A Single Escalating Dose Study Of Ertugliflozin (PF-04971729, MK-8835) Under Fed and Fasted Conditons In Healthy Volunteers (MK-8835-036)
Phase 1
Completed
- Conditions
- Type 2 Diabetes Mellitus
- Interventions
- Registration Number
- NCT00989079
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Ertugliflozin (PF-04971729, MK-8835) is a new compound proposed for the treatment of Type 2 diabetes mellitus. The primary purpose of this study is to evaluate the safety and tolerability along with the pharmacokinetics of single escalating doses of ertugliflozin under fed and fasted conditions in healthy volunteers.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
Inclusion Criteria
- Healthy male and/or female subjects of non childbearing potential.
- Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg
Exclusion Criteria
- Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Cohort 2 Sequence 1 Placebo to Ertugliflozin Period 1 (fasted) Placebo → Period 2 (fasted) E 30 mg → Period 3 (fasted) E 300 mg. Each dose of study drug will be separated by a minimum of 7 days. Cohort 1 Sequence 1 Placebo to Ertugliflozin Period 1 (fasted) Placebo → Period 2 (fasted) ertugliflozin (E) 10 mg → Period 3 (fasted) E 100 mg → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days. Cohort 1 Sequence 2 Placebo to Ertugliflozin Period 1 (fasted) E 0.5 mg → Period 2 (fasted) Placebo → Period 3 (fasted) E 100 mg → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days. Cohort 1 Sequence 3 Placebo to Ertugliflozin Period 1 (fasted) E 0.5 mg → Period 2 (fasted) E 10 mg → Period 3 (fasted) Placebo → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days. Cohort 2 Sequence 3 Placebo to Ertugliflozin Period 1 (fasted) E 2.5 mg → Period 2 (fasted) E 30 mg → Period 3 (fasted) Placebo. Each dose of study drug will be separated by a minimum of 7 days. Cohort 2 Sequence 2 Placebo to Ertugliflozin Period 1 (fasted) E 2.5 mg → Period 2 (fasted) Placebo → Period 3 (fasted) E 300 mg. Each dose of study drug will be separated by a minimum of 7 days. Cohort 1 Sequence 1 Ertugliflozin Period 1 (fasted) Placebo → Period 2 (fasted) ertugliflozin (E) 10 mg → Period 3 (fasted) E 100 mg → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days. Cohort 1 Sequence 2 Ertugliflozin Period 1 (fasted) E 0.5 mg → Period 2 (fasted) Placebo → Period 3 (fasted) E 100 mg → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days. Cohort 1 Sequence 3 Ertugliflozin Period 1 (fasted) E 0.5 mg → Period 2 (fasted) E 10 mg → Period 3 (fasted) Placebo → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days. Cohort 2 Sequence 1 Ertugliflozin Period 1 (fasted) Placebo → Period 2 (fasted) E 30 mg → Period 3 (fasted) E 300 mg. Each dose of study drug will be separated by a minimum of 7 days. Cohort 2 Sequence 2 Ertugliflozin Period 1 (fasted) E 2.5 mg → Period 2 (fasted) Placebo → Period 3 (fasted) E 300 mg. Each dose of study drug will be separated by a minimum of 7 days. Cohort 2 Sequence 3 Ertugliflozin Period 1 (fasted) E 2.5 mg → Period 2 (fasted) E 30 mg → Period 3 (fasted) Placebo. Each dose of study drug will be separated by a minimum of 7 days.
- Primary Outcome Measures
Name Time Method Number of Participants Experiencing an Adverse Event (AE) Up to Day 10 of each dosing period Number of Participants Discontinuing Study Drug Due to an AE Up to Day 8 of each dosing period Change from baseline in 24-hour urinary glucose excretion Baseline and 24 hours Area under the plasma concentration-time curve (AUC) from Time 0 to infinity (AUCinf) for ertugliflozin Up to Day 4 of each treatment period Area under the plasma concentration-time curve (AUC) from Time 0 to time of the last quantifiable concentration (AUClast) for ertugliflozin Up to Day 4 of each treatment period Maximum plasma concentration (Cmax) of ertugliflozin Up to Day 4 of each treatment period Time taken to reach the maximum observed plasma concentration (Tmax) of ertugliflozin Up to Day 4 of each treatment period Ertugliflozin half life (t1/2) Up to Day 4 of each treatment period Apparent clearance (CL/F) after a single dose of ertugliflozin Up to Day 4 of each treatment period Apparent volume of distribution (Vz/F) Up to Day 4 of each treatment period
- Secondary Outcome Measures
Name Time Method Urinary glucose excretion over 72 hours Up to 72 hours of each dosing period Change from baseline in 24-hour weighted mean glucose Baseline and 24 hours Inhibition of glucose reabsorption Up to 24 hours of each dosing period Renal clearance (CLr) of Ertugliflozin Up to 24 hours of each dosing period Urinary recovery of Ertugliflozin Up to 24 hours of each dosing period