Back to resultsMode of Action Study of Vilaprisan and Ulipristal Acetate in Patients With Uterine Fibroids for Whom Surgery is Planned
Primary Purpose
Leiomyoma
Status
Terminated
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Vilaprisan, BAY1002670
Ulipristal
Sponsored by
About this trial
This is an interventional other trial for Leiomyoma focused on measuring Uterine fibroids, Bleeding reduction, Vilaprisan, Mode of action, Hysterectomy, Myomectomy, Pharmacodynamic
Eligibility Criteria
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.
Sites / Locations
- Edinburgh Royal Infirmary/ NHS Lothian
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
No Intervention
Arm Label
Vilaprisan group
Ulipristal group
Control group
Arm Description
Vilaprisan 2 mg oral daily over 8-12 weeks
Ulipristal 5 mg oral daily over 8-12 weeks
Patients undergoing surgery without any prior treatment, as control group
Outcomes
Primary Outcome Measures
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
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
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
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
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
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
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
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
Fibroid tissue sample will be collected from the uterus following surgery (if possible within 24 hours) after end of VPR treatment
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03342859
Brief Title
Mode of Action Study of Vilaprisan and Ulipristal Acetate in Patients With Uterine Fibroids for Whom Surgery is Planned
Official Title
An Open-label, Parallel Group, Multi-center Study to Investigate Pharmacodynamic Effects After Daily Administration of Vilaprisan or Ulipristal Acetate for 8-12 Weeks in Patients With Uterine Fibroids for Whom Surgery (Hysterectomy or Myomectomy) is Planned
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Terminated
Why Stopped
Due to findings in the preclinical carcinogenicity studies for vilaprisan (BAY1002670)
Study Start Date
November 16, 2017 (Actual)
Primary Completion Date
December 17, 2018 (Actual)
Study Completion Date
January 13, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leiomyoma
Keywords
Uterine fibroids, Bleeding reduction, Vilaprisan, Mode of action, Hysterectomy, Myomectomy, Pharmacodynamic
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vilaprisan group
Arm Type
Experimental
Arm Description
Vilaprisan 2 mg oral daily over 8-12 weeks
Arm Title
Ulipristal group
Arm Type
Active Comparator
Arm Description
Ulipristal 5 mg oral daily over 8-12 weeks
Arm Title
Control group
Arm Type
No Intervention
Arm Description
Patients undergoing surgery without any prior treatment, as control group
Intervention Type
Drug
Intervention Name(s)
Vilaprisan, BAY1002670
Intervention Description
Daily single oral doses of 2 mg vilaprisan over 8-12 weeks
Intervention Type
Drug
Intervention Name(s)
Ulipristal
Intervention Description
Daily single oral doses of 5 mg ulipristal over 8-12 weeks
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
From pre-treatment biopsy to post-treatment biopsy_ Up to 20 weeks
Title
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
Description
Fibroid tissue sample will be collected from the uterus following surgery (if possible within 24 hours) after end of VPR treatment
Time Frame
After maximum 12 weeks of treatment
Title
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
Description
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
Time Frame
From pre-treatment biopsy to post-treatment biopsy_ Up to 20 weeks
Title
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
Description
Fibroid tissue sample will be collected from the uterus following surgery (if possible within 24 hours) after end of VPR treatment
Time Frame
After maximum 12 weeks of treatment
Title
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
Description
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
Time Frame
From pre-treatment biopsy to post-treatment biopsy_ Up to 20 weeks
Secondary Outcome Measure Information:
Title
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
Description
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
Time Frame
From pre-treatment biopsy to post-treatment biopsy_ Up to 20 weeks
Title
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
Description
Fibroid tissue sample will be collected from the uterus following surgery (if possible within 24 hours) after end of VPR treatment
Time Frame
After maximum 12 weeks of treatment
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
Facility Name
Edinburgh Royal Infirmary/ NHS Lothian
City
Edinburgh
ZIP/Postal Code
EH16 4TJ
Country
United Kingdom
12. IPD Sharing Statement
Links:
URL
http://clinicaltrials.bayer.com/
Description
Click here to find results for studies related to Bayer products
Learn more about this trial
Mode of Action Study of Vilaprisan and Ulipristal Acetate in Patients With Uterine Fibroids for Whom Surgery is Planned
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