title: Safety, tolerability, pharmacokinetics, and pharmacodynamics of compound SFDAC by intranasal administration of multiple escalating dose in healthy male subjects.
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.
authors.affiliation: Sun Pharma Advanced Research Company Ltd., Vadodara, India.
authors.forename: Rajamannar
authors.initials: R
authors.lastname: Thennati
authors.affiliation: Clinical Pharmacology Unit, Sun Pharmaceutical Industries Ltd., Vadodara, India.
authors.forename: Aman
authors.initials: A
authors.lastname: Khanna
authors.affiliation: Clinical Pharmacology Unit, Sun Pharmaceutical Industries Ltd., Vadodara, India.
authors.forename: Mallika
authors.initials: M
authors.lastname: Khanna
authors.affiliation: Clinical Pharmacology Unit, Sun Pharmaceutical Industries Ltd., Vadodara, India.
authors.forename: Tushar
authors.initials: T
authors.lastname: Sonaiya
authors.affiliation: Clinical Pharmacology Unit, Sun Pharmaceutical Industries Ltd., Vadodara, India.
authors.forename: Tejas
authors.initials: T
authors.lastname: Mehta
authors.affiliation: Clinical Pharmacology Unit, Sun Pharmaceutical Industries Ltd., Vadodara, India.
authors.forename: Kalpana
authors.initials: K
authors.lastname: Mehta
authors.affiliation: Pharmacokinetic Department, Sun Pharmaceutical Industries Ltd., Vadodara, India.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Shahi
authors.affiliation: Clinical Pharmacology Unit, Sun Pharmaceutical Industries Ltd., Vadodara, India.
authors.forename: Jigneshkumar
authors.initials: J
authors.lastname: Patel
mesh_terms: D000281:Administration, Intranasal; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000336:Aerosols; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001711:Biotransformation; D018592:Cross-Over Studies; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D006915:Hydroxytestosterones / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate
chemical_list: D000305:Adrenal Cortex Hormones; D000336:Aerosols; D015415:Biomarkers; D006915:Hydroxytestosterones; C000625976:SFDAC compound; D006854:Hydrocortisone
keywords: HPA axis; SFDAC nasal spray; pharmacokinetics; safety; tolerability