Matches in SemOpenAlex for { <https://semopenalex.org/work/W2995648519> ?p ?o ?g. }
Showing items 1 to 78 of
78
with 100 items per page.
- W2995648519 endingPage "924" @default.
- W2995648519 startingPage "924" @default.
- W2995648519 abstract "924 BACKGROUND: VEGF expression is highly regulated posttranscriptionally through the 59- and 39-untranslated regions (UTRs) of its mRNA. PTC299 is a novel, orally bioavailable, small molecule designed to act through the VEGF 59-UTR to inhibit tumor VEGF production. In multiple preclinical human tumor xenograft models, PTC299 reduces tumor and circulating plasma VEGF concentrations, decreases tumor microvessel density, and substantially slows tumor growth. When given together with cytotoxic agents or with other antiangiogenics, PTC299 enhances tumor growth delay. In a single-dose study in human healthy volunteers, PTC299 was well tolerated through the highest dose administered (3 mg/kg). Plasma concentrations active in preclinical models were achieved. METHODS AND MATERIALS: This Phase 1, randomized, double-blind, placebo-controlled, escalating multiple-dose study in healthy adult volunteers has evaluated oral PTC299 treatment given twice per day (BID) for 7 days to determine PTC299 safety, PK profile, and effects on plasma and serum VEGF levels; subjects have been followed with clinical observations, safety laboratory testing, and frequent plasma sampling over the dosing period and also at 7 and 14 days after the last PTC299 dose. RESULTS: 8 subjects (3 PTC299, 1 placebo per gender) have been enrolled at each of 3 progressively higher dose levels on a BID schedule, for a total of 24 subjects (12 males, 12 females; median age 46 [range, 21-64] years). PTC299 has been well tolerated with no serious, dose-limiting, or definitively drug-related adverse events. PK data indicates dose proportional increases in plasma exposures with an accumulation in Cmax and AUC0-24 of ~2-fold over 7 days. The target trough plasma concentration has been maintained at all dose levels with the highest dose tested achieving a mean trough plasma concentration ~5 times the target plasma concentration at 12 hours after the final PTC299 dose. Additional accrual to evaluate PTC299 doses given 3 times per day is currently ongoing. CONCLUSIONS: PTC299 is the first drug specifically designed to modulate post-transcriptional control mechanisms to treat human disease. In this initial, multiple-dose clinical study, PTC299 shows safety at plasma exposures associated with preclinical activity. Final clinical data on dose ranging, safety, PK, and plasma/serum VEGF levels will be presented at the meeting. PK modeling will be used to project an appropriate dosing regimen for subsequent studies in cancer patients." @default.
- W2995648519 created "2019-12-26" @default.
- W2995648519 creator A5004491253 @default.
- W2995648519 creator A5007632399 @default.
- W2995648519 creator A5032160958 @default.
- W2995648519 creator A5057785401 @default.
- W2995648519 creator A5063440637 @default.
- W2995648519 creator A5066010864 @default.
- W2995648519 creator A5085418762 @default.
- W2995648519 date "2007-05-01" @default.
- W2995648519 modified "2023-10-12" @default.
- W2995648519 title "A phase 1 multiple-dose safety, pharmacokinetic, and pharmacodynamic Study of PTC299, a novel VEGF expression inhibitor for treatment of solid tumors" @default.
- W2995648519 hasPublicationYear "2007" @default.
- W2995648519 type Work @default.
- W2995648519 sameAs 2995648519 @default.
- W2995648519 citedByCount "0" @default.
- W2995648519 crossrefType "journal-article" @default.
- W2995648519 hasAuthorship W2995648519A5004491253 @default.
- W2995648519 hasAuthorship W2995648519A5007632399 @default.
- W2995648519 hasAuthorship W2995648519A5032160958 @default.
- W2995648519 hasAuthorship W2995648519A5057785401 @default.
- W2995648519 hasAuthorship W2995648519A5063440637 @default.
- W2995648519 hasAuthorship W2995648519A5066010864 @default.
- W2995648519 hasAuthorship W2995648519A5085418762 @default.
- W2995648519 hasConcept C111113717 @default.
- W2995648519 hasConcept C112705442 @default.
- W2995648519 hasConcept C126322002 @default.
- W2995648519 hasConcept C142724271 @default.
- W2995648519 hasConcept C143998085 @default.
- W2995648519 hasConcept C197934379 @default.
- W2995648519 hasConcept C204787440 @default.
- W2995648519 hasConcept C22979827 @default.
- W2995648519 hasConcept C27081682 @default.
- W2995648519 hasConcept C2777288759 @default.
- W2995648519 hasConcept C71924100 @default.
- W2995648519 hasConcept C98274493 @default.
- W2995648519 hasConceptScore W2995648519C111113717 @default.
- W2995648519 hasConceptScore W2995648519C112705442 @default.
- W2995648519 hasConceptScore W2995648519C126322002 @default.
- W2995648519 hasConceptScore W2995648519C142724271 @default.
- W2995648519 hasConceptScore W2995648519C143998085 @default.
- W2995648519 hasConceptScore W2995648519C197934379 @default.
- W2995648519 hasConceptScore W2995648519C204787440 @default.
- W2995648519 hasConceptScore W2995648519C22979827 @default.
- W2995648519 hasConceptScore W2995648519C27081682 @default.
- W2995648519 hasConceptScore W2995648519C2777288759 @default.
- W2995648519 hasConceptScore W2995648519C71924100 @default.
- W2995648519 hasConceptScore W2995648519C98274493 @default.
- W2995648519 hasLocation W29956485191 @default.
- W2995648519 hasOpenAccess W2995648519 @default.
- W2995648519 hasPrimaryLocation W29956485191 @default.
- W2995648519 hasRelatedWork W1598597790 @default.
- W2995648519 hasRelatedWork W1902804987 @default.
- W2995648519 hasRelatedWork W1979937839 @default.
- W2995648519 hasRelatedWork W1983150723 @default.
- W2995648519 hasRelatedWork W2011827420 @default.
- W2995648519 hasRelatedWork W2040104879 @default.
- W2995648519 hasRelatedWork W2109295630 @default.
- W2995648519 hasRelatedWork W2143024384 @default.
- W2995648519 hasRelatedWork W2161720812 @default.
- W2995648519 hasRelatedWork W2240318953 @default.
- W2995648519 hasRelatedWork W2248559161 @default.
- W2995648519 hasRelatedWork W2268160049 @default.
- W2995648519 hasRelatedWork W2278176381 @default.
- W2995648519 hasRelatedWork W2280174469 @default.
- W2995648519 hasRelatedWork W2591414794 @default.
- W2995648519 hasRelatedWork W2958406986 @default.
- W2995648519 hasRelatedWork W3000617895 @default.
- W2995648519 hasRelatedWork W3035464854 @default.
- W2995648519 hasRelatedWork W3120034421 @default.
- W2995648519 hasRelatedWork W603336398 @default.
- W2995648519 hasVolume "67" @default.
- W2995648519 isParatext "false" @default.
- W2995648519 isRetracted "false" @default.
- W2995648519 magId "2995648519" @default.
- W2995648519 workType "article" @default.