An Open-label Study of the Effects of Elagolix in Adult Premenopausal Females

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1, Open-Label Study of the Effects of Elagolix on Ovarian Activity, Ovulation and Ovarian Reserve in Premenopausal Females

Conditions
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Folliculogenesis

Intervention / Treatment
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* Drug: Elagolix
* Drug: Elagolix
* Drug: Elagolix
* Drug: Elagolix
* Drug: Elagolix
* Drug: Elagolix
* Drug: elagolix


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Elagolix Dose Regimen 1<br>Elagolix Dose regimen 1 for 84 days | Drug: Elagolix<br>* Elagolix Dose Regimen 1 for 84 days<br>* Other names: ABT-620, elagolix sodium;|
| Experimental: Elagolix Dose Regimen 2<br>Elagolix Dose Regimen 2 for 84 days | Drug: Elagolix<br>* Elagolix Dose Regimen 2 for 84 days<br>* Other names: ABT-620, elagolix sodium;|
| Experimental: Elagolix Dose Regimen 3<br>Elagolix Dose Regimen 3 for 84 days | Drug: Elagolix<br>* Elagolix Dose Regimen 3 for 84 days<br>* Other names: ABT-620, elagolix sodium;|
| Experimental: Elagolix Dose Regimen 4<br>Elagolix Dose Regimen 4 for 84 days Additional Dose Regimens may be added and will be administered for 84 days. | Drug: Elagolix<br>* Elagolix Dose Regimen 4 for 84 days Other interventions may be added<br>* Other names: ABT-620, elagolix sodium;|
| Experimental: Elagolix Dose Regimen 5<br>Elagolix Dose Regimen 5 for 84 days | Drug: Elagolix<br>* Elagolix Dose Regimen 5 for 84 days<br>* Other names: ABT-620, elagolix sodium;|
| Experimental: Elagolix Dose Regimen 6<br>Elagolix Dose Regimen 6 for 84 days | Drug: Elagolix<br>* Elagolix Dose Regimen 6 for 84 days<br>* Other names: ABT-620, elagolix sodium;|
| Experimental: Elagolix Dose Regimen 7<br>Elagolix Dose Regimen 7 for 84 days | Drug: elagolix<br>* Elagolix plus Activella Dose Regimen 7 for 84 days<br>* Other names: ABT-620, elagolix sodium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ovulation Classification | Presence or absence of ovulation | During the baseline menstrual cycle and monthly during the treatment cycles 1, 2, and 3 for up to month 3. | 
| Ovarian Activity | As measured by the Hoogland and Skouby 6-point ovarian activity grading system | During the baseline menstrual cycle and monthly during the treatment cycles 1, 2, and 3 for up to month 3. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endocrine Parameters | Estuarial, Progesterone, luteinizing hormone, follicle stimulating hormone | During the 16 week study period (4 week screening period and 12 week treatment period) for up to month 3 | 
| Ovarian Reserve | Inhibin-B and Antimullerian hormone | During the baseline menstrual cycle and monthly during the treatment cycles 1, 2, and 3 for up to month 3. | 
| Adverse events | All adverse events will be collected by subject self-report and review of laboratory parameters, physical exam. vital sign measurements and electrocardiograms. | All adverse events occurring through the Final Visit will be reported | 
| Clinical Laboratory Tests | Chemistry, hematology, urinalysis | Change from baseline to Cycles 1, 2, and 3 or Final Visit | 
| 12-lead Electrocardiogram | 12-lead Electrocardiogram | Change from baseline to Week 4 and Final Visit | 
| Vital Signs | Blood pressure, heart rate, temperature | Change from baseline to Cycles 1, 2, and 3 or Final Visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy volunteers, elagolix, endometriosis, ovarian reserve, gonadotropin-releasing hormone antagonist, ovulation, ovarian activity