Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43873   clinical trials with a EudraCT protocol, of which   7293   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Multicentre, phase II, open label randomised clinical trial to assess the bleeding profile, tolerability and safety associated with the use of three prolonged release formulations containing a combination of dienogest and ethinyl estradiol versus a flexible regimen contraceptive containing drospirenone 3 mg and ethinyl estradiol 20 µg.

    Summary
    EudraCT number
    		 2016-003831-39
    Trial protocol
    		 LT   CZ  
    Global end of trial date
    24 Sep 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    22 Oct 2020
    First version publication date
    22 Oct 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    LPRI421-202
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Exeltis France
    Sponsor organisation address
    7 rue Victor Hugo, Sevres/Paris, France, 92310
    Public contact
    Project leader, Exeltis France S.A., 0033 14 9662 219 , ecoli@exeltis.com
    Scientific contact
    Project leader, Exeltis France S.A., 0033 14 9662 219 , ecoli@exeltis.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
    24 Jul 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Sep 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess vaginal bleeding pattern (subject paper diaries).
    Protection of trial subjects
    N/A
    Background therapy
    		 N/A
    Evidence for comparator
    		 The purpose of the trial was to demonstrate improved safety and tolerability of LPRI421 due to its prolonged release formulation and the lower hormone doses and to establish the most appropriate doses. Velmari® Langzyklus as an authorised COC for extended-regimen was chosen as an active comparator to demonstrate that LPRI421 is at least as safe as commonly used hormonal contraceptives and that the prolonged release formulation may even improve safety and tolerability.
    Actual start date of recruitment
    01 Apr 2017
    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
    Czech Republic: 119
    Country: Number of subjects enrolled
    Lithuania: 88
    Country: Number of subjects enrolled
    Ukraine: 138
    Worldwide total number of subjects
    345
    EEA total number of subjects
    207
    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)
    345
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Female healthy subjects aged 18 to 35 years with regular menstrual cycles during the last three months or at least three complete menstrual cycles after delivery/abortion/miscarriage, if pregnant within the last six months prior to entering this trial and willing to use an oral contraceptive for two extended 91-day treatment periods.

    Pre-assignment
    Screening details
    		 Female subjects 18-35 y., regular cycles during the last three months before consent, when not using hormonal contraception, at least 3 complete menstrual cycles after delivery/abortion/miscarriage (only women who were pregnant within the last 6 months), BMI: 18 kg/m2 ≤ BMI < 30 kg/m2, Systolic blood pressure < 140 mmHg and diastolic BP < 90 mmHg..

    Period 1
    Period 1 title
    Treatment Period 1 (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 IMP 1
    Arm description
    		 Subjects recieving IMP 1
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dienogest (DNG)/ethinyl estradiol (EE) 1 mg/10 ug tablets
    Investigational medicinal product code
    LPRI421 D1
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral administration once daily at approximately the same time each day. The duration of treatment for the individual subject was of 182 days.

    Arm title
    		 IMP 2
    Arm description
    		 Subjects recieving IMP 2
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dienogest (DNG)/ethinyl estradiol (EE) 2 mg/10 ug tablets
    Investigational medicinal product code
    LPRI421 D2
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral administration once daily at approximately the same time each day. The duration of treatment for the individual subject was of 182 days.

    Arm title
    		 IMP 3
    Arm description
    		 subjects recieving IMP 3
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dienogest (DNG)/ethinyl estradiol (EE) 2 mg/20 ug tablets
    Investigational medicinal product code
    LPRI421 D3
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral administration once daily at approximately the same time each day. The duration of treatment for the individual subject was of 182 days.

    Arm title
    		 Reference
    Arm description
    		 Subjects taking reference product
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Velmari Langzyklus
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Blister with 24 Velmari® Langzyklus tablets containing drospirenone (DRSP)/EE 3 mg/20 μg (“Velmari”). Oral administration once daily at approximately the same time each day. The duration of treatment for the individual subject was of 182 days.

    Number of subjects in period 1
    		IMP 1 IMP 2 IMP 3 Reference
    Started
    86
    84
    87
    88
    Completed
    70
    77
    75
    77
    Not completed
    16
    7
    12
    11
         Consent withdrawn by subject
    -
    3
    3
    4
         Adverse event, non-fatal
    11
    3
    7
    5
         Pregnancy or wish for pregnancy
    1
    1
    -
    -
         Lost to follow-up
    4
    -
    1
    -
         Ineligibiltiy/develpment of an exclusion criteria
    -
    -
    1
    -
         not specified
    -
    -
    -
    2

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    IMP 1
    Reporting group description
    		 Subjects recieving IMP 1

    Reporting group title
    IMP 2
    Reporting group description
    		 Subjects recieving IMP 2

    Reporting group title
    IMP 3
    Reporting group description
    		 subjects recieving IMP 3

    Reporting group title
    Reference
    Reporting group description
    		 Subjects taking reference product

    Reporting group values
    		 IMP 1 IMP 2 IMP 3 Reference Total
    Number of subjects
    		 86 84 87 88 345
    Age categorical
    Units: Subjects
        Adults (18-35)
    		 86 84 87 88 345
    Gender categorical
    Units: Subjects
        Female
    		 86 84 87 88 345
    Subject analysis sets

    Subject analysis set title
    Enrolled Set
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    all subjects who signed informed consent

    Subject analysis set title
    Randomised Set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    all subjects who were randomised

    Subject analysis set title
    Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    all subjects who were randomised and received at least one dose of IMP Additionally, subjects who were randomised, but IMP intake was not documented in any source and unused blisters were not returned, were included in safety set as well

    Subject analysis set title
    Per Protocol Set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    all subjects who were included in the SS and completed the trial as intended without any major protocol deviation

    Subject analysis sets values
    		 Enrolled Set Randomised Set Safety Set Per Protocol Set
    Number of subjects
    345
    345
    338
    266
    Age categorical
    Units: Subjects
        Adults (18-35)
    400
    345
    338
    266
    Age continuous
    Units:
        
    ±
    ±
    ±
    ±
    Gender categorical
    Units: Subjects
        Female
    400
    345
    338
    266

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    IMP 1
    Reporting group description
    		 Subjects recieving IMP 1

    Reporting group title
    IMP 2
    Reporting group description
    		 Subjects recieving IMP 2

    Reporting group title
    IMP 3
    Reporting group description
    		 subjects recieving IMP 3

    Reporting group title
    Reference
    Reporting group description
    		 Subjects taking reference product

    Subject analysis set title
    Enrolled Set
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    all subjects who signed informed consent

    Subject analysis set title
    Randomised Set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    all subjects who were randomised

    Subject analysis set title
    Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    all subjects who were randomised and received at least one dose of IMP Additionally, subjects who were randomised, but IMP intake was not documented in any source and unused blisters were not returned, were included in safety set as well

    Subject analysis set title
    Per Protocol Set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    all subjects who were included in the SS and completed the trial as intended without any major protocol deviation

    Primary: Total number of bleeding/spotting days

    		 Close Top of page
    End point title
    		 Total number of bleeding/spotting days [1]
    End point description
    The primary endpoint of this trial was the total number of bleeding/spotting days during the trial (overall and by extended treatment period).
    End point type
    Primary
    End point timeframe
    For 91-day treatment period: - 0-5 days - 6-10 days - 11-15 days - >15 days For the complete trial treatment phase overall: - 0-10 days - 11-20 days - 21-30 days - >30 days
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No hypothesis testing was performed in this trial
    End point values
    		 IMP 1 IMP 2 IMP 3 Reference Per Protocol Set
    Number of subjects analysed
    58
    68
    68
    88
    266
    Units: days
    58
    68
    68
    88
    266
    No statistical analyses for this end point

    Secondary: Total number of scheduled bleeding/spotting days

    		 Close Top of page
    End point title
    		 Total number of scheduled bleeding/spotting days
    End point description
    End point type
    Secondary
    End point timeframe
    It was measured at the end of first period of 91 days and at the end of the trial at day 182
    End point values
    		 IMP 1 IMP 2 IMP 3 Reference Safety Set
    Number of subjects analysed
    84
    82
    86
    86
    338
    Units: days
    84
    82
    86
    86
    338
    No statistical analyses for this end point

    Secondary: Total number of bleeding/spotting episodes

    		 Close Top of page
    End point title
    		 Total number of bleeding/spotting episodes
    End point description
    End point type
    Secondary
    End point timeframe
    It was measured at the end of first period of 91 days and at the end of the trial at day 182
    End point values
    		 IMP 1 IMP 2 IMP 3 Reference Safety Set
    Number of subjects analysed
    84
    82
    86
    86
    338
    Units: episodes
    84
    82
    86
    86
    338
    No statistical analyses for this end point

    Secondary: Duration of bleeding/spotting episodes

    		 Close Top of page
    End point title
    		 Duration of bleeding/spotting episodes
    End point description
    End point type
    Secondary
    End point timeframe
    It was measured at the end of first period of 91 days and at the end of the trial at day 182
    End point values
    		 IMP 1 IMP 2 IMP 3 Reference Safety Set
    Number of subjects analysed
    84
    82
    86
    86
    338
    Units: days
    84
    82
    86
    86
    338
    No statistical analyses for this end point

    Secondary: Intensity of bleeding/spotting episodes

    		 Close Top of page
    End point title
    		 Intensity of bleeding/spotting episodes
    End point description
    End point type
    Secondary
    End point timeframe
    It was measured at the end of first period of 91 days and at the end of the trial at day 182
    End point values
    		 IMP 1 IMP 2 IMP 3 Reference Safety Set
    Number of subjects analysed
    84
    82
    86
    86
    338
    Units: episodes with intensity
    84
    82
    86
    86
    338
    No statistical analyses for this end point

    Secondary: Rate of absence of all bleeding/spotting

    		 Close Top of page
    End point title
    		 Rate of absence of all bleeding/spotting
    End point description
    End point type
    Secondary
    End point timeframe
    It was measured at the end of first period of 91 days and at the end of the trial at day 182
    End point values
    		 IMP 1 IMP 2 IMP 3 Reference Safety Set
    Number of subjects analysed
    84
    82
    86
    86
    338
    Units: percentage
    84
    82
    86
    86
    338
    No statistical analyses for this end point

    Secondary: Treatment-emergent adverse events (TEAEs)

    		 Close Top of page
    End point title
    		 Treatment-emergent adverse events (TEAEs)
    End point description
    Only TEAEs, defined as AEs with onset or worsening after first intake of IMP until 14 days after last intake of IMP, were taken into account for the safety analysis
    End point type
    Secondary
    End point timeframe
    During the trial
    End point values
    		 IMP 1 IMP 2 IMP 3 Reference Safety Set
    Number of subjects analysed
    84
    82
    86
    86
    338
    Units: events
    84
    82
    86
    86
    338
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    during the trial
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Treatment IMP1
    Reporting group description
    		 -

    Reporting group title
    Treatment IMP2
    Reporting group description
    		 -

    Reporting group title
    Treatment IMP 3
    Reporting group description
    		 -

    Reporting group title
    Treatment Reference Product
    Reporting group description
    		 -

    Serious adverse events
    		 Treatment IMP1 Treatment IMP2 Treatment IMP 3 Treatment Reference Product
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 84 (3.57%)
    0 / 82 (0.00%)
    1 / 86 (1.16%)
    0 / 86 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cervix carcinoma stage 0
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 82 (0.00%)
    1 / 86 (1.16%)
    0 / 86 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Thrombophlebitis superficial
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 82 (0.00%)
    0 / 86 (0.00%)
    0 / 86 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Pyelonephritis acute
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 82 (0.00%)
    0 / 86 (0.00%)
    0 / 86 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Treatment IMP1 Treatment IMP2 Treatment IMP 3 Treatment Reference Product
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    22 / 84 (26.19%)
    20 / 82 (24.39%)
    15 / 86 (17.44%)
    22 / 86 (25.58%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 84 (0.00%)
    2 / 82 (2.44%)
    6 / 86 (6.98%)
    3 / 86 (3.49%)
         occurrences all number
    0
    2
    7
    4
    Reproductive system and breast disorders
    Metrorrhagia
         subjects affected / exposed
    8 / 84 (9.52%)
    7 / 82 (8.54%)
    5 / 86 (5.81%)
    10 / 86 (11.63%)
         occurrences all number
    9
    9
    5
    10
    Breast pain
         subjects affected / exposed
    4 / 84 (4.76%)
    3 / 82 (3.66%)
    2 / 86 (2.33%)
    2 / 86 (2.33%)
         occurrences all number
    4
    3
    2
    2
    Cervical dysplasia
         subjects affected / exposed
    4 / 84 (4.76%)
    2 / 82 (2.44%)
    2 / 86 (2.33%)
    3 / 86 (3.49%)
         occurrences all number
    4
    2
    2
    3
    Vaginal infection
         subjects affected / exposed
    1 / 84 (1.19%)
    2 / 82 (2.44%)
    3 / 86 (3.49%)
    0 / 86 (0.00%)
         occurrences all number
    1
    2
    3
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 82 (0.00%)
    3 / 86 (3.49%)
    0 / 86 (0.00%)
         occurrences all number
    1
    0
    3
    0
    Respiratory, thoracic and mediastinal disorders
    Viral upper respiratory tract infection
         subjects affected / exposed
    3 / 84 (3.57%)
    2 / 82 (2.44%)
    2 / 86 (2.33%)
    2 / 86 (2.33%)
         occurrences all number
    3
    2
    2
    2
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 84 (3.57%)
    1 / 82 (1.22%)
    2 / 86 (2.33%)
    2 / 86 (2.33%)
         occurrences all number
    3
    1
    3
    4
    Tonsillitis
         subjects affected / exposed
    4 / 84 (4.76%)
    1 / 82 (1.22%)
    0 / 86 (0.00%)
    1 / 86 (1.16%)
         occurrences all number
    4
    1
    0
    1
    Sinusitis
         subjects affected / exposed
    0 / 84 (0.00%)
    0 / 82 (0.00%)
    1 / 86 (1.16%)
    3 / 86 (3.49%)
         occurrences all number
    0
    0
    1
    3
    Infections and infestations
    Respiratory tract infection viral
         subjects affected / exposed
    5 / 84 (5.95%)
    3 / 82 (3.66%)
    5 / 86 (5.81%)
    1 / 86 (1.16%)
         occurrences all number
    6
    3
    5
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Tue May 07 13:30:21 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA