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

NCT01223339 | Completed Phase 1

• 1 other identifier: 8835-041
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

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

Keywords

Ertugliflozin; Japanese and Western population; pharmacokinetics; pharmacodynamics

Outcome Measures

Primary Outcomes (22)

• 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)

Study Arms (3)

Single Dose Japanese Cohort

EXPERIMENTAL

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; Drug: Placebo

Single dose Western cohort

EXPERIMENTAL

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

Multiple Dose Japanese Cohort

EXPERIMENTAL

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; Drug: Placebo

Interventions

Ertugliflozin DRUG

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

Single Dose Japanese Cohort; Single dose Western cohort

Placebo DRUG

Placebo tablets to Ertugliflozin administered in the fasted state

Single Dose Japanese Cohort

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Pfizer: collaborator

Related Publications (3)

• 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.

  PMID: 34213819 DERIVED

• 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.

  PMID: 33813736 DERIVED

• 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.

  PMID: 33434408 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

ertugliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2010
• First Posted: October 19, 2010
• Study Start: October 1, 2010
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: May 20, 2016

Record last verified: 2016-05