Clinical trial NCT00989079: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Keywords: Single Ascending Dose Study in healthy subjects
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2009-10-02
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.


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)

Primary outcomes:
measure: Number of Participants Experiencing an Adverse Event (AE)
timeFrame: Up to Day 10 of each dosing period
measure: Number of Participants Discontinuing Study Drug Due to an AE
timeFrame: Up to Day 8 of each dosing period
measure: Change from baseline in 24-hour urinary glucose excretion
timeFrame: Baseline and 24 hours
measure: Area under the plasma concentration-time curve (AUC) from Time 0 to infinity (AUCinf) for ertugliflozin
timeFrame: Up to Day 4 of each treatment period
measure: Area under the plasma concentration-time curve (AUC) from Time 0 to time of the last quantifiable concentration (AUClast) for ertugliflozin
timeFrame: Up to Day 4 of each treatment period
measure: Maximum plasma concentration (Cmax) of ertugliflozin
timeFrame: Up to Day 4 of each treatment period
measure: Time taken to reach the maximum observed plasma concentration (Tmax) of ertugliflozin
timeFrame: Up to Day 4 of each treatment period
measure: Ertugliflozin half life (t1/2)
timeFrame: Up to Day 4 of each treatment period
measure: Apparent clearance (CL/F) after a single dose of ertugliflozin
timeFrame: Up to Day 4 of each treatment period
measure: Apparent volume of distribution (Vz/F)
timeFrame: Up to Day 4 of each treatment period
Secondary outcomes:
measure: Urinary glucose excretion over 72 hours
timeFrame: Up to 72 hours of each dosing period
measure: Change from baseline in 24-hour weighted mean glucose
timeFrame: Baseline and 24 hours
measure: Inhibition of glucose reabsorption
timeFrame: Up to 24 hours of each dosing period
measure: Renal clearance (CLr) of Ertugliflozin
timeFrame: Up to 24 hours of each dosing period
measure: Urinary recovery of Ertugliflozin
timeFrame: Up to 24 hours of each dosing period
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.