PGL4001 Efficacy Assessment in Reduction of Symptoms Due to Uterine Leiomyomata

Phase 3

Completed

• Conditions: Uterine Fibroids
• Interventions: Drug: PGL4001 5 mg; Drug: PGL4001 10 mg

• Registration Number: NCT01629563
• Lead Sponsor: PregLem SA

Brief Summary

Phase III, multicentre, randomized, double-blind, parallel group, long-term study investigating the efficacy and safety of the 5mg and 10mg doses of PGL4001 for the treatment of uterine myoma.

Detailed Description

The target population is composed of pre-menopausal women with symptomatic uterine myoma(s) characterised by heavy bleeding.The main objective of this study is to assess the sustained efficacy and safety of long term on-off treatment with PGL4001 5 or 10mg doses on uterine bleeding, myoma size, pain and quality of life.

Study Timeline

• Study Start: 2012-06
• Study First Submitted: 2012-06-19
• Study First Submitted QC: 2012-06-25
• Study First Posted: 2012-06-27
• Primary Completion: 2015-01
• Study Completion: 2015-01
• Results First Submitted: 2019-04-04
• Status Verified: 2019-08
• Results First Submitted QC: 2019-08-30
• Last Update Submitted: 2019-08-30
• Results First Posted: 2019-09-04
• Last Update Posted: 2019-09-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 451

Inclusion Criteria

• Be a pre-menopausal woman between 18 and 50 years inclusive.
• Have a Body Mass Index (BMI) ≥ 18 and ≤ 40.
• Have FSH levels ≤ 20 mIU/mL
• Have excessive uterine bleeding due to myoma.
• Have regular menstrual cycles
• Have a myomatous uterus < 16 weeks with at least one myoma ≥ 3 cm in diameter.
• If of childbearing potential the subject must be practicing a non-hormonal method of contraception.

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).
• Has abnormal hepatic function at study entry.
• Has a positive pregnancy test, 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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ulipristal acetate (PGL4001) 5mg	PGL4001 5 mg	All subjects will be asked to take a 150mg size tablet (PGL4001 5mg or matching placebo: placebo 5) orally daily for repeated periods 84 days. The first treatment course will start on the first 4 days of menstruation and will be orally administered, once daily (1 tablet of 150mg size), for 84 days. The following three treatment courses should be started in the first two days of a menstrual period.
Ulipristal acetate (PGL4001) 10mg	PGL4001 10 mg	All subjects will be asked to take a 300mg size tablet (PGL4001 10mg or matching placebo: placebo 10 ) orally daily for repeated periods 84 days. The first treatment course will start on the first 4 days of menstruation and will be orally administered, once daily (1 tablet of 300mg size), for 84 days. The following three treatment courses should be started in the first two days of a menstrual period.

Primary Outcome Measures

Name	Time	Method
Percentage of Subjects Who Are in Amenorrhea at the End of All Four Treatment Courses	18 months study duration per subject (4 3-month intermittent treatment courses)	Amenorrhoea was defined as no more than 1 day of spotting within a 35 day interval. Subjects need to be in amenorrhoea at the end of all four treatment courses, i.e for at least 4x35 days.

Secondary Outcome Measures

Name	Time	Method
Percentage of Subjects Who Were in Amenorrhea at the End of Treatment Course 4	After 18 months	Amenorrhoea was defined as no more than 1 day of spotting within a 35 day interval.
Percentage of Subjects With Controlled Bleeding at the End of All 4 Treatment Courses	After 18 months	Controlled bleeding was defined as no episodes of heavy bleeding and a maximum of 8 days of bleeding during the last 56 days of a treatment course.; Subjects need to be in controlled bleeding at the end of all 4 treatment courses i.e. for at least 4x56 days.
Percentage of Change From Baseline to End of Treatment Course 4 in Pain Using a Visual Analogue Scale (VAS)	After 18 months	Pain was assessed using a Visual Analogue Scale (VAS) ranging from 0 to 100 with higher score indicating more severe pain.; Subjects were exposed to 4 3-month intermittent courses.
Percentage of Change From Baseline to End of Treatment Course 4 in the Total Volume of the 3 Largest Fibroids	After 18 months	For the 3 largest myomas at baseline and the 3 largest myomas at the end of treatment course 4 identified by transvaginal ultrasound, length, height and depth were measured and the volume was estimated by applying the equation for the voulme of an ellipsoid (length x height x depht x π/6).; Subjects were exposed to 4 3-month intermittent courses.
Percentage of Change From Baseline to End of Treatment Course 4 in Quality of Life (Uterine Fibroid Symptom Severity (UFSQoL)	After 18 months	Quality of Life was assessed using a validated questionnaire measuring uterine fibroid symptom severity (UFSQoL) where lower scores indicate fewer symtoms and where a level of 23 has been reported for healthy subject (scale 0-100).; Subjects were exposed to 4 3-month intermittent courses.
Percentage of Change From Baseline to End of Treatment Course 4 in Quality of Life -Uterine Fibroid Health Related Quality of Life (HRQL)	18 months	Quality of Life was measured using a validated uterine fibroid symptom questionnaire. Total score for health related quality of Life (HRQL) range from 0 to 100 with higher scores indicating better Quality of Life.; Subjects were exposed to 4 3-month intermittent courses.

Trial Locations

Locations (48)

Centrum ambulantni gynekologie a primarni pece; 🇨🇿 Brno, Czechia

Femina Sana, s.r.o.; 🇨🇿 Praha 3, Czechia

Nemocnice Jihlava Gynekologicko - porodnicke oddeleni; 🇨🇿 Jihlava, Czechia

Sanatorium SANUS; 🇨🇿 Hradec Kralove, Czechia

Cliniques Universitaires Saint-Luc Gynécologie-Obstétrique; 🇧🇪 Brussels, Belgium

UZ Leuven Campus Gasthuisberg; 🇧🇪 Leuven, Belgium

Fejer Megyei Szent Gyorgy Korhaz Szuleszeti es Nogyogyaszati Osztaly; 🇭🇺 Szekesfehervar, Hungary

Institution Robert Karoly Maganklinika; 🇭🇺 Budapest, Hungary

Family Medicine Centre"Seimos Gydytojas"; 🇱🇹 Vilnius, Lithuania

Centrul Medical SANA SRL; 🇷🇴 Bucuresti, Romania

CHU Mont-Godinne; 🇧🇪 Yvoir, Belgium

CHU de Liège, CHR de la Citadelle Gynécologie-Obstétrique; 🇧🇪 Liège, Belgium

FN Brno Gynekologicko - porodnická klinika; 🇨🇿 Brno, Czechia

FN Olomouc, Porodnicko-Gynekologicka klinika; 🇨🇿 Olomouc, Czechia

CHU Bretonneau Service de Gynécologie Obstétrique; 🇫🇷 Tours, France

Private practice; 🇩🇪 Hamburg, Germany

G-CENTRUM Olomouc s.r.o.; 🇨🇿 Olomouc, Czechia

Hôpital Bicêtre - APHP; 🇫🇷 Le Kremlin Bicêtre, France

Hôpital Bichat, Service de Gynécologie Obstétrique; 🇫🇷 Paris, France

Medizinische Hochschule Hannover Klinik für Frauenheilkunde und Geburtshilfe; 🇩🇪 Hannover, Germany

Praxis für Frauenheilkunde, Klinische Forschung und Weiterbildung; 🇩🇪 Magdeburg, Germany

Frauenarztpraxis; 🇩🇪 Hessen, Germany

Technische Universität München; 🇩🇪 München, Germany

Rethy Pal Korhaz és Rendelointezet Szuleszeti es Nogyogyaszati Osztaly; 🇭🇺 Bekescsaba, Hungary

Szent Anna Szuleszeti, Nogyogyaszati es Ultrahang Maganrendelo; 🇭🇺 Debrecen, Hungary

Josa Andras Oktatokorhaz; 🇭🇺 Nyiregyhaza, Hungary

Dipartimento di Ostetricia e Ginecologia, Università degli Studi di Catanzaro "Magna Graecia"; 🇮🇹 Catanzaro, Italy

Szuleszeti es Nogyogyaszati Osztaly; 🇭🇺 Szentes, Hungary

Sandor Dent Bt.; 🇭🇺 Szolnok, Hungary

Policlinico Universitario "Agostino Gemelli"; 🇮🇹 Roma, Italy

Riga 1. hospital; 🇱🇻 Riga, Latvia

Private Clinic "Maxmeda"; 🇱🇹 Vilnius, Lithuania

Latvian Medical Marine Center; 🇱🇻 Riga, Latvia

Medical Company "ARS"; 🇱🇻 Riga, Latvia

Saules Family Medicine Center; 🇱🇹 Kaunas, Lithuania

Spitalul Clinic Dr. I.Cantacuzino sectia Obstetrica-Ginecologie; 🇷🇴 Bucuresti, Romania

Fortis Medical Center SRL Obstetrica Ginecologie; 🇷🇴 Bucuresti, Romania

Spitalul Clinic de Obstetrica; 🇷🇴 Iasi, Romania

Centrul Medical EUROMED SRL, Departamentul de Obtetrica/Ginecologie; 🇷🇴 Bucuresti, Romania

Kharkiv City Perinatal Center Gynaecological Department #1; 🇺🇦 Kharkiv, Ukraine

Maternity Hospital#4 Department of Gynaecology; 🇺🇦 Zaporizhzhya, Ukraine

Municipal Institution "Maternity Hospital #1" City Center of family planning; 🇺🇦 Odessa, Ukraine

Norfolk & Norwich University Hospital; 🇬🇧 Norwich, United Kingdom

MRC Centre for Reproductive Health University of Edinburgh; 🇬🇧 Edinburgh, United Kingdom

North Middlesex University Hospital NHS Trust; 🇬🇧 London, United Kingdom

Women's Health, Royal Victoria Infirmary; 🇬🇧 Newcastle upon Tyne, United Kingdom

Private Clinic "Kardiolita"; 🇱🇹 Vilnius, Lithuania

Quantum Medical Center SRL Obstetrica-Ginecologie; 🇷🇴 Bucuresti, Romania