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

Diabetes Mellitus, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01054300
• Other study ID #: 8835-040
• Secondary ID: B1521007MK-8835-
• Status: Completed
• Phase: Phase 1
• Start date: February 17, 2010
• Est. completion date: April 7, 2010

Study information

• Verified date: November 2019
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: April 7, 2010
• Est. primary completion date: April 7, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adult
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Ertugliflozin 2 mg single dose
Ertugliflozin 2 mg dose (two 1 mg strength tablets), administered as a single dose
• Ertugliflozin 2 mg split into twice daily
Ertugliflozin 1 mg dose (1 mg strength tablet) administered twice daily x 1 day
• Ertugliflozin 4 mg single dose
Ertugliflozin 4 mg dose (four 1 mg strength tablets), administered as a single dose
• Ertugliflozin 4 mg split into twice daily
Ertugliflozin 2 mg dose (two 1 mg strength tablets) administered twice daily x 1 day
• Placebo
Placebo to ertugliflozin administered as a single dose

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.	Pfizer

References & Publications (1)

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: 10.54 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	0 to 24 hours after the morning dose
Primary	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.	At 0-4 hrs, 4-8 hrs, 8-12 hrs, and 12-24 hrs after the AM dose (up to 24 hours)
Primary	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.	Up to 24 hours
Primary	Weighted Mean Postprandial Plasma Glucose	The weighted mean postprandial glucose over the specified intervals were analyzed by cohort.	At 0-5 hours, 5-12 hrs, and 12-18 hrs after the morning dose (up to 18 hours)
Primary	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.	Up to 24 hours
Primary	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.	Up to 24 hours (0 and 24 hours)
Primary	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.	Up to 16 days
Primary	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.	Up to 8 days (Day 1 in each dosing period)
Primary	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.	0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose
Primary	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.	0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose
Primary	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.	0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose