PGL4001 Versus GnRH-agonist in Uterine Myomas

NCT00740831 | Completed Phase 3 Results DMC

• 1 other identifier: PGL07-022
• Study Type: interventional
• Target: 301
• Locations: 9 countries
• Sites: 46

Brief 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.

Conditions

Uterine Myomas

Keywords

Uterine Myomas

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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

Secondary Outcomes (1)

• Change in the Total Volume of the Three Largest Myomas From Baseline to Week 13

  3 months

Study Arms (3)

A (PGL4001 5 mg)

EXPERIMENTAL

Drug: PGL4001 5mg (oral tablets) and leuproreline matching placebo (intramuscular injection)

Drug: PGL4001

B (PGL4001 10mg)

EXPERIMENTAL

Drug: PGL4001 10 mg (oral tablets) and leuproreline matching placebo (intramuscular injection)

Drug: PGL4001

C (GnRH-agonist)

ACTIVE COMPARATOR

PGL4001 matching placebo (oral tablets) and leuprorelin 3.75 mg (intramuscular injection)

Drug: leuprorelin

Interventions

PGL4001 DRUG

tablets

Also known as: Ulipristal acetate

A (PGL4001 5 mg); B (PGL4001 10mg)

leuprorelin DRUG

solution for injection

Also known as: GnRH-agonist

C (GnRH-agonist)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• PregLem SA: lead

Study Sites (46)

Medical University Graz

Graz, 8036, Austria

Location

Medical University of Innsbruck

Innsbruck, 6020, Austria

Location

Landesklinikum Thermenregion Neunkirchen; Dept. For Gynecology

Neunkirchen, 2620, Austria

Location

Medical University Vienna

Vienna, 1090, Austria

Location

Hopital Erasme, Department of Obstetrics and Gynecology,

Brussels, 1070, Belgium

Location

Clinique Universitaire St-Luc

Brussels, 1200, Belgium

Location

CHR de la Citadelle

Liège, 4000, Belgium

Location

Clinique Universitaire de Mont-Godinne

Yvoir, 5530, Belgium

Location

Cabinet de Gynécologie Chirurgicale

Bordeaux, 33000, France

Location

CHU de Clermont-Ferrand - Polyclinique Gynécologie-Obstétrique

Clermont-Ferrand, 63058, France

Location

Klinik für Gynäkologie und Geburtshilfe

Chemnitz, Germany

Location

Universitätsklinikum Köln Klinik und poliklinik für Frauenheilkunde und Geburtshilfe

Cologne, 50931, Germany

Location

Private Practice

Frankfurt, 60322, Germany

Location

Medizinische Hochschule Hannover, Frauenklinik, Abt. I für Frauenheilkunde und Geburtshilfe,

Hanover, 30625, Germany

Location

Universität zu Lübeck, Klinik für Gynäkologie und Geburtshilfe

Lübeck, 23538, Germany

Location

Poliklinik fur Frauenheilkunde und Geburtshilfe

Münster, 48149, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Ammerland-Klinik GmbH Frauenklinik

Westerstede, 26655, Germany

Location

Soroka University Medical Center, Division of Obstetrics & Gynecology

Beersheba, 84101, Israel

Location

Hadassah University Hospital

Jerusalem, 91120, Israel

Location

Hadassah University Hospital, Mount Scopus

Jerusalem, Israel

Location

Meir Medical Center

Kfar Saba, Israel

Location

Western Galilee Hospital Nahariya

Nahariya, 22100, Israel

Location

Rabin Medical Center, Helen Schneider Hospital for Women

Petah Tikva, 49100, Israel

Location

Clinica Ostetrica e Ginecologica II - Università degli Studi di Bari

Bari, Italy

Location

Clinica Obstetrica - Azienda Ospedaliera Universitaria di Cagliari

Cagliari, Italy

Location

Azienda Ospedaliera S. Gerardo - U. O. Ostetricia e Ginecologia

Monza, Italy

Location

Policlinico Universitario Federico II

Napoli, Italy

Location

Universita di Padova-Dip scienze ginecologiche e della riproduzione umana

Padua, Italy

Location

Clinica Ostetrica e Ginecologica - A. O. U. Policlinico Paolo Giaccone

Palermo, 70100, Italy

Location

Policlinico Universitario "Agostino Gemelli"

Roma, 00168, Italy

Location

University Medical Center Utrecht, Gynecologist Reproductive Medicine and Surgery, Division for Reproductive Medicine

Utrecht, 3584 CX, Netherlands

Location

Prywatna Klinika Polozniczo-Ginekologiczna

Bialystok, 15-224, Poland

Location

INVICTA Sp. Z o.o.

Gdansk, 80-895, Poland

Location

Private Practice

Katowice, 40-084, Poland

Location

Samodzielny Publiczny Szpital Klinika Ginekologii Onkologicznej i Ginekologii

Lublin, 20-081, Poland

Location

Gabinet Lekarski Specjalistyczny "Sonus"

Warsaw, 02-066, Poland

Location

Institut Universitari Dexeus

Barcelona, 08028, Spain

Location

Hospital Universitario Vall d'Hebrón

Barcelona, 08035, Spain

Location

Hospital Clínic i Provincial

Barcelona, 08036, Spain

Location

Clínica Ginecológica CEOGA

Lugo, 27002, Spain

Location

Private Practice

Madrid, 28009, Spain

Location

Hospital Universitario Doce de Octubre

Madrid, 28041, Spain

Location

Hospital Virgen de la Arrixaca Servicio de Ginecología Carretera Madrid-Cartagena

Murcia, 30120, Spain

Location

Hospital Universitaris La Fe

Valencia, 46009, Spain

Location

Hospital Universitario Dr. Peset

Valencia, 46017, Spain

Location

Related Publications (1)

• Donnez J, Tomaszewski J, Vazquez F, Bouchard P, Lemieszczuk B, Baro 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 Feb 2;366(5):421-32. doi: 10.1056/NEJMoa1103180.

  PMID: 22296076 RESULT

MeSH Terms

Interventions

ulipristal acetate; Leuprolide; Gonadotropin-Releasing Hormone

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Dr Elke Bestel
• Organization: PregLem SA

medical@preglem.com

+41 22 884 03 40

Study Officials

• Dr Elke Bestel

  PregLem SA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2008
• First Posted: August 25, 2008
• Study Start: August 1, 2008
• Primary Completion: January 1, 2010
• Study Completion: June 1, 2010
• Last Updated: December 17, 2012
• Results First Posted: November 16, 2012

Record last verified: 2012-12

Locations

FR (2); BE (4); DE (8); IL (6); ES (9); IT (7); AU (4); PL (5); NL (1)