Back to resultsA Single Escalating Dose Study Of Ertugliflozin (PF-04971729, MK-8835) Under Fed and Fasted Conditons In Healthy Volunteers (MK-8835-036)
Primary Purpose
Type 2 Diabetes Mellitus
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Ertugliflozin
Placebo to Ertugliflozin
Sponsored by
About this trial
This is an interventional other trial for Type 2 Diabetes Mellitus focused on measuring Single Ascending Dose Study in healthy subjects
Eligibility Criteria
Inclusion Criteria:
- Healthy male and/or female subjects of non childbearing potential.
- Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg
Exclusion Criteria:
- Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1 Sequence 1
Cohort 1 Sequence 2
Cohort 1 Sequence 3
Cohort 2 Sequence 1
Cohort 2 Sequence 2
Cohort 2 Sequence 3
Arm Description
Period 1 (fasted) Placebo → Period 2 (fasted) ertugliflozin (E) 10 mg → Period 3 (fasted) E 100 mg → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days.
Period 1 (fasted) E 0.5 mg → Period 2 (fasted) Placebo → Period 3 (fasted) E 100 mg → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days.
Period 1 (fasted) E 0.5 mg → Period 2 (fasted) E 10 mg → Period 3 (fasted) Placebo → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days.
Period 1 (fasted) Placebo → Period 2 (fasted) E 30 mg → Period 3 (fasted) E 300 mg. Each dose of study drug will be separated by a minimum of 7 days.
Period 1 (fasted) E 2.5 mg → Period 2 (fasted) Placebo → Period 3 (fasted) E 300 mg. Each dose of study drug will be separated by a minimum of 7 days.
Period 1 (fasted) E 2.5 mg → Period 2 (fasted) E 30 mg → Period 3 (fasted) Placebo. Each dose of study drug will be separated by a minimum of 7 days.
Outcomes
Primary Outcome Measures
Number of Participants Experiencing an Adverse Event (AE)
Number of Participants Discontinuing Study Drug Due to an AE
Change from baseline in 24-hour urinary glucose excretion
Area under the plasma concentration-time curve (AUC) from Time 0 to infinity (AUCinf) for ertugliflozin
Area under the plasma concentration-time curve (AUC) from Time 0 to time of the last quantifiable concentration (AUClast) for ertugliflozin
Maximum plasma concentration (Cmax) of ertugliflozin
Time taken to reach the maximum observed plasma concentration (Tmax) of ertugliflozin
Ertugliflozin half life (t1/2)
Apparent clearance (CL/F) after a single dose of ertugliflozin
Apparent volume of distribution (Vz/F)
Secondary Outcome Measures
Urinary glucose excretion over 72 hours
Change from baseline in 24-hour weighted mean glucose
Inhibition of glucose reabsorption
Renal clearance (CLr) of Ertugliflozin
Urinary recovery of Ertugliflozin
Full Information
NCT ID
NCT00989079
First Posted
October 1, 2009
Last Updated
May 28, 2020
Sponsor
Merck Sharp & Dohme LLC
Collaborators
Pfizer
1. Study Identification
Unique Protocol Identification Number
NCT00989079
Brief Title
A Single Escalating Dose Study Of Ertugliflozin (PF-04971729, MK-8835) Under Fed and Fasted Conditons In Healthy Volunteers (MK-8835-036)
Official Title
A Phase 1 Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of PF-04971729 After Administration of Single Escalating Oral Doses Under Fed and Fasted Conditions in Healthy Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
October 16, 2009 (Actual)
Primary Completion Date
December 11, 2009 (Actual)
Study Completion Date
December 11, 2009 (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
Ertugliflozin (PF-04971729, MK-8835) is a new compound proposed for the treatment of Type 2 diabetes mellitus. The primary purpose of this study is to evaluate the safety and tolerability along with the pharmacokinetics of single escalating doses of ertugliflozin under fed and fasted conditions in healthy volunteers.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
Keywords
Single Ascending Dose Study in healthy subjects
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1 Sequence 1
Arm Type
Experimental
Arm Description
Period 1 (fasted) Placebo → Period 2 (fasted) ertugliflozin (E) 10 mg → Period 3 (fasted) E 100 mg → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days.
Arm Title
Cohort 1 Sequence 2
Arm Type
Experimental
Arm Description
Period 1 (fasted) E 0.5 mg → Period 2 (fasted) Placebo → Period 3 (fasted) E 100 mg → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days.
Arm Title
Cohort 1 Sequence 3
Arm Type
Experimental
Arm Description
Period 1 (fasted) E 0.5 mg → Period 2 (fasted) E 10 mg → Period 3 (fasted) Placebo → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days.
Arm Title
Cohort 2 Sequence 1
Arm Type
Experimental
Arm Description
Period 1 (fasted) Placebo → Period 2 (fasted) E 30 mg → Period 3 (fasted) E 300 mg. Each dose of study drug will be separated by a minimum of 7 days.
Arm Title
Cohort 2 Sequence 2
Arm Type
Experimental
Arm Description
Period 1 (fasted) E 2.5 mg → Period 2 (fasted) Placebo → Period 3 (fasted) E 300 mg. Each dose of study drug will be separated by a minimum of 7 days.
Arm Title
Cohort 2 Sequence 3
Arm Type
Experimental
Arm Description
Period 1 (fasted) E 2.5 mg → Period 2 (fasted) E 30 mg → Period 3 (fasted) Placebo. Each dose of study drug will be separated by a minimum of 7 days.
Intervention Type
Drug
Intervention Name(s)
Ertugliflozin
Intervention Description
Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.
Intervention Type
Drug
Intervention Name(s)
Placebo to Ertugliflozin
Intervention Description
Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution
Primary Outcome Measure Information:
Title
Number of Participants Experiencing an Adverse Event (AE)
Time Frame
Up to Day 10 of each dosing period
Title
Number of Participants Discontinuing Study Drug Due to an AE
Time Frame
Up to Day 8 of each dosing period
Title
Change from baseline in 24-hour urinary glucose excretion
Time Frame
Baseline and 24 hours
Title
Area under the plasma concentration-time curve (AUC) from Time 0 to infinity (AUCinf) for ertugliflozin
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
Time Frame
Up to Day 4 of each treatment period
Title
Maximum plasma concentration (Cmax) of ertugliflozin
Time Frame
Up to Day 4 of each treatment period
Title
Time taken to reach the maximum observed plasma concentration (Tmax) of ertugliflozin
Time Frame
Up to Day 4 of each treatment period
Title
Ertugliflozin half life (t1/2)
Time Frame
Up to Day 4 of each treatment period
Title
Apparent clearance (CL/F) after a single dose of ertugliflozin
Time Frame
Up to Day 4 of each treatment period
Title
Apparent volume of distribution (Vz/F)
Time Frame
Up to Day 4 of each treatment period
Secondary Outcome Measure Information:
Title
Urinary glucose excretion over 72 hours
Time Frame
Up to 72 hours of each dosing period
Title
Change from baseline in 24-hour weighted mean glucose
Time Frame
Baseline and 24 hours
Title
Inhibition of glucose reabsorption
Time Frame
Up to 24 hours of each dosing period
Title
Renal clearance (CLr) of Ertugliflozin
Time Frame
Up to 24 hours of each dosing period
Title
Urinary recovery of Ertugliflozin
Time Frame
Up to 24 hours of each dosing period
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.
Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg
Exclusion Criteria:
Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing)
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
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
32337660
Citation
Fediuk DJ, Nucci G, Dawra VK, Cutler DL, Amin NB, Terra SG, Boyd RA, Krishna R, Sahasrabudhe V. Overview of the Clinical Pharmacology of Ertugliflozin, a Novel Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor. Clin Pharmacokinet. 2020 Aug;59(8):949-965. doi: 10.1007/s40262-020-00875-1.
Results Reference
result
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
33314761
Citation
Callegari E, Lin J, Tse S, Goosen TC, Sahasrabudhe V. Physiologically-Based Pharmacokinetic Modeling of the Drug-Drug Interaction of the UGT Substrate Ertugliflozin Following Co-Administration with the UGT Inhibitor Mefenamic Acid. CPT Pharmacometrics Syst Pharmacol. 2021 Feb;10(2):127-136. doi: 10.1002/psp4.12581. Epub 2020 Dec 30.
Results Reference
derived
Learn more about this trial
A Single Escalating Dose Study Of Ertugliflozin (PF-04971729, MK-8835) Under Fed and Fasted Conditons In Healthy Volunteers (MK-8835-036)
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