A phase II, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of VT-1161 oral tablets in the treatment of patients with distal and lateral subungual onychomycosis of the toenail
| Autor: | B. Elewski, S. Brand, T. Degenhardt, S. Curelop, R. Pollak, R. Schotzinger, A. Tavakkol, Javier Alonso‐Llamazares, Scott J. Ashton, Neal Bhatia, Michael Billings, Andrew Blauvelt, Norman Bystol, Brandt Dodson, Michael H. Gold, Kimberly Grande, Michael Jarratt, Terry S. Jones, Maria A. Kasper, Steven E. Kempers, Brock McConnehey, Michael Noss, David Pariser, Lawrence Parish, Phoebe Rich, Joseph Ahmad Samady, Joel Schlessinger, Doug Schumacher, Kenneth Stein, Cynthia Strout, Eduardo Tschen, John H. Tu, Max Weisfeld |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
medicine.medical_specialty Antifungal Agents Adolescent Pyridines Population Tetrazoles Dermatology Placebo Gastroenterology law.invention 030207 dermatology & venereal diseases 03 medical and health sciences Young Adult 0302 clinical medicine Randomized controlled trial Double-Blind Method law Internal medicine Onychomycosis Medicine Humans Dosing education Adverse effect Aged Foot Dermatoses education.field_of_study business.industry Arthrodermataceae Middle Aged Dose-ranging study Clinical trial Treatment Outcome Nails Liver function business Tablets |
| Zdroj: | The British journal of dermatologyReferences. 184(2) |
| ISSN: | 1365-2133 |
| Popis: | BACKGROUND Onychomycosis is a fungal disease that affects the fingernails and toenails and is predominantly caused by dermatophytes. VT-1161 is a novel inhibitor of fungal CYP51 through the inhibition of lanosterol demethylase, and has demonstrated potent activity against Trichophyton rubrum and Trichophyton mentagrophytes. OBJECTIVES To evaluate the safety and efficacy of four dosing regimens of orally administered VT-1161 compared with placebo in patients with moderate-to-severe distal and lateral subungual onychomycosis of the toenail. METHODS This was a phase II, randomized, double-blind, placebo-controlled, multicentre study (ClinicalTrials.gov identifier NCT02267356). Patients aged 18-70 years (n = 259) who had 25-75% mycotic involvement were randomized to five treatment groups. They received 300 mg VT-1161 as a 2-week daily dose, followed by a once-weekly dose for either 10 or 22 weeks, or 600 mg VT-1161 as a 2-week daily dose, followed by a once-weekly dose for either 10 or 22 weeks. All treatments were followed by a nontreatment period of 36 weeks. A matching placebo arm was included. RESULTS In the intent-to-treat population, at week 48 the complete cure rates were 0% in the placebo group and ranged from 32% to 42% in the VT-1161 treatment groups (P < 0·001 vs. placebo). VT-1161 was well tolerated, with no evidence of an adverse effect on liver function or QT intervals. CONCLUSIONS VT-1161 treatment led to high nail clearance rates and a favourable safety profile. VT-1161 exhibits characteristics that appear promising for the treatment of this chronic and difficult-to-treat condition and warrants further evaluation in larger studies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text