1. Bioequivalence of Metformin in Ertugliflozin/Metformin Fixed-Dose Combination Tablets to Canadian-Sourced Metformin Coadministered With Ertugliflozin Under Fasted and Fed States.
- Author
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Dawra VK, Pelletier K, Matschke K, Shi H, Hickman A, Zhou S, Krishna R, and Sahasrabudhe V
- Subjects
- Adult, Area Under Curve, Bridged Bicyclo Compounds, Heterocyclic adverse effects, Bridged Bicyclo Compounds, Heterocyclic pharmacokinetics, Canada, Cross-Over Studies, Drug Combinations, Drug Therapy, Combination, Female, Humans, Hypoglycemic Agents adverse effects, Hypoglycemic Agents pharmacokinetics, Male, Metformin adverse effects, Metformin pharmacokinetics, Middle Aged, Sodium-Glucose Transporter 2 Inhibitors adverse effects, Sodium-Glucose Transporter 2 Inhibitors pharmacokinetics, Tablets, Therapeutic Equivalency, Young Adult, Bridged Bicyclo Compounds, Heterocyclic administration & dosage, Hypoglycemic Agents administration & dosage, Metformin administration & dosage, Sodium-Glucose Transporter 2 Inhibitors administration & dosage
- Abstract
A fixed-dose combination (FDC) product of a selective sodium-glucose cotransporter 2 inhibitor ertugliflozin and immediate-release metformin is approved for type 2 diabetes mellitus in the United States, European Union countries, Canada, and other countries. Two studies were conducted to assess the bioequivalence of metformin in the ertugliflozin/metformin FDC tablets to the corresponding doses of Canadian-sourced metformin (Glucophage) coadministered with ertugliflozin. Both studies were phase 1 randomized, open-label, 2-period, single-dose crossover studies (n = 32) in which healthy subjects received an ertugliflozin/metformin FDC tablet (2.5/500 mg or 7.5/850 mg) and the respective doses of the individual components (ertugliflozin coadministered with Canadian-sourced metformin) under fasted (n = 18) or fed (n = 14) conditions. Blood samples were collected 72 hours postdose to determine metformin concentrations. The 90% confidence intervals were within the bioequivalence acceptance criteria for the adjusted geometric mean ratios (FDC:coadministered) for metformin area under the plasma concentration-time curve from time zero to time t, where t is the last point with a measurable concentration and peak observed plasma concentration for both dose strengths under fasted and fed conditions. All study medications were well tolerated. Bioequivalence was demonstrated for the metformin component of the ertugliflozin/metformin FDC tablets and the corresponding doses of the Canadian-sourced metformin coadministered with ertugliflozin., (© 2020 Pfizer Inc. Meck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)
- Published
- 2021
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