rescue therapy with open-label glimepiride.
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. Excluding rescue approach excludes all data following the initiation of rescue, in order to avoid the confounding influence of the rescue therapy with open-label glimepiride.
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 26 A1C minus the Week 0 A1C. Excluding recue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.
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. Including rescue approach data analysis included data following the initiation of rescue therapy.
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. Including rescue approach data analysis included data following the initiation of rescue therapy.
A1C is measured as percent. Thus this change from baseline reflects the Week 26 A1C percent minus the Week 0 A1C percent. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of rescue therapy.
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. Data presented include data following the initiation of rescue therapy.
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. Data presented include data following the initiation of rescue therapy.
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 52 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received open-label sitagliptin glycemic rescue medication. The primary study objective was the MK-8835 15 mg vs. glimepiride comparison; the MK-8835 5mg vs glimerpiride comparison was a secondary study objective.
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.
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.
A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 26 A1C minus the Week 0 A1C (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
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 26 A1C minus the Week 0 A1C. Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.
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.
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 to the first occurrence of any of the following adjudicated components of the primary composite endpoint (3-point major adverse cardiovascular events (MACE)): cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)), non-fatal MI, and non-fatal stroke. The on-treatment approach included confirmed events that occurred between the date of first dose of study medication and the on-treatment censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, last contact date, or 365 days after the last dose).
A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This baseline reflects the Week 0 A1C.
A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 18 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This baseline reflects the Week 0 A1C.
A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 18 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This baseline reflects Week 0 A1C.
A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 18 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. "Excluding Rescue" excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy.
A1C is measured as percent. The change from baseline is the Week 26 A1C percent minus the Week 0 A1C percent. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of rescue therapy.
Area under the plasma concentration-time profile from time zero to time of the last quantifiable concentration (AUClast).
Area under the plasma concentration-time profile from time zero extrapolated to infinite time (AUCinf).
| Arm | Type | Description |
|---|---|---|
| Ertugliflozin 5 mg | EXPERIMENTAL | All participants initially received 5 mg ertugliflozin (ERTU) once daily (QD) and placebo to 15 mg ERTU QD until Week 54 (WK54). At Week 12 (WK12), participants who did not meet the up-titration criteria remained on 5 mg ERTU and placebo to 15 mg ERTU. Participants remained on their background metformin with/without insulin treatment throughout the study. |
| Ertugliflozin 5 mg/5 mg | EXPERIMENTAL | All participants initially received 5 mg ERTU QD and placebo to 15 mg ERTU QD until Week 12. Participants remained on their background metformin with/without insulin treatment throughout the study. Participants who met the up-titration criteria at the WK12 second randomization were re-randomized to remain on 5 mg ERTU and placebo to 15 mg ERTU from WK12 to WK54. |
| Ertugliflozin 5 mg/15 mg | EXPERIMENTAL | All participants initially received 5 mg ERTU QD and placebo to 15 mg ERTU QD until Week 12. Participants remained on their background metformin with/without insulin treatment throughout the study. Participants who met the up-titration criteria at the WK12 second randomization were up-titrated to 15 mg ERTU and placebo to 5 mg ERTU from WK12 to WK54. |
| Placebo | PLACEBO_COMPARATOR | All participants received matched placebo to 5 mg ERTU and 15 mg ERTU from baseline to WK54. Participants remained on their background metformin with/without insulin treatment throughout the study. |
| Ertugliflozin 15 mg | EXPERIMENTAL | Ertugliflozin 15 mg (ertugliflozin 5 mg + ertugliflozin 10 mg) administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values. |
| Ertugliflozin 5 mg and Sitagliptin 100 mg | EXPERIMENTAL | Ertugliflozin, 5 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks. Placebo to ertugliflozin, 10 mg, administered orally, once daily for 26 weeks. |
| Ertugliflozin 15 mg and Sitagliptin 100 mg | EXPERIMENTAL | Ertugliflozin, 15 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks. |
| Placebo to Ertugliflozin and Placebo to Sitagliptin | PLACEBO_COMPARATOR | Placebo to ertugliflozin, 5 mg and 10 mg, administered orally, once daily for 26 weeks. Placebo to sitagliptin, 100 mg, administered orally, once daily for 26 weeks. |
| Ertugliflozin 5 mg + sitagliptin 100 mg | EXPERIMENTAL | Ertugliflozin 5 mg + sitagliptin 100 mg, oral, once daily for 52 weeks |
| Ertugliflozin 15 mg + sitagliptin 100 mg | EXPERIMENTAL | Ertugliflozin 15 mg + sitagliptin 100 mg, oral, once daily for 52 weeks |
| Sitagliptin 100 mg | ACTIVE_COMPARATOR | Sitagliptin 100 mg, oral, once daily for 52 weeks |
| Glimepiride up to 8 mg | ACTIVE_COMPARATOR | Glimepiride to a maximum of 8 mg QD from Day 1 to Week 104 |
| Ertuglifozin 5 mg | EXPERIMENTAL | Ertugliflozin 5 mg orally, once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received glimepiride/placebo. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated. |
| Placebo/Glimepiride | PLACEBO_COMPARATOR | Placebo to ertugliflozin, orally once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received blinded glimepiride. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated. |
| Ertugliflozin (5 mg) | EXPERIMENTAL | Ertugliflozin, 5 mg, oral, one 5 mg ertugliflozin tablet and one placebo tablet, once daily for 52 weeks |
| Ertugliflozin (15 mg) | EXPERIMENTAL | Ertugliflozin, 15 mg, oral, one 5 mg and one 10 mg tablet, once daily for 52 weeks |
| Ertugliflozin, 15 mg | EXPERIMENTAL | Ertugliflozin 15 mg administered orally once daily for up to approximately 6 years |
| Ertugliflozin, 5 mg | EXPERIMENTAL | Ertugliflozin 5 mg administered orally once daily for up to approximately 6 years |
| Ertugliflozin 5 mg/Ertugliflozin 5 mg | EXPERIMENTAL | Phase A: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. |
| Ertugliflozin 15 mg/Ertugliflozin 15 mg | EXPERIMENTAL | Phase A: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. |
| Placebo/Metformin | OTHER | Phase A: Placebo to ertugliflozin administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Participants not rescued with open-label metformin in Phase A will also receive blinded metformin up to twice daily for 26 weeks in addition to placebo. Participants rescued with metformin in Phase A will continue to receive open-label metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. |
| Ertugliflozin 15 mg - Moderate Hepatic Impairment | EXPERIMENTAL | Participants receive a single 15 mg oral dose (tablet) of ertugliflozin |
| Ertugliflozin 15 mg - Healthy Participants | OTHER | Participants receive a single 15 mg oral dose (tablet) of ertugliflozin |
| Ertugliflozin 15 mg - Mild Hepatic Impairment | EXPERIMENTAL | Participants receive a single 15 mg oral dose (tablet) of ertugliflozin |
| Cohort 1 Sequence 1 | EXPERIMENTAL | Period 1 (fasted) Placebo → Period 2 (fasted) ertugliflozin (E) 10 mg → Period 3 (fasted) E 100 mg → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days. |
| Cohort 1 Sequence 2 | EXPERIMENTAL | Period 1 (fasted) E 0.5 mg → Period 2 (fasted) Placebo → Period 3 (fasted) E 100 mg → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days. |
| Cohort 1 Sequence 3 | EXPERIMENTAL | Period 1 (fasted) E 0.5 mg → Period 2 (fasted) E 10 mg → Period 3 (fasted) Placebo → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days. |
| Cohort 2 Sequence 1 | EXPERIMENTAL | Period 1 (fasted) Placebo → Period 2 (fasted) E 30 mg → Period 3 (fasted) E 300 mg. Each dose of study drug will be separated by a minimum of 7 days. |
| Cohort 2 Sequence 2 | EXPERIMENTAL | Period 1 (fasted) E 2.5 mg → Period 2 (fasted) Placebo → Period 3 (fasted) E 300 mg. Each dose of study drug will be separated by a minimum of 7 days. |
| Cohort 2 Sequence 3 | EXPERIMENTAL | Period 1 (fasted) E 2.5 mg → Period 2 (fasted) E 30 mg → Period 3 (fasted) Placebo. Each dose of study drug will be separated by a minimum of 7 days. |
| Name | Type | Description |
|---|---|---|
| Ertugliflozin 5 mg | DRUG | Ertugliflozin 5 mg, oral, 1 tablet QD |
| Ertugliflozin 15 mg | DRUG | Ertugliflozin 15 mg, oral, 1 tablet QD |
| Placebo to ertugliflozin 15 mg | DRUG | Placebo to ertugliflozin 15 mg, oral, 1 tablet QD |
| Placebo to ertugliflozin 5 mg | DRUG | Placebo to ertugliflozin 5 mg, oral, 1 tablet QD |
| Insulin | BIOLOGICAL | Participants on insulin at screening continued to receive a stable dose of background insulin. The initiation and titration of insulin for rescue therapy was at the discretion of the investigator, based on local/regional/country guidelines. |
| Metformin | DRUG | Participants received stable dose of background metformin. |
| Placebo matching ertugliflozin | DRUG | Placebo matching ertugliflozin (5-mg and/or 10-mg tablet) oral taken once daily |
| Glimepiride | DRUG | Glycemic rescue therapy with open-label glimepiride will be initiated in participants with glucose values exceeding protocol-specified values. Dosing and titration of open-label glimepiride rescue therapy will be at the Investigator's discretion. |
| Ertugliflozin | DRUG | Ertugliflozin, 5 mg or 15 mg, administered orally, once daily for 26 weeks. |
| Sitagliptin | DRUG | Sitagliptin, 100 mg, administered orally, once daily for 26 weeks. |
| Placebo to Ertugliflozin | DRUG | Matching placebo to ertugliflozin administered orally, once daily for 26 weeks. |
| Placebo to Sitagliptin | DRUG | Matching placebo to sitagliptin administered orally, once daily for 26 weeks. |
| Matching Placebo to Ertugliflozin 5 mg | DRUG | Placebo to ertugliflozin 5 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period |
| Matching Placebo to Ertugliflozin 10 mg | DRUG | Placebo to ertugliflozin 10 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period |
| Matching Placebo to sitagliptin 100 mg | DRUG | Placebo to sitagliptin 100 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period |
| Ertugliflozin 10 mg | DRUG | Ertugliflozin 10 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period |
| Sitagliptin 100 mg | DRUG | Sitagliptin 100 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period |
| Metformin >= 1500 mg/day | DRUG | Metformin \>= 1500 mg/day, tablets, oral, for 52 weeks while receiving blinded investigational product during the double-blind treatment period |
| Insulin Glargine Rescue Medication | BIOLOGICAL | Open-label insulin glargine, subcutaneous injection, as required as a rescue medication; dose determined per the investigator's discretion |
| Glimepiride Rescue Medication | DRUG | Open-label glimepiride tablets, oral, as required as a rescue medication, dose determined per the investigator's discretion |
| Placebo for ertugliflozin 5 mg | DRUG | Matching placebo for ertugliflozin 5 mg, oral, once daily for 52 weeks |
| Placebo for ertugliflozin 10 mg | DRUG | Matching placebo for ertugliflozin 10 mg, oral, once daily for 52 weeks |
| Glimerpiride | DRUG | Glimepiride, oral tablets, initiated at 1 mg daily and titrated up to the maximum approved dose (8 mg daily based on the local country label) or maximum tolerated dose |
| Placebo to Glimepiride | DRUG | Matching placebo to glimepiride, 1 mg or 2 mg, oral, once daily, from Day 1 to Week 104. |
| Basal Insulin | BIOLOGICAL | Basal insulin will be administered in the initial 26-week period for participants with glucose values exceeding protocol-specified values and for participants requiring rescue therapy in the 78-week extension period. Dosing and titration of basal insulin is at the discretion of the Investigator. |
| Placebo 5 mg | DRUG | Placebo to ertugliflozin, oral, tablet, 5 mg tablet once daily for 52 weeks |
| Placebo 10 mg | DRUG | Placebo to ertugliflozin, oral, tablet, 10 mg tablet once daily for 52 weeks |
| Placebo | DRUG | Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years |
| Glycemic Rescue | DRUG | Doses of background anti-hyperglycemic agents (AHA), medications will be required to be held constant in all participants enrolled for the initial 18 weeks of the trial with 2 exceptions: First, participant will be prescribed glycemic rescue therapy if they meet specific, progressively more stringent, glycemic thresholds based on repeated, confirmed fasting plasma glucose (FPG) measured at a central laboratory. Second, a participant experiencing clinically significant hypoglycemia according to the investigator at any time during the trial is permitted to have the dose of appropriate background AHA (e.g., insulin, sulfonylurea \[SU\], glinide) reduced or discontinued as per the judgment of the investigator or the treating physician. Choice and dosing of glycemic rescue will be at the discretion of the investigator or the treating physician consistent with standards of care for management of patients with Type 2 diabetes mellitus (T2DM) within the country of the investigational site. |
| Placebo to Metformin | DRUG | 1 tablet in the morning and 1 tablet in the evening for 2 weeks, 2 tablets in the morning and 1 tablet in the evening for 2 weeks and 2 tablets in the morning and 2 tablets in the evening, thereafter. |
Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Be ≥10 years and ≤17 years of age, when the informed consent is signed * Has diabetes diagnosed by one of the American Diabetes Association (ADA) criteria. * Has body mass index (BMI) ≥85th percentile a...