A Phase II, Randomized, Double-Blind, Placebo- and Active-Controlled Study to Assess the Efficacy and Safety of NBI-56418 in Subjects With Endometriosis
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 174
- Primary Endpoint
- Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain
Study Overview
Brief Summary
This study is designed to evaluate the safety and beneficial effects of elagolix (NBI-56418) compared to placebo and leuprorelin (an approved endometriosis therapy) over a three month period followed by an additional three months of treatment on elagolix.
Detailed Description
The study followed a parallel-group design in which participants were randomized (1:1:1:1) to one of the following treatment groups for the first 12 weeks of dosing: 150 mg elagolix once daily (q.d.); 250 mg elagolix q.d.; placebo; or leuprorelin acetate depot injection 3.75 mg (monthly). Blinding was achieved using a double-dummy design. Following 12 weeks of dosing, participants continued in the study for an additional 12 weeks; participants randomized to elagolix continued to receive their assigned dose and participants randomized to placebo or leuprorelin acetate were re-randomized to receive one of the two doses of elagolix (150 mg q.d. or 250 mg q.d.) for 12 weeks in a double-blind fashion. Six weeks after the last dose of the study drug at the end of Week 24, a follow-up visit was performed (end of Week 30).
There was no pre-specified primary efficacy end point as there was no single key efficacy outcome measure in this exploratory Phase 2 study. For purposes of results reported here, Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain is designated as the primary outcome measure.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- •Received a Gonadotropin-releasing hormone (GnRH) agonist, GnRH antagonist, danazol, or have received any of these agents within 6 months of the start of screening.
- •Received subcutaneous medroxyprogesterone acetate (DMPA-SC) or intramuscular (i.m.) medroxyprogesterone acetate (DMPA-IM), or have received either of these agents within 3 months of the start of screening.
- •Are currently using hormonal contraception or other forms of hormonal therapy or received such treatment within the last month
- •Have had surgery for endometriosis within the last month
- •Are using systemic steroids on a chronic or regular basis within 3 months
- •Have uterine fibroids or other pelvic lesions ≥ 3 cm in diameter
- •Have had a hysterectomy or oophorectomy
- •Have pelvic pain that is not caused by endometriosis
- •Have unstable medical condition or chronic disease
- •Have been pregnant within the last 6 months and is currently breast feeding
Arms & Interventions
Placebo
Participants received placebo tablets once a day and placebo intramuscular injection once a month for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) for 12 weeks.
Intervention: Placebo to Elagolix (Drug)
Placebo
Participants received placebo tablets once a day and placebo intramuscular injection once a month for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) for 12 weeks.
Intervention: Placebo to Leuprorelin Acetate (Drug)
Elagolix 150 mg
Participants received elagolix 150 mg tablets once a day and placebo intramuscular injection once a month for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg for an additional 12 weeks.
Intervention: Elagolix (Drug)
Elagolix 150 mg
Participants received elagolix 150 mg tablets once a day and placebo intramuscular injection once a month for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg for an additional 12 weeks.
Intervention: Placebo to Leuprorelin Acetate (Drug)
Elagolix 250 mg
Participants received elagolix 250 mg tablets once a day and placebo intramuscular injection once a month for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Intervention: Elagolix (Drug)
Elagolix 250 mg
Participants received elagolix 250 mg tablets once a day and placebo intramuscular injection once a month for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Intervention: Placebo to Leuprorelin Acetate (Drug)
Leuprorelin
Participants received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) for 12 weeks.
Intervention: Leuprorelin Acetate Depot (Drug)
Leuprorelin
Participants received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) for 12 weeks.
Intervention: Placebo to Elagolix (Drug)
Outcomes
Primary Outcomes
Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain
Time Frame: Baseline and Weeks 4, 8, and 12
The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly mean NRS is the average of the daily values reported during the 4 weeks prior to each visit.
Secondary Outcomes
- Change From Baseline in the Monthly Mean Dysmenorrhea Score(Baseline and Weeks 4, 8, and 12)
- Change From Baseline in the Monthly Peak Numerical Rating Score (NRS) for Endometriosis Pain(Baseline and Weeks 4, 8, and 12)
- Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score(Baseline and Weeks 4, 8, and 12)
- Change From Baseline in the Monthly Mean Sum of Dysmenorrhea and Non-menstrual Pelvic Pain Scores(Baseline and Weeks 4, 8, and 12)
- Change From Baseline in the Percentage of Days of Any Analgesic Use(Baseline, Weeks 4, 8 and 12)
- Change From Baseline in the Percentage of Days of Prescription Analgesic Use(Baseline, Weeks 4, 8 and 12)
- Change From Baseline in the Percentage of Days of Narcotic Analgesic Use(Baseline, Weeks 4, 8 and 12)
- Change From Baseline in Dysmenorrhea Component of the CPSSS(Baseline and Week 12)
- Change From Baseline in Non-menstrual Pelvic Pain CPSSS Component(Baseline and Week 12)
- Patient Global Impression of Change at Weeks 4, 8 and 12(Weeks 4, 8 and 12)
- Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved(Weeks 4, 8 and 12)
- Change From Baseline in Dyspareunia Component of the Composite Pelvic Signs and Symptoms Score (CPSSS)(Baseline and Weeks 4, 8, and 12)
- Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved(Weeks 4, 8 and 12)
- Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12(Baseline and week 12)
- Concentration of Serum Estradiol(Baseline and Weeks 4, 8 and 12)
- Percent Change From Baseline in Bone Mineral Density of the Femur at Week 12(Baseline and week 12)
- Percent Change From Baseline in Bone Mineral Density of the Spine at Week 12(Baseline and week 12)
- Percent Change From Baseline in Bone Mineral Density of the Femur at Week 24(Baseline and Week 24)
- Percent Change From Baseline in Bone Mineral Density of the Spine at Week 24(Baseline and Week 24)
- Change From Baseline in Serum N-telopeptide Concentration at Week 12(Baseline and week 12)
- Average Number of Hot Flashes Per Day(Screening (8 weeks prior to day 1), Treatment phase (weeks 1 to 12 for participants in the placebo and leuprorelin treatment groups and weeks 1 to 24 for participants in the elagolix treatment groups))
- Percentage of Days With Uterine Bleeding(Screening (8 weeks prior to day 1), Treatment phase (weeks 1 to 12 for participants in the placebo and leuprorelin treatment groups and weeks 1 to 24 for participants in the elagolix treatment groups))
- Number of Days to First Posttreatment Menses(From last day of study drug up to 6 weeks after the last dose.)