Robert A Feldman1, Yi-Lin Chiu2, Cheri E Klein3, Juki Ng4. 1. Obstetrics and Gynecology, Baptist Health Medical Group, 6141 Sunset Drive, Suite 401, Miami, FL, 33143, USA. 2. Data and Statistics, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA. 3. Clinical Pharmacology and Pharmacometrics, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA. 4. Pharmaceutical Development, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA. juki.ng@abbvie.com.
Abstract
BACKGROUND: Two pharmacokinetic/pharmacodynamic studies were conducted to evaluate the potential drug-drug interaction between elagolix, an oral gonadotropin-releasing hormone receptor antagonist, and an oral contraceptive (ethinylestradiol [EE] 0.035 mg and norgestimate 0.18/0.215/0.25 mg) or progestin-only contraceptive (norethindrone 0.35 mg) in healthy premenopausal women. METHODS: These phase I studies used a two-period, sequential design, where period 1 included treatment with oral contraceptives, followed by period 2 with contraceptives coadministered with elagolix 150 mg once daily. RESULTS: In study 1, pharmacokinetic exposures for EE in period 2 increased by 30% and the norgestimate metabolites decreased by approximately 15% when coadministered with elagolix. Mean hormone exposure appeared lower for follicle-stimulating hormone (FSH; 31%), luteinizing hormone (LH; 38%), and estradiol (E2; 16%). The percentage of women with consecutive progesterone (P) concentrations above 5 nmol/L was similar in both periods. Norethindrone pharmacokinetic exposures were comparable in both periods. The hormone exposure for LH and FSH was similar, and mean E2 exposure was 32% lower in period 2. The percentage of subjects with consecutive ovulatory P concentrations was also similar in both periods (study 2). Safety and tolerability profiles were unremarkable in both studies. CONCLUSIONS: Coadministration of elagolix 150 mg once daily with oral contraceptives containing EE and norgestimate, or norethindrone, resulted in small pharmacokinetic changes in the oral contraceptive components. Similar or lower FSH, LH, and E2 exposures were observed during coadministration, with ovulatory P concentrations also comparable in both periods. The pharmacodynamic profiles of the oral contraceptives were maintained when coadministered with elagolix.
BACKGROUND: Two pharmacokinetic/pharmacodynamic studies were conducted to evaluate the potential drug-drug interaction between elagolix, an oral gonadotropin-releasing hormone receptor antagonist, and an oral contraceptive (ethinylestradiol [EE] 0.035 mg and norgestimate 0.18/0.215/0.25 mg) or progestin-only contraceptive (norethindrone 0.35 mg) in healthy premenopausal women. METHODS: These phase I studies used a two-period, sequential design, where period 1 included treatment with oral contraceptives, followed by period 2 with contraceptives coadministered with elagolix 150 mg once daily. RESULTS: In study 1, pharmacokinetic exposures for EE in period 2 increased by 30% and the norgestimate metabolites decreased by approximately 15% when coadministered with elagolix. Mean hormone exposure appeared lower for follicle-stimulating hormone (FSH; 31%), luteinizing hormone (LH; 38%), and estradiol (E2; 16%). The percentage of women with consecutive progesterone (P) concentrations above 5 nmol/L was similar in both periods. Norethindrone pharmacokinetic exposures were comparable in both periods. The hormone exposure for LH and FSH was similar, and mean E2 exposure was 32% lower in period 2. The percentage of subjects with consecutive ovulatory P concentrations was also similar in both periods (study 2). Safety and tolerability profiles were unremarkable in both studies. CONCLUSIONS: Coadministration of elagolix 150 mg once daily with oral contraceptives containing EE and norgestimate, or norethindrone, resulted in small pharmacokinetic changes in the oral contraceptive components. Similar or lower FSH, LH, and E2 exposures were observed during coadministration, with ovulatory P concentrations also comparable in both periods. The pharmacodynamic profiles of the oral contraceptives were maintained when coadministered with elagolix.
Authors: Robin M Pokrzywinski; Ahmed M Soliman; Jun Chen; Michael Snabes; Michael P Diamond; Eric Surrey; Karin S Coyne Journal: Fertil Steril Date: 2019-06-18 Impact factor: 7.329
Authors: 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 Journal: Obstet Gynecol Date: 2018-07 Impact factor: 7.661
Authors: David F Archer; Juki Ng; Kristof Chwalisz; Yi-Lin Chiu; Eve C Feinberg; Charles E Miller; Robert A Feldman; Cheri E Klein Journal: J Clin Endocrinol Metab Date: 2020-03-01 Impact factor: 5.958
Authors: Mohamad Shebley; Akshanth R Polepally; Ahmed Nader; Juki W Ng; Insa Winzenborg; Cheri E Klein; Peter Noertersheuser; Megan A Gibbs; Nael M Mostafa Journal: Clin Pharmacokinet Date: 2020-03 Impact factor: 6.447