Hormonal Effects of the Oral Gonadotropin Releasing Hormone (GnRH) Antagonist at Different Periods of the Menstrual Cycle

NCT04060992 | Unknown Phase 4 FDA Drug

• 1 other identifier: APP-19-02687
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is twofold: First, to see if elagolix can suppress gonadotropin and ovarian hormones in the short-term period, when only administered for a 72-hour period. If elagolix effectively suppresses gonadotropin and ovarian hormones in a timely manner, it could be used to alter aspects of the menstrual cycle, depending on when administered. Second, is there a window for when elagolix functions best? While other studies initiate elagolix at the start of a woman's menstrual cycle, investigators of this study want to determine if administering elagolix at various points in a woman's menstrual cycle alters its ability to suppress gonadal and ovarian hormones.

Conditions

Ovulation; Failure or Lack of

Outcome Measures

Primary Outcomes (1)

• Suppression of gonadotropin and pituitary hormones as measured by hormonal assay status post short-term administration of elagolix

  Measure serum concentrations of follicle stimulation hormone (FSH), luteinizing hormone (LH), estradiol, progesterone at baseline and throughout three-day course of elagolix

  measured over 4 days

Secondary Outcomes (1)

• Time interval to next menses

  up to 4 weeks

Study Arms (3)

Early Follicular Phase

EXPERIMENTAL

Women enrolled will be anywhere from cycle day 1 through 5 of their menstrual cycle and take elagolix 200mg oral tablet BID for 3 days total.

Drug: Elagolix 200 MG Oral Tablet [Orilissa]

Late Follicular Phase

ACTIVE COMPARATOR

Women enrolled will be anywhere from cycle day 8 through 13 of their menstrual cycle and take elagolix 200mg oral tablet BID for 3 days total.

Drug: Elagolix 200 MG Oral Tablet [Orilissa]

Luteal Phase

ACTIVE COMPARATOR

Women enrolled will be anywhere from cycle day 21 through cycle day 26 of their menstrual cycle and take elagolix 200mg oral tablet BID for 3 days total.

Drug: Elagolix 200 MG Oral Tablet [Orilissa]

Interventions

Elagolix 200 MG Oral Tablet [Orilissa] DRUG

oral tablet given twice daily

Early Follicular Phase; Late Follicular Phase; Luteal Phase

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers from USC Fertility
• Documented ovulation with a serum mid-luteal progesterone ≥3pg/mL
• Ovulatory with a 24-35-day cycle
• Ages 18-39
• Body Mass Index (BMI) 18.1-30.0kg/m2
• Consistent condom use for contraception
• Not desiring or seeking pregnancy

You may not qualify if:

• Allergy to injectable or oral GnRH-antagonist
• FSH ≥ 10 IU/L or LH ≥ 10 IU/L in early follicular phase iii. Known liver disease iv. Known osteoporosis v. Pregnancy vi. Current use of drugs metabolized by the liver enzyme CYP3A, specifically ketoconazole, rifampin, digoxin, oral midazolam, or rosuvastatin.

Sponsors & Collaborators

• University of Southern California: lead

Related Publications (11)

• Kumar P, Sharma A. Gonadotropin-releasing hormone analogs: Understanding advantages and limitations. J Hum Reprod Sci. 2014 Jul;7(3):170-4. doi: 10.4103/0974-1208.142476.

  PMID: 25395741 RESULT

• Andreyko JL, Marshall LA, Dumesic DA, Jaffe RB. Therapeutic uses of gonadotropin-releasing hormone analogs. Obstet Gynecol Surv. 1987 Jan;42(1):1-21.

  PMID: 3543765 RESULT

• Fluker M, Grifo J, Leader A, Levy M, Meldrum D, Muasher SJ, Rinehart J, Rosenwaks Z, Scott RT Jr, Schoolcraft W, Shapiro DB; North American Ganirelix Study Group. Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation. Fertil Steril. 2001 Jan;75(1):38-45. doi: 10.1016/s0015-0282(00)01638-1.

  PMID: 11163814 RESULT

• Garcia-Velasco JA, Isaza V, Vidal C, Landazabal A, Remohi J, Simon C, Pellicer A. Human ovarian steroid secretion in vivo: effects of GnRH agonist versus antagonist (cetrorelix). Hum Reprod. 2001 Dec;16(12):2533-9. doi: 10.1093/humrep/16.12.2533.

  PMID: 11726570 RESULT

• Fluker MR, Marshall LA, Monroe SE, Jaffe RB. Variable ovarian response to gonadotropin-releasing hormone antagonist-induced gonadotropin deprivation during different phases of the menstrual cycle. J Clin Endocrinol Metab. 1991 Apr;72(4):912-9. doi: 10.1210/jcem-72-4-912.

  PMID: 2005218 RESULT

• Depalo R, Jayakrishan K, Garruti G, Totaro I, Panzarino M, Giorgino F, Selvaggi LE. GnRH agonist versus GnRH antagonist in in vitro fertilization and embryo transfer (IVF/ET). Reprod Biol Endocrinol. 2012 Apr 13;10:26. doi: 10.1186/1477-7827-10-26.

  PMID: 22500852 RESULT

• Ng J, Chwalisz K, Carter DC, Klein CE. Dose-Dependent Suppression of Gonadotropins and Ovarian Hormones by Elagolix in Healthy Premenopausal Women. J Clin Endocrinol Metab. 2017 May 1;102(5):1683-1691. doi: 10.1210/jc.2016-3845.

  PMID: 28323948 RESULT

• Elagolix (Orilissa)--an oral GnRH antagonist for endometriosis pain. Med Lett Drugs Ther. 2018 Sep 24;60(1556):158-160. No abstract available.

  PMID: 30383729 RESULT

• Surrey E, Taylor HS, Giudice L, Lessey BA, Abrao MS, Archer DF, Diamond MP, Johnson NP, Watts NB, Gallagher JC, Simon JA, Carr BR, Dmowski WP, Leyland N, Singh SS, Rechberger T, Agarwal SK, Duan WR, Schwefel B, Thomas JW, Peloso PM, Ng J, Soliman AM, Chwalisz K. Long-Term Outcomes of Elagolix in Women With Endometriosis: Results From Two Extension Studies. Obstet Gynecol. 2018 Jul;132(1):147-160. doi: 10.1097/AOG.0000000000002675.

  PMID: 29889764 RESULT

• Taylor HS, Giudice LC, Lessey BA, Abrao MS, Kotarski J, Archer DF, Diamond MP, Surrey E, Johnson NP, Watts NB, Gallagher JC, Simon JA, Carr BR, Dmowski WP, Leyland N, Rowan JP, Duan WR, Ng J, Schwefel B, Thomas JW, Jain RI, Chwalisz K. Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist. N Engl J Med. 2017 Jul 6;377(1):28-40. doi: 10.1056/NEJMoa1700089. Epub 2017 May 19.

  PMID: 28525302 RESULT

• Danis RB, Sriprasert I, Stanczyk FZ, Paulson RJ, Winer SA, Ho JR. Does timing matter when initiating elagolix in a natural menstrual cycle? F S Rep. 2021 May 31;2(3):308-313. doi: 10.1016/j.xfre.2021.05.009. eCollection 2021 Sep.

  PMID: 34553156 DERIVED

MeSH Terms

Conditions

Anovulation

Interventions

elagolix; Tablets

Condition Hierarchy (Ancestors)

Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Central Study Contacts

Rachel B Danis, MD

CONTACT

5169931812; rachel.danis@med.usc.edu

Frank Stanczyk, PhD

CONTACT

818-694-7522; fstanczyk@att.net

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Progessor of Obstetrics & Gynecology

Model Details: Observational study design, prospective cohort study

Study Record Dates

• First Submitted: August 7, 2019
• First Posted: August 19, 2019
• Study Start: October 1, 2019
• Primary Completion: October 30, 2020
• Study Completion: July 1, 2021
• Last Updated: August 19, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share