Adenomyosis and Ulipristal Acetate (FRA-IIT-UPA)

Pilot Phase II, Randomized , and Control in Double Blind Placebo Effectiveness a 3 Months on Bleeding Fibroids Treatment With ULIPRISTAL ACETATE 10 mg/Day in Patients Suffering From Symptomatic Endometriosis

Evaluation of efficiency of selective progesterone receptor modulators (SPRM) (Ulipristal acetate) on bleeding control and pain for patients with adenomyosis and wish to keep fertility.

Study Overview

• Status: Completed
• Conditions: Adenomyosis
• Intervention / Treatment: Drug: Placebo; Drug: Ulipristal acetate

Detailed Description

After inclusion according to criteria, 2 arms : placebo and Ulipristal acetate (UA) 10mg with randomisation, 1 patient with placebo for 3 patients with UA.

48 patients will be included in this trial. The end point will be the bleeding evaluated by Pictorial Blood-loss Assessment Chart (PBAC) score, the amenorrhea rate and the pain evaluated with visual analogic scale.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Le Kremlin Bicêtre, France, 94275
    • AP-HP, Bicêtre Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 26 years to 46 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Not postmenopausal women aged 30 to 50,
• Accepting to give consent informed in writing,
• Suffering from a symptomatic pelvic endometriosis (menorrhagia isolated or associated with pain)
• Diagnosis information, confirmed the adenomyosis (T2-weighted) MRI and/or transvaginal ultrasonography, in the 6 months preceding the inclusion-having a score of bleeding (PBAC) > 100 from J1 to J8 of the menstruation before the visit of inclusion,
• With an index of body mass (IMC) ≥18 and < 40,
• Using a reliable method of non-hormonal contraception (non-hormonal intrauterine device (IUDs), sexual abstinence, diaphragm, condoms or vasectomy by the partner, or having undergone a surgical sterilization),
• Willing and able to complete auto-questionnaires in french
• Had no difficulties to understand and communicate with the investigator and his representatives
• Affiliation to a social security or assign.

Exclusion Criteria:

• Patient with a hormonal oral contraceptive or with a hormonal intrauterine Device (IUD) contraceptive
• Patient with a history of surgery (other than a caesarean or a cervical conization) uterus, ablation endometrial or uterine artery embolization,
• With other than the endometriosis endometrial pathology,
• Suffering of myoma of type 0, 1, 2 or 3,
• Requiring a transfusion or having a ≤6g/dL hemoglobin
• Existence of systemic coagulation,
• History of thromboembolism
• Progestagen taking severe disorders in the month preceding the tour selection, and corticosteroids and aspirin in the previous week,
• Existence of Pathology renal, respiratory or cardiac severe or progressive,
• Having a disturbed liver function (defined by the aspartate aminotransferase (ASAT), Alanine Amino Transferase (ALAT), γGlutamylTranspeptidase, alkaline phosphatase or total bilirubin above 2 times the upper limit of normal),
• Existence or suspicion of malignancy,
• Considering pregnancy in the coming year,
• Pregnant patient or nursing
• Any clinical condition that the investigator considers incompatible with the conduct of the study in terms of acceptable security,
• Participation in courses at another clinical study
• Patient whose accession to the test procedures may be insufficient or for which a long term follow-up seems difficult to achieve
• Person under authorship or curators under safeguard of justice
• History of hypersensitivity to the ulipristal or any of the excipients of ESMYA ® 5 mg tablet.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ulipristal acetate; ESMYA® : 2 tablets of 5mg per day during 3 months, per os	Drug: Ulipristal acetate; Other Names: ESMYA®
Placebo Comparator: Placebo; 2 tablets of 5mg per day during 3 months, per os	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients with a control uterine bleeding estimated by a score of Pictorial Blood-loss Assessment Chart (PABC) < 75 of 28 days to the discontinuation of the study (S13)	after 12 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evolution of the PBAC score over 28 days compared to pre-treatment score (J1)		at week5 (day29), week9 (day57), week13 (day85) and month6 (week26, week28) after starting of the treatment
Percentage of patients with uterine bleeding control estimated by a score of PBAC < 75 on 28 days		at week5 (day29), week9 (day57), week13 (day85) and month6 (week26, week28) after starting of the treatment (Day1)
Evolution of the PBAC score calculated from the sum on the 28 days during the treatment period for the first day of control of uterine bleeding;		at Day 29
percentage of patients with amenorrhea estimated by a score of PBAC ≤2 on 28 days		to week5 (day29), week9 (day57), week13 (day85) and month6 (week26, week28) after starting of the treatment (Day1)
Evolution of the PBAC score calculated from the sum on the 28 days during the treatment period for the first day of amenorrhea		for the first day of amenorrhea after the treatment
Evolution of pain through a Visual scale analogue between J1 and S5 (J29) S13 (J85) and M6 (S26 S28),		between day1 (before treatment) and week5 (day29), week9 (day57), week13 (day85) and month6 (week26, week28) after starting of the treatment (Day1)
Evolution of analgesics using between each visit (number of days of treatment and the percentage of patients without analgesic over each period of 28 days of collection of the PBAC) and by bearing the information provided by the investigator		between day1 (before treatment) and week5 (day29), week9 (day57), week13 (day85) and month6 (week26, week28) after starting of the treatment (Day1)
Evolution quality of life questionnaire with Uterine Fibroid Symptom and health related Quality of Life (UFS - QOL) questionnaire		between day1 (before treatment) and week5 (day29), week9 (day57), week13 (day85) and month6 (week26, week28) after starting of the treatment (Day1)
Evolution of anemia by hemoglobin and ferritin concentration and coagulation by the CAW		between day1 (before treatment) and week5 (day29), week9 (day57), week13 (day85) and month6 (week26, week28) after starting of the treatment (Day1)
Evaluation of the adenomyosis by MRI or ultrasound transvaginal : existence/absence, focal length/diffuse, shallow/deep		Before the treatment and 6 months after beginning of the treatment
blood pressure and heart rate, respiratory rate		Before the treatment and up to 6 months after beginning of the treatment
Number of participants with adverse events and their grades as assessed by CTCAE v4.0		Before the treatment and up to 6 months after beginning of the treatment
biological examinations: hemoglobin, ferritin, TCA.	Safety assessment	Before the treatment and up to 6 months after beginning of the treatment
Frequency of flashes of heat, headache, thickening of the endometrium, uterine bleeding, ovarian cyst.		Before the treatment and up to 6 months after beginning of the treatment

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Gedeon Richter Ltd.
• Investigators: Principal Investigator: Hervé FERNANDEZ, MD, PhD, AP-HP, Bicêtre Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2015
• Primary Completion (Actual): February 2, 2018
• Study Completion (Actual): March 17, 2020

Study Registration Dates

• First Submitted: May 29, 2015
• First Submitted That Met QC Criteria: October 23, 2015
• First Posted (Estimate): October 27, 2015

Study Record Updates

• Last Update Posted (Actual): September 27, 2022
• Last Update Submitted That Met QC Criteria: September 26, 2022
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: sonography; ulipristal acetate; adenomyosis; Magnetic resonance imaging [MRI]; Pictorial Blood-loss Assessment Chart [PBAC]
• Additional Relevant MeSH Terms: Uterine Diseases; Adenomyosis; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Ulipristal acetate
• Other Study ID Numbers: P141201; 2014-004403-75 (EudraCT Number)