A Phase 3 Study to Evaluate the Efficacy and Safety of Elagolix in Combination with Estradiol/Norethindrone Acetate for the Management of Heavy Menstrual Bleeding Associated with Uterine Fibroids in Premenopausal Women
- Clements University Hospital
- UT Southwestern Ambulatory Services
Bruce Carr, M.D.
The objectives of this study are to:
* assess the efficacy, safety and tolerability of elagolix 300 mg BiD in
combination with e2/neTa (estradiol 1.0 mg/norethindrone acetate 0.5 mg
QD), versus placebo to reduce HMB associated with uterine fibroids in
premenopausal women 18 to 51 years of age.
* The study will also characterize the impact of e2/neTa on the
safety/tolerability (including BMD and other hypoestrogenic side effects) and
efficacy of elagolix.
This Phase 3, randomized, double-blind, multicenter, placebo-controlled study is designed to evaluate the efficacy, safety and tolerability of elagolix alone and in combination with e2/neTa in the management of premenopausal women with HMB associated with uterine fibroids. approximately 400 subjects will be randomized in a 1:1:2 ratio to 1 of the following 3 treatment groups:
* placebo (n [?] 100)
* elagolix 300 mg BiD (n [?] 100)
* elagolix 300 mg BiD plus e2/neTa (estradiol 1.0 mg/norethindrone acetate
0.5 mg) QD (n [?] 200)
This study is designed to enroll approximately 400 subjects across approximately 125 clinical study sites to meet scientific and regulatory objectives without enrolling an undue number of subjects in alignment with ethical considerations. if the target number of enrolled subjects has been met, there is a possibility that additional subjects in screening will not be enrolled.
The study consists of 4 periods as follows:
1. Washout Period prior to Screening (if applicable)
2. Screening Period of approximately 2.5 to 3.5 months prior to first dose of study drug
3. 6-Month Treatment Period
4. 12-month Post-Treatment Follow-up Period (oR Subjects may enter an extension study [Study M12-816] if they are willing and qualify, based on safety parameters, to receive an additional 6 months of treatment, followed by 12 months of follow-up).
The primary endpoint will be the percentage of subjects meeting a composite endpoint consisting of these two bleeding assessments:
* MBL volume [Less Than] 80 mL during the Final Month (the last 28 days of treatment), anD
* 50% or greater reduction in MBL volume from baseline to the Final Month (the last 28 days of treatment).
Secondary efficacy Variables:
* MBL volume assessed using alkaline hematin methodology and uBQ
* Bleeding days
* Hemoglobin concentration
* Fibroid and uterine volume
* uFS-QoL Questionnaire
* euroQol (eQ-5D-5L) Questionnaire
* Health Care Resource utilization (HCRu) Questionnaire
* Patient Global impression of Change (PGiC) Questionnaires
* Work Productivity and activity impairment (WPai) Questionnaire
1. Subject has voluntarily signed and dated the informed consent form (ICF), approved by an Institutional Review Board/Ethics Committee (IRB/EC), prior to washout (if applicable), or initiation of any screening or study-specific procedures.
2. Subject is a premenopausal female 18 to 51 years of age at the time of Screening.
3. Subject has a diagnosis of uterine fibroids documented by a Pelvic Ultrasound
(TAU, TVU) assessed by a central reader and verification that a fibroid present
meets at least one of the following criteria:
* Intramural, submucosal non-pedunculated fibroid with a diameter >= 2 cm (longest diameter)
* Solitary subserosal fibroid >= 4 cm
* Multiple small fibroids with a total uterine volume of >= 200 cm3 to
<= 2,500 cm3
4. Subject has HMB associated with uterine fibroids as evidenced by MBL > 80 mL during each of two menses in Screening as measured by the alkaline hematin method.
5. Subject has a Screening FSH level of < 35 mIU/mL (35 IU/L).
6. Subject has a negative urine and/or serum pregnancy test(s) during the Washout (if applicable) and/or Screening Periods, and has a negative urine pregnancy test just prior to first dose.
7. Subject must agree to use two forms of non-hormonal contraception (dual
contraception) consistently during the Washout (if applicable), Screening,
Treatment and Post-Treatment Periods (Subject may start hormonal contraception
after completion of the Post-Treatment Month 2 Visit provided her menses has
returned). Acceptable methods of dual contraception include the following
* Condom with spermicide (cream, spray, foam, gel, suppository or polymer
* Diaphragm with spermicide (condom may or may not be used)
* Cervical cap with spermicide (condom may or may not be used)
* Vaginal sponge impregnated with spermicide used with a condom
Subject is not required to use dual contraception methods if:
* Sexual partner(s) is vasectomized, at least 6 months prior to Screening.
* Subject practices total abstinence from sexual intercourse, as the preferred
lifestyle of the subject; periodic abstinence is not acceptable.
* Subject had a bilateral tubal occlusion (including ligation and blockage methods such as Essure(RegisteredTM)), at least 4 months prior to Screening. Subjects with
Essure(RegisteredTM) must have prior confirmation of tubal occlusion with Essure(RegisteredTM)
confirmation test (e.g., hysterosalpingogram).
* Subject is not sexually active with men; periodic sexual relationship(s) with
men requires the use of dual non-hormonal contraception as noted above.
8. Subject has an adequate endometrial biopsy performed during Screening, the
results of which show no clinically significant endometrial pathology.
9. Subject >= 39 years of age at the time of randomization has a normal mammogram
(BI-RADS Classification 1 to 3 or equivalent) during Screening or within 3 months prior to Screening.
10. Subject must agree to the Washout Intervals for hormonal therapies, including any other medication that may require washout as specified in Section 184.108.40.206.
11. Subject has not taken exclusionary hormonal therapies within the specified washout interval as specified in Section 220.127.116.11 prior to the initiation of any screening procedures and must have at least 1 menses prior to initiation of any screening procedures.