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

• ClinicalTrials.gov Identifier: NCT01156857
• Recruitment Status: Completed
• First Posted: July 5, 2010
• Last Update Posted: January 15, 2016
• Sponsor: PregLem SA
• Information provided by (Responsible Party): PregLem SA

Tracking Information

• First Submitted Date: July 1, 2010
• First Posted Date: July 5, 2010
• Last Update Posted Date: January 15, 2016
• Study Start Date: July 2010
• Actual Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 14, 2016)

• Efficacy endpoints [ Time Frame: From baseline to end of PGL4001 treatment (3months treatment) and to approximately 2 weeks after double blind treatment with progestin/placebo. ]
  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).
• Number and proportion of subjects experiencing open label treatment-emergent adverse events [ Time Frame: From baseline to end of PGL4001 treatment (3months treatment) ]

Original Primary Outcome Measures (submitted: July 2, 2010)

• Efficacy endpoints [ Time Frame: From baseline to end of PGL4001 treatment (3months treatment) and to approximately 2 weeks after double blind treatment with progestin/placebo. ]
  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).
• Safety endpoints [ Time Frame: 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 treatment-emergent adverse events observed by physical examination, transvaginal ultrasound and blood samples.
• Exploratory endpoints [ Time Frame: From baseline to end of PGL4001 treatment (3months treatment) ]
  Assessment of the strengh of the first menstraual bleed after PGL4001 treament using the Pictorial Bleeding Assessment Chart (PBAC).

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PGL4001 Efficacy Assessment in Reduction of Symptoms Due to Uterine Leiomyomata
• Official Title: 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.
• Brief Summary: 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.
• 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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Uterine Fibroids

Intervention

• Drug: PGL4001, placebo
  PGL4001 10mg once daily (oral tablets) for 3 months followed by a period of 10 days of placebo (oral tablets).
  Other Name: Ulipristal acetate
• 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 Name: Ulipristal acetate

Study Arms

• Experimental: A
  Drug: PGL4001 10mg (oral tablets) for 3 months followed by a period of 10 days of placebo (oral tablets).
  Intervention: Drug: PGL4001, placebo
• Experimental: B
  Drug: PGL4001 10mg (oral tablets) for 3 months followed by a period of 10 days of progestin (oral tablets).
  Intervention: Drug: PGL4001, progestin

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 6, 2013): 209
• Original Estimated Enrollment (submitted: July 2, 2010): 200
• Actual Study Completion Date: February 2012
• Actual Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 48 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Poland, Spain

Administrative Information

• NCT Number: NCT01156857
• Other Study ID Numbers: PGL09-026
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: PregLem SA
• Original Responsible Party: Dr Elke Bestel, PregLem SA
• Current Study Sponsor: PregLem SA
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: PregLem SA
• Verification Date: June 2013