Clinical trial NCT01054300: Effects of Once and Twice Daily Dosing Regimen of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes (MK-8835-040)
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, 2-Period, Cross-Over Single Day Evaluation Of The Pharmacokinetic-Pharmacodynamic Effect Of Once And Twice Daily Oral Administration Of PF-04971729 In Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Adult
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2010-01-22
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Participants with type 2 diabetes mellitus, either treatment-naïve or on up to 2 acceptable oral anti-diabetes drugs for at least 8-weeks prior to study.

Exclusion Criteria:

* Participants with type 1 diabetes mellitus, participants with stroke, unstable angina, heart attack in last 6-months, uncontrolled blood pressure.

Primary outcomes:
measure: Cumulative Urinary Glucose Excretion Over 0 to 24 Hours
timeFrame: 0 to 24 hours after the morning dose
measure: Urinary Glucose Excretion by Time Period
timeFrame: At 0-4 hrs, 4-8 hrs, 8-12 hrs, and 12-24 hrs after the AM dose (up to 24 hours)
measure: 24-hour Weighted Mean Plasma Glucose
timeFrame: Up to 24 hours
measure: Weighted Mean Postprandial Plasma Glucose
timeFrame: At 0-5 hours, 5-12 hrs, and 12-18 hrs after the morning dose (up to 18 hours)
measure: Fasting Plasma Glucose
timeFrame: Up to 24 hours
measure: Fasting C-peptide
timeFrame: Up to 24 hours (0 and 24 hours)
measure: Number of Participants Experiencing an Adverse Event
timeFrame: Up to 16 days
measure: Number of Participants Discontinuing Study Drug Due to an Adverse Event
timeFrame: Up to 8 days (Day 1 in each dosing period)
measure: Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration (AUClast) for Ertugliflozin
timeFrame: 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose
measure: Maximum Plasma Concentration (Cmax) of Ertugliflozin
timeFrame: 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose
measure: Time Taken to Reach the Maximum Observed Plasma Concentration (Tmax) of Ertugliflozin
timeFrame: 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Dawra VK, Liang Y, Shi H, Bass A, Hickman A, Terra SG, Zhou S, Cutler D, Sahasrabudhe V. A PK/PD study comparing twice-daily to once-daily dosing regimens of ertugliflozin in healthy subjects . Int J Clin Pharmacol Ther. 2019 Apr;57(4):207-216. doi: 10.5414/CP203343.
citation: Fediuk DJ, Sahasrabudhe V, Dawra VK, Zhou S, Sweeney K. Population Pharmacokinetic Analyses of Ertugliflozin in Select Ethnic Populations. Clin Pharmacol Drug Dev. 2021 Nov;10(11):1297-1306. doi: 10.1002/cpdd.970. Epub 2021 Jul 2.