PGL4001 Efficacy Assessment in Reduction of Symptoms Due to Uterine Leiomyomata (PEARLIII)

A Phase III, Multicentre, Clinical Study Investigating the Efficacy and Safety of 3-months Open-label Treatment With PGL4001, Followed by a Randomised, Double-blind Placebo Controlled Period of 10 Days Treatment With Progestin, in Subjects With Myomas and Heavy Uterine Bleeding.

This is a multicentre, Phase III, efficacy and safety open-label study with PGL4001 10mg once daily for 3 months, blinded towards the administration of progestin or placebo after end of PGL4001 treatment.

Study Overview

• Status: Completed
• Conditions: Uterine Fibroids
• Intervention / Treatment: Drug: PGL4001, placebo; Drug: PGL4001, progestin

Detailed Description

PGL4001 will be administered daily to all subjects in an open-label manner with no control group. The three months open label treatment period will be followed by a ten day double blind treatment with progestin or matching placebo. Subjects will be randomly assigned to progestin or matching placebo arm with a 1:1 ratio.

• Study Type: Interventional
• Enrollment (Actual): 209
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8047
    • Medical University Graz, department of obstetrics and gynecology
  • Vienna, Austria, 1090
    • Medical University Vienna, department of obstetrics and gynecology
• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques universitaires Saint-Luc
  • Liège, Belgium, 4000
    • CHR de la Citadelle
  • Yvoir, Belgium, 5530
    • Cliniques Universitaires UCL de Mont-Godinne
• Poland
  • Bialystok, Poland, 15-224
    • Prywatna Klinika Polozniczo-Ginekologiczna
  • Gdańsk, Poland, 80-895
    • INVICTA Sp. Z o.o.
  • Katowice, Poland, 40-724
    • Private Practice
  • Lodz, Poland, 90-602
    • Private Practice
  • Lublin, Poland, 20-081
    • Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie Klinika Ginekologii Onkologicznej i Ginekologii
  • Warszawa, Poland, 00-815
    • Private Practice
  • Warszawa, Poland, 02-066
    • Private Practice
  • Warszawa, Poland, 02-507
    • Centralny Szpital Kliniczny MSWiA w Warszawie, Klinika Poloznictwa, Chorob Kobiecych i Ginekologii Onkologicznej
  • Wroclaw, Poland, 50-369
    • Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wrocławiu, I Katedra i Klinika Ginekologii i Położnictwa
• Spain
  • Barcelona, Spain, 08028
    • Institut Universitari Dexeus Departamento de Ginecología
  • Barcelona, Spain, 08035
    • Hospital Universitario Hebron, gynecology department
  • Barcelona, Spain, 08036
    • Hospital Clinic i provincial de Barcelona, gynecology department
  • Ciudad Real, Spain, 13005
    • Hospital General de Ciudad Real Gynecology
  • Guadalajara, Spain, 19002
    • Hospital Universitario de Guadalajara Consultas de Ginecología (Planta 0)
  • Lugo, Spain, 27002
    • Clinica Ginecologica CEOGA, departamento de Ginecologia
  • Madrid, Spain, 28009
    • Private pratice
  • Madrid, Spain, 28041
    • Hospital universitario 12 de Octubre, departamento de ginecologia
  • Malaga, Spain, 29010
    • CHIP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Subject is a pre-menopausal woman aged between 18 and 48 years inclusive.
• Subject with a Body Mass Index ≥18 and ≤40.
• Subject with myomatous uterus size < 16 weeks.
• Subject must have at least one uterine myoma of at least 3 cm diameter in size and no myoma larger than 10 cm diameter diagnosed by ultrasound.
• Subject complained of strong uterine bleeding.
• Subject is eligible for hysterectomy or myomectomy.
• Females of childbearing potential have to practice a non-hormonal method of contraception.

Exclusion Criteria:

• Subject has a history of or current uterus, cervix, ovarian or breast cancer.
• Subject has a history of endometrium hyperplasia or adenocarcinoma in a biopsy performed within the past 6 months or similar lesions in the screening biopsy.
• Subject has a known severe coagulation disorder.
• Subject has a history of treatment for myoma with a SPRM, including ulipristal acetate.
• Subject has abnormal hepatic function at study entry.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Drug: PGL4001 10mg (oral tablets) for 3 months followed by a period of 10 days of placebo (oral tablets).	Drug: PGL4001, placebo; PGL4001 10mg once daily (oral tablets) for 3 months followed by a period of 10 days of placebo (oral tablets).; Other Names: Ulipristal acetate
Experimental: B; Drug: PGL4001 10mg (oral tablets) for 3 months followed by a period of 10 days of progestin (oral tablets).	Drug: PGL4001, progestin; PGL4001 10mg once daily (oral tablets) for 3 months followed by a period of 10 days of progestin Norethisterone acetate 10mg once daily (oral tablets).; Other Names: Ulipristal acetate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy endpoints	Investigate efficacy of PGL4001 on uterine bleeding (% of subjects in amenorrhea at end of PGL4001 treatment), myoma size (transvaginal ultrasound), pain (short Mc Gill questionnaire) and quality of life (specific UFS-QoL questionnaire and general EQ-5D questionnaire).	From baseline to end of PGL4001 treatment (3months treatment) and to approximately 2 weeks after double blind treatment with progestin/placebo.
Number and proportion of subjects experiencing open label treatment-emergent adverse events		From baseline to end of PGL4001 treatment (3months treatment)

Collaborators and Investigators

• Sponsor: PregLem SA

Publications and helpful links

General Publications

• Donnez J, Vazquez F, Tomaszewski J, Nouri K, Bouchard P, Fauser BC, Barlow DH, Palacios S, Donnez O, Bestel E, Osterloh I, Loumaye E; PEARL III and PEARL III Extension Study Group. Long-term treatment of uterine fibroids with ulipristal acetate ☆. Fertil Steril. 2014 Jun;101(6):1565-73.e1-18. doi: 10.1016/j.fertnstert.2014.02.008. Epub 2014 Mar 12.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: July 1, 2010
• First Submitted That Met QC Criteria: July 2, 2010
• First Posted (Estimate): July 5, 2010

Study Record Updates

• Last Update Posted (Estimate): January 15, 2016
• Last Update Submitted That Met QC Criteria: January 14, 2016
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Muscle Tissue; Leiomyoma; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Progestins; Ulipristal acetate
• Other Study ID Numbers: PGL09-026