title: Safety, bioavailability, and pharmacokinetics of VGX-1027-A novel oral anti-inflammatory drug in healthy human subjects.
abstract: VGX-1027, a novel oral immune modulator, is under development for the treatment of rheumatoid arthritis. The safety, tolerability, and pharmacokinetics of single (1-800 mg) and multiple (40-400 mg) oral doses were evaluated in 2 clinical studies. The doses were well tolerated up to 800 mg in a single dose and 200 mg twice daily in multiple doses. Adverse events were mild to moderate in severity with no identifiable dose-related pattern. There were no clinically significant physical or laboratory findings. The pharmacokinetic data indicated that increases in Cmax and AUC0-inf were dose-proportional, and AUC0- τ was approximately dose-proportional. For the single-dose study, median Tmax ranged from 0.5 to 2 hours and mean t1/2 ranged from 4.9 to 8.7 hours. For the multiple-dose study, median Tmax ranged from 0.5 to 2.0 hours and mean t1/2 ranged from 7.05 to 10.05 hours. No accumulation of the drug was observed after day 1, indicating that steady-state concentrations were attained with single and multiple dosing for 5 days. Approximately 90% of the administered dose was excreted in urine as unchanged drug.
authors.affiliation: Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA, USA.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Lee
authors.affiliation: University of New Haven, Tagliatela School of Engineering, West Haven, CT, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Menacherry
authors.affiliation: Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA, USA.
authors.forename: Malissa C
authors.initials: MC
authors.lastname: Diehl
authors.affiliation: Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA, USA.
authors.forename: Mary D
authors.initials: MD
authors.lastname: Giffear
authors.affiliation: C. Jo White Consulting, Lower Gwynedd, PA, USA.
authors.forename: C Jo
authors.initials: CJ
authors.lastname: White
authors.affiliation: Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA, USA.
authors.forename: Rob
authors.initials: R
authors.lastname: Juba
authors.affiliation: Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA, USA.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Bagarazzi
authors.affiliation: University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Karuppiah
authors.initials: K
authors.lastname: Muthumani
authors.affiliation: University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Boyer
authors.affiliation: NorthEast Bioanalytical Laboratories LLC, Hamden, CT, USA.
authors.forename: Vipin
authors.initials: V
authors.lastname: Agarwal
authors.affiliation: Department of Biomedical and Biotechnological Sciences, the University of Catania, Catania, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.affiliation: Optimal Research LLC, Rockville, MD, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Bart
authors.affiliation: Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA, USA.
authors.forename: J Joseph
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
authors.affiliation: Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA, USA.
authors.forename: Niranjan Y
authors.initials: NY
authors.lastname: Sardesai
mesh_terms: D000085:Acetates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000284:Administration, Oral; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D010080:Oxazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: C518641:3-phenyl-4,5-dihydro-5-isoxazole acetic acid; D000085:Acetates; D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors; D010080:Oxazoles
keywords: anti-inflammatory; bioavailability; pharmacokinetics; rheumatoid arthritis; safety