Effects of Once and Twice Daily Dosing Regimen of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes (MK-8835-040)

Primary outcomes

1. Cumulative Urinary Glucose Excretion Over 0 to 24 Hours

   Time frame: 0 to 24 hours after the morning dose

   Urine for analysis of glucose was collected at prespecified intervals. Each participant emptied his/her bladder just before dosing, and the collection started after the morning dose (collection times: 0-4 hours, 4-8 hours, 8-12 hours, and 12-24 hours after the morning dose). The average amount of urinary glucose excreted from 0 to 24 hours after the morning dose is presented in the table below.

2. Urinary Glucose Excretion by Time Period

   Time frame: At 0-4 hrs, 4-8 hrs, 8-12 hrs, and 12-24 hrs after the AM dose (up to 24 hours)

   Urine for analysis of glucose was collected at prespecified intervals. Each participant emptied his/her bladder just before dosing, and the collection started after the morning dose (collection times: 0-4 hours, 4-8 hours, 8-12 hours, and 12-24 hours after the morning dose). The average amount of urinary glucose excreted during the pre-specified time frame is presented in the table below.

3. 24-hour Weighted Mean Plasma Glucose

   Time frame: Up to 24 hours

   Blood was collected during each treatment period at pre-dose (fasted) on Day 1 (Hour 0) and post-dose (fed) on Day 1 at 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 12.5, 13, 14, 15, 16, 18, and 24 hours.

4. Weighted Mean Postprandial Plasma Glucose

   Time frame: At 0-5 hours, 5-12 hrs, and 12-18 hrs after the morning dose (up to 18 hours)

   The weighted mean postprandial glucose over the specified intervals were analyzed by cohort.

5. Fasting Plasma Glucose

   Time frame: Up to 24 hours

   Blood samples were to be collected following a fast from all food and drink (except water) for at least 8 hours. Fasting Plasma Glucose was collected as part of the assessment of weighted mean 24-hour plasma glucose. As such, it was not specified as an endpoint in the Statistical Analysis Plan and was not analyzed or summarized separately.

6. Fasting C-peptide

   Time frame: Up to 24 hours (0 and 24 hours)

   The fasting c-peptide was analyzed by cohort using a mixed-effects model with sequence, period, and treatment as fixed effects and participant within sequence as a random effect.

7. Number of Participants Experiencing an Adverse Event

   Time frame: Up to 16 days

   An adverse event is any untoward medical occurrence in a clinical investigation participant administered a product or medical device. The table below includes all data collected since the first dose of study drug.

8. Number of Participants Discontinuing Study Drug Due to an Adverse Event

   Time frame: Up to 8 days (Day 1 in each dosing period)

   An adverse event is any untoward medical occurrence in a clinical investigation participant administered a product or medical device. The table below includes all data collected since the first dose of study drug. Data include participants discontinued due to adverse events, participants with dose reduced or temporary discontinuation due to adverse events.

9. Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration (AUClast) for Ertugliflozin

   Time frame: 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose

   Pharmacokinetic (PK) parameter of AUClast for study drug. Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis.

10. Maximum Plasma Concentration (Cmax) of Ertugliflozin

    Time frame: 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose

    PK parameter of Cmax for study drug. Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis.

11. Time Taken to Reach the Maximum Observed Plasma Concentration (Tmax) of Ertugliflozin

    Time frame: 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose

    PK parameter of Tmax for study drug. Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis.