Clinical trial NCT00437658: Elagolix Versus Subcutaneous Depot Medroxyprogesterone Acetate for the Treatment of Endometriosis
Official title: A Phase II, Randomized, Double-blind, Active-controlled Study to Assess the Safety and Efficacy of NBI-56418 in Subjects With Endometriosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Endometriosis
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2007-02-21
Enrollment: 252
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to assess the effects of elagolix versus subcutaneous depot medroxyprogesterone acetate (DMPA-SC; also known as depo-provera) on bone mineral density (BMD) during treatment for 24 weeks with a subsequent 24-week post-treatment period.


Eligibility criteria: Inclusion Criteria:

* Be female, aged 18 to 49 years, inclusive
* Have a total CPSSS of ≥ 6 at screening and baseline (Day 1) in the following categories: dysmenorrhea, dyspareunia, nonmenstrual pelvic pain, pelvic tenderness and induration. The total score must include a total of at least 2 in each of the categories of dysmenorrhea and nonmenstrual pelvic pain.
* Have had a diagnosis of endometriosis made following laparoscopic visualization of the disease within 8 years of the start of screening with recurrent or persistent symptoms.
* Have documented negative mammogram results within 12 months of screening if over the age of 40 years.
* Have menstrual cycles (28 days ±5 days). Assessment of cycle duration should be based on observations in the absence of drugs or conditions that are known to affect the cycle (e.g., oral contraceptives, leuprolide, pregnancy).
* Have a Body Mass Index (BMI) between 18 and 36 kg/m², inclusive.
* Agree to use two forms of nonhormonal contraception (e.g. condom with spermicide) during the study.

Exclusion Criteria:

* Are currently receiving gonadotropin-releasing hormone (GnRH) agonist, GnRH antagonist, danazol, or have received any of these agents within 6 months of the start of screening.
* Are currently receiving subcutaneous medroxyprogesterone acetate (DMPA-SC) or intramuscular medroxyprogesterone acetate (DMPA-IM) or have received any of these agents within 3 months of the start of screening.
* Have been nonresponsive to GnRH agonist or antagonist therapy for the management of endometriosis.
* Are currently using hormonal contraception or other forms of hormonal therapy or received such treatment within 1 month of the start of screening.
* Have had surgical treatment for endometriosis (laparoscopy) within 1 month of the start of screening.
* Have had a hysterectomy or bilateral oophorectomy.
* Have had prior treatment with NBI-56418.
* Have uterine fibroids or other pelvic lesions ≥ 5 cm in diameter
* Have any of the following abnormal cervical smear results at screening (based on the 2001 Bethesda System):

  * Benign endometrial cells (BEC) present, provided subject has irregular uterine bleeding or is over 40 years old
  * Atypical squamous cells of undetermined significance (ASC-US) present, and human papilloma virus (HPV) reflex testing is positive for high risk types or the testing outcome is unknown
  * Atypical squamous cells present, and high-grade squamous intraepithelial lesion (ASC-H) cannot be excluded
  * Atypical glandular cells of uncertain significance (AGUS/AGC): not otherwise specified (NOS), favor neoplasia (FN), favor endocervical, or favor endometrial origin types
  * Low-grade squamous intraepithelial lesion (LSIL) present
  * High-grade squamous intraepithelial lesion (HSIL) present
  * Adenocarcinoma in situ (AIS) / malignant cells present
* Have BMD with either lumbar spine or femur T-scores below -1.5 at screening as determined by the central DXA facility or have history of pathologic or compression fractures.
* Have been pregnant within 6 months of screening or currently breast feeding
* Are using systemic steroids on a chronic or regular basis within 3 months
* Have unstable medical condition or chronic disease
* Have chronic pelvic pain that is not caused by endometriosis

Primary outcomes:
measure: Percent Change From Baseline in Bone Mineral Density of the Spine at Week 24
timeFrame: Baseline and week 24
measure: Percent Change From Baseline in Bone Mineral Density of the Femur at Week 24
timeFrame: Baseline and week 24
Secondary outcomes:
measure: Percent Change From Baseline in Bone Mineral Density of the Spine at Weeks 12 and 48
timeFrame: Baseline and weeks 12 and 48
measure: Percent Change From Baseline in Bone Mineral Density of the Femur at Weeks 12 and 48
timeFrame: Baseline and weeks 12 and 48
measure: Change From Baseline in N-telopeptide at Weeks 12, 24 and 48
timeFrame: Baseline and weeks 12, 24 and 48
measure: Percentage of Participants With a Response in the Dysmenorrhea Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) at Week 24
timeFrame: Baseline and week 24
measure: Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS at Week 24
timeFrame: Baseline and week 24
measure: Percentage of Participants With a Response in the Dysmenorrhea Component of the CPSSS Over Time
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, 24, 28, 36, and 48
measure: Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS Over Time
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, 24, 28, 36, and 48
measure: Change From Baseline in Total CPSSS During the Treatment Period
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in Total CPSSS Excluding Dyspareunia During the Treatment Period
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in Dysmenorrhea Component of the CPSSS During the Treatment Period
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in Dyspareunia Component of the CPSSS During the Treatment Period
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in Non-menstrual Pelvic Pain Component of the CPSSS During the Treatment Period
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in Pelvic Tenderness Component of the CPSSS During the Treatment Period
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in Pelvic Induration Component of the CPSSS During the Treatment Period
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in in Monthly Peak Visual Analog Scale (VAS) for Pelvic Pain
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in in Monthly Mean Visual Analog Scale (VAS) for Pelvic Pain
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in Endometriosis Health Profile-5 (EHP-5) Pain Dimension
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in EHP-5 Control and Powerlessness Dimension
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in EHP-5 Emotional Well-being Dimension
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in EHP-5 Social Support Dimension
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in EHP-5 Self Image Dimension
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in EHP-5 Work Dimension
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in EHP-5 Relationship With Children Dimension
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in EHP-5 Intercourse Dimension
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in EHP-5 Medical Profession Dimension
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in EHP-5 Treatment Dimension
timeFrame: Baseline and weeks 4, 8, 12, 16, 20, and 24
measure: Percentage of Participants Using Analgesics During the Treatment Phase
timeFrame: 24 weeks
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References: