Mode of Action Study of Vilaprisan and Ulipristal Acetate in Patients With Uterine Fibroids for Whom Surgery is Planned

Phase 1

Terminated

• Conditions: Leiomyoma
• Interventions: Drug: Vilaprisan, BAY1002670; Drug: Ulipristal

• Registration Number: NCT03342859
• Lead Sponsor: Bayer

Brief Summary

To investigate the clinical effects of vilaprisan and ulipristal acetate at molecular and cellular level on uterine and fibroid tissue taken from patients (after surgery / biopsy)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-10-26
• Study First Submitted QC: 2017-11-10
• Study Start: 2017-11-16
• Study First Posted: 2017-11-17
• Primary Completion: 2018-12-17
• Study Completion: 2020-01-13
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-05
• Last Update Posted: 2021-01-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 10

Inclusion Criteria

• Patients 18 years and older and premenopausal (based on gynecological history i.e. still menstruating; no significant estrogen deficiency symptoms)
• Diagnosis of uterine fibroids documented by ultrasound and relevant symptoms reported by the patient (e.g. heavy menstrual bleeding, pelvic pressure)
• Patients for whom surgery (hysterectomy or myomectomy) for the treatment of symptomatic uterine fibroids is planned
• Patients who are otherwise healthy as shown by medical history, physical and gynecological examinations, and laboratory test results

Exclusion Criteria

• Contraindications for the progesterone receptor modulators (PRM) vilaprisan or ulipristal acetate
• Use of medication that might interfere with the conduct of the study or the interpretation of the results (e.g. continuing use of hormonal contraceptives, tranexamic acid or other treatments for heavy menstrual bleeding, progesterone receptor modulators, gonadotropin-releasing hormone agonist, anticoagulants, moderate and strong CYP3A4 inducers and moderate and strong CYP3A4 inhibitors within a defined time period before treatment starts.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vilaprisan group	Vilaprisan, BAY1002670	Vilaprisan 2 mg oral daily over 8-12 weeks
Ulipristal group	Ulipristal	Ulipristal 5 mg oral daily over 8-12 weeks

Primary Outcome Measures

Name	Time	Method
The expression level of biomarker for glandular and stromal cell proliferation (Ki-67) in the endometrium of the same patient before treatment and when treated with VPR (vilaprisan) prior to surgery	From pre-treatment biopsy to post-treatment biopsy_ Up to 20 weeks	Pre-treatment biopsy: The endometrial biopsy will be performed between Day 6 to 13 of the menstrual cycle that occurs after the screening visit and before treatment commences. Post-treatment biopsy as second endometrial biopsy is taken (if possible within 24 hours) after end of VPR treatment.
The expression level of biomarkers for apoptotic regulation in fibroid tissue (BCL-2, caspase 3) of patients not treated with PRM and those who have been treated with VPR prior to surgery	After maximum 12 weeks of treatment	Fibroid tissue sample will be collected from the uterus following surgery (if possible within 24 hours) after end of VPR treatment
The expression level of nuclear hormone receptors in the endometrium (progesterone receptor (PR), PR-B, estrogen receptor (ER), androgen receptor (AR)) of the same patient before treatment and when treated with VPR prior to surgery	From pre-treatment biopsy to post-treatment biopsy_ Up to 20 weeks	Pre-treatment biopsy: The endometrial biopsy will be performed between Day 6 to 13 of the menstrual cycle that occurs after the screening visit and before treatment commences. Post-treatment biopsy as second endometrial biopsy is taken (if possible within 24 hours) after end of VPR treatment
The expression level of biomarker for myoma cell proliferation (Ki-67) in fibroid tissue of patients not treated with PRM (progesterone receptor modulator )and those who have been treated with VPR prior to surgery	After maximum 12 weeks of treatment	Fibroid tissue sample will be collected from the uterus following surgery (if possible within 24 hours) after end of VPR treatment
The expression level of biomarkers for apoptotic regulation in the endometrium (BCL-2 (B-cell lymphoma 2), caspase 3) of the same patient before treatment and when treated with VPR prior to surgery	From pre-treatment biopsy to post-treatment biopsy_ Up to 20 weeks	Pre-treatment biopsy: The endometrial biopsy will be performed between Day 6 to 13 of the menstrual cycle that occurs after the screening visit and before treatment commences. Post-treatment biopsy as second endometrial biopsy is taken (if possible within 24 hours) after end of VPR treatment

Secondary Outcome Measures

Name	Time	Method
The expression levels of biomarkers (Ki-67, caspase 3 and BCL-2) in the endometrium of the same patient before treatment and when treated with UPA prior to surgery	From pre-treatment biopsy to post-treatment biopsy_ Up to 20 weeks	Pre-treatment biopsy: The endometrial biopsy will be performed between Day 6 to 13 of the menstrual cycle that occurs after the screening visit and before treatment commences. Post-treatment biopsy as second endometrial biopsy is taken (if possible within 24 hours) after end of treatment. Fibroid tissue sample will be collected from the uterus following surgery (if possible within 24 hours) after end of treatment
The expression levels of biomarkers (Ki-67, caspase 3 and BCL-2) in fibriod tissue of patients not treated with PRM and those who have been treated with UPA prior to surgery	After maximum 12 weeks of treatment	Fibroid tissue sample will be collected from the uterus following surgery (if possible within 24 hours) after end of VPR treatment

Trial Locations

Locations (1)

Edinburgh Royal Infirmary/ NHS Lothian; 🇬🇧 Edinburgh, United Kingdom