A Single Escalating Dose Study Of Ertugliflozin (PF-04971729, MK-8835) Under Fed and Fasted Conditons In Healthy Volunteers (MK-8835-036)

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1 Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of PF-04971729 After Administration of Single Escalating Oral Doses Under Fed and Fasted Conditions in Healthy Volunteers

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Ertugliflozin
* Drug: Placebo to Ertugliflozin


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 Sequence 1<br>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<br>* Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.<br>Drug: Placebo to Ertugliflozin<br>* Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution<br>|
| Experimental: Cohort 1 Sequence 2<br>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<br>* Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.<br>Drug: Placebo to Ertugliflozin<br>* Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution<br>|
| Experimental: Cohort 1 Sequence 3<br>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<br>* Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.<br>Drug: Placebo to Ertugliflozin<br>* Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution<br>|
| Experimental: Cohort 2 Sequence 1<br>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<br>* Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.<br>Drug: Placebo to Ertugliflozin<br>* Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution<br>|
| Experimental: Cohort 2 Sequence 2<br>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<br>* Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.<br>Drug: Placebo to Ertugliflozin<br>* Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution<br>|
| Experimental: Cohort 2 Sequence 3<br>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<br>* Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.<br>Drug: Placebo to Ertugliflozin<br>* Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Single Ascending Dose Study in healthy subjects