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

Diabetes Mellitus, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01223339
• Other study ID #: 8835-041
• Status: Completed
• Phase: Phase 1
• First received: October 13, 2010
• Last updated: May 19, 2016
• Start date: October 2010
• Est. completion date: February 2011

Study information

• Verified date: May 2016
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

Drug:
• Ertugliflozin
Dose escalation of 1, 5, and 25 mg Ertugliflozin administered in the fasted state
• Placebo
Placebo tablets to Ertugliflozin administered in the fasted state
• Ertugliflozin
Ertugliflozin 25 mg tablets administered once daily in the fed state for 7 days
• Placebo
Placebo tablets administered once daily in the fed state for 7 days

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.	Pfizer

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum plasma concentration (Cmax) of ertugliflozin for the Single Dose Cohort		Up to Day 4 of each treatment period	No
Primary	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	No
Primary	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	No
Primary	AUC from Hour 0 to infinity (AUCinf) for ertugliflozin for the Single Dose Cohort		Up to Day 4 of each treatment period	No
Primary	Ertugliflozin half life (t1/2) for the Single Dose Cohort		Up to Day 4 of each treatment period	No
Primary	Apparent clearance (CL/F) of ertugliflozin for the Single Dose Cohort		Up to Day 4 of each treatment period	No
Primary	Apparent volume of distribution (Vz/F) for the Single Dose Cohort		Up to Day 4 of each treatment period	No
Primary	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	No
Primary	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)	Yes
Primary	Number of participants who discontinued study drug due to an AE for the Single Dose Cohort		Up to Day 1 of each treatment period	Yes
Primary	Urinary Glucose Excretion over 24 hours for the Single Dose Cohort		Up to 24 hours postdose (Up to Day 2)	No
Primary	Cmax of ertugliflozin for the Multiple Dose Cohort		Up to Day 10	No
Primary	Tmax of ertugliflozin for the Multiple Dose Cohort		Up to Day 10	No
Primary	AUClast for ertugliflozin for the Multiple Dose Cohort		Up to Day 10	No
Primary	AUCinf for ertugliflozin for the Multiple Dose Cohort		Up to Day 10	No
Primary	t1/2 for the Multiple Dose Cohort		Up to Day 10	No
Primary	CL/F of ertugliflozin for the Multiple Dose Cohort		Up to Day 10	No
Primary	Vz/F for the Multiple Dose Cohort		Up to Day 10	No
Primary	Rac for the Single Dose Cohort		Up to Day 10	No
Primary	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)	Yes
Primary	Number of participants who discontinued study drug due to an AE for the Multiple Dose Cohort		Up to Day 7	Yes
Primary	Urinary Glucose Excretion over 24 hours for the Multiple Dose Cohort		Up to 24 hours postdose (Up to Day 8)	No