新一代降糖药gosogliptin

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2012 THOMSON REUTERS. For more information go to /copyright/
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2007, and the study was expected to complete in June 2008 [ 868416]. In June 2009, data from the trial were presented at the 69th ADA scientific sessions in New Orleans, LA. A total of 289 patients were treated with 20 or 30 mg of gosogliptin qd or placebo. At week 12, both doses significantly reduced HbA1c compared with placebo, with 55.8 and 52.2% of patients in the 20 and 30 mg dose groups, respectively, achieving HbA1c less than 7% compared with only 23.8% of the placebo group. The drug was well tolerated with the most common adverse events being pain in extremity, pharyngolaryngeal pain, headache and dyspepsia [1013516 ].
Target
Dipeptidyl peptidase IV
Update date
17-JUL-2012
Reason for update
One or more development status entries have been updated, Indexing updated
. OVERVIEW
. . DRUG NAME .
Names associated with this drug
Name
Type
gosogliptin
INN,USAN
PF-00734200
Research Code
PF-734200
Research Code
Satyor
Trade Name
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SatRx, a subsidiary of ChemRar Hi-Tech, under license from Pfizer, is developing gosogliptin (Satyor; PF-00734200; structure shown), a dipeptidyl peptidase IV (DPP-IV) inhibitor, for the potential treatment of type 2 diabetes (T2D) [1306668]. By July 2012, phase II studies were ongoing in RuJune 2007, a 12 week placebo-controlled, randomized, parallel group, multiple-dose phase II trial (; A7941005) was initiated in subjects (estimated n = 320) with type 2 diabetes on stable treatment with metformin in the US. Subjects were expected to receive placebo or one of four doses of gosogliptin (2, 5, 10, or 20 mg, po qd). The primary endpoints were change from baseline to 12 weeks of HbA1c levels and evaluation of dose response in subjects on a stable dose of metformin hydrochloride. Enrollment was ongoing in December
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Pfizer was previously developing gosogliptin for T2D. By September 2008, phase II/III trials had commenced in the US and EU [950369]; however, by January 2010, the compound was no longer listed on Pfizer's pipeline [1071193].
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Phase I In June 2009, pharmacokinetic data from patients with mild and severe renal failure and end-stage renal disease were presented at the 69th ADA Scientific Sessions in New Orleans, LA.Patients experiencing moderate to severe renal impairment had 2- to 3-fold higher AUC values for the drug, compared with individuals with normal renal function, indicating that gosogliptin exposure increases as renal function decreases. Cmax and Tmax values were not altered significantly. In patients requiring chronic hemodialysis, only 26% of the drug was removed following 4 h of hemodialysis. Gosogliptin was found to be well tolerated in all patients [1013807], [1016176].
Actions
DPP IV inhibitor antidiabetic product; Hypoglycemic agent; Dipeptidyl peptidase IV inhibitor
Technologies Oral formulation; Small molecule therapeutic
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In June 2007, data were presentedat the 67th ADA Scientific Sessions in Chicago, IL. In a randomized, placebo controlled, single oral dose study in healthy adults (n = 27), DPP-IV inhibition by gosogliptin resulted in a nonlinear increase in plasma GLP-1 levels. A maximal 10 mg dose of the compound resulted in a 2.3-fold increase in GLP-1, compared to placebo. However, the nonlinear results suggested another pathway for GLP-1 elimination other than DPP-IV enzymatic breakdown [844506].
DRUG REPORT : gosogliptin
. SUMMARY .
Drug Name
gosogliptin
Company
Pfizer Inc
Highest Dev Status
Phase 2 Clinical
Therapy Areas Non-insulin dependent diabetes
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PREMARKETING STUDIES Phase II By July 2012, SatRx had commenced phase II studies in Russia [1306669], [1306668].
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By September 2008, phase II/III EU and US trials had begun [950369]; however, by January 2010, the compound was no longer listed on Pfizer's pipeline [1071193].
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In February 2008, a phase II study was initiated (; A7941006) worldwide. Subjects (estimated n = 225) were to receive placebo, or gosogliptin (20 or 30 mg qd), for 12 weeks. The primary endpoint was HbA1c at 12 weeks. This study was expected to complete in September 2008 [878568].
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PRECLINICAL STUDIES In September 2007, preclinical data were presented on the identification of gosogliptin at the 14th RCA-SCI Medicinal Chemistry Conference in Cambridge, UK. Rapid optimization of a prolyl pyrrolidine led to compounds with nM potencies from which gosogliptin was selected based on potency, cellular permeability and low HERG activity. The eutomer had an IC50 value of 14 nM and a Ki value of 2 nM. It was highly bioavailable (greater than 70%) , with a long half-life (7.6 h) in monkeys and was effective in mice at a dose of 1 mg/kg following OGTTs [837272].
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In September 2007, data were presented at the 14th RSC-SCI Medicinal Chemistry Conference in Cambridge, UK. Following oral glucose tolerance tests (OGTTs), gosogliptin was shown to be well tolerated in humans at doses of 0.3 to 300 mg/kg. Human pharmacokinetics were dose proportional with a long terminal half-life [837272].