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Safety, tolerability, pharmacokinetics, and pharmacodynamics of compound SFDAC by intranasal administration of multiple escalating dose in healthy male subjects
Author(s) -
Thennati Rajamannar,
Khanna Aman,
Khanna Mallika,
Sonaiya Tushar,
Mehta Tejas,
Mehta Kalpana,
Shahi Pradeep,
Patel Jigneshkumar
Publication year - 2014
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.136
Subject(s) - medicine , fluticasone propionate , pharmacokinetics , nasal administration , tolerability , nasal spray , pharmacodynamics , pharmacology , placebo , active metabolite , bioequivalence , corticosteroid , anesthesia , adverse effect , alternative medicine , pathology
Abstract A novel corticosteroid compound (short form of IUPAC name: SFDAC) has been discovered by Sun Pharma Advanced Research Company (SPARC) Ltd. A randomized, observer‐blind, active‐controlled, parallel‐groups, intranasal multiple escalating dose study was conducted in healthy male subjects to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of compound SFDAC formulated as an aqueous suspension for intranasal administration. Intranasal sprays of SFDAC, active control fluticasone propionate (FP) and placebo were administered once in a day for 14 days as per randomization. Various clinical evaluations including 24‐hour serum cortisol and urinary free cortisol (UFC) profiles were carried out. Blood samples were collected at pre‐defined time‐points and analyzed using a validated chromatographic method for estimation of SFDAC and its metabolite. The results of the study indicate that multiple dose of SFDAC intranasal spray upto 3,200 µg is safe and tolerated. Clinically significant suppression of hypothalamic pituitary adrenal (HPA) axis was not observed. The plasma concentration of SFDAC was found to be below the lower limit of quantification (LLQ) at most time‐points for all subjects. SFDAC M1 metabolite was detected only at picogram level in plasma. The safety and pharmacokinetic characteristics of SFDAC observed in this study support further clinical development of the SFDAC nasal spray.