Effect of Renal Impairment on the Pharmacokinetics of a Single Oral Dose of Danuglipron in Participants With Type 2 Diabetes

Danuglipron (PF‐06882961) is an oral, small‐molecule glucagon‐like peptide‐1 receptor agonist in development for the treatment of type 2 diabetes (T2D) and obesity. Impaired renal function is prevalent in patients with T2D. This Phase 1, open‐label study evaluated the effect of renal impairment on t...

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Veröffentlicht in:Journal of clinical pharmacology 2024-04, Vol.64 (4), p.449-460
Hauptverfasser: Fediuk, Daryl J., Gorman, Donal N., Stoddard, Stephanie‐An, Zhang, Yizhong, Ogden, Adam G., Winton, Jennifer A., Saxena, Aditi R.
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container_issue 4
container_start_page 449
container_title Journal of clinical pharmacology
container_volume 64
creator Fediuk, Daryl J.
Gorman, Donal N.
Stoddard, Stephanie‐An
Zhang, Yizhong
Ogden, Adam G.
Winton, Jennifer A.
Saxena, Aditi R.
description Danuglipron (PF‐06882961) is an oral, small‐molecule glucagon‐like peptide‐1 receptor agonist in development for the treatment of type 2 diabetes (T2D) and obesity. Impaired renal function is prevalent in patients with T2D. This Phase 1, open‐label study evaluated the effect of renal impairment on the pharmacokinetics, safety, and tolerability of danuglipron (20 mg) in healthy participants with normal renal function (estimated glomerular filtration rate [eGFR] unnormalized for body surface area: ≥90 mL/min), in participants with T2D and normal renal function (eGFR ≥90 mL/min), and in participants with T2D and mild (eGFR 60‐89 mL/min), moderate (eGFR 30‐59 mL/min), or severe (eGFR
doi_str_mv 10.1002/jcph.2371
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Impaired renal function is prevalent in patients with T2D. This Phase 1, open‐label study evaluated the effect of renal impairment on the pharmacokinetics, safety, and tolerability of danuglipron (20 mg) in healthy participants with normal renal function (estimated glomerular filtration rate [eGFR] unnormalized for body surface area: ≥90 mL/min), in participants with T2D and normal renal function (eGFR ≥90 mL/min), and in participants with T2D and mild (eGFR 60‐89 mL/min), moderate (eGFR 30‐59 mL/min), or severe (eGFR &lt;30 mL/min) renal impairment (N = 39). Log‐linear regression analyses and analyses of variance showed no evidence of a clinically significant effect of reduced renal function on danuglipron pharmacokinetics. Renal clearance of unchanged danuglipron was minimal (&lt;1% across all renal function groups). Danuglipron pharmacokinetics were similar between healthy participants and participants with T2D and normal renal function. A single 20‐mg oral dose of danuglipron was generally safe and well tolerated in all participant groups. In participants with T2D, renal impairment had no clinically meaningful effect on the pharmacokinetic, safety, and tolerability profiles of danuglipron, indicating that dose adjustment of danuglipron will not be required when administered to patients with T2D and reduced renal function.</description><identifier>ISSN: 0091-2700</identifier><identifier>EISSN: 1552-4604</identifier><identifier>DOI: 10.1002/jcph.2371</identifier><identifier>PMID: 37840155</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Area Under Curve ; chronic kidney disease ; danuglipron ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - drug therapy ; Epidermal growth factor receptors ; Glomerular Filtration Rate ; GLP-1 receptor agonists ; GLP‐1 receptor agonist ; Glucagon ; Humans ; Hypoglycemic Agents - therapeutic use ; Pharmacokinetics ; Renal function ; renal impairment ; Renal Insufficiency - drug therapy ; type 2 diabetes</subject><ispartof>Journal of clinical pharmacology, 2024-04, Vol.64 (4), p.449-460</ispartof><rights>2023 Pfizer Inc. published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.</rights><rights>2023 Pfizer Inc. 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A single 20‐mg oral dose of danuglipron was generally safe and well tolerated in all participant groups. 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A single 20‐mg oral dose of danuglipron was generally safe and well tolerated in all participant groups. In participants with T2D, renal impairment had no clinically meaningful effect on the pharmacokinetic, safety, and tolerability profiles of danuglipron, indicating that dose adjustment of danuglipron will not be required when administered to patients with T2D and reduced renal function.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>37840155</pmid><doi>10.1002/jcph.2371</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
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subjects Area Under Curve
chronic kidney disease
danuglipron
Diabetes
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - drug therapy
Epidermal growth factor receptors
Glomerular Filtration Rate
GLP-1 receptor agonists
GLP‐1 receptor agonist
Glucagon
Humans
Hypoglycemic Agents - therapeutic use
Pharmacokinetics
Renal function
renal impairment
Renal Insufficiency - drug therapy
type 2 diabetes
title Effect of Renal Impairment on the Pharmacokinetics of a Single Oral Dose of Danuglipron in Participants With Type 2 Diabetes
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