Uterine MyomasPhase 3PEARLINCT00755755

PGL4001 Versus Placebo in Uterine Myomas

A Phase 3 study testing PGL4001 (ulipristal) and iron in people with Uterine Myomas, run by PregLem SA at 38 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This trial will assess the efficacy and safety of PGL4001 with concomitant iron administration versus placebo with concomitant iron administration, over a 3-month period for the pre-operative treatment of pre-menopausal women suffering from excessive uterine bleeding due to uterine myoma. Read more about this study

Who is it for?: Ages 18 to 50 years, women only
Conditions the study is for: Uterine Myomas
What is being tested?: PGL4001 (ulipristal) and iron
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 241 participants
Where: 38 sitesin 6 countries
Study dates: Oct 2008to Aug 2010
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
Women only
No healthy volunteers
Adult

Who may be able to join

Be a pre-menopausal woman between 18 and 50 years inclusive.
Have excessive uterine bleeding due to myoma.
Have a myoma-related anaemia.
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.

Who cannot join

Has a history of or current uterine, cervical, ovarian or breast cancer.
Has a history of or current endometrium atypical hyperplasia.
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 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.

Trial locations and contacts

38 sites in 6 countries.

Country

City, postcode or hospital

38 sites in 6 countries

Russia9 sites

Northern State Medical University
Arkhangelsk, 163001
Kursk State Medical University
Kursk, 305035
American Medical Clinic
Saint Petersburg, 190000
Saint-Petersburg City Alexandrovsky Hospital
Saint Petersburg, 193312
Military Medical Academy n.a.S.M Kirov, chair of Obstetrics and Gynecology
Saint Petersburg, 194044
Medical Research Institute (MRI)
Saint Petersburg, 196084
Russian Scientific Research Center of Radiology and Surgical Technologies
Saint Petersburg, 197758
Scientific Research Institute of Obstetrics and Gynecology n.a. D.O.Ott of RAMS
Saint Petersburg, 199034
OAO "Medical company IDK"
Samara, 443067

Other trials in Russia

Ukraine7 sites

Donetsk National Medical University, Department of Obstetrics, Gynecology and Perinatology FPE
Donetsk
City Clinical Hospital N9
Kiev, 04112
Institute of Pediatrics, Obstetrics and Gynecology, Department of Endocrine Gynecology
Kiev
Kiev Maternity Hospital No.2
Kiev
State Enterprise "Institute of Pediatrics, Obstetrics and Gynecology of AMS of Ukraine
Kyiv
Lviv National Medical University named after Danylo Halytskyy
Lviv, 79032
Medical Sanitory Centre VAT "Motor Sich" Gynecology department
Zaporizhzhya

Other trials in Ukraine

Hungary6 sites

Rethy-Pal Hospital-Clinic Bekescsaba, Department of Obstetrics and Gynecology
Békéscsaba, 5600
Saint Stephen Hospital of Budapest,Department of Obstetrics, Gynecology and Gynecological Oncology
Budapest, 1096
Fovarosi Bajcsy-Zsilinszky Hospital, Department of Obstetrics and Gynecology
Budapest, 1106
Saint George Hospital of Fejer County, Department of Obstetrics and Gynecology
Székesfehérvár, 8000
Dr. Bugyi Istvan Hospital, Department of Obstetrics and Gynecology
Szentes, 6600
Saint Borbala Hospital of Komarom-Esztergom County, Department of Obstetrics and Gynecology
Tatabánya, 2800

Other trials in Hungary

India6 sites

M. S. Ramaiah Medical College and Memorial Hospital
Bangalore, 560054
Divakars Speciality Hospital
Bangalore, 560078
Sri Ramachandra Medical College and Research Institute
Chennai, 600116
Dr. Jilla Hospital
Chhatrapati Sambhajinagar, 431001
Om Women's Hospital
Nagpur, 440010
Nagpur Test Tube Baby Centre
Nagpur, 440022

Other trials in India

Romania6 sites

Central Medical Sanador
Bucharest, 011026
Departamentul de Obstretica Ginecologie si Nou Nascuti
Bucharest, 020395
Centrul Medical Euromed, departementul de Obstetrica/Ginecologie
Bucharest, 020762
Sectia Obstretica-Ginecologie Spitalul Clinic Dr. Ioan Cantacuzino
Bucharest, 70266
Spitalul Clinic de Obstetrica Ginecologie Oradea
Oradea, 410053
Spitalul Clinic Judetean de urgenta, sectia de obstetrica Ginecologie I
Târgu Mureş, 540136

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Czechia4 sites

Gynekologicko-porodnicka klinika FN Brno
Brno, 625 00
Mediva
Prague, 110 00
Gynekologicko-porodnicka klinika 1.LF UK a VFN
Prague, 128 00
Gynekologicko-porodnicka klinika UK 2.LF a FN
Prague, 150 06

Other trials in Czechia

About this study

Official title: A Phase III, Randomized, Parallel Group, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy and Safety of PGL4001 (Ulipristal) Versus Placebo for Pre-Operative Treatment of Symptomatic Uterine Myomas

Conditions: Uterine Myomas
Being tested: PGL4001 (ulipristal) and iron, PGL4001 matching placebo and iron

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PGL4001 (ulipristal) and ironDrug
Also called Ulipristal acetate
tablets
PGL4001 matching placebo and ironDrug
Also called Placebo of ulipristal
tablets
PGL4001 (ulipristal) and ironDrug
Also called Ulipristal acetate
Tablets

Study groups in NCT00755755
Study group	Role	What they receive
A (PGL4001 5mg)	Experimental	PGL4001 5 mg (oral tablets) with concomitant oral administration of 1 tablet containing 80 mg Fe2+ Receives: Drug: PGL4001 (ulipristal) and iron
B (PGL4001 10mg)	Experimental	PGL4001 10 mg (oral tablets) with concomitant oral administration of 1 tablet containing 80 mg Fe2+ Receives: Drug: PGL4001 (ulipristal) and iron
C (placebo)	Placebo comparator	PGL4001 matching placebo (oral tablets) with concomitant oral administration of 1 tablet containing 80 mg Fe2+ Receives: Drug: PGL4001 matching placebo and iron

What is being measured

The primary outcome is the main question the study is designed to answer.

Co-primary Endpoint: Percentage of Subjects With Reduction in Uterine Bleeding Defined as a Pictorial Blood-loss Assessment Chart (PBAC) Score <75 at End-of-treatment Visit (Week 13)
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.
Measured: Week 13 visit
Co-primary Endpoint: Percent Change in Total Myoma Volume Assessed by Magnetic Resonance Imaging (MRI) From Screening to End of Treatment Visit (Week 13 Visit)
Percent change in total fibroid volume from screening to end of treatment visit (Week 13 visit) assessed by MRI and read centrally by a radiologist who was unaware of the study-group assignments. The total fibroid volume was the sum of the individual fibroid volumes.
Measured: Week 13

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2008Aug 2010

First posted19 Sep 2008 (estimated)
Study startOct 2008
Primary completionMar 2010
Study completionAug 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Uterine MyomasStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 241 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00755755
Sponsor's protocol ID: PGL07-021
Acronym: PEARLI
Status last verified: Dec 2012
First submitted: 18 Sep 2008
Last updated: 13 Dec 2012
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Donnez J, Tatarchuk TF, Bouchard P, Puscasiu L, Zakharenko NF, Ivanova T, Ugocsai G, Mara M, Jilla MP, Bestel E, Terrill P, Osterloh I, Loumaye E; PEARL I Study Group. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med. 2012 Feb 2;366(5):409-20. doi: 10.1056/NEJMoa1103182.
PubMed 22296075
Barlow DH, Lumsden MA, Fauser BC, Terrill P, Bestel E. Individualized vaginal bleeding experience of women with uterine fibroids in the PEARL I randomized controlled trial comparing the effects of ulipristal acetate or placebo. Hum Reprod. 2014 Mar;29(3):480-9. doi: 10.1093/humrep/det467. Epub 2014 Jan 23.
PubMed 24457604

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Association of Ultrasound Features of the Myometrium Suggestive of Adenomyosis and Clinical Symptoms
Adenomyosis of Uterus
RecruitingPhase 4
Prescription of Letrozole for Uterine Myoma
Leiomyoma, Uterine, Leiomyoma
Recruiting
Prevention of Intra-uterine Adhesions Following Laparoscopic and Laparotomic Myomectomy
Myoma
Not yet recruitingObservational study
Prospective Perioperative Clinical Registry for Women Undergoing Benign Gynecological Surgery
Benign Gynecological Disease, Uterine Fibroids
Not yet recruiting
Terlipressin vs Placebo to Reduce Bleeding in Fibroid Surgery
Uterine Fibroids (Leiomyoma), Uterine Myoma

All Uterine Myomas trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III, Randomized, Parallel Group, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy and Safety of PGL4001 (Ulipristal) Versus Placebo for Pre-Operative Treatment of Symptomatic Uterine Myomas
ClinicalTrials.gov ID: NCT00755755
Acronym / sponsor ID: PEARLI / PGL07-021
Conditions: Uterine Myomas
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 241 participants (actual)
Lead sponsor: PregLem SAIndustry (pharma, biotech, devices)
Study start: Oct 2008
Primary completion: Mar 2010 (actual)
Study completion: Aug 2010 (actual)
First posted: 19 Sep 2008 (estimated)
Results: Posted 16 Nov 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
A (PGL4001 5mg)	Experimental	Drug: PGL4001 (ulipristal) and ironPGL4001 5 mg (oral tablets) with concomitant oral administration of 1 tablet containing 80 mg Fe2+
B (PGL4001 10mg)	Experimental	Drug: PGL4001 (ulipristal) and ironPGL4001 10 mg (oral tablets) with concomitant oral administration of 1 tablet containing 80 mg Fe2+
C (placebo)	Placebo comparator	Drug: PGL4001 matching placebo and ironPGL4001 matching placebo (oral tablets) with concomitant oral administration of 1 tablet containing 80 mg Fe2+

Who may qualify

Ages: 18 to 50 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (7 listed)

Be a pre-menopausal woman between 18 and 50 years inclusive.
Have excessive uterine bleeding due to myoma.
Have a myoma-related anaemia.
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.

Key exclusion criteria (8 listed)

Has a history of or current uterine, cervical, ovarian or breast cancer.
Has a history of or current endometrium atypical hyperplasia.
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 abnormal hepatic function at study entry.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PGL4001 (ulipristal) and ironAlso: Ulipristal acetatetablets	Drug	A (PGL4001 5mg)
PGL4001 matching placebo and ironAlso: Placebo of ulipristaltablets	Drug	C (placebo)
PGL4001 (ulipristal) and ironAlso: Ulipristal acetateTablets	Drug	B (PGL4001 10mg)

Primary outcome

Co-primary Endpoint: Percentage of Subjects With Reduction in Uterine Bleeding Defined as a Pictorial Blood-loss Assessment Chart (PBAC) Score <75 at End-of-treatment Visit (Week 13)
Time frame: 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.
Co-primary Endpoint: Percent Change in Total Myoma Volume Assessed by Magnetic Resonance Imaging (MRI) From Screening to End of Treatment Visit (Week 13 Visit)
Time frame: Week 13
Percent change in total fibroid volume from screening to end of treatment visit (Week 13 visit) assessed by MRI and read centrally by a radiologist who was unaware of the study-group assignments. The total fibroid volume was the sum of the individual fibroid volumes.

Results and safety

Results posted to the registry on 16 Nov 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
A (PGL4001 5mg)	95	89
B (PGL4001 10mg)	98	90
C (Placebo)	48	45

Primary outcome: Co-primary Endpoint: Percentage of Subjects With Reduction in Uterine Bleeding Defined as a Pictorial Blood-loss Assessment Chart (PBAC) Score <75 at End-of-treatment Visit (Week 13)

Time frame: Week 13 visit. Number. Unit: percentage of patients

Measure	A (PGL4001 5mg) n = 94	B (PGL4001 10mg) n = 93	C (Placebo) n = 48
Value	91.5	92.5	18.8

A (PGL4001 5mg) vs C (Placebo): Difference in proportions: 72.7 (95% CI 55.1 to 83.2), p <0.001, Cochran-Mantel-Haenszel
B (PGL4001 10mg) vs C (Placebo): Difference in proportions: 73.7 (95% CI 56.2 to 84.0), p <0.001, Cochran-Mantel-Haenszel

Population analysed: Intent-to-treat

Primary outcome: Co-primary Endpoint: Percent Change in Total Myoma Volume Assessed by Magnetic Resonance Imaging (MRI) From Screening to End of Treatment Visit (Week 13 Visit)

Time frame: Week 13. Median (Full Range). Unit: percentage of change

Measure	A (PGL4001 5mg) n = 85	B (PGL4001 10mg) n = 80	C (Placebo) n = 45
Value	-21.2 (-100 to 223.4)	-12.3 (-100 to 146.6)	3 (-100 to 134.8)

A (PGL4001 5mg) vs C (Placebo): Median Difference (Final Values): -22.6 (95% CI -36.1 to -8.2), p = 0.002, Wilcoxon (Mann-Whitney)
B (PGL4001 10mg) vs C (Placebo): Median Difference (Final Values): -18.2 (95% CI -33.0 to -5.2), p = 0.006, Wilcoxon (Mann-Whitney)

Population analysed: Intent-to-treat

Adverse events

Time frame: 3 years 2 months. Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
A (PGL4001 5mg)	2 of 95 (2.1%)	47 of 95 (49.5%)	Not reported
B (PGL4001 10mg)	1 of 98 (1%)	52 of 98 (53.1%)	Not reported
C (Placebo)	2 of 48 (4.2%)	22 of 48 (45.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 22296075Donnez J, Tatarchuk TF, Bouchard P, Puscasiu L, Zakharenko NF, Ivanova T, Ugocsai G, Mara M, Jilla MP, Bestel E, Terrill P, Osterloh I, Loumaye E; PEARL I Study Group. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med. 2012 Feb 2;366(5):409-20. doi: 10.1056/NEJMoa1103182.
Derived from this study: PubMed 24457604Barlow DH, Lumsden MA, Fauser BC, Terrill P, Bestel E. Individualized vaginal bleeding experience of women with uterine fibroids in the PEARL I randomized controlled trial comparing the effects of ulipristal acetate or placebo. Hum Reprod. 2014 Mar;29(3):480-9. doi: 10.1093/humrep/det467. Epub 2014 Jan 23.

Related trials for Uterine Myomas

RecruitingObservational study
Association of Ultrasound Features of the Myometrium Suggestive of Adenomyosis and Clinical Symptoms
Adenomyosis of Uterus
RecruitingPhase 4
Prescription of Letrozole for Uterine Myoma
Leiomyoma, Uterine, Leiomyoma
Recruiting
Prevention of Intra-uterine Adhesions Following Laparoscopic and Laparotomic Myomectomy
Myoma
Not yet recruitingObservational study
Prospective Perioperative Clinical Registry for Women Undergoing Benign Gynecological Surgery
Benign Gynecological Disease, Uterine Fibroids
Not yet recruiting
Terlipressin vs Placebo to Reduce Bleeding in Fibroid Surgery
Uterine Fibroids (Leiomyoma), Uterine Myoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Dr Elke Bestel study director

PregLem SA

38 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing PGL4001 (ulipristal) and iron in people with Uterine Myomas, run by PregLem SA at 38 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in Russia, Ukraine, Hungary, India, Romania and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Nov 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Co-primary Endpoint: Percentage of Subjects With Reduction in Uterine Bleeding Defined as a Pictorial Blood-loss Assessment Chart (PBAC) Score <75 at End-of-treatment Visit (Week 13) (time frame: Week 13 visit). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00755755, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2012.