A multicentre phase III study comparing efficacy and safety of novel extended-release versus conventional formulation of dydrogesterone in Indian patients with endometriosis

Abstract

Background: The aim of the study was to compare the efficacy and safety of novel once-daily extended-release (ER) dydrogesterone 20 mg versus conventional twice-daily dydrogesterone 10 mg in Indian patients with endometriosis. Methods: A phase III prospective, randomized, double-blind, single-dummy, two-arm, active-controlled, parallel, multicenter study was performed in six gynecology centers across India. The patients of 18 to 45 years of age with a confirmed diagnosis of endometriosis on ultrasonography (USG) and having endometriosis-associated pelvic pain score (EAPP) of at least 30 mm on a 100 mm visual analog scale (VAS) were randomly assigned to a 1:1 ratio to either once-daily dydrogesterone ER 20 mg or twice-daily dydrogesterone 10 mg arms for a treatment period of 90 days. The primary outcome was a change from baseline in EAPP score at the end of the treatment. Results: A total of 228 patients with a mean age of 31.8±6.9 years were enrolled in the study. At day 90, both the treatment arms showed a significant reduction (p<0.05) in EAPP score from baseline (i.e. -34.2±15.3 mm and -33.1±14.8 mm in once daily dydrogesterone ER and twice daily dydrogesterone 10 mg, respectively), with no significant difference between the two arms (p=0.53). With both formulations, patients experienced a significant reduction in the size of endometrioma, serum vascular endothelial growth factors (VEGF) levels, use of rescue analgesics, and significant improvement in the health-related quality-of-life parameters. A favorable safety profile of dydrogesterone was confirmed, and no significant safety concerns were reported during the study. Conclusions: Once daily dydrogesterone ER 20 mg and twice daily dydrogesterone 10 mg demonstrated a significant and similar reduction in EAPP and all other secondary parameters along with marked improvements in parameters related to quality of life.