A Phase 2b Study to Evaluate the Safety and Efficacy of Elagolix in Premenopausal Women with Heavy Menstrual Bleeding Associated with Uterine Fibroids
This Phase 2b, randomized, double-blind, multicenter, placebo-controlled study is
designed to evaluate the safety and efficacy of elagolix alone and in combination with two different
strengths of add-back therapy in the treatment of premenopausal women with HMB associated with
uterine fibroids. approximately 280 subjects will be randomized in a 1:1:1:1 ratio of active to placebo
to one of the following four treatment arms:
* placebo (n [?] 70)
* elagolix 300 mg BiD alone (n [?] 70)
* elagolix 300 mg BiD plus low-dose estradiol/norethindrone acetate Tablets QD (n [?] 70)
* elagolix 300 mg BiD plus standard-dose estradiol/norethindrone acetate Tablets QD (n [?] 70)
The study consists of 3 periods:
* Screening Period x 2.5 to 3.5 months prior to first dose of study drug
* Treatment Period x 6-month treatment duration
* Post-Treatment Follow-up Period x 6-month period
a Washout Period prior to Screening, if applicable, may also be required.
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 49 years of age at the time of Screening.
3. Subject has regular menstrual cycles (i.e., occurring every 24 to 35 days) or a history (prior to
diagnosis of uterine fibroids) of regular menstrual cycles (i.e., occurring every 24 to 35 days)
4. Subject has a diagnosis of uterine fibroids documented by a Pelvic Ultrasound (TAU and TVU)
assessed by a central reader and verification that a fibroid present meets the following criteria:
* At least one fibroid with diameter >= 3 cm (longest diameter), or multiple small fibroids with a
total uterine volume of >= 200 cm3 to <= 2,500 cm3 (2,500 cm3 is equivalent to approximately
22 weeks gestation), as documented by a centrally-read imaging vendor.
* Only intramural, submucosal non-pedunculated, and only subserosal fibroids in combination
with intramural or submucosal non-pedunculated fibroids will qualify subjects for enrollment.
Intracavitary pedunculated fibroids (with or without an additional qualifying fibroid), and
solitary subserosal fibroids are exclusionary; subjects may be re-screened after the removal of
an intracavitary pedunculated fibroid.
Ultrasound procedures will be performed during the Screening Period, and subjects will not be
randomized until the investigator has reviewed the central reader results verifying the inclusion
5. Subject has HMB associated with uterine fibroids as evidenced by MBL > 80 mL during each of
two screening menstrual cycles, as measured by the alkaline hematin method.
6. Subject has a Screening FSH level of < 35 mIU/mL (35 IU/L).
7. Subject has a negative urine pregnancy test(s) during washout, if applicable, negative urine and
serum pregnancy tests during the Screening Period and a negative urine pregnancy test on Day 1,
prior to administration of first dose.
8. Subject must agree to use two forms of non-hormonal contraception (dual contraception)
consistently during the Washout (if applicable), Screening and Treatment periods, and through
Month 3 of the Post-Treatment Follow-Up period. Acceptable methods of dual contraception
include the following combinations:
* Condom with spermicide (cream, spray, foam, gel, suppository or polymer film)
* 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 tubal occlusion (including ligation and blockage methods such as Essure(RegisteredTM)), at
least 3 months prior to Screening
* Subject is not sexually active with men; periodic sexual relationship(s) with men requires the
use of dual non hormonal contraception as noted above
9. Subject had a Pap test performed in the 6 months prior to Screening or has a Pap test collected at
Screening that contains adequate endocervical cells and shows no evidence of malignancy or
10. Subject has an endometrial biopsy performed during Screening, the results of which show no
significant endometrial pathology (e.g., hyperplasia [with or without atypia], endometrial polyp
[confirmed by SIS], endometritis or endometrial cancer). An adequate biopsy sample must be
obtained before the subject may be randomized. In case of an inadequate sample, the biopsy may
11. Subject >= 40 years of age has a normal mammogram during Screening or within 1 year of
randomization (subjects with BI-RADS Classification 1 to 3 are eligible for randomization).
12. Subject must agree to the Washout Intervals for hormonal therapies, if applicable.
13. Subject has not taken exclusionary hormonal therapies within the specified washout interval prior
to the initiation of any screening procedures and must have returned to at least 1 regular menstrual
cycle prior to initiation of any screening procedures.