FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2922349247> ?p ?o ?g. }

• W2922349247 endingPage "2336" @default.
• W2922349247 startingPage "2336" @default.
• W2922349247 abstract "Abstract Background: Iron overload is a significant complication in patients with hereditary hemochromatosis and hereditary hemolytic anemia (esp. sickle cell disease and thalassemia). LJPC-401, a synthetically produced peptide identical to endogenous human hepcidin, is being developed as a therapeutic intervention for iron overload in these conditions. Methods: Phase 1, randomized, double-blind, two-arm, placebo-controlled, single dose escalation, and multiple dose study to assess the safety, tolerability, and pharmacokinetics (PK) /pharmacodynamics (PD) of LJPC-401 in healthy adults. Eligible healthy adults were randomized in a 3:1 ratio to receive either LJPC-401 or placebo as a subcutaneous (SC) injection in single-dose cohorts (Arm A) or a multiple-dose cohort (Arm B, twice weekly for two weeks). Subjects were assigned to receive LJPC-401 at doses of 4, 10, or 20 mg. Serial blood samples were collected up to one-week post dose in the single-dose cohort and up to two weeks in the multiple-dose cohort for PK and PD assessments. PD assessments included effects on serum iron, ferritin, unsaturated iron binding capacity (UIBC), and transferrin saturation (TSAT). Results: Twenty-one healthy adults were randomized and included in analyses (12 from Arm A and 9 from Arm B). In Arm A, dose-related increases in mean baseline-corrected LJPC-401 concentrations were observed following single SC doses of 4, 10, and 20 mg LJPC-401. Peak concentrations were observed at approximately 2 hours postdose for all doses. LJPC-401 concentrations returned to near baseline by approximately 1 day postdose for the 4- and 10-mg dose groups and by 7 days postdose for all groups. In Arm A, dose-dependent decreases in serum iron were observed in all LJPC-401 dose groups, beginning at 2 hours postdose. The largest percent decrease in serum iron for the LJPC-401 groups occurred at the 12-hour postdose timepoint and was a mean (SD) of−56.0% (16.9%) in the 4-mg group, −66.9% (6.1%) in the 10-mg group, and −79.7% (4.1%) in the 20-mg group. Serum iron levels returned to baseline within approximately 24 hours in the 4-mg dose group and within approximately 48 hours after dosing in the 10 and 20 mg dose groups. In Arm B (10 mg dose twice weekly), decreases in mean serum iron from baseline were observed after each dose of LJPC-401. The largest percent decreases in serum iron for the LJPC-401 group was observed at Hours 8 and 12 for the Day 1 dose (mean (SD): −69.1% [9.6%] and −69.2% [17.8%], respectively) and at Hour 12 for the Day 11 dose (−73.0% [13.1%]). Dose-related increases in UIBC were observed, along with dose-related decreases in TSAT, which were similar to those observed for serum iron. Dose-related prolonged increases in serum ferritin were observed. Diurnal variation patterns were seen in endogenous hepcidin and baseline iron levels in placebo subjects. No treatment-emergent serious adverse events were reported. One subject discontinued treatment due to a TEAE (exacerbation of pre-existing atopic dermatitis) two days after initial 10 mg dose. No trends were observed in clinical laboratory data, vital signs, ECGs, or concomitant medications. No subjects tested positive for antibodies specific to LJPC-401. Conclusion: LJPC-401 was well tolerated at single doses between 4 and 20 mg (the highest dose tested), and at doses of 10 mg twice weekly in healthy adults, and resulted in decreases in serum iron levels compared with baseline. Serum ferritin increased over the time course of observations, consistent with an increased distribution of iron into the macrophage compartment, secondary to decreased iron egress into the plasma transferrin compartment. These results warrant further research in longer-term studies. Disclosures Porter: Agios: Honoraria; Novartis: Consultancy; Cerus: Honoraria. Taher:Celgene Corp.: Research Funding; Protagonist Therapeutics: Consultancy; Novartis: Consultancy, Honoraria, Research Funding; La Jolla Pharmaceutical: Research Funding; Ionis Pharmaceuticals: Consultancy. Shen:La Jolla Pharmaceutical Company: Employment, Equity Ownership. Chen:La Jolla Pharmaceutical Company: Employment, Equity Ownership. Chawla:La Jolla Pharmaceutical Company: Employment, Equity Ownership. Tidmarsh:La Jolla Pharmaceutical Company: Employment, Equity Ownership." @default.
• W2922349247 created "2019-03-22" @default.
• W2922349247 creator A5034715126 @default.
• W2922349247 creator A5048872234 @default.
• W2922349247 creator A5049244658 @default.
• W2922349247 creator A5062654616 @default.
• W2922349247 creator A5072237761 @default.
• W2922349247 creator A5082147062 @default.
• W2922349247 creator A5089235509 @default.
• W2922349247 creator A5091028785 @default.
• W2922349247 date "2018-11-29" @default.
• W2922349247 modified "2023-09-26" @default.
• W2922349247 title "Effect of Ljpc-401 (synthetic human hepcidin) on Iron Parameters in Healthy Adults" @default.
• W2922349247 doi "https://doi.org/10.1182/blood-2018-99-110885" @default.
• W2922349247 hasPublicationYear "2018" @default.
• W2922349247 type Work @default.
• W2922349247 sameAs 2922349247 @default.
• W2922349247 citedByCount "4" @default.
• W2922349247 countsByYear W29223492472019 @default.
• W2922349247 countsByYear W29223492472021 @default.
• W2922349247 countsByYear W29223492472022 @default.
• W2922349247 crossrefType "journal-article" @default.
• W2922349247 hasAuthorship W2922349247A5034715126 @default.
• W2922349247 hasAuthorship W2922349247A5048872234 @default.
• W2922349247 hasAuthorship W2922349247A5049244658 @default.
• W2922349247 hasAuthorship W2922349247A5062654616 @default.
• W2922349247 hasAuthorship W2922349247A5072237761 @default.
• W2922349247 hasAuthorship W2922349247A5082147062 @default.
• W2922349247 hasAuthorship W2922349247A5089235509 @default.
• W2922349247 hasAuthorship W2922349247A5091028785 @default.
• W2922349247 hasBestOaLocation W29223492471 @default.
• W2922349247 hasConcept C112705442 @default.
• W2922349247 hasConcept C126322002 @default.
• W2922349247 hasConcept C142724271 @default.
• W2922349247 hasConcept C153852466 @default.
• W2922349247 hasConcept C168563851 @default.
• W2922349247 hasConcept C197934379 @default.
• W2922349247 hasConcept C203092338 @default.
• W2922349247 hasConcept C204243189 @default.
• W2922349247 hasConcept C204787440 @default.
• W2922349247 hasConcept C27081682 @default.
• W2922349247 hasConcept C2776590208 @default.
• W2922349247 hasConcept C2776710925 @default.
• W2922349247 hasConcept C2776768029 @default.
• W2922349247 hasConcept C2777417653 @default.
• W2922349247 hasConcept C2778248108 @default.
• W2922349247 hasConcept C2778319317 @default.
• W2922349247 hasConcept C2778375690 @default.
• W2922349247 hasConcept C2778917026 @default.
• W2922349247 hasConcept C3018783601 @default.
• W2922349247 hasConcept C71924100 @default.
• W2922349247 hasConcept C72563966 @default.
• W2922349247 hasConcept C90924648 @default.
• W2922349247 hasConceptScore W2922349247C112705442 @default.
• W2922349247 hasConceptScore W2922349247C126322002 @default.
• W2922349247 hasConceptScore W2922349247C142724271 @default.
• W2922349247 hasConceptScore W2922349247C153852466 @default.
• W2922349247 hasConceptScore W2922349247C168563851 @default.
• W2922349247 hasConceptScore W2922349247C197934379 @default.
• W2922349247 hasConceptScore W2922349247C203092338 @default.
• W2922349247 hasConceptScore W2922349247C204243189 @default.
• W2922349247 hasConceptScore W2922349247C204787440 @default.
• W2922349247 hasConceptScore W2922349247C27081682 @default.
• W2922349247 hasConceptScore W2922349247C2776590208 @default.
• W2922349247 hasConceptScore W2922349247C2776710925 @default.
• W2922349247 hasConceptScore W2922349247C2776768029 @default.
• W2922349247 hasConceptScore W2922349247C2777417653 @default.
• W2922349247 hasConceptScore W2922349247C2778248108 @default.
• W2922349247 hasConceptScore W2922349247C2778319317 @default.
• W2922349247 hasConceptScore W2922349247C2778375690 @default.
• W2922349247 hasConceptScore W2922349247C2778917026 @default.
• W2922349247 hasConceptScore W2922349247C3018783601 @default.
• W2922349247 hasConceptScore W2922349247C71924100 @default.
• W2922349247 hasConceptScore W2922349247C72563966 @default.
• W2922349247 hasConceptScore W2922349247C90924648 @default.
• W2922349247 hasIssue "Supplement 1" @default.
• W2922349247 hasLocation W29223492471 @default.
• W2922349247 hasOpenAccess W2922349247 @default.
• W2922349247 hasPrimaryLocation W29223492471 @default.
• W2922349247 hasRelatedWork W1510975655 @default.
• W2922349247 hasRelatedWork W1971455039 @default.
• W2922349247 hasRelatedWork W1998361979 @default.
• W2922349247 hasRelatedWork W2041715899 @default.
• W2922349247 hasRelatedWork W2070785335 @default.
• W2922349247 hasRelatedWork W2110177671 @default.
• W2922349247 hasRelatedWork W2144207984 @default.
• W2922349247 hasRelatedWork W2996302374 @default.
• W2922349247 hasRelatedWork W3028115072 @default.
• W2922349247 hasRelatedWork W3134535943 @default.
• W2922349247 hasVolume "132" @default.
• W2922349247 isParatext "false" @default.
• W2922349247 isRetracted "false" @default.
• W2922349247 magId "2922349247" @default.
• W2922349247 workType "article" @default.