Back to resultsEffects of Once and Twice Daily Dosing Regimen of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes (MK-8835-040)
Primary Purpose
Diabetes Mellitus, Type 2, Adult
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Ertugliflozin 2 mg single dose
Ertugliflozin 2 mg split into twice daily
Ertugliflozin 4 mg single dose
Ertugliflozin 4 mg split into twice daily
Placebo
Sponsored by
About this trial
This is an interventional other trial for Diabetes Mellitus, Type 2
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1: Ertu 2 mg/Placebo (Pbo)→Ertu 1 mg/Ertu 1 mg
Cohort 1: Ertu 1 mg/Ertu 1 mg→Ertu 2 mg/Pbo
Cohort 2: Ertu 4 mg/Pbo→Ertu 2 mg/Ertu 2 mg
Cohort 2: Ertu 2 mg/Ertu 2 mg→Ertu 4 mg/Pbo
Arm Description
Period 1: Ertu 2 mg in the AM and Pbo in the PM for 1 day. Period 2: Ertu 1 mg in the AM and Ertu 1 mg in the PM for 1 day. There was a >= 7 day washout period between Period 1 and Period 2.
Period 1: Ertu 1 mg in the AM and Ertu 1 mg in the PM for 1 day. Period 2: Ertu 2 mg in the AM and Pbo in the PM for 1 day. There was a >= 7 day washout period between Period 1 and Period 2.
Period 1: Ertu 4 mg in the AM and Pbo in the PM for 1 day. Period 2: Ertu 2 mg in the AM and Ertu 2 mg in the PM for 1 day. There was a >= 7 day washout period between Period 1 and Period 2.
Period 1: Ertu 2 mg in the AM and Ertu 2 mg in the PM for 1 day. Period 2: Ertu 4 mg in the AM and Pbo in the PM for 1 day. There was a >= 7 day washout period between Period 1 and Period 2.
Outcomes
Primary Outcome Measures
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.
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.
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.
Weighted Mean Postprandial Plasma Glucose
The weighted mean postprandial glucose over the specified intervals were analyzed by cohort.
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.
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.
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.
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.
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.
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 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.
Secondary Outcome Measures
Full Information
NCT ID
NCT01054300
First Posted
January 20, 2010
Last Updated
November 8, 2019
Sponsor
Merck Sharp & Dohme LLC
Collaborators
Pfizer
1. Study Identification
Unique Protocol Identification Number
NCT01054300
Brief Title
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
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
February 17, 2010 (Actual)
Primary Completion Date
April 7, 2010 (Actual)
Study Completion Date
April 7, 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
Collaborators
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2, Adult
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1: Ertu 2 mg/Placebo (Pbo)→Ertu 1 mg/Ertu 1 mg
Arm Type
Experimental
Arm Description
Period 1: Ertu 2 mg in the AM and Pbo in the PM for 1 day. Period 2: Ertu 1 mg in the AM and Ertu 1 mg in the PM for 1 day. There was a >= 7 day washout period between Period 1 and Period 2.
Arm Title
Cohort 1: Ertu 1 mg/Ertu 1 mg→Ertu 2 mg/Pbo
Arm Type
Experimental
Arm Description
Period 1: Ertu 1 mg in the AM and Ertu 1 mg in the PM for 1 day. Period 2: Ertu 2 mg in the AM and Pbo in the PM for 1 day. There was a >= 7 day washout period between Period 1 and Period 2.
Arm Title
Cohort 2: Ertu 4 mg/Pbo→Ertu 2 mg/Ertu 2 mg
Arm Type
Experimental
Arm Description
Period 1: Ertu 4 mg in the AM and Pbo in the PM for 1 day. Period 2: Ertu 2 mg in the AM and Ertu 2 mg in the PM for 1 day. There was a >= 7 day washout period between Period 1 and Period 2.
Arm Title
Cohort 2: Ertu 2 mg/Ertu 2 mg→Ertu 4 mg/Pbo
Arm Type
Experimental
Arm Description
Period 1: Ertu 2 mg in the AM and Ertu 2 mg in the PM for 1 day. Period 2: Ertu 4 mg in the AM and Pbo in the PM for 1 day. There was a >= 7 day washout period between Period 1 and Period 2.
Intervention Type
Drug
Intervention Name(s)
Ertugliflozin 2 mg single dose
Intervention Description
Ertugliflozin 2 mg dose (two 1 mg strength tablets), administered as a single dose
Intervention Type
Drug
Intervention Name(s)
Ertugliflozin 2 mg split into twice daily
Intervention Description
Ertugliflozin 1 mg dose (1 mg strength tablet) administered twice daily x 1 day
Intervention Type
Drug
Intervention Name(s)
Ertugliflozin 4 mg single dose
Intervention Description
Ertugliflozin 4 mg dose (four 1 mg strength tablets), administered as a single dose
Intervention Type
Drug
Intervention Name(s)
Ertugliflozin 4 mg split into twice daily
Intervention Description
Ertugliflozin 2 mg dose (two 1 mg strength tablets) administered twice daily x 1 day
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo to ertugliflozin administered as a single dose
Primary Outcome Measure Information:
Title
Cumulative Urinary Glucose Excretion Over 0 to 24 Hours
Description
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
Title
Urinary Glucose Excretion by Time Period
Description
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)
Title
24-hour Weighted Mean Plasma Glucose
Description
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
Title
Weighted Mean Postprandial Plasma Glucose
Description
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)
Title
Fasting Plasma Glucose
Description
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.
Time Frame
Up to 24 hours
Title
Fasting C-peptide
Description
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)
Title
Number of Participants Experiencing an Adverse Event
Description
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
Title
Number of Participants Discontinuing Study Drug Due to an Adverse Event
Description
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)
Title
Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration (AUClast) for Ertugliflozin
Description
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
Title
Maximum Plasma Concentration (Cmax) of Ertugliflozin
Description
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
Title
Time Taken to Reach the Maximum Observed Plasma Concentration (Tmax) of Ertugliflozin
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
30802200
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.
Results Reference
result
PubMed Identifier
34213819
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.
Results Reference
derived
Learn more about this trial
Effects of Once and Twice Daily Dosing Regimen of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes (MK-8835-040)
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