Elagolix for Endometriosis

Recruiting at 1 trial location

Overseen By Nina Stachenfeld, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase < 1

Sponsor: Yale University

Disqualifiers: Smoking, Diabetes, Sleep apnea, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug Elagolix for treating endometriosis?

Research shows that Elagolix significantly reduces pain associated with endometriosis, including menstrual and non-menstrual pelvic pain, and helps decrease fatigue in women with moderate to severe endometriosis-related pain. ^{1 2 3 4 5}

Is Elagolix safe for humans?

Elagolix has been approved by the U.S. FDA for managing pain associated with endometriosis, and studies have evaluated its safety over 12 months. It is generally considered safe, but like any medication, it may have side effects, which healthcare providers can discuss with you. ^{1 2 3 5 6}

How is the drug Elagolix unique for treating endometriosis?

Elagolix is unique because it is an oral medication that works by blocking gonadotropin-releasing hormone (GnRH) receptors, which reduces hormone levels like estrogen and progesterone, helping to decrease inflammation and the growth of endometrial tissue, thus relieving pain associated with endometriosis. ^{2 4 6 7 8}

What is the purpose of this trial?

To test the hypothesis that estrogen suppression impairs endothelial dysfunction in endometriosis.

Research Team

Nina Stachenfeld, MD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for young women aged 18-45, both healthy and those with endometriosis. It's not open to women who have diabetes, severe acute pain from endometriosis needing immediate treatment, high blood pressure (BP>140/90), sleep apnea, or those who smoke.

Inclusion Criteria

I am a woman aged between 18 and 45.

I am a woman aged 18-45 with endometriosis.

Exclusion Criteria

You are a smoker.

I have diabetes.

I do not have severe acute pain from endometriosis needing immediate treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive estrogen suppression treatment to assess its impact on endothelial dysfunction and cardiovascular risk

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Elagolix
• Ganirelix Acetate

Trial Overview The study is testing Elagolix to see if reducing estrogen levels affects the health of blood vessels in women with endometriosis. The idea is that less estrogen might lead to worse vessel function.

Participant Groups

Group I: patients with endometriosis Experimental Treatment 1 Intervention

Endometriosis will be diagnosed by history of the disease seen at the time of prior surgery or will be diagnosed by classic clinical symptoms of the disease (cyclic progressive pelvic pain) using prior surgical report reviewed by Dr. Taylor.

Group II: patients without endometriosis Active Control 1 Intervention

Control subjects will be healthy women, with regular menses every 26-34 days. Subjects will be excluded if they have any symptoms of endometriosis, including severe dysmenorrhea or progressive cyclic pelvic pain or prior surgery showing evidence of endometriosis

Elagolix is already approved in United States for the following indications:

Approved in United States as Orilissa for:

• Management of moderate to severe pain associated with endometriosis

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

In a phase III trial involving 860 women, elagolix, an oral GnRH antagonist, significantly reduced fatigue levels in women suffering from moderate to severe endometriosis-associated pain, with notable improvements observed at 6 months.

Women taking elagolix at 200 mg twice daily experienced the greatest reduction in fatigue, with a significant decrease in fatigue T-scores compared to those on placebo, highlighting its efficacy in managing fatigue related to endometriosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of elagolix treatment on fatigue experienced by women with moderate to severe pain associated with endometriosis. Surrey, ES., Soliman, AM., Agarwal, SK., et al.[2019]

Elagolix, a medication for managing endometriosis and uterine fibroids, was studied in a large population of 2168 women across 13 clinical trials, showing that its pharmacokinetics are consistent and do not require dose adjustments based on patient-related factors.

The study found that only body weight and a specific genetic factor had minor effects on the drug's absorption and distribution, indicating that the standard dosage of 300 mg twice daily remains effective and safe for women with heavy menstrual bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Elagolix in Combination with Low-Dose Estradiol/Norethindrone Acetate in Women with Uterine Fibroids. Beck, D., Winzenborg, I., Liu, M., et al.[2022]

Elagolix (ORILISSA™) is an FDA-approved oral medication for managing moderate to severe pain from endometriosis, based on positive results from two phase III trials.

It is currently being tested in additional phase III trials for both endometriosis and heavy menstrual bleeding associated with uterine fibroids, indicating its potential for broader applications in treating reproductive hormone-dependent disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elagolix: First Global Approval. Lamb, YN.[2019]

Elagolix, a GnRH receptor antagonist, significantly reduces dysmenorrhea and non-menstrual pelvic pain in women with moderate to severe endometriosis, based on pooled data from over 1600 participants in two 6-month phase 3 studies.

The treatment was effective across various subgroups, with significant improvements in pain reported at 3 months and enhancements in health-related quality of life, indicating its broad applicability for different women with endometriosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reductions in endometriosis-associated pain among women treated with elagolix are consistent across a range of baseline characteristics reflective of real-world patients. Abrao, MS., Surrey, E., Gordon, K., et al.[2022]

After 12 months of treatment with elagolix, 52.1% of women taking 150 mg once daily and 78.2% taking 200 mg twice daily reported significant reductions in dysmenorrhea, indicating its efficacy in managing endometriosis-associated pain.

The treatment was generally safe, with no new safety concerns identified; however, some participants experienced decreased bone mineral density and increased lipid levels, which are consistent with reduced estrogen levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes of Elagolix in Women With Endometriosis: Results From Two Extension Studies. Surrey, E., Taylor, HS., Giudice, L., et al.[2019]

Elagolix (Orilissa) is an FDA-approved oral treatment for endometriosis-related pain that works by blocking gonadotropin-releasing hormone receptors, leading to reduced hormone levels and decreased inflammation of endometrial tissue.

This medication is significant for the estimated 10% of reproductive-age women affected by endometriosis, as it addresses symptoms like chronic pelvic pain and dysmenorrhea, although it also has contraindications and potential adverse effects that healthcare providers need to consider.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elagolix as a Novel Treatment for Endometriosis-Related Pain. Fantasia, HC.[2020]

Elagolix effectively suppresses ovulation in a dose-dependent manner, with the lowest ovulation rates observed at higher doses (27% at 300 mg BID), indicating its potential as a contraceptive method for women with endometriosis.

The treatment also leads to significant suppression of key hormones like luteinizing hormone and estradiol, but does not affect ovarian reserve, suggesting it may be a safe option for managing endometriosis-associated pain without compromising fertility in the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elagolix Suppresses Ovulation in a Dose-Dependent Manner: Results From a 3-Month, Randomized Study in Ovulatory Women. Archer, DF., Ng, J., Chwalisz, K., et al.[2020]

A novel and sensitive LC-MS-compatible method was developed to quantify organic impurities in elagolix sodium tablets, achieving significant resolution of impurities in just 46 minutes.

The method demonstrated high stability and specificity, effectively identifying major degradation products under various stress conditions, making it suitable for quality control in pharmaceutical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LC-MS-Compatible Chromatographic Method for Quantification of Potential Organic Impurities of Elagolix Sodium in Tablet Dosage Form with Identification of Major Degradation Products. Desai, P., Prajapati, R., Chokshi, A.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Impact of elagolix treatment on fatigue experienced by women with moderate to severe pain associated with endometriosis. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Elagolix in Combination with Low-Dose Estradiol/Norethindrone Acetate in Women with Uterine Fibroids. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Elagolix: First Global Approval. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Reductions in endometriosis-associated pain among women treated with elagolix are consistent across a range of baseline characteristics reflective of real-world patients. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes of Elagolix in Women With Endometriosis: Results From Two Extension Studies. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Elagolix as a Novel Treatment for Endometriosis-Related Pain. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Elagolix Suppresses Ovulation in a Dose-Dependent Manner: Results From a 3-Month, Randomized Study in Ovulatory Women. [2020]

8. England pubmed.ncbi.nlm.nih.gov

LC-MS-Compatible Chromatographic Method for Quantification of Potential Organic Impurities of Elagolix Sodium in Tablet Dosage Form with Identification of Major Degradation Products. [2023]