PGL4001 Versus GnRH-agonist in Uterine Myomas (PEARLII)

• Percentage of Subjects With Reduction of Uterine Bleeding at Week 13 Visit Defined as Pictorial Blood-loss Assessment Chart (PBAC) Score < 75 at End-of-treatment Visit (Week 13 Visit) [ Time Frame: 3 months ] [ Designated as safety issue: No ]

  Uterine bleeding was assessed with the use of the PBAC, a validated self-reporting method to estimate menstrual blood loss.

  Patients recorded daily the number of tampons and towels used and the degree to which individual items were soiled with blood (plus small or large clots). Monthly scores range from 0 (amenorrhea) to more than 500, with higher numbers indicating more bleeding.

  A slightly stained tampon/towel scores 1, a partially stained tampon/towel scores 5, a completely saturated tampon scores 10 and a completely saturated towel scores 20. Small clots/flooding (2cm) score 1. Large clots/flooding (3cm) score 5.

  Menorrhagia is defined as a PBAC > 100 during one menstrual period which approximates to a blood loss of > 80 mL. A PBAC of 400 corresponds to a blood loss of around 300 mL or approximately 80 tampons/towels used.

  The week 13 PBAC score was calculated using the last 28 days of treatment.

• Co-primary Safety Endpoint: Serum Estradiol Levels at End of Treatment Visit (Week 13 Visit) for PGL4001 Compared With GnRHagonist [ Time Frame: Week 13 visit ] [ Designated as safety issue: Yes ]
  Measured by log 10 (log pg/ml) transformed values for estradiol (E2) in blood samples
• Co-primary Safety Endpoint: % of Subjects Reporting Moderate or Severe Hot Flushes as Adverse Events Throughout the Treatment Period for PGL4001 Compared With GnRH-agonist [ Time Frame: Up to week 17 ] [ Designated as safety issue: Yes ]

  Difference in percentage of subjects reporting moderate or severe hot flushes:

  Frequency and severity of this adverse event(as spontaneously reported by patients or elicited by nonleading questions) were recorded on standard forms at every visit up to week 17.

This trial will assess the efficacy and safety of PGL4001 versus GnRH agonist, over a 3-month period for the pre-operative treatment of pre-menopausal women suffering from excessive uterine bleeding due to uterine myoma.

• Drug: PGL4001
  tablets
  Other Name: Ulipristal acetate
• Drug: leuprorelin
  solution for injection
  Other Name: GnRH-agonist

• Experimental: A (PGL4001 5 mg)
  Drug: PGL4001 5mg (oral tablets) and leuproreline matching placebo (intramuscular injection)
  Intervention: Drug: PGL4001
• Experimental: B (PGL4001 10mg)
  Drug: PGL4001 10 mg (oral tablets) and leuproreline matching placebo (intramuscular injection)
  Intervention: Drug: PGL4001
• Active Comparator: C (GnRH-agonist)
  PGL4001 matching placebo (oral tablets) and leuprorelin 3.75 mg (intramuscular injection)
  Intervention: Drug: leuprorelin

Inclusion Criteria:

• Be a pre-menopausal woman between 18 and 50 years inclusive.
• Have excessive uterine bleeding due to myoma
• Have a myomatous uterus with at least one myoma of ≥ 3 cm diameter in size
• Be eligible for one surgical procedure: e.g. hysterectomy, myomectomy or others.
• If of childbearing potential the subject must be practicing a non-hormonal method of contraception.
• Have a Body Mass Index (BMI) ≥ 18 and ≤ 40.

Exclusion Criteria:

• Has a history of or current uterine, cervical, ovarian or breast cancer.
• Has a history of or current endometrium atypical hyperplasia or adenocarcinoma.
• Has a known severe coagulation disorder.
• Has a history of or current treatment for myoma with a Selective Progesterone Receptor Modulator (SPRM) or a GnRH-agonist.
• Has a history of or known current osteoporosis.
• Has abnormal hepatic function at study entry.
• Has a positive pregnancy test at baseline or is nursing or planning a pregnancy during the course of the study.
• Has a current (within twelve months) problem with alcohol or drug abuse.
• Is currently enrolled in an investigational drug or device study or has participated in such a study within the last 30 days.