Type 2 Diabetes Mellitus
Conditions
Brief summary
This study evaluated the safety and efficacy of ertugliflozin (MK-8835) in pediatric participants with T2DM on metformin with/without insulin. The primary hypothesis of the study was that the addition of ertugliflozin reduces hemoglobin A1C (HbA1C) more than the addition of placebo after 24 weeks of treatment.
Detailed description
Participants were randomized on Day 1 to the following arms: * 5 mg ERTU and placebo to 15 mg ERTU (5 mg Ertugliflozin) * placebo to 5 mg ERTU and placebo to 15 mg ERTU (Placebo) At Week 12, participants who met the up-titration criteria were re-randomized to the following arms for Weeks 12 to 54: * 5 mg ERTU and placebo to 15 mg ERTU (5 mg/5 mg Ertugliflozin) * 15 mg ERTU and placebo to 5 mg ERTU (5 mg/15 mg Ertugliflozin) Participants who did not meet the up-titration criteria remained on 5 mg ERTU and placebo to 15 mg ERTU from Week 12 to Week 54. The placebo arm continued receiving placebo from Week 12 to Week 54.
Interventions
Ertugliflozin 5 mg, oral, 1 tablet QD
Ertugliflozin 15 mg, oral, 1 tablet QD
DRUGPlacebo to ertugliflozin 15 mg
Placebo to ertugliflozin 15 mg, oral, 1 tablet QD
DRUGPlacebo to ertugliflozin 5 mg
Placebo to ertugliflozin 5 mg, oral, 1 tablet QD
BIOLOGICALInsulin
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.
DRUGMetformin
Participants received stable dose of background metformin.
Sponsors
Pfizer
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
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 at screening OR participant has a history of being overweight or obese at time of diagnosis of Type 2 diabetes mellitus (T2DM). * T2DM for ≥2 years, OR T2DM for \<2 years and a fasting C-peptide value \>0.6 ng/mL at Screening. * On stable metformin monotherapy (≥1500 mg/day, for ≥8 weeks prior to Screening, OR on a stable metformin dose (≥1500 mg/day, for ≥8 weeks prior to Screening and a stable dose of insulin for ≥8 weeks prior to Screening. * Contraceptive use by male participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * Is a non-sterilized female who is currently not sexually active OR who agrees to abstain from heterosexual activity OR who agrees to start contraception prior to initiating sexual activity and who agrees to use an adequate method of contraception. Contraceptive use by females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * Have a family member or adult who, along with the participant, will be closely involved in the participant's daily activities (in the opinion of the investigator) and in the participant's treatment and study procedures.
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Discontinued Study Treatment Due to an AE Up to Week 54 | Up to Week 54 | 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. |
| Change From Baseline in Hemoglobin A1C (HbA1C) at Week 24 (Combined Ertugliflozin Versus Placebo) | Baseline and Week 24 | 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. |
| Number of Participants Who Experienced an Adverse Event (AE) Up to Week 24 | Up to Week 24 | 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. |
| Number of Participants Who Experienced an AE Up to Week 54 | Up to Week 54 | 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. |
| Number of Participants Who Discontinued Study Treatment Due to an AE Up to Week 24 | Up to Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1C at Week 24 (Dose-optimized Ertugliflozin Versus Placebo) | Baseline and Week 24 | 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. |
| Change From Baseline in Hemoglobin A1C at Week 24 (5 mg Ertugliflozin Versus Placebo) | Baseline and Week 24 | 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. |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline and Week 24 | Blood glucose is measured on a fasting basis. FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 24 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 24 minus FPG at baseline). A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. Per protocol, the ertugliflozin arms were combined for this analysis. |
| Change From Baseline in Hemoglobin A1C at Week 54 | Baseline and Week 54 | Hemoglobin A1C is a measure of the percentage of glycated HbA1C in the blood. Participant whole blood samples were collected at baseline and Week 54 to determine the A1C change from baseline (i.e., A1C at Week 54 minus A1C at baseline). A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. Per protocol, the ertugliflozin arms were combined for this analysis. |
| Change From Baseline in FPG at Week 54 | Baseline and Week 54 | Blood glucose is measured on a fasting basis. FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 54 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 54 minus FPG at baseline). A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. Per protocol, the ertugliflozin arms were combined for this analysis. |
Countries
Belgium, Canada, Colombia, Costa Rica, Dominican Republic, France, Guatemala, Hungary, Israel, Italy, Malaysia, Mauritius, Mexico, Philippines, Poland, Russia, Saudi Arabia, Turkey (Türkiye), Ukraine, United Arab Emirates, United Kingdom, United States
Participant flow
Pre-assignment details
Participants were screened up to 4 weeks before dosing. Participants were confirmed at screening to have T2DM for ≥2 years, conform to T2DM protocol specific requirements and be on stable metformin with or without insulin. The first randomization was stratified according to the following factors collected at screening: age (10 to 14 years of age/15 to 17 years) and insulin use (yes/no). Treatment randomization at Week 12 was stratified according to insulin use (yes/no) at screening.
Participants by arm
| Arm | Count |
|---|---|
| 5 mg Ertugliflozin Participants 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. | 63 |
| 5 mg/5 mg Ertugliflozin Participants initially received 5 mg ERTU QD and placebo to 15 mg ERTU QD until WK12. 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. | 22 |
| 5 mg/15 mg Ertugliflozin Participants initially received 5 mg ERTU QD and placebo to 15 mg ERTU QD until WK12. 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. | 26 |
| Placebo 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. | 55 |
| Total | 166 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo | 5 mg/15 mg Ertugliflozin | 5 mg/5 mg Ertugliflozin | 5 mg Ertugliflozin |
|---|---|---|---|---|---|
| Age at Screening 10 to 14 years of age | 69 Years | 23 Years | 8 Years | 11 Years | 27 Years |
| Age at Screening 15 to 17 years of age | 97 Years | 32 Years | 18 Years | 11 Years | 36 Years |
| Age, Continuous | 14.8 years STANDARD_DEVIATION 1.9 | 15.1 years STANDARD_DEVIATION 1.7 | 15.6 years STANDARD_DEVIATION 1.8 | 14.6 years STANDARD_DEVIATION 2 | 14.4 years STANDARD_DEVIATION 2 |
| Age, Customized 85 years and over | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 152 Participants | 52 Participants | 24 Participants | 20 Participants | 56 Participants |
| Age, Customized Adults (18-64 years) | 5 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants |
| Age, Customized Children (2-11 years) | 9 Participants | 1 Participants | 0 Participants | 2 Participants | 6 Participants |
| Age, Customized From 65-84 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized In utero | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Preterm newborn infants (gestational age < 37 wks) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Baseline A1C | 8.0 A1C Percentage STANDARD_DEVIATION 1.1 | 8.0 A1C Percentage STANDARD_DEVIATION 1 | 8.8 A1C Percentage STANDARD_DEVIATION 0.9 | 8.5 A1C Percentage STANDARD_DEVIATION 1.1 | 7.6 A1C Percentage STANDARD_DEVIATION 1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 72 Participants | 22 Participants | 9 Participants | 8 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 93 Participants | 33 Participants | 17 Participants | 13 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Insulin Use at Screening No | 93 Participants | 31 Participants | 9 Participants | 8 Participants | 45 Participants |
| Insulin Use at Screening Yes | 73 Participants | 24 Participants | 17 Participants | 14 Participants | 18 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 19 Participants | 5 Participants | 5 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 25 Participants | 10 Participants | 3 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 1 Participants | 4 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 18 Participants | 8 Participants | 1 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 99 Participants | 31 Participants | 13 Participants | 12 Participants | 43 Participants |
| Sex: Female, Male Female | 98 Participants | 30 Participants | 20 Participants | 10 Participants | 38 Participants |
| Sex: Female, Male Male | 68 Participants | 25 Participants | 6 Participants | 12 Participants | 25 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 63 | 0 / 22 | 0 / 26 | 0 / 26 | 0 / 55 |
| other Total, other adverse events | 29 / 63 | 11 / 22 | 8 / 26 | 14 / 26 | 31 / 55 |
| serious Total, serious adverse events | 2 / 63 | 1 / 22 | 0 / 26 | 1 / 26 | 0 / 55 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1C (HbA1C) at Week 24 (Combined Ertugliflozin Versus Placebo)
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.
Time frame: Baseline and Week 24
Population: This analysis includes all participants who received at least 1 dose of study treatment and excludes data following initiation of rescue therapy as well as data collected more than 5 days after the discontinuation of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Combined Ertugliflozin | Change From Baseline in Hemoglobin A1C (HbA1C) at Week 24 (Combined Ertugliflozin Versus Placebo) | -0.55 A1C Percentage |
| Placebo | Change From Baseline in Hemoglobin A1C (HbA1C) at Week 24 (Combined Ertugliflozin Versus Placebo) | 0.12 A1C Percentage |
Comparison: This analysis is based on a Bayesian ANCOVA model including terms for Baseline A1C, treatment, age (10 to 14 years/15 to 17 years), and insulin use (yes/no) at Screening and calculated by Rubin's Rule. The 95% confidence interval actually refers to a credible interval.95% CI: [-1.06, -0.29]
Primary
Number of Participants Who Discontinued Study Treatment Due to an AE Up to Week 24
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.
Time frame: Up to Week 24
Population: The analysis population includes all randomized participants who received at least one dose of study treatment up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined Ertugliflozin | Number of Participants Who Discontinued Study Treatment Due to an AE Up to Week 24 | 0 Participants |
| Placebo | Number of Participants Who Discontinued Study Treatment Due to an AE Up to Week 24 | 0 Participants |
Comparison: This analysis is based on Miettinen \& Nurminen method.
Primary
Number of Participants Who Discontinued Study Treatment Due to an AE Up to Week 54
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.
Time frame: Up to Week 54
Population: The analysis population includes all randomized participants who received at least one dose of study treatment up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined Ertugliflozin | Number of Participants Who Discontinued Study Treatment Due to an AE Up to Week 54 | 0 Participants |
| Placebo | Number of Participants Who Discontinued Study Treatment Due to an AE Up to Week 54 | 1 Participants |
Comparison: This analysis is based on Miettinen \& Nurminen method.
Primary
Number of Participants Who Experienced an Adverse Event (AE) Up to Week 24
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.
Time frame: Up to Week 24
Population: The analysis population includes all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined Ertugliflozin | Number of Participants Who Experienced an Adverse Event (AE) Up to Week 24 | 59 Participants |
| Placebo | Number of Participants Who Experienced an Adverse Event (AE) Up to Week 24 | 33 Participants |
Comparison: This analysis is based on Miettinen \& Nurminen method.95% CI: [-22.2, 9.3]
Primary
Number of Participants Who Experienced an AE Up to Week 54
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.
Time frame: Up to Week 54
Population: The analysis population includes all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined Ertugliflozin | Number of Participants Who Experienced an AE Up to Week 54 | 71 Participants |
| Placebo | Number of Participants Who Experienced an AE Up to Week 54 | 42 Participants |
Comparison: This analysis is based on Miettinen \& Nurminen method.95% CI: [-25.9, 2.8]
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Blood glucose is measured on a fasting basis. FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 24 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 24 minus FPG at baseline). A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. Per protocol, the ertugliflozin arms were combined for this analysis.
Time frame: Baseline and Week 24
Population: This analysis includes all participants who received at least 1 dose of study treatment and excludes data following initiation of rescue therapy as well as data collected more than 5 days after the discontinuation of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Combined Ertugliflozin | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | -20.8 mg/dL |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | 8.2 mg/dL |
Comparison: This analysis is based on a constrained longitudinal data analysis (cLDA) model including terms for treatment, time, age (10 to 14 years/15 to 17 years), insulin use (yes/no), interaction of time by treatment with the constraint that the model estimated a single baseline mean (applicable to all treatment groups).p-value: 0.00195% CI: [-44.4, -13.6]cLDA
Secondary
Change From Baseline in FPG at Week 54
Blood glucose is measured on a fasting basis. FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 54 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 54 minus FPG at baseline). A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. Per protocol, the ertugliflozin arms were combined for this analysis.
Time frame: Baseline and Week 54
Population: This analysis includes all participants who received at least 1 dose of study treatment and excludes data following initiation of rescue therapy as well as data collected more than 5 days after the discontinuation of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Combined Ertugliflozin | Change From Baseline in FPG at Week 54 | -12.1 mg/dL |
| Placebo | Change From Baseline in FPG at Week 54 | 21.0 mg/dL |
Comparison: This analysis is based on a constrained longitudinal data analysis (cLDA) model including terms for treatment, time, age (10 to 14 years/15 to 17 years), insulin use (yes/no), interaction of time by treatment with the constraint that the model estimated a single baseline mean (applicable to all treatment groups).p-value: 0.00195% CI: [-53, -13.1]cLDA
Secondary
Change From Baseline in Hemoglobin A1C at Week 24 (5 mg Ertugliflozin Versus Placebo)
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.
Time frame: Baseline and Week 24
Population: This analysis includes all participants randomized to ertugliflozin and either did not meet the re-randomization criteria at Week 12 or were re-randomized to 5 mg ertugliflozin, and all data following initiation of rescue therapy as well as data collected after the discontinuation of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Combined Ertugliflozin | Change From Baseline in Hemoglobin A1C at Week 24 (5 mg Ertugliflozin Versus Placebo) | -0.54 A1C Percentage |
| Placebo | Change From Baseline in Hemoglobin A1C at Week 24 (5 mg Ertugliflozin Versus Placebo) | 0.32 A1C Percentage |
Comparison: This analysis is based on an ANCOVA model including terms for Baseline A1C, treatment, age (10 to 14 years/15 to 17 years), and insulin use (yes/no) at Screening and calculated by Rubin's Rule.p-value: 0.00195% CI: [-1.39, -0.33]ANCOVA
Secondary
Change From Baseline in Hemoglobin A1C at Week 24 (Dose-optimized Ertugliflozin Versus Placebo)
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.
Time frame: Baseline and Week 24
Population: This analysis includes all participants who were randomized to ertugliflozin and either did not meet the re-randomization criteria at Week 12 or were re-randomized to ertugliflozin 15 mg, took at least 1 dose of study treatment, and includes all data following initiation of rescue therapy as well as data collected after the discontinuation of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Combined Ertugliflozin | Change From Baseline in Hemoglobin A1C at Week 24 (Dose-optimized Ertugliflozin Versus Placebo) | -0.42 A1C Percentage |
| Placebo | Change From Baseline in Hemoglobin A1C at Week 24 (Dose-optimized Ertugliflozin Versus Placebo) | 0.25 A1C Percentage |
Comparison: This analysis is based on an ANCOVA model including terms for Baseline A1C, treatment, age (10 to 14 years/15 to 17 years), and insulin use (yes/no) at Screening and calculated by Rubin's Rule.p-value: 0.02195% CI: [-1.23, -0.1]ANCOVA
Secondary
Change From Baseline in Hemoglobin A1C at Week 54
Hemoglobin A1C is a measure of the percentage of glycated HbA1C in the blood. Participant whole blood samples were collected at baseline and Week 54 to determine the A1C change from baseline (i.e., A1C at Week 54 minus A1C at baseline). A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. Per protocol, the ertugliflozin arms were combined for this analysis.
Time frame: Baseline and Week 54
Population: This analysis includes all participants who received at least 1 dose of study treatment and excludes data following initiation of rescue therapy as well as data collected more than 5 days after the discontinuation of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Combined Ertugliflozin | Change From Baseline in Hemoglobin A1C at Week 54 | -0.22 AIC Percentage |
| Placebo | Change From Baseline in Hemoglobin A1C at Week 54 | 0.81 AIC Percentage |
Comparison: This analysis is a based on a constrained longitudinal data analysis (cLDA) model including terms for treatment, time, age (10 to 14 years/15 to 17 years), insulin use (yes/no), interaction of time by treatment with the constraint that the model estimated a single baseline mean (applicable to all treatment groups).p-value: 0.00395% CI: [-1.7, -0.35]cLDA