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    Clinical Trial Results:
    A randomized, parallel-group, double-blind placebo-controlled and open label active-controlled, multi-center study to assess the efficacy and safety of vilaprisan in patients with uterine fibroids

    Summary
    EudraCT number
    2014-004221-41
    Trial protocol
    SE   DE   PT   NL   GB   FI   AT   CZ   HU   LT   BE   ES   PL  
    Global end of trial date
    26 Oct 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    27 Oct 2017
    First version publication date
    27 Oct 2017
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    BAY1002670/17541
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02465814
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Bayer AG
    Sponsor organisation address
    Kaiser-Wilhelm-Allee, D-51368 Leverkusen, Germany,
    Public contact
    Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
    Scientific contact
    Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    26 Oct 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Oct 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to assess the efficacy of vilaprisan in subjects with uterine fibroids compared to placebo.
    Protection of trial subjects
    The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent form was read by and explained to all subjects. Participating subjects signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    01 Jun 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 4
    Country: Number of subjects enrolled
    Norway: 8
    Country: Number of subjects enrolled
    Poland: 50
    Country: Number of subjects enrolled
    Portugal: 4
    Country: Number of subjects enrolled
    Spain: 1
    Country: Number of subjects enrolled
    Sweden: 7
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    Austria: 1
    Country: Number of subjects enrolled
    Belgium: 4
    Country: Number of subjects enrolled
    Bulgaria: 7
    Country: Number of subjects enrolled
    Czech Republic: 29
    Country: Number of subjects enrolled
    Finland: 4
    Country: Number of subjects enrolled
    Germany: 12
    Country: Number of subjects enrolled
    Hungary: 15
    Country: Number of subjects enrolled
    Lithuania: 10
    Country: Number of subjects enrolled
    Italy: 13
    Worldwide total number of subjects
    172
    EEA total number of subjects
    172
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    172
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Study was conducted at 47 study centers in Austria, Belgium, Bulgaria, Czech Republic, Finland, Germany, Hungary, Italy, Lithuania, Netherlands, Norway, Poland, Portugal, Spain, Sweden, and United Kingdom, between 01 June 2015 (first subject first visit) and 26 October 2016 (last subject last visit).

    Pre-assignment
    Screening details
    Overall, 244 subjects were screened, of them 72 subjects did not complete screening. A total of 172 subjects were randomized, of them 164 subjects received treatment in one of the 7 treatment arms and total 145 subjects completed the study.

    Period 1
    Period 1 title
    Treatment period
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator
    Blinding implementation details
    The study included both double-blind, placebo-controlled and open label active-controlled parts. A double-blind placebo-controlled design was considered necessary to differentiate drug effects from the natural course of disease and background findings. An active comparator was considered appropriate to examine comparative efficacy and safety.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Treatment A1: 2mg Vilaprisan + 2mg Vilaprisan
    Arm description
    Subjects received 2 milligram (mg) oral dose of vilaprisan (BAY1002670) immediate release (IR) tablet once daily for 12 weeks during both the treatment periods 1 (TP1) and 2 (TP2). Treatment period 2 started on the day following the end of treatment period 1.
    Arm type
    Experimental

    Investigational medicinal product name
    Vilaprisan
    Investigational medicinal product code
    BAY1002670
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during both TP1 and TP2.

    Arm title
    Treatment A2: Placebo + 2mg Vilaprisan
    Arm description
    Subjects received placebo matched to 2 mg vilaprisan IR tablet once daily for 12 weeks during TP1; followed by 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP2. Treatment period 2 started on the day following the end of TP1.
    Arm type
    Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to 2 mg vilaprisan IR tablet once daily for 12 weeks during TP1.

    Investigational medicinal product name
    Vilaprisan
    Investigational medicinal product code
    BAY1002670
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP2.

    Arm title
    Treatment B1: 2mg Vilaprisan+1 Bleeding Episode+2mg Vilaprisan
    Arm description
    Subjects received 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP1; followed by 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the first bleeding episode following the end of TP1.
    Arm type
    Experimental

    Investigational medicinal product name
    Vilaprisan
    Investigational medicinal product code
    BAY1002670
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during both TP1 and TP2.

    Arm title
    Treatment B2: Placebo + 1 Bleeding Episode + 2mg Vilaprisan
    Arm description
    Subjects received placebo matched to 2 mg vilaprisan IR tablet once daily for 12 weeks during TP1; followed by 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the first bleeding episode following the end of TP1.
    Arm type
    Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to 2 mg vilaprisan IR tablet once daily for 12 weeks during TP1.

    Investigational medicinal product name
    Vilaprisan
    Investigational medicinal product code
    BAY1002670
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP2.

    Arm title
    Treatment C1:5mg Ulipristal+2 Bleeding Episodes+5mg Ulipristal
    Arm description
    Subjects received 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP1; followed by 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the second bleeding episode following the end of TP1.
    Arm type
    Experimental

    Investigational medicinal product name
    Ulipristal
    Investigational medicinal product code
    Other name
    Esmya 5 mg
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during both TP1 and TP2.

    Arm title
    Treatment C2: Placebo + 2 Bleeding Episodes + 5mg Ulipristal
    Arm description
    Subjects received placebo matched to 5 mg ulipristal IR tablet once daily for 12 weeks during TP1; followed by 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the second bleeding episode following the end of TP1.
    Arm type
    Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to 5 mg ulipristal IR tablet once daily for 12 weeks during TP1.

    Investigational medicinal product name
    Ulipristal
    Investigational medicinal product code
    Other name
    Esmya 5 mg
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP2.

    Arm title
    Treatment C3: 5mg Ulipristal + 2 Bleeding Episodes + Placebo
    Arm description
    Subjects received 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP1; followed by placebo matched to 5 mg ulipristal IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the second bleeding episode following the end of TP1.
    Arm type
    Experimental

    Investigational medicinal product name
    Ulipristal
    Investigational medicinal product code
    Other name
    Esmya 5 mg
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP1.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to 5 mg ulipristal IR tablet once daily for 12 weeks during TP2.

    Number of subjects in period 1
    Treatment A1: 2mg Vilaprisan + 2mg Vilaprisan Treatment A2: Placebo + 2mg Vilaprisan Treatment B1: 2mg Vilaprisan+1 Bleeding Episode+2mg Vilaprisan Treatment B2: Placebo + 1 Bleeding Episode + 2mg Vilaprisan Treatment C1:5mg Ulipristal+2 Bleeding Episodes+5mg Ulipristal Treatment C2: Placebo + 2 Bleeding Episodes + 5mg Ulipristal Treatment C3: 5mg Ulipristal + 2 Bleeding Episodes + Placebo
    Started
    37
    7
    36
    8
    39
    7
    38
    Completed treatment 1
    33
    6
    35
    7
    36
    6
    32
    Completed post – treatment 1
    33
    6
    34
    7
    31
    6
    30
    Completed treatment 2
    32
    6
    31
    7
    30
    6
    27
    Completed post – treatment 2
    32
    6
    31
    7
    30
    6
    26
    Completed
    32
    6
    31
    7
    30
    6
    26
    Not completed
    5
    1
    5
    1
    9
    1
    12
         Other
    -
    -
    1
    -
    -
    -
    1
         Protocol driven decision point
    -
    -
    -
    -
    2
    -
    -
         Protocol violation
    3
    -
    -
    -
    1
    1
    1
         Adverse event
    1
    -
    1
    1
    2
    -
    5
         Pregnancy
    -
    -
    -
    -
    1
    -
    1
         Consent withdrawn by subject
    1
    1
    3
    -
    3
    -
    4
    Period 2
    Period 2 title
    Follow-up period
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator

    Arms
    Are arms mutually exclusive
    No

    Arm title
    Treatment A1: 2mg Vilaprisan + 2mg Vilaprisan
    Arm description
    Subjects received 2 milligram (mg) oral dose of vilaprisan (BAY1002670) immediate release (IR) tablet once daily for 12 weeks during both the treatment periods 1 (TP1) and 2 (TP2). Treatment period 2 started on the day following the end of treatment period 1.
    Arm type
    Experimental

    Investigational medicinal product name
    Vilaprisan
    Investigational medicinal product code
    BAY1002670
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during both TP1 and TP2.

    Arm title
    Treatment A2: Placebo + 2mg Vilaprisan
    Arm description
    Subjects received placebo matched to 2 mg vilaprisan IR tablet once daily for 12 weeks during TP1; followed by 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP2. Treatment period 2 started on the day following the end of TP1.
    Arm type
    Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to 2 mg vilaprisan IR tablet once daily for 12 weeks during TP1.

    Investigational medicinal product name
    Vilaprisan
    Investigational medicinal product code
    BAY1002670
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP2.

    Arm title
    Treatment B1: 2mg Vilaprisan+1 Bleeding Episode+2mg Vilaprisan
    Arm description
    Subjects received 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP1; followed by 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the first bleeding episode following the end of TP1.
    Arm type
    Experimental

    Investigational medicinal product name
    Vilaprisan
    Investigational medicinal product code
    BAY1002670
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during both TP1 and TP2.

    Arm title
    Treatment B2: Placebo + 1 Bleeding Episode + 2mg Vilaprisan
    Arm description
    Subjects received placebo matched to 2 mg vilaprisan IR tablet once daily for 12 weeks during TP1; followed by 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the first bleeding episode following the end of TP1.
    Arm type
    Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to 2 mg vilaprisan IR tablet once daily for 12 weeks during TP1.

    Investigational medicinal product name
    Vilaprisan
    Investigational medicinal product code
    BAY1002670
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP2.

    Arm title
    Treatment C1:5mg Ulipristal+2 Bleeding Episodes+5mg Ulipristal
    Arm description
    Subjects received 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP1; followed by 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the second bleeding episode following the end of TP1.
    Arm type
    Experimental

    Investigational medicinal product name
    Ulipristal
    Investigational medicinal product code
    Other name
    Esmya 5 mg
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during both TP1 and TP2.

    Arm title
    Treatment C2: Placebo + 2 Bleeding Episodes + 5mg Ulipristal
    Arm description
    Subjects received placebo matched to 5 mg ulipristal IR tablet once daily for 12 weeks during TP1; followed by 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the second bleeding episode following the end of TP1.
    Arm type
    Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to 5 mg ulipristal IR tablet once daily for 12 weeks during TP1.

    Investigational medicinal product name
    Ulipristal
    Investigational medicinal product code
    Other name
    Esmya 5 mg
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP2.

    Arm title
    Treatment C3: 5mg Ulipristal + 2 Bleeding Episodes + Placebo
    Arm description
    Subjects received 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP1; followed by placebo matched to 5 mg ulipristal IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the second bleeding episode following the end of TP1.
    Arm type
    Experimental

    Investigational medicinal product name
    Ulipristal
    Investigational medicinal product code
    Other name
    Esmya 5 mg
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP1.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to 5 mg ulipristal IR tablet once daily for 12 weeks during TP2.

    Number of subjects in period 2
    Treatment A1: 2mg Vilaprisan + 2mg Vilaprisan Treatment A2: Placebo + 2mg Vilaprisan Treatment B1: 2mg Vilaprisan+1 Bleeding Episode+2mg Vilaprisan Treatment B2: Placebo + 1 Bleeding Episode + 2mg Vilaprisan Treatment C1:5mg Ulipristal+2 Bleeding Episodes+5mg Ulipristal Treatment C2: Placebo + 2 Bleeding Episodes + 5mg Ulipristal Treatment C3: 5mg Ulipristal + 2 Bleeding Episodes + Placebo
    Started
    34
    6
    31
    7
    34
    6
    29
    Completed
    33
    6
    30
    7
    34
    6
    29
    Not completed
    1
    0
    1
    0
    0
    0
    0
         Pregnancy
    -
    -
    1
    -
    -
    -
    -
         Consent withdrawn by subject
    1
    -
    -
    -
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Treatment A1: 2mg Vilaprisan + 2mg Vilaprisan
    Reporting group description
    Subjects received 2 milligram (mg) oral dose of vilaprisan (BAY1002670) immediate release (IR) tablet once daily for 12 weeks during both the treatment periods 1 (TP1) and 2 (TP2). Treatment period 2 started on the day following the end of treatment period 1.

    Reporting group title
    Treatment A2: Placebo + 2mg Vilaprisan
    Reporting group description
    Subjects received placebo matched to 2 mg vilaprisan IR tablet once daily for 12 weeks during TP1; followed by 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP2. Treatment period 2 started on the day following the end of TP1.

    Reporting group title
    Treatment B1: 2mg Vilaprisan+1 Bleeding Episode+2mg Vilaprisan
    Reporting group description
    Subjects received 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP1; followed by 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the first bleeding episode following the end of TP1.

    Reporting group title
    Treatment B2: Placebo + 1 Bleeding Episode + 2mg Vilaprisan
    Reporting group description
    Subjects received placebo matched to 2 mg vilaprisan IR tablet once daily for 12 weeks during TP1; followed by 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the first bleeding episode following the end of TP1.

    Reporting group title
    Treatment C1:5mg Ulipristal+2 Bleeding Episodes+5mg Ulipristal
    Reporting group description
    Subjects received 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP1; followed by 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the second bleeding episode following the end of TP1.

    Reporting group title
    Treatment C2: Placebo + 2 Bleeding Episodes + 5mg Ulipristal
    Reporting group description
    Subjects received placebo matched to 5 mg ulipristal IR tablet once daily for 12 weeks during TP1; followed by 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the second bleeding episode following the end of TP1.

    Reporting group title
    Treatment C3: 5mg Ulipristal + 2 Bleeding Episodes + Placebo
    Reporting group description
    Subjects received 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP1; followed by placebo matched to 5 mg ulipristal IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the second bleeding episode following the end of TP1.

    Reporting group values
    Treatment A1: 2mg Vilaprisan + 2mg Vilaprisan Treatment A2: Placebo + 2mg Vilaprisan Treatment B1: 2mg Vilaprisan+1 Bleeding Episode+2mg Vilaprisan Treatment B2: Placebo + 1 Bleeding Episode + 2mg Vilaprisan Treatment C1:5mg Ulipristal+2 Bleeding Episodes+5mg Ulipristal Treatment C2: Placebo + 2 Bleeding Episodes + 5mg Ulipristal Treatment C3: 5mg Ulipristal + 2 Bleeding Episodes + Placebo Total
    Number of subjects
    37 7 36 8 39 7 38 172
    Age categorical
    Units: subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    40.9 ± 6.5 42 ± 2.8 43.5 ± 4.4 43.1 ± 5.8 41.5 ± 5.4 40.3 ± 8.2 42.9 ± 5.2 -
    Gender categorical
    Units: subjects
        Female
    37 7 36 8 39 7 38 172
    Menstrual blood loss volume for 28 days by menstrual pictogram
    Subjects documented their menstrual fluid loss per sanitary product (towels and/or tampons) using a visual scoring system for 28 days by menstrual pictogram.
    Units: milliliter (mL)
        arithmetic mean (standard deviation)
    246.938 ± 165.406 238.393 ± 249.792 206.523 ± 169.936 225.775 ± 90.95 199.729 ± 101.5 193.288 ± 81.259 200.89 ± 129.016 -
    Menstrual blood loss volume for 35 days by menstrual pictogram
    Subjects documented their menstrual fluid loss per sanitary product (towels and/or tampons) using a visual scoring system for 35 days by menstrual pictogram.
    Units: milliliter (mL)
        arithmetic mean (standard deviation)
    247.003 ± 165.369 238.393 ± 249.792 207.605 ± 170.672 225.775 ± 90.95 199.729 ± 101.5 193.288 ± 81.259 201.07 ± 128.951 -
    Volume of 3 largest fibroids by ultrasound
    The largest transverse, longitudinal, and antero-posterior diameters of these 3 fibroids were documented at each efficacy ultrasound examination for volume calculation.
    Units: milliliter (mL)
        arithmetic mean (standard deviation)
    104.549 ± 132.82 100.302 ± 94.301 100.278 ± 104.074 94.811 ± 113.219 119.713 ± 135.195 134.645 ± 114.341 98.742 ± 113.309 -
    Uterine volume by ultrasound
    The dimensions of the uterus was calculated by using ultrasound examination.
    Units: milliliter (mL)
        arithmetic mean (standard deviation)
    228.798 ± 132.66 315.548 ± 236.319 320.839 ± 230.024 217.07 ± 112.671 363.451 ± 346.984 279.142 ± 81.885 298.391 ± 216.267 -

    End points

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    End points reporting groups
    Reporting group title
    Treatment A1: 2mg Vilaprisan + 2mg Vilaprisan
    Reporting group description
    Subjects received 2 milligram (mg) oral dose of vilaprisan (BAY1002670) immediate release (IR) tablet once daily for 12 weeks during both the treatment periods 1 (TP1) and 2 (TP2). Treatment period 2 started on the day following the end of treatment period 1.

    Reporting group title
    Treatment A2: Placebo + 2mg Vilaprisan
    Reporting group description
    Subjects received placebo matched to 2 mg vilaprisan IR tablet once daily for 12 weeks during TP1; followed by 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP2. Treatment period 2 started on the day following the end of TP1.

    Reporting group title
    Treatment B1: 2mg Vilaprisan+1 Bleeding Episode+2mg Vilaprisan
    Reporting group description
    Subjects received 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP1; followed by 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the first bleeding episode following the end of TP1.

    Reporting group title
    Treatment B2: Placebo + 1 Bleeding Episode + 2mg Vilaprisan
    Reporting group description
    Subjects received placebo matched to 2 mg vilaprisan IR tablet once daily for 12 weeks during TP1; followed by 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the first bleeding episode following the end of TP1.

    Reporting group title
    Treatment C1:5mg Ulipristal+2 Bleeding Episodes+5mg Ulipristal
    Reporting group description
    Subjects received 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP1; followed by 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the second bleeding episode following the end of TP1.

    Reporting group title
    Treatment C2: Placebo + 2 Bleeding Episodes + 5mg Ulipristal
    Reporting group description
    Subjects received placebo matched to 5 mg ulipristal IR tablet once daily for 12 weeks during TP1; followed by 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the second bleeding episode following the end of TP1.

    Reporting group title
    Treatment C3: 5mg Ulipristal + 2 Bleeding Episodes + Placebo
    Reporting group description
    Subjects received 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP1; followed by placebo matched to 5 mg ulipristal IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the second bleeding episode following the end of TP1.
    Reporting group title
    Treatment A1: 2mg Vilaprisan + 2mg Vilaprisan
    Reporting group description
    Subjects received 2 milligram (mg) oral dose of vilaprisan (BAY1002670) immediate release (IR) tablet once daily for 12 weeks during both the treatment periods 1 (TP1) and 2 (TP2). Treatment period 2 started on the day following the end of treatment period 1.

    Reporting group title
    Treatment A2: Placebo + 2mg Vilaprisan
    Reporting group description
    Subjects received placebo matched to 2 mg vilaprisan IR tablet once daily for 12 weeks during TP1; followed by 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP2. Treatment period 2 started on the day following the end of TP1.

    Reporting group title
    Treatment B1: 2mg Vilaprisan+1 Bleeding Episode+2mg Vilaprisan
    Reporting group description
    Subjects received 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP1; followed by 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the first bleeding episode following the end of TP1.

    Reporting group title
    Treatment B2: Placebo + 1 Bleeding Episode + 2mg Vilaprisan
    Reporting group description
    Subjects received placebo matched to 2 mg vilaprisan IR tablet once daily for 12 weeks during TP1; followed by 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the first bleeding episode following the end of TP1.

    Reporting group title
    Treatment C1:5mg Ulipristal+2 Bleeding Episodes+5mg Ulipristal
    Reporting group description
    Subjects received 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP1; followed by 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the second bleeding episode following the end of TP1.

    Reporting group title
    Treatment C2: Placebo + 2 Bleeding Episodes + 5mg Ulipristal
    Reporting group description
    Subjects received placebo matched to 5 mg ulipristal IR tablet once daily for 12 weeks during TP1; followed by 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the second bleeding episode following the end of TP1.

    Reporting group title
    Treatment C3: 5mg Ulipristal + 2 Bleeding Episodes + Placebo
    Reporting group description
    Subjects received 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during TP1; followed by placebo matched to 5 mg ulipristal IR tablet once daily for 12 weeks during TP2. Treatment period 2 started within the first 3 days of the second bleeding episode following the end of TP1.

    Subject analysis set title
    Safety analysis set (SAF)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    SAF (N=164) included all randomized subjects who took at least 1 dose of study drug. Subjects were analyzed as treated.

    Subject analysis set title
    Full analysis set (FAS)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    FAS (N=164) included all randomized subjects who took at least 1 dose of study drug. Subjects were analyzed as randomized.

    Subject analysis set title
    Vilaprisan 12 weeks-A1 (TP1)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects (N=35) received 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks in treatment period 1.

    Subject analysis set title
    Vilaprisan 12 weeks-B1 (TP1)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects (N=35) received 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks in treatment period 1.

    Subject analysis set title
    Ulipristal 12 weeks-C1 (TP1)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects (N=37) received 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks in treatment period 1.

    Subject analysis set title
    Ulipristal 12 weeks-C3 (TP1)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects (N=37) received 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks in treatment period 1.

    Subject analysis set title
    Placebo: Pooled A2, B2 and C2 (TP1)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects (N=20) received placebo matched to vilaprisan and ulipristal IR tablets once daily for 12 weeks in treatment period 1.

    Primary: Amenorrhea Rate

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    End point title
    Amenorrhea Rate [1]
    End point description
    Amenorrhea (yes or no) was defined as no scheduled or unscheduled bleeding/spotting after end of the initial bleeding episode until the end of the respective treatment period.
    End point type
    Primary
    End point timeframe
    From start of the study treatment up to End of Treatment (12 weeks for groups B and C, 24 weeks for group A)
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for the pooled placebo has been reported here instead of individual placebo groups.
    End point values
    Treatment A1: 2mg Vilaprisan + 2mg Vilaprisan Vilaprisan 12 weeks-A1 (TP1) Vilaprisan 12 weeks-B1 (TP1) Ulipristal 12 weeks-C1 (TP1) Ulipristal 12 weeks-C3 (TP1) Placebo: Pooled A2, B2 and C2 (TP1)
    Number of subjects analysed
    35 [2]
    35 [3]
    35 [4]
    35 [5]
    35 [6]
    35 [7]
    Units: percentage of amenorrheic subjects
        number (confidence interval 95%)
    25.71 (12.49 to 43.26)
    57.14 (39.35 to 73.68)
    62.86 (44.92 to 78.53)
    59.46 (42.1 to 75.25)
    51.35 (34.4 to 68.08)
    0 (0 to 16.84)
    Notes
    [2] - FAS
    [3] - FAS
    [4] - FAS
    [5] - FAS
    [6] - FAS
    [7] - FAS
    Statistical analysis title
    Vilaprisan 12 weeks vs Placebo 12 weeks
    Statistical analysis description
    Amenorrhea (yes or no) was defined as no scheduled or unscheduled bleeding/spotting after end of the initial bleeding episode until the end of the respective treatment period. The amenorrhea rates of vilaprisan vs placebo was analyzed using Fisher’s exact tests at a 5% two sided significance level. A hierarchical (fixed sequence) testing procedure was used and 95% confidence intervals were calculated. P-value calculated with respect to Placebo 12 weeks.
    Comparison groups
    Vilaprisan 12 weeks-B1 (TP1) v Placebo: Pooled A2, B2 and C2 (TP1)
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Fisher’s exact tests
    Confidence interval
         level
    95%
    Statistical analysis title
    Vilaprisan 24 weeks vs Placebo 12 weeks
    Statistical analysis description
    Amenorrhea (yes or no) was defined as no scheduled or unscheduled bleeding/spotting after end of the initial bleeding episode until the end of the respective treatment period. The amenorrhea rates of vilaprisan vs placebo was analyzed using Fisher’s exact tests at a 5% two sided significance level. A hierarchical (fixed sequence) testing procedure was used and 95% confidence intervals were calculated. P-value calculated with respect to Placebo 12 weeks.
    Comparison groups
    Treatment A1: 2mg Vilaprisan + 2mg Vilaprisan v Placebo: Pooled A2, B2 and C2 (TP1)
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.019
    Method
    Fisher’s exact tests
    Confidence interval
         level
    95%

    Secondary: Number of Bleeding Days

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    End point title
    Number of Bleeding Days [8]
    End point description
    Number of bleeding days from Day 1 of the first treatment period until the day before the next treatment period would start again normalized to 28 days. Arithmetic mean and standard deviation of bleeding days (normalized to 28 days) was reported.
    End point type
    Secondary
    End point timeframe
    From Day 1 of the first treatment period until the day before the next treatment period (normalized to 28 days)
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for the pooled placebo has been reported here instead of individual placebo groups.
    End point values
    Treatment A1: 2mg Vilaprisan + 2mg Vilaprisan Treatment B1: 2mg Vilaprisan+1 Bleeding Episode+2mg Vilaprisan Treatment C1:5mg Ulipristal+2 Bleeding Episodes+5mg Ulipristal Vilaprisan 12 weeks-A1 (TP1) Vilaprisan 12 weeks-B1 (TP1) Ulipristal 12 weeks-C1 (TP1) Ulipristal 12 weeks-C3 (TP1) Placebo: Pooled A2, B2 and C2 (TP1)
    Number of subjects analysed
    35 [9]
    35 [10]
    37 [11]
    35 [12]
    35 [13]
    37 [14]
    37 [15]
    20 [16]
    Units: bleeding days
        arithmetic mean (standard deviation)
    1.69 ± 1.79
    1.46 ± 0.7
    2.05 ± 1.15
    1.54 ± 1.27
    1.69 ± 0.8
    1.68 ± 1.13
    3.03 ± 4.7
    5.1 ± 1.62
    Notes
    [9] - FAS
    [10] - FAS
    [11] - FAS
    [12] - FAS
    [13] - FAS
    [14] - FAS
    [15] - FAS
    [16] - FAS
    No statistical analyses for this end point

    Secondary: Time to Onset of Controlled Bleeding

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    End point title
    Time to Onset of Controlled Bleeding
    End point description
    Onset of controlled bleeding was defined based on the menstrual blood loss of all constructed moving evaluation time windows (METW) starting from the first day of treatment up to the end of treatment. Each completed METW was 28 days in length and each incomplete METW was less than 28 days. Onset of controlled bleeding was defined by the first day, for which the menstrual blood loss (MBL) assessed by menstrual pictogram for all subsequent 28-day periods up to the end of the treatment period was less than 80 mL. Kaplan-Meier estimated time to onset of controlled bleeding (days) was calculated and reported. In the below table, '99999' refers to data was not calculated as most subjects did not show controlled bleeding.
    End point type
    Secondary
    End point timeframe
    From start of the study treatment up to 28 days
    End point values
    Vilaprisan 12 weeks-A1 (TP1) Vilaprisan 12 weeks-B1 (TP1) Ulipristal 12 weeks-C1 (TP1) Ulipristal 12 weeks-C3 (TP1) Placebo: Pooled A2, B2 and C2 (TP1)
    Number of subjects analysed
    35 [17]
    35 [18]
    37 [19]
    37 [20]
    20 [21]
    Units: days
        median (inter-quartile range (Q1-Q3))
    3 (2 to 4)
    3 (2 to 4)
    3 (1 to 4)
    3 (2 to 4)
    99999 (33 to 99999)
    Notes
    [17] - FAS
    [18] - FAS
    [19] - FAS
    [20] - FAS
    [21] - FAS
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Volume of Largest Fibroid

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    End point title
    Percent Change From Baseline in Volume of Largest Fibroid
    End point description
    Percent change in volume of largest fibroid compared to baseline measured by magnetic resonance imaging was reported.
    End point type
    Secondary
    End point timeframe
    From start of the study treatment up to follow up period
    End point values
    Treatment A1: 2mg Vilaprisan + 2mg Vilaprisan Treatment A2: Placebo + 2mg Vilaprisan Treatment B1: 2mg Vilaprisan+1 Bleeding Episode+2mg Vilaprisan Treatment B2: Placebo + 1 Bleeding Episode + 2mg Vilaprisan Treatment C1:5mg Ulipristal+2 Bleeding Episodes+5mg Ulipristal Treatment C2: Placebo + 2 Bleeding Episodes + 5mg Ulipristal Treatment C3: 5mg Ulipristal + 2 Bleeding Episodes + Placebo
    Number of subjects analysed
    29 [22]
    6 [23]
    28 [24]
    7 [25]
    31 [26]
    6 [27]
    29 [28]
    Units: percent change
    arithmetic mean (standard deviation)
        TP1 (Treatment Visit 3) (n=29,6,28,7,31,6,29)
    -27 ± 39.4
    -1.5 ± 22.3
    -29.6 ± 19.3
    9.1 ± 22.4
    -21.8 ± 30.2
    9 ± 12.2
    -25.2 ± 32.2
        TP2 (Treatment Visit 6) (n=27,6,27,7,29,6,25)
    -35.6 ± 47.3
    -43.2 ± 14.7
    -47.6 ± 19
    -27 ± 18.8
    -15.9 ± 46.4
    -2.6 ± 27.3
    -14.5 ± 28.9
        FUP period (FUP Visit) (n=23,6,23,7,26,5,25)
    -39.2 ± 41.3
    -37.6 ± 28.1
    -36 ± 30.2
    -13 ± 29.9
    -1.5 ± 59.9
    -1 ± 28.3
    -2 ± 35.6
    Notes
    [22] - FAS with evaluable subjects for this endpoint.
    [23] - FAS
    [24] - FAS with evaluable subjects for this endpoint.
    [25] - FAS with evaluable subjects for this endpoint.
    [26] - FAS with evaluable subjects for this endpoint.
    [27] - FAS
    [28] - FAS with evaluable subjects for this endpoint.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Endometrial Biopsy Results-at the End of Treatment Period 2

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    End point title
    Number of Subjects With Endometrial Biopsy Results-at the End of Treatment Period 2
    End point description
    Endometrial biopsies were assessed for immediate information about safety and for major consensus during the whole treatment phase. By endometrial biopsies pathologists documented proliferative / secretory / atrophic endometrium, endometrial hyperplasia.
    End point type
    Secondary
    End point timeframe
    At the end of Treatment Period 2
    End point values
    Treatment A1: 2mg Vilaprisan + 2mg Vilaprisan Treatment A2: Placebo + 2mg Vilaprisan Treatment B1: 2mg Vilaprisan+1 Bleeding Episode+2mg Vilaprisan Treatment B2: Placebo + 1 Bleeding Episode + 2mg Vilaprisan Treatment C1:5mg Ulipristal+2 Bleeding Episodes+5mg Ulipristal Treatment C2: Placebo + 2 Bleeding Episodes + 5mg Ulipristal Treatment C3: 5mg Ulipristal + 2 Bleeding Episodes + Placebo
    Number of subjects analysed
    26 [29]
    5 [30]
    27 [31]
    7 [32]
    25 [33]
    5 [34]
    22 [35]
    Units: subjects
        Benign Endometrium (Atrophic)
    0
    0
    1
    0
    2
    0
    0
        Benign Endometrium (Inactive)
    1
    0
    0
    1
    1
    0
    0
        Benign Endometrium (Proliferative)
    12
    3
    19
    2
    12
    4
    16
        Benign Endometrium (Secretory)
    7
    2
    5
    2
    6
    0
    5
        Benign Endometrium (Menstrual)
    3
    0
    0
    1
    0
    0
    0
        No Consensus
    3
    0
    2
    1
    4
    1
    1
        Endometrial Polyps (Functional)
    0
    0
    2
    0
    0
    0
    0
        No Endometrial Hyperplasia
    26
    5
    27
    7
    25
    5
    22
        No Malignant Neoplasm
    26
    5
    27
    7
    25
    5
    22
    Notes
    [29] - SAF with evaluable subjects for this endpoint.
    [30] - SAF with evaluable subjects for this endpoint.
    [31] - SAF with evaluable subjects for this endpoint.
    [32] - SAF with evaluable subjects for this endpoint.
    [33] - SAF with evaluable subjects for this endpoint.
    [34] - SAF with evaluable subjects for this endpoint.
    [35] - SAF with evaluable subjects for this endpoint.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Endometrial Biopsy Results-At the End of Follow-up Period

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    End point title
    Number of Subjects With Endometrial Biopsy Results-At the End of Follow-up Period
    End point description
    Endometrial biopsies were assessed for immediate information about safety and for major consensus during the whole treatment phase. By endometrial biopsies pathologists documented proliferative / secretory / atrophic endometrium, endometrial hyperplasia.
    End point type
    Secondary
    End point timeframe
    At the end of Follow-up Period
    End point values
    Treatment A1: 2mg Vilaprisan + 2mg Vilaprisan Treatment A2: Placebo + 2mg Vilaprisan Treatment B1: 2mg Vilaprisan+1 Bleeding Episode+2mg Vilaprisan Treatment B2: Placebo + 1 Bleeding Episode + 2mg Vilaprisan Treatment C1:5mg Ulipristal+2 Bleeding Episodes+5mg Ulipristal Treatment C2: Placebo + 2 Bleeding Episodes + 5mg Ulipristal Treatment C3: 5mg Ulipristal + 2 Bleeding Episodes + Placebo
    Number of subjects analysed
    22 [36]
    5 [37]
    21 [38]
    5 [39]
    20 [40]
    5 [41]
    23 [42]
    Units: subjects
        Benign Endometrium (Inactive)
    2
    0
    0
    0
    0
    0
    0
        Benign Endometrium (Proliferative)
    13
    2
    17
    4
    16
    4
    16
        Benign Endometrium (Secretory)
    1
    2
    3
    0
    1
    0
    3
        Benign Endometrium (Menstrual)
    2
    1
    0
    0
    0
    0
    3
        No Consensus
    4
    0
    1
    1
    3
    1
    1
        Endometrial Polyps (Functional)
    0
    0
    0
    0
    1
    0
    0
        No Endometrial Hyperplasia
    22
    5
    21
    5
    20
    5
    23
        No Malignant Neoplasm
    22
    5
    21
    5
    20
    5
    23
    Notes
    [36] - SAF with evaluable subjects for this endpoint.
    [37] - SAF with evaluable subjects for this endpoint.
    [38] - SAF with evaluable subjects for this endpoint.
    [39] - SAF with evaluable subjects for this endpoint.
    [40] - SAF with evaluable subjects for this endpoint.
    [41] - SAF with evaluable subjects for this endpoint.
    [42] - SAF with evaluable subjects for this endpoint.
    No statistical analyses for this end point

    Secondary: Endometrial Thickness Measured by Transvaginal Ultrasound

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    End point title
    Endometrial Thickness Measured by Transvaginal Ultrasound
    End point description
    Endometrial thickness weres measured by transvaginal ultrasound. Arithmetic mean and standard deviation were reported.
    End point type
    Secondary
    End point timeframe
    Baseline, end of TP1, TP2 and Follow-up
    End point values
    Treatment A1: 2mg Vilaprisan + 2mg Vilaprisan Treatment A2: Placebo + 2mg Vilaprisan Treatment B1: 2mg Vilaprisan+1 Bleeding Episode+2mg Vilaprisan Treatment B2: Placebo + 1 Bleeding Episode + 2mg Vilaprisan Treatment C1:5mg Ulipristal+2 Bleeding Episodes+5mg Ulipristal Treatment C2: Placebo + 2 Bleeding Episodes + 5mg Ulipristal Treatment C3: 5mg Ulipristal + 2 Bleeding Episodes + Placebo
    Number of subjects analysed
    35 [43]
    6 [44]
    35 [45]
    8 [46]
    37 [47]
    6 [48]
    37 [49]
    Units: millimeter
    arithmetic mean (standard deviation)
        Baseline
    8.97 ± 3.63
    7.5 ± 2.59
    7.51 ± 3
    6.75 ± 2.05
    7.7 ± 2.46
    8.33 ± 3.01
    8.22 ± 2.96
        At end of TP1
    8.64 ± 4.47
    10.17 ± 3.37
    9.11 ± 4.78
    8.57 ± 4.47
    9.38 ± 5.16
    8.17 ± 3.6
    9 ± 4.74
        At end of TP2
    10.24 ± 5.25
    10.5 ± 4.42
    7.88 ± 3.81
    7.86 ± 2.48
    7.29 ± 3.35
    7.67 ± 4.32
    8.7 ± 3.07
        At end of Follow-up
    6.56 ± 2.78
    7 ± 2.53
    7.83 ± 3.11
    6.14 ± 2.55
    7.42 ± 3.92
    8.5 ± 5.58
    8.14 ± 2.46
    Notes
    [43] - SAF
    [44] - SAF
    [45] - SAF
    [46] - SAF
    [47] - SAF
    [48] - SAF
    [49] - SAF
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From start of study drug administration up to 12 weeks after the end of the treatment period 2 (Week 36)
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    2 mg Vilaprisan
    Reporting group description
    2 mg Vilaprisan: Subjects received 2 mg oral dose of vilaprisan IR tablet once daily for 12 weeks during both the TP1 and TP2, or only during TP2.

    Reporting group title
    5 mg Ulipristal
    Reporting group description
    5 mg Ulipristal: Subjects received 5 mg oral dose of ulipristal IR tablet once daily for 12 weeks during both the TP1 and TP2, or only during TP1, or only during TP2.

    Reporting group title
    Placebo
    Reporting group description
    Placebo: Subjects received placebo matched to 2 mg vilaprisan or 5 mg ulipristal IR tablet once daily for 12 weeks.

    Serious adverse events
    2 mg Vilaprisan 5 mg Ulipristal Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 83 (3.61%)
    4 / 80 (5.00%)
    0 / 50 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Haemangioma of bone
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 80 (1.25%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 80 (1.25%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Surgical failure
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 80 (1.25%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Menorrhagia
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 80 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pelvic pain
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 80 (1.25%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uterine haemorrhage
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 80 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 80 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    2 mg Vilaprisan 5 mg Ulipristal Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    44 / 83 (53.01%)
    44 / 80 (55.00%)
    17 / 50 (34.00%)
    Vascular disorders
    Hot flush
         subjects affected / exposed
    10 / 83 (12.05%)
    5 / 80 (6.25%)
    1 / 50 (2.00%)
         occurrences all number
    13
    5
    2
    Investigations
    Weight increased
         subjects affected / exposed
    6 / 83 (7.23%)
    1 / 80 (1.25%)
    0 / 50 (0.00%)
         occurrences all number
    6
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    21 / 83 (25.30%)
    18 / 80 (22.50%)
    9 / 50 (18.00%)
         occurrences all number
    34
    19
    11
    Reproductive system and breast disorders
    Cervical dysplasia
         subjects affected / exposed
    1 / 83 (1.20%)
    1 / 80 (1.25%)
    3 / 50 (6.00%)
         occurrences all number
    1
    1
    3
    Ovarian cyst
         subjects affected / exposed
    1 / 83 (1.20%)
    12 / 80 (15.00%)
    1 / 50 (2.00%)
         occurrences all number
    2
    15
    2
    Pelvic pain
         subjects affected / exposed
    4 / 83 (4.82%)
    4 / 80 (5.00%)
    1 / 50 (2.00%)
         occurrences all number
    4
    4
    1
    Vaginal haemorrhage
         subjects affected / exposed
    6 / 83 (7.23%)
    3 / 80 (3.75%)
    0 / 50 (0.00%)
         occurrences all number
    6
    3
    0
    Endometrial thickening
         subjects affected / exposed
    5 / 83 (6.02%)
    7 / 80 (8.75%)
    0 / 50 (0.00%)
         occurrences all number
    5
    7
    0
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    5 / 83 (6.02%)
    0 / 80 (0.00%)
    0 / 50 (0.00%)
         occurrences all number
    5
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    5 / 83 (6.02%)
    3 / 80 (3.75%)
    1 / 50 (2.00%)
         occurrences all number
    5
    3
    1
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    6 / 83 (7.23%)
    11 / 80 (13.75%)
    5 / 50 (10.00%)
         occurrences all number
    6
    11
    5

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Aug 2015
    After the European Union label of the active reference drug Esmya (ulipristal acetate 5 mg tablets) had been changed, the former labelled indication of short-term use of Esmya before surgical treatment of uterine fibroids was extended to repeated intermittent use. Consequently, the inclusion criterion “Eligible to undergo surgical treatment for uterine fibroids at the end of study treatment” and related protocol sections could be deleted.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Occurrence of "±” in relation with geometric CV is auto-generated and cannot be deleted. Decimal places were automatically truncated if last decimal equals zero.

    Online references

    http://www.ncbi.nlm.nih.gov/pubmed/28185997
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