This is a Phase 1 randomized, double-blind, sponsor open, 4 arm, 2 way cross-over study using 2 cohorts. The objective of the study is to evaluate the pharmacodynamics (PD) effects and the pharmacokinetic (PK) of single day dosing of 2 mg and 4 mg doses of ertugliflozin (Ertu, PF-04971729/MK-8835) each administered once vs twice daily (morning \[AM\] and evening \[PM\]) in adults with type 2 diabetes.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
DOUBLE
Enrollment
52
Ertugliflozin 2 mg dose (two 1 mg strength tablets), administered as a single dose
Ertugliflozin 1 mg dose (1 mg strength tablet) administered twice daily x 1 day
Ertugliflozin 4 mg dose (four 1 mg strength tablets), administered as a single dose
Cumulative Urinary Glucose Excretion Over 0 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 from 0 to 24 hours after the morning dose is presented in the table below.
Time frame: 0 to 24 hours after the morning dose
Urinary Glucose Excretion by Time Period
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.
Time frame: At 0-4 hrs, 4-8 hrs, 8-12 hrs, and 12-24 hrs after the AM dose (up to 24 hours)
24-hour Weighted Mean Plasma Glucose
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.
Time frame: Up to 24 hours
Weighted Mean Postprandial Plasma Glucose
The weighted mean postprandial glucose over the specified intervals were analyzed by cohort.
Time frame: At 0-5 hours, 5-12 hrs, and 12-18 hrs after the morning dose (up to 18 hours)
Fasting Plasma Glucose
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.
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Ertugliflozin 2 mg dose (two 1 mg strength tablets) administered twice daily x 1 day
Placebo to ertugliflozin administered as a single dose
Time frame: Up to 24 hours
Fasting C-peptide
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.
Time frame: Up to 24 hours (0 and 24 hours)
Number of Participants Experiencing an Adverse Event
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.
Time frame: Up to 16 days
Number of Participants Discontinuing Study Drug Due to an Adverse Event
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.
Time frame: Up to 8 days (Day 1 in each dosing period)
Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration (AUClast) for Ertugliflozin
Pharmacokinetic (PK) parameter of AUClast for study drug. Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis.
Time frame: 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose
Maximum Plasma Concentration (Cmax) of Ertugliflozin
PK parameter of Cmax for study drug. Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis.
Time frame: 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose
Time Taken to Reach the Maximum Observed Plasma Concentration (Tmax) of Ertugliflozin
PK parameter of Tmax for study drug. Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis.
Time frame: 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose