Synthesis of [H ‐3] and [C‐14] Labeled Elagolix†
Gonadotropin ‐releasing hormone (GnRH) receptor antagonists are an important class of compounds designed to block the pituitary gland from synthesizing follicle stimulating hormone and luteinizing hormone for the treatment of sex hormone dependent disorders. Elagolix (Orilissa™, ABT‐620) is currently appro ved for the treatment of pain associated with endometriosis1 and ORIAHNN ™ (elagolix, estradiol and norethindrone acetate) is approved for management of heavy menstrual bleeding due to uterine fibroids in pre‐menopausal women.2 In order to support the development of elagolix, we prepared [3H]elagolix for precli...
Source: Journal of Labelled Compounds and Radiopharmaceuticals - March 9, 2021 Category: Biochemistry Authors: Eric D. Soli,
Bruce W. Surber,
Aimee D. Reed Tags: RESEARCH ARTICLE Source Type: research
Elagolix in the treatment of heavy menstrual bleeding associated with uterine fibroids in premenopausal women
Expert Rev Clin Pharmacol. 2021 Mar 8. doi: 10.1080/17512433.2021.1900726. Online ahead of print.ABSTRACTINTRODUCTION: Uterine fibroids (UFs) are the most common benign tumor arising from myometrium of reproductive age women, with significant financial burden estimated in hundreds of billions of dollars. Unfortunately, there are limitations in available long-term treatment options. Thus, there is a large unmet need in the UF space for noninvasive therapeutics.AREAS COVERED: Authors reviewed the literature available for elagolix; an orally bioavailable, second-generation, non-peptide gonadotropin-releasing hormone (GnRH) an...
Source: Expert Review of Clinical Pharmacology - March 8, 2021 Category: Drugs & Pharmacology Authors: Mohamed Ali Sara A R Ayman Al Hendy Source Type: research
Synthesis of [H ‐3] and [C‐14] Labeled Elagolix†
Gonadotropin ‐releasing hormone (GnRH) receptor antagonists are an important class of compounds designed to block the pituitary gland from synthesizing follicle stimulating hormone and luteinizing hormone for the treatment of sex hormone dependent disorders. Elagolix (Orilissa™, ABT‐620) is currently appro ved for the treatment of pain associated with endometriosis1 and ORIAHNN ™ (elagolix, estradiol and norethindrone acetate) is approved for management of heavy menstrual bleeding due to uterine fibroids in pre‐menopausal women.2 In order to support the development of elagolix, we prepared [3H]elagolix for precli...
Source: Journal of Labelled Compounds and Radiopharmaceuticals - March 6, 2021 Category: Biochemistry Authors: Eric D. Soli,
Bruce W. Surber,
Aimee D. Reed Tags: RESEARCH ARTICLE Source Type: research
Effect of Elagolix Exposure on Clinical Efficacy End Points in Phase III Trials in Women With Endometriosis ‐Associated Pain: An Application of Markov Model
The objective of this work was to characterize the relationships between elagolix exposures and clinical efficacy response rates for dysmenorrhea (DYS) and nonmenstrual pelvic pain (NMPP) in premenopausal women enrolled in the pivotal phase III studies with moderate‐to‐severe pain associated with endometriosis. Relationships between elagolix average concentrations (Cavg) and efficacy responses (DYS and NMPP) were characterized using a nonlinear mixed ‐effects discrete‐time first order Markov modeling approach. Only age was statistically significant for NMPP but not considered clinically relevant. This work indicate...
Source: CPT: Pharmacometrics and Systems Pharmacology - August 18, 2020 Category: Drugs & Pharmacology Authors: Insa Winzenborg,
Akshanth R. Polepally,
Ahmed Nader,
Nael M. Mostafa,
Peter Noertersheuser,
Juki Ng Tags: Article Source Type: research
Drug –Drug Interaction Studies of Elagolix with Oral and Transdermal Low-Dose Hormonal Add-Back Therapy
ConclusionsAlthough changes in E2/E1 exposures were observed when oral E2/NETA was co-administered with elagolix, these changes are not considered clinically relevant; and no dose adjustments are recommended when elagolix is co-administered with oral or transdermal low-dose add-back therapy. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - July 20, 2020 Category: Drugs & Pharmacology Source Type: research
Drugs for Menopausal Symptoms
Date: August 10, 2020
Issue #:
1604Summary:
The primary symptoms of menopause are genitourinary
(genitourinary syndrome of menopause; GSM) and
vasomotor (VMS). Vulvovaginal atrophy can cause
vaginal burning, irritation and dryness, dyspareunia, and
dysuria, and increase the risk of urinary tract infections.
Vasomotor symptoms ( " hot flashes " ) cause daytime
discomfort and night sweats that may disrupt sleep.
Hormone therapy is the most effective treatment for both
genitourinary and vasomotor symptoms. (Source: The Medical Letter)
Source: The Medical Letter - July 2, 2020 Category: Drugs & Pharmacology Authors: admin Tags: Activella acupuncture Alora Angeliq Antidepressants bazedoxifene Bijuva Bioidentical Hormones Brisdelle Climara Combi-Patch Ditropan Divigel Drospirenone Duavee Duavive Dyspareunia Effexor Elestrin Escitalopram Estr Source Type: research
Elagolix Treatment for Up to 12 Months in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas.
CONCLUSION: Up to 12 months of elagolix with add-back therapy provided sustained reduction in menstrual blood loss in women with uterine leiomyomas, with the addition of add-back therapy attenuating the hypoestrogenic effects of elagolix alone. No new or unexpected safety concerns were associated with an additional 6 months of elagolix with addback therapy.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02925494.
FUNDING SOURCE: AbbVie Inc funded this study.
PMID: 32459423 [PubMed - in process] (Source: Obstetrics and Gynecology)
Source: Obstetrics and Gynecology - May 29, 2020 Category: OBGYN Authors: Simon JA, Al-Hendy A, Archer DF, Barnhart KT, Bradley LD, Carr BR, Dayspring T, Feinberg EC, Gillispie V, Hurtado S, Kim J, Liu R, Owens CD, Muneyyirci-Delale O, Wang A, Watts NB, Schlaff WD Tags: Obstet Gynecol Source Type: research
Elagolix suppresses ovulation in a dose-dependent manner: Results from a 3-month, randomized study in ovulatory women.
CONCLUSION: Women being treated with elagolix may ovulate and should use effective methods of contraception. The rate of ovulation was lowest with elagolix 300 mg BID plus E2/NETA 1/0.5 mg QD.
PMID: 31650182 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Endocrinology and Metabolism)
Source: The Journal of Clinical Endocrinology and Metabolism - October 24, 2019 Category: Endocrinology Authors: Archer DF, Ng J, Chwalisz K, Chiu YL, Feinberg EC, Miller CE, Feldman RA, Klein CE Tags: J Clin Endocrinol Metab Source Type: research
Treatment of symptoms of uterine fibroids with relugolix combination therapy: efficacy and safety results from the phase 3 liberty 1 clinical trial
To evaluate the efficacy and safety of 24 weeks of treatment with the oral GnRH receptor antagonist, relugolix, in combination with estradiol (E2) and norethindrone acetate (NETA) compared with placebo in women with uterine fibroid (UF)-associated heavy menstrual bleeding (HMB). (Source: Fertility and Sterility)
Source: Fertility and Sterility - August 31, 2019 Category: Reproduction Medicine Authors: Ayman Al-Hendy, Andrea S. Lukes, Alfred Poindexter, Roberta Venturella, Claudio Villarroel, Yulan Li, Laura F. McKain, Elizabeth A. Stewart Tags: Late-Breaking 1 Source Type: research
Estradiol/Progesterone (Bijuva) for Menopausal Vasomotor Symptoms
Date: July 1, 2019
Issue #:
1575Summary:
The FDA has approvedBijuva (TherapeuticsMD), a
fixed-dose combination of estradiol and progesterone,
for oral treatment of moderate to severe vasomotor
symptoms (hot flashes) due to menopause in women
with an intact uterus. The manufacturer is marketingBijuva as " the first and only FDA-approved combination
of bio-identical estradiol and bio-identical progesterone
in a single daily oral capsule " . (Source: The Medical Letter)
Source: The Medical Letter - May 29, 2019 Category: Drugs & Pharmacology Authors: admin Tags: Activella Alora Angeliq bazedoxifene Bijuva Bioidentical Hormones Climara Combi-Patch Divigel Drospirenone Duavee Elestrin Estrogens Evamist femhrt Femring Hot flashes Medroxyprogesterone Menest Menopause Premarin Source Type: research
Elagolix Alone or With Add-Back Therapy in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas: A Randomized Controlled Trial.
CONCLUSION: Elagolix with and without add-back significantly reduced menstrual blood loss in women with uterine leiomyomas. Add-back therapy reduced hypoestrogenic effects on bone mineral density.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01817530; EU Clinical Trial Register, 2013-000082-37.
PMID: 30303923 [PubMed - as supplied by publisher] (Source: Obstetrics and Gynecology)
Source: Obstetrics and Gynecology - October 5, 2018 Category: OBGYN Authors: Carr BR, Stewart EA, Archer DF, Al-Hendy A, Bradley L, Watts NB, Diamond MP, Gao J, Owens CD, Chwalisz K, Duan WR, Soliman AM, Dufek MB, Simon JA Tags: Obstet Gynecol Source Type: research
GnRH Receptor Antagonist Mono- And Combination Therapy With E2/NETA Add-Back - Pharmacodynamics And Safety Of OBE2109.
Conclusions: OBE2109 promptly lowers E2 levels, add-back may be required to prevent adverse bone impact in subjects treated at 200mg and in some subjects at 100mg. Our results provide a basis for OBE2109 regimen selection to treat sex-hormone-dependent diseases.
PMID: 29216361 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Endocrinology and Metabolism)
Source: The Journal of Clinical Endocrinology and Metabolism - December 4, 2017 Category: Endocrinology Authors: Pohl O, Marchand L, Fawkes N, Gotteland JP, Loumaye E Tags: J Clin Endocrinol Metab Source Type: research
17 β-Estradiol induces proliferation of endometrial NK cells (CD56+) in postmenopausal women.
CONCLUSION: 17β-Estradiol induced the proliferation of endometrial uterine natural killer cells (CD56+) in postmenopausal women.
PMID: 28933961 [PubMed - as supplied by publisher] (Source: Climacteric)
Source: Climacteric - September 21, 2017 Category: Geriatrics Authors: Sho T, Hachisuga T, Koi C, Kurita T, Kagami S, Kawagoe T, Matsuura Y, Yoshimura K, Hisaoka M Tags: Climacteric Source Type: research
