Endometriosis MedDRA version: 9.1 Level: LLT Classification code 10014778 Term: Endometriosis
Conditions
Interventions
Product Name: NBI-56418 Na 100 mg IR Tablet
Pharmaceutical Form: Tablet
INN or Proposed INN: Elagolix sodium
CAS Number: 932720-36-2
Current Sponsor code: NBI-56418 Na
Other descriptive name: NBI-5641
Sponsors
Neurocrine Biosciences, INC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To participate in this study, subjects must: • Be female, aged 18 to 45 years, inclusive. • Have a total Composite Pelvic Signs and Symptoms Score (CPSSS) of =6 at screening. • Have a score of at least 2 for the dysmenorrhea CPSSS component and at least 1 for the nonmenstrual pelvic pain CPSSS component at baseline (Day 1, Week 1). • Be at 2 to 5 days (inclusive) after the onset of menses prior to randomization • Have had a diagnosis of endometriosis made following laparoscopic visualization of the disease within 5 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 a history of regular spontaneous menstrual cycles. 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, leuprorelin, pregnancy) • Have a spontaneous menstrual cycle of 28 days (±5 days) prior to randomization. • Have a Body Mass Index (BMI) of 18 to 32 kg/m2, inclusive. • Agree to use two forms of nonhormonal contraception (e.g. condom and spermicide) during the study (from the signing of the consent until the final study visit [end of Week 30 or early termination]). • Have a negative urine pregnancy test at screening and prior to dosing (at baseline) at the beginning of Week 1. • Have a minimum of 7 days of e-Diary data entries prior to randomization. • Be willing to comply with all study procedures and restrictions. • Be able to read and understand the Patient Information Sheet (PIS), and sign the consent before entering into the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects will be excluded from the study if they: • Were administered a GnRH agonist, GnRH antagonist, danazol, or have received any of these agents within 6 months of the start of screening. • Were administered subcutaneous medroxyprogesterone acetate (DMPA-SC) or i.m. medroxyprogesterone acetate (DMPA-IM), or have received either 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 (for endometriosis or contraception) or other forms of hormonal therapy for endometriosis or have received such therapy within 1 month of the start of screening. • Have had diagnostic laparoscopy or surgical intervention for endometriosis within 1 month of the start of screening. • Have had a hysterectomy or oopherectomy. • Have had prior treatment with NBI-56418. • Have uterine fibroids =3 cm in diameter as determined by transvaginal ultrasound at screening. • Have any of the following abnormal cervical smear results at screening (based on the 2001 Bethesda System [Solomon et al., 2002]): - 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 - 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 a history of pathologic or compression fractures. • Have been pregnant within 6 months of the start of screening. • Are currently breastfeeding. • Are using systemic steroids on a chronic or regular basis within 3 months of the start of screening. • Have a chronic, unstable endocrine abnormality causing dysregulation of the hypothalamic-pituitary-gonadal axis that leads to ovarian dysfunction. • Have an unstable medical condition or chronic disease (including history of neurological [including cognitive], psychological, hepatic, renal, cardiovascular, GI, or pulmonary disease), irritable bowel syndrome, interstitial cystitis, or malignancy that could confound interpretation of the study outcomes. • Have chronic pelvic pain that is not caused by endometriosis (e.g., uterine fibroids). • Have a history of poor compliance in clinical research studies. • Have a medically significant illness in the 30 days before the beginning of Week 1. • Have a clinically significant abnormality based on assessments at screening or the beginning of Week 1. • Are using any investigational drug within 2 months of the start of screening. • Have a positive human immunodeficiency virus antibody (HIV-Ab), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (HCV-Ab) assay at screening or have a history of a positive result. • Have an allergy, hypersensitivity, or intolerance to a GnRH agonist or antagonist.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of 150 mg and 250 mg once-daily doses of NBI- 56418 in the treatment of pelvic pain due to endometriosis.;Secondary Objective: • To evaluate the safety of 150 mg and 250 mg once-daily doses of NBI-56418. • To evaluate the effect of 6 months of NBI-56418 treatment on bone mineral density (BMD). • To describe the temporal characteristics of NBI-56418 and leuprorelin in terms of safety and efficacy outcome measures.;Primary end point(s): Safety endpoints will include the following: • Adverse events • Clinical laboratory data (clinical chemistry, hematology, and urinalysis) • Posttreatment menses and ovulation • Hot flashes • Serum N-telopeptide • BMD (spine and femur) • Vaginal bleeding • Vital signs • 12-lead ECGs • Concomitant medications • Physical examinations (including pelvic examination at Week 30 or early termination) Efficacy: Statistical comparisons between each NBI-56418 dose level (150 mg and 250 mg) and placebo, between each NBI-56418 dose level and leuprorelin, and between leuprorelin and placebo, will be performed for the numerical rating scale (NRS) change from baseline (CFB) mean values at Weeks 4, 8, and 12 using an analysis of covariance (ANCOVA) model. A preliminary efficacy analysis will be conducted after all subjects have completed Week 12 of the study, but prior to full study completion (and therefore prior to full database lock). The purpose of this early analysis is to explore and understand the efficacy of the two NBI-56418 dose levels, and to fully characterize the study efficacy endpoints (analysis variables), for purposes of planning future efficacy studies in the NBI-56418 development program in conjunction with an end-of-Phase II meeting with the US Food and Drug Administration (FDA). | — |
Countries
Bulgaria, Hungary, Poland
Outcome results
None listed