Clinical trial NCT00797225: Efficacy and Safety Study of Elagolix Versus Placebo or Leuprorelin Acetate in Endometriosis
Official title: A Phase II, Randomized, Double-Blind, Placebo- and Active-Controlled Study to Assess the Efficacy and Safety of NBI-56418 in Subjects With Endometriosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Endometriosis
Keywords: bone mineral density,endometriosis,pelvic pain
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2008-11-25
Enrollment: 174
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria

* Female, aged 18 to 45 years, inclusive
* Have moderate to severe pelvic pain due to endometriosis
* Have been surgically (laparoscopy) diagnosed with endometriosis within the last 5 years and have recurrent or persistent endometriosis symptoms
* Have regular menstrual cycle (23-33 day)
* Agree to use two forms of non-hormonal contraception during the study

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

Primary outcomes:
measure: Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain
timeFrame: Baseline and Weeks 4, 8, and 12
Secondary outcomes:
measure: Change From Baseline in the Monthly Peak Numerical Rating Score (NRS) for Endometriosis Pain
timeFrame: Baseline and Weeks 4, 8, and 12
measure: Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score
timeFrame: Baseline and Weeks 4, 8, and 12
measure: Change From Baseline in the Monthly Mean Dysmenorrhea Score
timeFrame: Baseline and Weeks 4, 8, and 12
measure: Change From Baseline in the Monthly Mean Sum of Dysmenorrhea and Non-menstrual Pelvic Pain Scores
timeFrame: Baseline and Weeks 4, 8, and 12
measure: Change From Baseline in the Percentage of Days of Any Analgesic Use
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in the Percentage of Days of Prescription Analgesic Use
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in the Percentage of Days of Narcotic Analgesic Use
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in Dyspareunia Component of the Composite Pelvic Signs and Symptoms Score (CPSSS)
timeFrame: Baseline and Weeks 4, 8, and 12
measure: Change From Baseline in Dysmenorrhea Component of the CPSSS
timeFrame: Baseline and Week 12
measure: Change From Baseline in Non-menstrual Pelvic Pain CPSSS Component
timeFrame: Baseline and Week 12
measure: Patient Global Impression of Change at Weeks 4, 8 and 12
timeFrame: Weeks 4, 8 and 12
measure: Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved
timeFrame: Weeks 4, 8 and 12
measure: Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved
timeFrame: Weeks 4, 8 and 12
measure: Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12
timeFrame: Baseline and week 12
measure: Concentration of Serum Estradiol
timeFrame: Baseline and Weeks 4, 8 and 12
measure: Percent Change From Baseline in Bone Mineral Density of the Femur at Week 12
timeFrame: Baseline and week 12
measure: Percent Change From Baseline in Bone Mineral Density of the Spine at Week 12
timeFrame: Baseline and week 12
measure: Percent Change From Baseline in Bone Mineral Density of the Femur at Week 24
timeFrame: Baseline and Week 24
measure: Percent Change From Baseline in Bone Mineral Density of the Spine at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Serum N-telopeptide Concentration at Week 12
timeFrame: Baseline and week 12
measure: Average Number of Hot Flashes Per Day
timeFrame: 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)
measure: Percentage of Days With Uterine Bleeding
timeFrame: 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)
measure: Number of Days to First Posttreatment Menses
timeFrame: From last day of study drug up to 6 weeks after the last dose.
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References: