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

Sponsor

Merck Sharp & Dohme LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT01223339

Collaborator

Pfizer (Industry)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Ertugliflozin Drug: Placebo Drug: Ertugliflozin Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2010

Actual Primary Completion Date :

Feb 1, 2011

Actual Study Completion Date :

Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single Dose Japanese Cohort 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 Dose escalation of 1, 5, and 25 mg Ertugliflozin administered in the fasted state Drug: Placebo Placebo tablets to Ertugliflozin administered in the fasted state
Experimental: Single dose Western cohort 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 Dose escalation of 1, 5, and 25 mg Ertugliflozin administered in the fasted state
Experimental: Multiple Dose Japanese Cohort 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 Ertugliflozin 25 mg tablets administered once daily in the fed state for 7 days Drug: Placebo Placebo tablets administered once daily in the fed state for 7 days

Arm

Intervention/Treatment

Experimental: Single Dose Japanese Cohort

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

Dose escalation of 1, 5, and 25 mg Ertugliflozin administered in the fasted state

Drug: Placebo

Placebo tablets to Ertugliflozin administered in the fasted state

Experimental: Single dose Western cohort

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

Dose escalation of 1, 5, and 25 mg Ertugliflozin administered in the fasted state

Experimental: Multiple Dose Japanese Cohort

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

Ertugliflozin 25 mg tablets administered once daily in the fed state for 7 days

Drug: Placebo

Placebo tablets administered once daily in the fed state for 7 days

Outcome Measures

Primary Outcome Measures

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.