Evaluation of Pharmacokinetics, Safety, And Tolerability Of Ertugliflozin (PF-04971729, MK-8835) In Japanese And Western Healthy Participants (MK-8835-041)

Study Overview
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Brief Summary
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This study is to characterize the pharmacokinetics, safety, tolerability, and pharmacodynamics of single and multiple oral doses (SD, MD) of ertugliflozin (PF-04971729, MK-8835) in Japanese healthy participants. The secondary objective is to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of ertugliflozin in Western healthy participants as compared to Japanese healthy participants.

Official Title
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A Phase 1, Randomized, Double Blind, Placebo-Controlled, Parallel Cohort, Single Dose Escalation And Multiple Dose Study In Japanese Healthy Subjects, And Open Label, Single Dose Escalation Study In Western Healthy Subjects To Investigate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of PF-04971729

Conditions
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Diabetes Mellitus, Type 2

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female subjects of non-childbearing potential, between the ages of 18 and 55 years, inclusive Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs). Japanese subjects must have four Japanese grandparents who were born in Japan. Mean body weight and the body weight range of Western subjects are similar to those of Japanese subjects with a 10% plus and minus error. An informed consent document signed and dated by the subject. Subjects who are willing and able to comply with scheduled visits, treatment plan,laboratory tests, and other study procedures. Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease Asian or Polynesian subjects in Western subject groups. Any condition possibly affecting drug absorption (eg, gastrectomy). A positive urine drug screen. History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males within 6 months of screening. History or evidence of habitual use of tobacco or nicotine containing products within 3 months of Screening, with the exception of light smoking (up to 5 cigarettes per day or the equivalent). Treatment with an investigational drug within 30 days or 5 half-lives preceding the first dose of study medication. 12-lead ECG demonstrating QTc >450 msec at screening. Subjects with ANY of the following abnormalities on safety laboratory tests): Evidence of glycosuria, as defined by a positive urine dipstick test; Fasting serum triglyceride >300 mg/dL; Fasting LDL-cholesterol > than or equal to 190 mg/dL. Fasting serum glucose >125 mg/dL.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Dose Japanese Cohort<br>This will be a single dose Cohort in which Japanese healthy participants will receive 3 ascending single doses (1 mg, 5 mg, and 25 mg) of ertugliflozin or placebo through 3 dosing periods. A minimum wash out period of 7-days will be set between each dose administration. | Drug: Ertugliflozin<br>* Dose escalation of 1, 5, and 25 mg Ertugliflozin administered in the fasted state<br>Drug: Placebo<br>* Placebo tablets to Ertugliflozin administered in the fasted state<br>|
| Experimental: Single dose Western cohort<br>This will be a single dose Cohort in which Western healthy participants will receive 3 ascending single doses (1 mg, 5 mg, and 25 mg) of ertugliflozin through 3 dosing periods. A minimum wash out period of 7-days will be set between each dose administration. | Drug: Ertugliflozin<br>* Dose escalation of 1, 5, and 25 mg Ertugliflozin administered in the fasted state<br>|
| Experimental: Multiple Dose Japanese Cohort<br>This will be a multiple dose Cohort in which Japanese healthy participants will receive once-daily 25 mg ertugliflozin or placebo for 7 days. | Drug: Ertugliflozin<br>* Ertugliflozin 25 mg tablets administered once daily in the fed state for 7 days<br>Drug: Placebo<br>* Placebo tablets administered once daily in the fed state for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) of ertugliflozin for the Single Dose Cohort |  | Up to Day 4 of each treatment period | 
| Time taken to reach the maximum observed plasma concentration (Tmax) of ertugliflozin for the Single Dose Cohort |  | 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 for the Single Dose Cohort |  | Up to Day 4 of each treatment period | 
| AUC from Hour 0 to infinity (AUCinf) for ertugliflozin for the Single Dose Cohort |  | Up to Day 4 of each treatment period | 
| Ertugliflozin half life (t1/2) for the Single Dose Cohort |  | Up to Day 4 of each treatment period | 
| Apparent clearance (CL/F) of ertugliflozin for the Single Dose Cohort |  | Up to Day 4 of each treatment period | 
| Apparent volume of distribution (Vz/F) for the Single Dose Cohort |  | Up to Day 4 of each treatment period | 
| Accumulation Ratio of Area Under the Curve for the dosing interval of ertugliflozin (Rac) for the Single Dose Cohort |  | Up to Day 4 of each treatment period | 
| Number of participants who experienced an adverse event (AE) for the Single Dose Cohort |  | Up to 10 days after the final dose of study drug (Up to Day 11) | 
| Number of participants who discontinued study drug due to an AE for the Single Dose Cohort |  | Up to Day 1 of each treatment period | 
| Urinary Glucose Excretion over 24 hours for the Single Dose Cohort |  | Up to 24 hours postdose (Up to Day 2) | 
| Cmax of ertugliflozin for the Multiple Dose Cohort |  | Up to Day 10 | 
| Tmax of ertugliflozin for the Multiple Dose Cohort |  | Up to Day 10 | 
| AUClast for ertugliflozin for the Multiple Dose Cohort |  | Up to Day 10 | 
| AUCinf for ertugliflozin for the Multiple Dose Cohort |  | Up to Day 10 | 
| t1/2 for the Multiple Dose Cohort |  | Up to Day 10 | 
| CL/F of ertugliflozin for the Multiple Dose Cohort |  | Up to Day 10 | 
| Vz/F for the Multiple Dose Cohort |  | Up to Day 10 | 
| Rac for the Single Dose Cohort |  | Up to Day 10 | 
| Number of participants who experienced an AE for the Multiple Dose Cohort |  | Up to 10 days after the final dose of study drug (Up to Day 17) | 
| Number of participants who discontinued study drug due to an AE for the Multiple Dose Cohort |  | Up to Day 7 | 
| Urinary Glucose Excretion over 24 hours for the Multiple Dose Cohort |  | Up to 24 hours postdose (Up to Day 8) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ertugliflozin, Japanese and Western population, pharmacokinetics, pharmacodynamics