A Single Escalating Dose Study Of Ertugliflozin (PF-04971729, MK-8835) Under Fed and Fasted Conditons In Healthy Volunteers (MK-8835-036)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1 Sequence 1 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. |
Drug: Ertugliflozin
Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.
Drug: Placebo to Ertugliflozin
Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution
|
| Experimental: Cohort 1 Sequence 2 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. |
Drug: Ertugliflozin
Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.
Drug: Placebo to Ertugliflozin
Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution
|
| Experimental: Cohort 1 Sequence 3 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. |
Drug: Ertugliflozin
Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.
Drug: Placebo to Ertugliflozin
Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution
|
| Experimental: Cohort 2 Sequence 1 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. |
Drug: Ertugliflozin
Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.
Drug: Placebo to Ertugliflozin
Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution
|
| Experimental: Cohort 2 Sequence 2 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. |
Drug: Ertugliflozin
Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.
Drug: Placebo to Ertugliflozin
Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution
|
| Experimental: Cohort 2 Sequence 3 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. |
Drug: Ertugliflozin
Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.
Drug: Placebo to Ertugliflozin
Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
Eligibility Criteria
Criteria
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)
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
- Pfizer
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 8835-036