Back to resultsEvaluation of Pharmacokinetics, Safety, And Tolerability Of Ertugliflozin (PF-04971729, MK-8835) In Japanese And Western Healthy Participants (MK-8835-041)
Primary Purpose
Diabetes Mellitus, Type 2
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Ertugliflozin
Placebo
Ertugliflozin
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring Ertugliflozin, Japanese and Western population, pharmacokinetics, pharmacodynamics
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Single Dose Japanese Cohort
Single dose Western cohort
Multiple Dose Japanese Cohort
Arm Description
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.
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.
This will be a multiple dose Cohort in which Japanese healthy participants will receive once-daily 25 mg ertugliflozin or placebo for 7 days.
Outcomes
Primary Outcome Measures
Maximum plasma concentration (Cmax) of ertugliflozin for the Single Dose Cohort
Time taken to reach the maximum observed plasma concentration (Tmax) of ertugliflozin for the Single Dose Cohort
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
AUC from Hour 0 to infinity (AUCinf) for ertugliflozin for the Single Dose Cohort
Ertugliflozin half life (t1/2) for the Single Dose Cohort
Apparent clearance (CL/F) of ertugliflozin for the Single Dose Cohort
Apparent volume of distribution (Vz/F) for the Single Dose Cohort
Accumulation Ratio of Area Under the Curve for the dosing interval of ertugliflozin (Rac) for the Single Dose Cohort
Number of participants who experienced an adverse event (AE) for the Single Dose Cohort
Number of participants who discontinued study drug due to an AE for the Single Dose Cohort
Urinary Glucose Excretion over 24 hours for the Single Dose Cohort
Cmax of ertugliflozin for the Multiple Dose Cohort
Tmax of ertugliflozin for the Multiple Dose Cohort
AUClast for ertugliflozin for the Multiple Dose Cohort
AUCinf for ertugliflozin for the Multiple Dose Cohort
t1/2 for the Multiple Dose Cohort
CL/F of ertugliflozin for the Multiple Dose Cohort
Vz/F for the Multiple Dose Cohort
Rac for the Single Dose Cohort
Number of participants who experienced an AE for the Multiple Dose Cohort
Number of participants who discontinued study drug due to an AE for the Multiple Dose Cohort
Urinary Glucose Excretion over 24 hours for the Multiple Dose Cohort
Secondary Outcome Measures
Full Information
NCT ID
NCT01223339
First Posted
October 13, 2010
Last Updated
May 19, 2016
Sponsor
Merck Sharp & Dohme LLC
Collaborators
Pfizer
1. Study Identification
Unique Protocol Identification Number
NCT01223339
Brief Title
Evaluation of Pharmacokinetics, Safety, And Tolerability Of Ertugliflozin (PF-04971729, MK-8835) In Japanese And Western Healthy Participants (MK-8835-041)
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 Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
February 2011 (Actual)
Study Completion Date
February 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
Collaborators
Pfizer
4. Oversight
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
Keywords
Ertugliflozin, Japanese and Western population, pharmacokinetics, pharmacodynamics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single Dose Japanese Cohort
Arm Type
Experimental
Arm Description
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.
Arm Title
Single dose Western cohort
Arm Type
Experimental
Arm Description
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.
Arm Title
Multiple Dose Japanese Cohort
Arm Type
Experimental
Arm Description
This will be a multiple dose Cohort in which Japanese healthy participants will receive once-daily 25 mg ertugliflozin or placebo for 7 days.
Intervention Type
Drug
Intervention Name(s)
Ertugliflozin
Intervention Description
Dose escalation of 1, 5, and 25 mg Ertugliflozin administered in the fasted state
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo tablets to Ertugliflozin administered in the fasted state
Intervention Type
Drug
Intervention Name(s)
Ertugliflozin
Intervention Description
Ertugliflozin 25 mg tablets administered once daily in the fed state for 7 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo tablets administered once daily in the fed state for 7 days
Primary Outcome Measure Information:
Title
Maximum plasma concentration (Cmax) of ertugliflozin for the Single Dose Cohort
Time Frame
Up to Day 4 of each treatment period
Title
Time taken to reach the maximum observed plasma concentration (Tmax) of ertugliflozin for the Single Dose Cohort
Time Frame
Up to Day 4 of each treatment period
Title
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
Time Frame
Up to Day 4 of each treatment period
Title
AUC from Hour 0 to infinity (AUCinf) for ertugliflozin for the Single Dose Cohort
Time Frame
Up to Day 4 of each treatment period
Title
Ertugliflozin half life (t1/2) for the Single Dose Cohort
Time Frame
Up to Day 4 of each treatment period
Title
Apparent clearance (CL/F) of ertugliflozin for the Single Dose Cohort
Time Frame
Up to Day 4 of each treatment period
Title
Apparent volume of distribution (Vz/F) for the Single Dose Cohort
Time Frame
Up to Day 4 of each treatment period
Title
Accumulation Ratio of Area Under the Curve for the dosing interval of ertugliflozin (Rac) for the Single Dose Cohort
Time Frame
Up to Day 4 of each treatment period
Title
Number of participants who experienced an adverse event (AE) for the Single Dose Cohort
Time Frame
Up to 10 days after the final dose of study drug (Up to Day 11)
Title
Number of participants who discontinued study drug due to an AE for the Single Dose Cohort
Time Frame
Up to Day 1 of each treatment period
Title
Urinary Glucose Excretion over 24 hours for the Single Dose Cohort
Time Frame
Up to 24 hours postdose (Up to Day 2)
Title
Cmax of ertugliflozin for the Multiple Dose Cohort
Time Frame
Up to Day 10
Title
Tmax of ertugliflozin for the Multiple Dose Cohort
Time Frame
Up to Day 10
Title
AUClast for ertugliflozin for the Multiple Dose Cohort
Time Frame
Up to Day 10
Title
AUCinf for ertugliflozin for the Multiple Dose Cohort
Time Frame
Up to Day 10
Title
t1/2 for the Multiple Dose Cohort
Time Frame
Up to Day 10
Title
CL/F of ertugliflozin for the Multiple Dose Cohort
Time Frame
Up to Day 10
Title
Vz/F for the Multiple Dose Cohort
Time Frame
Up to Day 10
Title
Rac for the Single Dose Cohort
Time Frame
Up to Day 10
Title
Number of participants who experienced an AE for the Multiple Dose Cohort
Time Frame
Up to 10 days after the final dose of study drug (Up to Day 17)
Title
Number of participants who discontinued study drug due to an AE for the Multiple Dose Cohort
Time Frame
Up to Day 7
Title
Urinary Glucose Excretion over 24 hours for the Multiple Dose Cohort
Time Frame
Up to 24 hours postdose (Up to Day 8)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
34213819
Citation
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.
Results Reference
derived
PubMed Identifier
33813736
Citation
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.
Results Reference
derived
PubMed Identifier
33434408
Citation
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.
Results Reference
derived
Learn more about this trial
Evaluation of Pharmacokinetics, Safety, And Tolerability Of Ertugliflozin (PF-04971729, MK-8835) In Japanese And Western Healthy Participants (MK-8835-041)
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