Clinical trial NCT01403038: An Open-label Study of the Effects of Elagolix in Adult Premenopausal Females
Official title: A Phase 1, Open-Label Study of the Effects of Elagolix on Ovarian Activity, Ovulation and Ovarian Reserve in Premenopausal Females
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Folliculogenesis
Keywords: healthy volunteers
elagolix
endometriosis
ovarian reserve
gonadotropin-releasing hormone antagonist
ovulation
ovarian activity
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Neurocrine Biosciences
First posted: 2011-07-27
Enrollment: 216
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This is an open-label Phase 1 study in healthy premenopausal females evaluating the effects of different dosing regimens of elagolix on ovarian activity, ovulation, and ovarian reserve and to assess the effect of elagolix on selected endocrine/hormone levels.

Detailed description: This is an open-label, multiple-dose, Phase 1 study in premenopausal subjects aged 18 years to 40 years, with a history of regular menstrual cycles (24 to 32 days long) and no evidence of significant gynecological disorders. The objective of the study is to determine the effects of different dosing regimens of elagolix on ovulation, ovarian activity, and ovarian reserve. The study consists of 3 periods: a Screening Period of up to 50 days prior to the first dose, a Treatment Period of 3 months duration (Cycles 1-3), and a Follow-up Period of up to 60 days. During the Screening and Treatment menstrual cycles, serial transvaginal ultrasounds and determination of serum levels of luteinizing hormone, follicle-stimulating hormone, estradiol, progesterone, and inhibin B will be performed three times weekly. Subjects will maintain a daily diary of uterine bleeding. Pregnancy testing will be performed frequently throughout the study. Subjects will be required to use nonhormonal dual contraception consistently during the study, and will be counseled on appropriate and effective forms of birth control to promote pregnancy prevention.

Eligibility criteria: Inclusion Criteria:

- Premenopausal female, between 18 and 40 years of age, inclusive - History of regular menstrual cycles - Endocrine and ultrasonographic evidence of ovulation and normal ovulatory cycle during the screening period - Follicle-stimulating hormone level of \<35 mIU/mL - Agrees to use required birth control methods during the entire length of participation in the study

Exclusion Criteria:

- Screening ultrasound results show a clinically significant gynecological disorder - Surgical history of hysterectomy without oophorectomy, unilateral or bilateral oophorectomy, removal of ovarian cysts - Less than 6 months postpartum or post-lactation at the start of study drug dosing - Pregnant or breast feeding or is planning a pregnancy within the next 12 months - Testosterone concentration \>120 ng/dL at screening

Primary outcomes:
measure: Ovulation Classification
timeFrame: During the baseline menstrual cycle and monthly during the treatment cycles 1, 2, and 3 for up to month 3.
measure: Ovarian Activity
timeFrame: During the baseline menstrual cycle and monthly during the treatment cycles 1, 2, and 3 for up to month 3.
Secondary outcomes:
measure: Endocrine Parameters
timeFrame: During the 16 week study period (4 week screening period and 12 week treatment period) for up to month 3
measure: Ovarian Reserve
timeFrame: During the baseline menstrual cycle and monthly during the treatment cycles 1, 2, and 3 for up to month 3.
measure: Adverse events
timeFrame: All adverse events occurring through the Final Visit will be reported
measure: Clinical Laboratory Tests
timeFrame: Change from baseline to Cycles 1, 2, and 3 or Final Visit
measure: 12-lead Electrocardiogram
timeFrame: Change from baseline to Week 4 and Final Visit
measure: Vital Signs
timeFrame: Change from baseline to Cycles 1, 2, and 3 or Final Visit
Other outcomes:
Locations:
city: Colorado Springs
country: United States
facility: Site Reference ID/Investigator# 50805
state: Colorado
city: Colorado Springs
country: United States
facility: Site Reference ID/Investigator# 51270
state: Colorado
city: Denver
country: United States
facility: Site Reference ID/Investigator# 50884
state: Colorado
city: Lonetree
country: United States
facility: Site Reference ID/Investigator# 50404
state: Colorado
city: Miami
country: United States
facility: Site Reference ID/Investigator# 50904
state: Florida
city: South Miami
country: United States
facility: Site Reference ID/Investigator# 50402
state: Florida
city: Tampa
country: United States
facility: Site Reference ID/Investigator# 50808
state: Florida
city: Naperville
country: United States
facility: Site Reference ID/Investigator# 50807
state: Illinois
city: Oak Brook
country: United States
facility: Site Reference ID/Investigator# 50804
state: Illinois
city: Durham
country: United States
facility: Site Reference ID/Investigator# 50762
state: North Carolina
city: Winston-Salem
country: United States
facility: Site Reference ID/Investigator# 50403
state: North Carolina
city: Cincinnati
country: United States
facility: Site Reference ID/Investigator# 50810
state: Ohio
city: Portland
country: United States
facility: Site Reference ID/Investigator# 50883
state: Oregon
city: Philadelphia
country: United States
facility: Site Reference ID/Investigator# 50803
state: Pennsylvania
city: Philadelphia
country: United States
facility: Site Reference ID/Investigator# 51546
state: Pennsylvania
city: San Antonio
country: United States
facility: Site Reference ID/Investigator# 50806
state: Texas
city: San Antonio
country: United States
facility: Site Reference ID/Investigator# 51342
state: Texas
city: Sandy
country: United States
facility: Site Reference ID/Investigator# 50811
state: Utah
city: Norfolk
country: United States
facility: Site Reference ID/Investigator# 50902
state: Virginia
city: Seattle
country: United States
facility: Site Reference ID/Investigator# 50882
state: Washington
city: San Juan
country: Puerto Rico
facility: Site Reference ID/Investigator# 53363
city: Santurce
country: Puerto Rico
facility: Site Reference ID/Investigator# 53362
Study officials:
affiliation: AbbVie
name: Kristof Chwalisz, MD, PhD, MD
role: STUDY_DIRECTOR
References:
citation: Archer DF, Ng J, Chwalisz K, Chiu YL, Feinberg EC, Miller CE, Feldman RA, Klein CE. Elagolix Suppresses Ovulation in a Dose-Dependent Manner: Results From a 3-Month, Randomized Study in Ovulatory Women. J Clin Endocrinol Metab. 2020 Mar 1;105(3):dgz086. doi: 10.1210/clinem/dgz086.
citation: Winzenborg I, Nader A, Polepally AR, Liu M, Degner J, Klein CE, Mostafa NM, Noertersheuser P, Ng J. Population Pharmacokinetics of Elagolix in Healthy Women and Women with Endometriosis. Clin Pharmacokinet. 2018 Oct;57(10):1295-1306. doi: 10.1007/s40262-018-0629-6.