PGL4001 Versus GnRH-agonist in Uterine Myomas

Uterine Myomas Clinical Trial

— PEARLII  

Official title:

A Phase III, Randomised, Parallel Group, Double-blind, Double-dummy, Active Comparator-controlled, Multicenter Study to Assess the Efficacy and Safety of PGL4001 vs GnRH-agonist for Pre-operative Ttt of Symptomatic Uterine Myomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00740831
• Other study ID #: PGL07-022
• Status: Completed
• Phase: Phase 3
• First received: August 22, 2008
• Last updated: December 13, 2012
• Start date: August 2008
• Est. completion date: June 2010

Study information

• Verified date: December 2012
• Source: PregLem SA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsBelgium: Institutional Review BoardAustria: Agency for Health and Food SafetyAustria: EthikkommissionItaly: Ethics CommitteeSpain: Comité Ético de Investigación ClínicaSpain: Spanish Agency of MedicinesIsrael: Ethics CommissionGermany: Federal Institute for Drugs and Medical DevicesFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Poland: Ministry of HealthNetherlands: Medicines Evaluation Board (MEB)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 301
• Est. completion date: June 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leiomyoma
• Myoma
• Uterine Myomas

Intervention

Drug:
• PGL4001
tablets
• leuprorelin
solution for injection

Locations

Country	Name	City	State
Austria	Medical University Graz	Graz
Austria	Medical University of Innsbruck	Innsbruck
Austria	Landesklinikum Thermenregion Neunkirchen; Dept. For Gynecology	Neunkirchen
Austria	Medical University Vienna	Vienna
Belgium	Clinique Universitaire St-Luc	Brussels
Belgium	Hopital Erasme, Department of Obstetrics and Gynecology,	Brussels
Belgium	CHR de la Citadelle	Liège
Belgium	Clinique Universitaire de Mont-Godinne	Yvoir
France	Cabinet de Gynécologie Chirurgicale	Bordeaux
France	CHU de Clermont-Ferrand - Polyclinique Gynécologie-Obstétrique	Clermont Ferrand
Germany	Klinik für Gynäkologie und Geburtshilfe	Chemnitz
Germany	Private Practice	Frankfurt
Germany	Medizinische Hochschule Hannover, Frauenklinik, Abt. I für Frauenheilkunde und Geburtshilfe,	Hannover
Germany	Universitätsklinikum Köln Klinik und poliklinik für Frauenheilkunde und Geburtshilfe	Köln
Germany	Universität zu Lübeck, Klinik für Gynäkologie und Geburtshilfe	Lübeck
Germany	Poliklinik fur Frauenheilkunde und Geburtshilfe	Münster
Germany	Universitätsklinikum Tübingen	Tübingen
Germany	Ammerland-Klinik GmbH Frauenklinik	Westerstede
Israel	Soroka University Medical Center, Division of Obstetrics & Gynecology	Be'er Sheva
Israel	Hadassah University Hospital	Jerusalem
Israel	Hadassah University Hospital, Mount Scopus	Jerusalem
Israel	Meir Medical Center	Kfar-Saba
Israel	Western Galilee Hospital Nahariya	Nahariya
Israel	Rabin Medical Center, Helen Schneider Hospital for Women	Petach Tikva
Italy	Clinica Ostetrica e Ginecologica II - Università degli Studi di Bari	Bari
Italy	Clinica Obstetrica - Azienda Ospedaliera Universitaria di Cagliari	Cagliari
Italy	Azienda Ospedaliera S. Gerardo - U. O. Ostetricia e Ginecologia	Monza
Italy	Policlinico Universitario Federico II	Napoli
Italy	Universita di Padova-Dip scienze ginecologiche e della riproduzione umana	Padova
Italy	Clinica Ostetrica e Ginecologica - A. O. U. Policlinico Paolo Giaccone	Palermo
Italy	Policlinico Universitario "Agostino Gemelli"	Roma
Netherlands	University Medical Center Utrecht, Gynecologist Reproductive Medicine and Surgery, Division for Reproductive Medicine	Utrecht
Poland	Prywatna Klinika Polozniczo-Ginekologiczna	Bialystok
Poland	INVICTA Sp. Z o.o.	Gdansk
Poland	Private Practice	Katowice
Poland	Samodzielny Publiczny Szpital Klinika Ginekologii Onkologicznej i Ginekologii	Lublin
Poland	Gabinet Lekarski Specjalistyczny "Sonus"	Warszawa
Spain	Hospital Clínic i Provincial	Barcelona
Spain	Hospital Universitario Vall d'Hebrón	Barcelona
Spain	Institut Universitari Dexeus	Barcelona
Spain	Clínica Ginecológica CEOGA	Lugo
Spain	Hospital Universitario Doce de Octubre	Madrid
Spain	Private Practice	Madrid
Spain	Hospital Virgen de la Arrixaca Servicio de Ginecología Carretera Madrid-Cartagena	Murcia
Spain	Hospital Universitario Dr. Peset	Valencia
Spain	Hospital Universitaris La Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
PregLem SA

Countries where clinical trial is conducted

Austria,  Belgium,  France,  Germany,  Israel,  Italy,  Netherlands,  Poland,  Spain, 

References & Publications (1)

Donnez J, Tomaszewski J, Vázquez F, Bouchard P, Lemieszczuk B, Baró F, Nouri K, Selvaggi L, Sodowski K, Bestel E, Terrill P, Osterloh I, Loumaye E; PEARL II Study Group. Ulipristal acetate versus leuprolide acetate for uterine fibroids. N Engl J Med. 2012 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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.	3 months	No
Primary	Co-primary Safety Endpoint: Serum Estradiol Levels at End of Treatment Visit (Week 13 Visit) for PGL4001 Compared With GnRHagonist	Measured by log 10 (log pg/ml) transformed values for estradiol (E2) in blood samples	Week 13 visit	Yes
Primary	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	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.	Up to week 17	Yes
Secondary	Change in the Total Volume of the Three Largest Myomas From Baseline to Week 13	Assessment of PGL4001 capacity to decrease volume of the three largest myomas was performed at each center by means of ultrasonography at baseline and at week 13.; The total volume of the three largest myomas assessed at screening and at end-of-treatment visit (Week 13) was analysed on a logarithm transformed scale (to base 10).	3 months	No