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| Name | Class |
|---|---|
| Pfizer | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 Sequence 1 | Experimental | 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. |
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| Cohort 1 Sequence 2 | Experimental | 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. |
|
| Cohort 1 Sequence 3 | Experimental | 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. |
|
| Cohort 2 Sequence 1 | Experimental | 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. |
|
| Cohort 2 Sequence 2 | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ertugliflozin | Drug | Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Experiencing an Adverse Event (AE) | Up to Day 10 of each dosing period | |
| Number of Participants Discontinuing Study Drug Due to an AE | Up to Day 8 of each dosing period | |
| Change from baseline in 24-hour urinary glucose excretion | Baseline and 24 hours | |
| Area under the plasma concentration-time curve (AUC) from Time 0 to infinity (AUCinf) for ertugliflozin | 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 | Up to Day 4 of each treatment period | |
| Maximum plasma concentration (Cmax) of ertugliflozin | Up to Day 4 of each treatment period | |
| Time taken to reach the maximum observed plasma concentration (Tmax) of ertugliflozin | Up to Day 4 of each treatment period | |
| Ertugliflozin half life (t1/2) | Up to Day 4 of each treatment period | |
| Apparent clearance (CL/F) after a single dose of ertugliflozin | Up to Day 4 of each treatment period | |
| Apparent volume of distribution (Vz/F) |
| Measure | Description | Time Frame |
|---|---|---|
| Urinary glucose excretion over 72 hours | Up to 72 hours of each dosing period | |
| Change from baseline in 24-hour weighted mean glucose | Baseline and 24 hours | |
| Inhibition of glucose reabsorption |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32337660 | Result | 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. | |
| 34213819 | Derived | 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. |
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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.
|
| Cohort 2 Sequence 3 | Experimental | 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. |
|
| Placebo to Ertugliflozin | Drug | Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution |
|
| Up to Day 4 of each treatment period |
| Up to 24 hours of each dosing period |
| Renal clearance (CLr) of Ertugliflozin | Up to 24 hours of each dosing period |
| Urinary recovery of Ertugliflozin | Up to 24 hours of each dosing period |
| 33813736 | 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. |
| 33314761 | Derived | 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. |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C570288 | ertugliflozin |
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