Effects of Once and Twice Daily Dosing Regimen of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes (MK-8835-040)
- Conditions
- Diabetes Mellitus, Type 2Adult
- Interventions
- Registration Number
- NCT01054300
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 52
- 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.
- Participants with type 1 diabetes mellitus, participants with stroke, unstable angina, heart attack in last 6-months, uncontrolled blood pressure.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Cohort 1: Ertu 2 mg/Placebo (Pbo)→Ertu 1 mg/Ertu 1 mg Ertugliflozin 2 mg split into twice daily 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. Cohort 2: Ertu 4 mg/Pbo→Ertu 2 mg/Ertu 2 mg Ertugliflozin 4 mg single dose 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. Cohort 2: Ertu 2 mg/Ertu 2 mg→Ertu 4 mg/Pbo Ertugliflozin 4 mg single dose 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. Cohort 2: Ertu 4 mg/Pbo→Ertu 2 mg/Ertu 2 mg Ertugliflozin 4 mg split into twice daily 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. Cohort 1: Ertu 2 mg/Placebo (Pbo)→Ertu 1 mg/Ertu 1 mg Placebo 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. Cohort 1: Ertu 1 mg/Ertu 1 mg→Ertu 2 mg/Pbo Ertugliflozin 2 mg single dose 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. Cohort 1: Ertu 2 mg/Placebo (Pbo)→Ertu 1 mg/Ertu 1 mg Ertugliflozin 2 mg single dose 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. Cohort 1: Ertu 1 mg/Ertu 1 mg→Ertu 2 mg/Pbo Placebo 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. Cohort 2: Ertu 4 mg/Pbo→Ertu 2 mg/Ertu 2 mg Placebo 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. Cohort 2: Ertu 2 mg/Ertu 2 mg→Ertu 4 mg/Pbo Placebo 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. Cohort 1: Ertu 1 mg/Ertu 1 mg→Ertu 2 mg/Pbo Ertugliflozin 2 mg split into twice daily 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. Cohort 2: Ertu 2 mg/Ertu 2 mg→Ertu 4 mg/Pbo Ertugliflozin 4 mg split into twice daily 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.
- Primary Outcome Measures
Name Time Method Fasting C-peptide 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.
Number of Participants Experiencing an Adverse Event 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.
Number of Participants Discontinuing Study Drug Due to an Adverse Event 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.
Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration (AUClast) for Ertugliflozin 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.
Maximum Plasma Concentration (Cmax) of Ertugliflozin 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.
Time Taken to Reach the Maximum Observed Plasma Concentration (Tmax) of Ertugliflozin 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.
Cumulative Urinary Glucose Excretion Over 0 to 24 Hours 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.
Urinary Glucose Excretion by Time Period 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.
24-hour Weighted Mean Plasma Glucose 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.
Weighted Mean Postprandial Plasma Glucose 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.
Fasting Plasma Glucose 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.
- Secondary Outcome Measures
Name Time Method