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Simone Ferrero, Fabio Barra, Umberto Leone Roberti Maggiore
Endometriosis is a chronic benign disease that affects women of reproductive age. Medical therapy is often the first line of management for women with endometriosis in order to ameliorate symptoms or to prevent post-surgical disease recurrence. Currently, there are several medical options for the management of patients with endometriosis. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of chronic inflammatory conditions, being efficacious in relieving primary dysmenorrhea. Combined oral contraceptives (COCs) and progestins, available for multiple routes of administration, are effective first-line hormonal options...
July 2018: Drugs
Hugh S Taylor
No abstract text is available yet for this article.
July 2018: Journal of Obstetrics and Gynaecology Canada: JOGC, Journal D'obstétrique et Gynécologie du Canada: JOGC
Eric Surrey, Hugh S Taylor, Linda Giudice, Bruce A Lessey, Mauricio S Abrao, David F Archer, Michael P Diamond, Neil P Johnson, Nelson B Watts, J Chris Gallagher, James A Simon, Bruce R Carr, W Paul Dmowski, Nicholas Leyland, Sukhbir S Singh, Tomasz Rechberger, Sanjay K Agarwal, W Rachel Duan, Brittany Schwefel, James W Thomas, Paul M Peloso, Juki Ng, Ahmed M Soliman, Kristof Chwalisz
OBJECTIVE: To evaluate the efficacy and safety of elagolix, an oral, nonpeptide gonadotropin-releasing hormone antagonist, over 12 months in women with endometriosis-associated pain. METHODS: Elaris Endometriosis (EM)-III and -IV were extension studies that evaluated an additional 6 months of treatment after two 6-month, double-blind, placebo-controlled phase 3 trials (12 continuous treatment months) with two elagolix doses (150 mg once daily and 200 mg twice daily)...
July 2018: Obstetrics and Gynecology
G Legendre, L Delbos, E Hudon, N Chabbert-Buffet, S Geoffron, M Sauvan, H Fernandez, P-E Bouet, P Descamps
OBJECTIVE: The objective of this work is to evaluate the place of new treatments in the management of endometriosis outside the context of infertility. METHODS: A review of the literature was conducted by consulting Medline data until July 2017. RESULTS: Dienogest is effective compared to placebo in short term (NP2) and long term (NP4) for the treatment of painful endometriosis. In comparison with GnRH agonists, dienogest is also effective in terms of decreased pain and improved quality of life in non-operated patients (NP2) as well as for recurrence of lesions and symptomatology postoperatively (NP2)...
March 2018: Gynecologie, Obstetrique, Fertilite & Senologie
Insa Winzenborg, Ahmed Nader, Akshanth R Polepally, Mohan Liu, Jacob Degner, Cheri E Klein, Nael M Mostafa, Peter Noertersheuser, Juki Ng
INTRODUCTION: Elagolix is a novel, orally active, non-peptide, competitive gonadotropin-releasing hormone (GnRH) receptor antagonist in development for the management of endometriosis with associated pain and heavy menstrual bleeding due to uterine fibroids. The pharmacokinetics of elagolix have been well-characterized in phase I studies; however, elagolix population pharmacokinetics have not been previously reported. Therefore, a robust model was developed to describe elagolix population pharmacokinetics and to evaluate factors affecting elagolix pharmacokinetic parameters...
February 23, 2018: Clinical Pharmacokinetics
Seon-Mi Kim, Minhee Lee, So Young Lee, Soo-Min Lee, Eun Jeong Kim, Jae Sun Kim, Jihyae Ann, Jiyoun Lee, Jeewoo Lee
We investigated a series of uracil analogues by introducing various substituents on the phenyl ring of the N-3 aminoethyl side chain and evaluated their antagonistic activity against human gonadotropin-releasing hormone (GnRH) receptors. Analogues with substituents at the ortho or meta position demonstrated potent in vitro antagonistic activity. Specifically, the introduction of a 2-OMe group enhanced nuclear factor of activated T-cells (NFAT) inhibition up to 6-fold compared to the unsubstituted analogue...
February 10, 2018: European Journal of Medicinal Chemistry
Erica C Dun, Hugh S Taylor
No abstract text is available yet for this article.
November 21, 2017: Oncotarget
Alexandra Perricos, René Wenzl
Much research has gone into developing medications that can be used to alleviate endometriosis-associated symptoms. In addition to already established medications, a new GnRH antagonist, elagolix, is in development. The novelty of this drug compared to other GnRH antagonists, is its nonpeptide structure, allowing it to be administered orally. Areas covered: We analyzed several Phase I, II and III clinical trials that have evaluated the safety and efficacy of this new medication. Expert opinion: Since many medications have been put on the market and have gained popularity for the treatment of endometriosis-associated symptoms, the demonstration of equality or superiority of effect, tolerability, as well as patient compliance should be assessed when introducing a new drug...
September 2017: Expert Opinion on Pharmacotherapy
Conor A Bradley
No abstract text is available yet for this article.
August 2017: Nature Reviews. Endocrinology
David F Archer, Elizabeth A Stewart, Rita I Jain, Robert A Feldman, Andrea S Lukes, Janine D North, Ahmed M Soliman, Jingjing Gao, Juki W Ng, Kristof Chwalisz
OBJECTIVE: To evaluate the safety and efficacy of elagolix vs. placebo and elagolix with low-dose E2 /progestogen add-back therapy. DESIGN: Proof-of-concept, dose-ranging, multiple-cohort study. SETTING: Clinics. PATIENT(S): Premenopausal women with fibroids and heavy menstrual bleeding (menstrual blood loss [MBL] >80 mL per cycle). INTERVENTION(S): Three months' treatment with elagolix alone: 100 mg twice daily (BID), 200 mg BID, 300 mg BID, 400 mg once daily (QD), or 600 mg QD (all but the 600 mg QD arm were placebo controlled); or elagolix plus add-back therapy: 200 mg BID plus continuous low-dose E2 0...
July 2017: Fertility and Sterility
Hugh S Taylor, Linda C Giudice, Bruce A Lessey, Mauricio S Abrao, Jan Kotarski, David F Archer, Michael P Diamond, Eric Surrey, Neil P Johnson, Nelson B Watts, J Chris Gallagher, James A Simon, Bruce R Carr, W Paul Dmowski, Nicholas Leyland, Jean P Rowan, W Rachel Duan, Juki Ng, Brittany Schwefel, James W Thomas, Rita I Jain, Kristof Chwalisz
BACKGROUND: Endometriosis is a chronic, estrogen-dependent condition that causes dysmenorrhea and pelvic pain. Elagolix, an oral, nonpeptide, gonadotropin-releasing hormone (GnRH) antagonist, produced partial to nearly full estrogen suppression in previous studies. METHODS: We performed two similar, double-blind, randomized, 6-month phase 3 trials (Elaris Endometriosis I and II [EM-I and EM-II]) to evaluate the effects of two doses of elagolix - 150 mg once daily (lower-dose group) and 200 mg twice daily (higher-dose group) - as compared with placebo in women with surgically diagnosed endometriosis and moderate or severe endometriosis-associated pain...
July 6, 2017: New England Journal of Medicine
Juki Ng, Kristof Chwalisz, David C Carter, Cheri E Klein
Context: Elagolix is a nonpeptide, oral gonadotropin-releasing hormone (GnRH) antagonist being developed for sex-hormone-dependent diseases in women. Objective: We evaluated the pharmacokinetics and pharmacodynamics of elagolix. Design, Setting, and Participants: This study was a randomized, double-blind, placebo-controlled, multiple-ascending dose study in 45 healthy premenopausal women at a research unit. Interventions: Elagolix [150 mg once daily or 100, 200, 300, or 400 mg twice daily (BID)] or placebo was administered for 21 days...
May 1, 2017: Journal of Clinical Endocrinology and Metabolism
Pontis Alessandro, Nappi Luigi, Sorrentino Felice, Paoletti Anna Maria, Melis Gian Benedetto, Angioni Stefano
PURPOSE: Limitated studies have reported the efficacy of GnRH antagonist on endometriosis symptoms. The aim of our study was to review all available trials to investigate the medical treatment of endometriosis with only GnRH antagonists, with special attention to pharmacodynamic activity, safety, and efficacy. METHODS: Pub Med and Sciencedirect database were searched using terms of "endometriosis treatment", "GnRH antagonist", and "Elagolix". The search was limited to clinical studies published in English...
April 2017: Archives of Gynecology and Obstetrics
Seon-Mi Kim, Minhee Lee, So Young Lee, Euisun Park, Soo-Min Lee, Eun Jeong Kim, Min Young Han, Taekyung Yoo, Jihyae Ann, Suyoung Yoon, Jiyoun Lee, Jeewoo Lee
We developed a compound library for orally available gonadotropin-releasing hormone (GnRH) receptor antagonists that were based on a uracil scaffold. On the basis of in vitro activity and CYP inhibition profile, we selected 18a (SKI2496) for further in vivo studies. Compound 18a exhibited more selective antagonistic activity toward the human GnRH receptors over the GnRHRs in monkeys and rats, and this compound also showed inhibitory effects on GnRH-mediated signaling pathways. Pharmacokinetic and pharmacodynamic evaluations of 18a revealed improved bioavailability and superior gonadotropic suppression activity compared with Elagolix, the most clinically advanced compound...
October 13, 2016: Journal of Medicinal Chemistry
Gian Benedetto Melis, Manuela Neri, Valentina Corda, Maria Elena Malune, Bruno Piras, Silvia Pirarba, Stefano Guerriero, Marisa Orrù, Maurizio Nicola D'Alterio, Stefano Angioni, Anna Maria Paoletti
INTRODUCTION: Suppression of sex-steroid secretion is required in a variety of gynecological conditions. This can be achieved using gonadotropin releasing hormone (GnRH) agonists that bind pituitary gonadotropin receptors and antagonize the link-receptor of endogenous GnRH, inhibiting the mechanism of GnRH pulsatility. On the other hand, GnRH antagonists immediately reduce gonadal steroid levels, avoiding the initial stimulatory phase of the agonists. Potential benefits of GnRH antagonists over GnRH agonists include a rapid onset and reversibility of action...
May 2016: Expert Opinion on Drug Metabolism & Toxicology
Ahmed M Soliman, Hongbo Yang, Ella Xiaoyan Du, Caroline Kelley, Craig Winkel
STUDY QUESTION: What is the economic burden of endometriosis? SUMMARY ANSWER: The identified studies indicate that there is a significant economic burden associated with endometriosis, as observed by both direct and indirect costs. WHAT IS KNOWN ALREADY: Two previous systematic literature reviews suggested that there were considerable direct costs associated with endometriosis and there was a general lack of measurement of indirect costs. STUDY DESIGN, SIZE, DURATION: We performed a systematic literature review...
April 2016: Human Reproduction
Emanuela Tafi, Umberto Leone Roberti Maggiore, Franco Alessandri, Stefano Bogliolo, Barbara Gardella, Valerio Gaetano Vellone, Federica Grillo, Luca Mastracci, Simone Ferrero
INTRODUCTION: Endometriosis is an estrogen-dependent chronic disease requiring long-term therapy. Therefore, the choice of medical treatment should be based on efficacy, preference of patients, incidence and severity of adverse effects and cost. AREAS COVERED: This review briefly summarizes the currently available medical treatment for endometriosis. The treatments most recently proposed for endometriosis will be described in detail, including gonadotropin-releasing hormone (GnRH) antagonists, aromatase inhibitors (AIs) and the flexible extended combined oral contraceptive...
2015: Expert Opinion on Pharmacotherapy
Seon Mi Kim, Taekyung Yoo, So Young Lee, Eun Jeong Kim, Soo Min Lee, Min Hee Lee, Min Young Han, Seung-Hyun Jung, Jung-Hye Choi, Keun Ho Ryu, Hun-Taek Kim
AIMS: Suppression of the hypothalamic-pituitary-gonadal axis has been widely utilized for the management of gonadal-hormone-dependent diseases such as endometriosis. Efforts to develop orally available gonadotropin-releasing hormone (GnRH) antagonists for the treatment of gonadal-hormone-dependent diseases led to the discovery of SKI2670, a novel non-peptide GnRH antagonist. The present study was undertaken to pharmacologically characterize SKI2670 in vitro and in vivo. MAIN METHODS: We measured binding affinity and antagonistic activity of SKI2670 for the GnRH receptors...
October 15, 2015: Life Sciences
Mohammad Ezzati, Bruce R Carr
Suppression of estrogen production and reduction of menstrual blood flow are the mainstays of medical treatment of endometriosis-related pain and have been traditionally achieved by methods such as combined hormonal contraception, progestins and GnRH analogs, all with comparable efficacies, though different side-effect profiles. Elagolix is the frontrunner among an emerging class of GnRH antagonists, which unlike their peptide predecessors has a nonpeptide structure resulting in its oral bioavailability. Phase I and II clinical trials have demonstrated safety of elagolix and its efficacy in partial and reversible suppression of ovarian estrogen production resulting in improvements in endometriosis-related pain...
January 2015: Women's Health
Bruce Carr, W Paul Dmowski, Chris O'Brien, Ping Jiang, Joshua Burke, Roland Jimenez, Elizabeth Garner, Kristof Chwalisz
This randomized double-blind study, with 24-week treatment and 24-week posttreatment periods, evaluated the effects of elagolix (150 mg every day, 75 mg twice a day) versus subcutaneous depot medroxyprogesterone acetate (DMPA-SC) on bone mineral density (BMD), in women with endometriosis-associated pain (n = 252). All treatments induced minimal mean changes from baseline in BMD at week 24 (elagolix 150 mg: -0.11%/-0.47%, elagolix 75 mg: -1.29%/-1.2%, and DMPA-SC: 0.99%/-1.29% in the spine and total hip, respectively), with similar or less changes at week 48 (posttreatment)...
November 2014: Reproductive Sciences
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