PGL14-001 (PREMIUM) - non-interventional study, safety of Esmya
Research type
Research Study
Full title
A prospective, multi-national, multicentre, non-interventional study to evaluate the long term safety of Esmya, in particular the endometrial safety, and the current prescription and management patterns of Esmya in a long term treatment setting.
IRAS ID
194366
Contact name
Edward Morris
Contact email
Sponsor organisation
PregLem S.A.
Clinicaltrials.gov Identifier
Duration of Study in the UK
6 years, 8 months, 25 days
Research summary
Research Summary
The aim of this non-interventional study is to evaluate the long term safety, including the safety of the endometrium (the lining of the womb), of Esmya (ulipristal acetate (UPA)), as well as its prescription patterns in standard medical practice. The study also has an exploratory objective of assessing participants' quality of life in a long term setting.Esmya has been approved in Europe for pre-operative treatment and for repeated courses of treatment of moderate to severe symptoms of uterine fibroids (a non-cancerous tumours of the womb). Uterine fibroids occur in about 20-40% of women of childbearing age. In addition to adversely affecting quality of life and fertility, fibroids can cause heavy menstrual bleeding, pelvic pressure and pain, menstrual cramps and chronic tiredness.
The study population will include women with moderate to severe symptoms of uterine fibroids, and for whom a treatment with Esmya in a long term manner is planned, and subjects who were previously exposed to UPA in long term Phase III studies. The plan is to enrol approximately 1,500 participants at approximately 100-150 European Union (EU) clinical practice sites in approximately 15 countries. The participants will be followed for an observation period of 60 months (5 years) from treatment start. Investigators are to manage and treat the participants according to their standard medical practice.
Summary of Results
This was a prospective, multicentre, non-interventional study in female patients who had been diagnosed with moderate to severe symptoms of uterine fibroids and were initiating long-term treatment with Esmya (PGL14-001, PREMIUM) or subjects who were previously exposed to ulipristal acetate 5 or 10 mg in the long-term Phase III (LT Phase III) studies.
Eligible, consenting patients were to be enrolled consecutively from approximately 100 to 150 clinical practice sites in the EU and United Kingdom (UK), and were followed for an observation period of 60 months from treatment start. Study visits occurred at enrolment and were then followed by visits according to their standard medical practice of the physician. Standard medical practice was assumed to include, at minimum, visits approximately every 8 months (i.e. after approximately two treatment courses). However, requested study data were collected, when available, at visits during regular clinical practice regardless of the time since the last visit.
The primary objective of this study is to provide real-world data related to the long-term safety, including endometrial safety, and current prescription patterns of Esmya as treatment for symptomatic uterine fibroids. This study also aimed to address the following safety concerns included in the current ulipristal acetate Risk Management Plan (RMP). The safety concerns addressed:
• Inappropriate management of endometrium thickening (unnecessary interventions or treatments) A total of 7 (0.5%) patients have been identified with suspected inappropriate management of endometrium thickening.
• Inappropriate diagnosis of endometrial hyperplasia (mistaking progesterone receptor modulator‐associated endometrial changes [PAEC] for hyperplasia) A total of 2 (0.15%) patients have been identified with suspected inappropriate diagnosis of endometrial hyperplasia, both from Germany and using an ultrasound for such diagnoses. There was no case identified with an inappropriate diagnosis of endometrial hyperplasia (mistaking PAEC for hyperplasia) among biopsies reviewed by the independent external expert pathologist.
• Acute uterine bleeding requiring immediate intervention A total of 11 (0.8%) patients have been reported with suspected acute uterine bleeding requiring immediate intervention. No trend could be identified for these cases, e.g. related to treatment course length, treatment course number, or demographics. One of the main symptoms that affects patients with uterine fibroids is strong uterine bleeding, which constitutes a significant confounding factor in interpreting the data in this population.
• Treatment course(s) beyond 3 months A total of 104 (7.7%) patients were reported with continuous treatment courses beyond 3 months. No safety concern was identified among these patients compared to the rest of the study population.
• Long-term effects of prolonged treatment on the endometrium No long-term effects of prolonged treatment on the endometrium (continuous course beyond 3 months or more than 4 intermittent treatment courses) were identified.
• Delayed diagnosis of atypical endometrial hyperplasia or adenocarcinoma One case of atypical hyperplasia and one case of endometrial adenocarcinoma were reported, however there were no cases identified with delayed diagnosis of atypical endometrial hyperplasia or adenocarcinoma.
• Impact on surgery There were no identified reports of Esmya treatment having either a beneficial or adverse impact on (uterine fibroid) surgery.
At the end of the study, data were available from 1359 patients who had received at least one dose of Esmya/ulipristal acetate, providing real-world data related to the current treatment patterns and clinical outcomes of Esmya as a treatment for symptomatic uterine fibroids. No new safety concerns have been identified in this study.REC name
West Midlands - Black Country Research Ethics Committee
REC reference
16/WM/0250
Date of REC Opinion
25 May 2016
REC opinion
Favourable Opinion