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

NCT ID: NCT01223339

Last Updated: 2016-05-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2011-02-28

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.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Ertugliflozin

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

Placebo tablets to Ertugliflozin administered in the fasted state

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.

Group Type: EXPERIMENTAL

Ertugliflozin

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Ertugliflozin

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

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

Interventions

Ertugliflozin

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

Intervention Type: DRUG

Placebo

Placebo tablets to Ertugliflozin administered in the fasted state

Intervention Type: DRUG

Ertugliflozin

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Fediuk DJ, Sahasrabudhe V, Dawra VK, Zhou S, Sweeney K. Population Pharmacokinetic Analyses of Ertugliflozin in Select Ethnic Populations. Clin Pharmacol Drug Dev. 2021 Nov;10(11):1297-1306. doi: 10.1002/cpdd.970. Epub 2021 Jul 2.

Reference Type: DERIVED

PMID: 34213819 (View on PubMed)

Marshall JC, Liang Y, Sahasrabudhe V, Tensfeldt T, Fediuk DJ, Zhou S, Krishna R, Dawra VK, Wood LS, Sweeney K. Meta-Analysis of Noncompartmental Pharmacokinetic Parameters of Ertugliflozin to Evaluate Dose Proportionality and UGT1A9 Polymorphism Effect on Exposure. J Clin Pharmacol. 2021 Sep;61(9):1220-1231. doi: 10.1002/jcph.1866. Epub 2021 Jun 19.

Reference Type: DERIVED

PMID: 33813736 (View on PubMed)

Li Y, Nucci G, Yamamoto Y, Fediuk DJ, Sahasrabudhe V. Pharmacokinetics and Pharmacodynamics of Ertugliflozin in Healthy Japanese and Western Subjects. Clin Pharmacol Drug Dev. 2021 Jul;10(7):765-776. doi: 10.1002/cpdd.908. Epub 2021 Jan 12.

Reference Type: DERIVED

PMID: 33434408 (View on PubMed)

Other Identifiers

8835-041

Identifier Type: -

Identifier Source: org_study_id