June 2024 · Volume 13 · Issue 6 Page 1425 International Journal of Reproduction, Contraception, Obstetrics and Gynecology Sasikala T et al. Int J Reprod Contracept Obstet Gynecol. 2024 Jun;13(6):1425-1431 www.ijrcog.org pISSN 2320-1770 | eISSN 2320-1789 Original Research Article A multicentre phase III study comparing efficacy and safety of novel extended-release versus conventional formulation of dydrogesterone in Indian patients with endometriosis T. Sasikala 1 , Shikha Kushwaha 2 , Mukta Agarwal 3 , Vandana Jain 4 , Deepti Bawa 5 , Suchitra Narayan 6 , Pavankumar Daultani 7 , Ashok Jaiswal 8 , Monika Chinda 8 *, Anit Singh 9 DOI: https://dx.doi.org/10.18203/2320-1770.ijrcog20241298 1 Department of Gynaecology, Government Medical College and Government General Hospital (old RIMSSGH), Srikakulam, Andhra Pradesh, India 2 Department of Obstetrics and Gynecology, Prakhar Hospital Pvt Ltd, Kanpur, Uttar Pradesh, India 3 Department of Obstetrics and Gynecology, All India Institute of Medical Science, Phulwari, Patna, Bihar, India 4 Department of Gynecology, Unity Hospital, Ahmedabad, Gujarat, India 5 Department of Gynecology, Citizen Hospital, Bangalore, Karnataka, India 6 Jawahar Lal Nehru Medical College, Ajmer, Rajasthan, India 7 New Product Development, Zydus Healthcare Limited, Ahmedabad, Gujarat, India 8 Medical Affairs, Zydus Healthcare Limited, Mumbai, Maharashtra, India 9 Clinical Research Network, Noida, Uttar Pradesh, India Received: 21 April 2024 Revised: 07 May 2024 Accepted: 08 May 2024 *Correspondence: Dr. Monika Chinda, E-mail: monika.chinda@zyduslife.com Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 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. Keywords: Dydrogesterone, Endometriosis, Extended-release, Pelvic pain, Progesterone