This is a study to evaluate the efficacy and safety of ertugliflozin (MK-8835/PF-04971729) in combination with sitagliptin in the treatment of participants with Type 2 diabetes mellitus (T2DM) with inadequate glycemic control on diet and exercise. The primary hypothesis of the study is that ertugliflozin plus sitagliptin is more effective in lowering of hemoglobin A1C (HbA1C) than placebo.
Each participant will be in the study for approximately 39 weeks including: a 1-week screening period, an 8-week (or greater) antihyperglycemic agent (AHA) wash-off period, a 2-week single-blind placebo run-in period, a 26-week double-blind treatment period, and a post-treatment telephone contact 14 days after the last dose of study drug.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
291
Ertugliflozin, 5 mg or 15 mg, administered orally, once daily for 26 weeks.
Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.
Matching placebo to ertugliflozin administered orally, once daily for 26 weeks.
Matching placebo to sitagliptin administered orally, once daily for 26 weeks.
Open-label glimepiride rescue therapy will be initiated at 1 or 2 mg/day and may be titrated to the maximum labeled dose or maximum tolerated dose (if lower than labeled dose), as considered appropriate by the investigator, based on blood glucose measurements and in accordance with the local, approved label.
Change From Baseline in Hemoglobin A1C (HbA1C) at Week 26 - Full Analysis Set (FAS Population Excluding Rescue Approach
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.
Time frame: Baseline and Week 26
Percentage of Participants Who Experienced an Adverse Event (AE) - All Participants as Treated Excluding Rescue Approach
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.
Time frame: Up to Week 28
Percentage of Participants Who Discontinued Study Medication Due to an AE - All Participants as Treated Excluding Rescue Approach
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.
Time frame: Up to Week 26
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 - Full Analysis Set Excluding Rescue Approach
Blood glucose was measured after a ≥10 hour fast. Blood was drawn at predose on Day 1 and after 26 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 26 minus FPG at baseline). 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.
Time frame: Baseline and Week 26
Change From Baseline in 2-hour Post-Meal Glucose (PMG) at Week 26 - Full Analysis Set Excluding Rescue Approach
Change from baseline at Week 26 is defined as 2-hour PMG at Week 26 minus 2-hour PMG at Week 0. Two-hour post-meal glucose was measured following a standard meal. 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.
Time frame: Baseline and Week 26
Percentage of Participants With HbA1C <7% (<53 mmol/Mol) at Week 26
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.
Time frame: Week 26
Change From Baseline in Body Weight at Week 26 - Full Analysis Set Excluding Rescue Approach
Body weight was measured using a standardized, digital scale at each of the pre-defined nominal time points. Weight was taken in duplicate throughout the trial at approximately the same time of day, after voiding (i.e., forced void) and while wearing only a gown and underwear. 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.
Time frame: Baseline and Week 26
Change From Baseline in Sitting Systolic Blood Pressure at Week 26 - Full Analysis Set Excluding Rescue Approach
Blood pressure measurements were taken after at least 5 minutes of rest. Three measurements were taken approximately 2 minutes apart with the triplicate set recorded. 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.
Time frame: Baseline and Week 26
Change From Baseline in Sitting Diastolic Blood Pressure at Week 26 - Full Analysis Set Excluding Rescue Approach
Blood pressure measurements were taken after at least 5 minutes of rest. Three measurements were taken approximately 2 minutes apart with the triplicate set recorded. 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.
Time frame: Baseline and Week 26
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