A Phase 2b Study to Evaluate the Safety and Efficacy of Elagolix in Premenopausal Women with Heavy Menstrual Bleeding Associated with Uterine Fibroids

Study ID
STU 052013-052

Cancer Related
No

Healthy Volunteers
No

Study Sites

Contact
Linda Boykin-Pierce
214-648-9781
linda.boykin-pierce@utsouthwestern.edu

Principal Investigator
Bruce Carr

Summary

This Phase 2b, randomized, double-blind, multicenter, placebo-controlled cohort-design
study is designed to evaluate the safety and efficacy of two different elagolix treatment regimens (QD
and BiD) 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 520 subjects
(260 subjects per cohort) will be randomized in a 1:1:1:1 ratio of active to placebo to one of the
following four treatment arms per cohort:
Cohort 1:
* placebo (n [?] 65)
* elagolix 300 mg BiD alone (n [?] 65)
* elagolix 300 mg BiD plus low-dose estradiol/norethindrone acetate Tablets QD (n [?] 65)
* elagolix 300 mg BiD plus standard-dose estradiol/norethindrone acetate Tablets QD (n [?] 65)
Cohort 2:
* placebo (n [?] 65)
* elagolix 600 mg QD alone (n [?] 65)
* elagolix 600 mg QD plus low-dose estradiol/norethindrone acetate Tablets QD (n [?] 65)
* elagolix 600 mg BiD plus standard-dose estradiol/norethindrone acetate Tablets QD (n [?] 65)
Cohort 1 will fully enroll prior to subjects enrolling into Cohort 2.
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.

Participant Eligibility

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. Inclusion criterion 3 deleted with Amendment 1.
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, 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
requirements.
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
pre-malignant changes.
10. Subject has an endometrial biopsy performed during Screening or within 6 months prior to
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 be repeated.
11. Subject >= 40 years of age (or the age at which mammograms are routinely performed according to
local or country guidelines) has a normal mammogram during Screening or within 1 year of
Screening. (Subjects with BI-RADS Classification 1 to 3 are eligible for randomization.)
12. Subject must agree to the Washout Intervals for hormonal therapies, including any other
medication that may require washout following discussion with the AbbVie SDP.
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.
14. If a pedunculated fibroid was removed, the procedure was performed at least 1 month prior to
Screening, inclusion criterion 4 is still met, and the subject has returned to at least one normal
menses prior to entering the Screening Period.