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   43865   clinical trials with a EudraCT protocol, of which   7286   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:
    The Efficacy and Safety of ROSUvastatin Dose Titration in the Treatment of PATients with Hyperlipidemia (ROSU-PATH)

    Summary
    EudraCT number
    		 2012-004799-21
    Trial protocol
    		 SI   CZ   HU  
    Global end of trial date
    31 Jul 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    24 Jun 2020
    First version publication date
    24 Jun 2020
    Other versions
    Summary report(s)
    		 ROSU-PATH Final Report Synopsis

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    KCT03/2012
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Krka, d.d., Novo mesto
    Sponsor organisation address
    Dunajska cesta 65, Ljubljana, Slovenia, 1000
    Public contact
    Tanja Kohek, Krka, d.d., Novo mesto Dunajska cesta 65 1000 Ljubljana, 00386 1 4751236, tanja.kohek@krka.biz
    Scientific contact
    Tanja Kohek, Krka, d.d., Novo mesto Dunajska cesta 65 1000 Ljubljana, 00386 1 4751236, tanja.kohek@krka.biz
    Sponsor organisation name
    Krka ČR, s.r.o.
    Sponsor organisation address
    Sokolovská 192/79, Prague, Czech Republic, 180 00
    Public contact
    Martin Sustr, Krka ČR, s.r.o. Sokolovská 192/79 180 00 Prague, 00420 602 486846, martin.sustr@krka.biz
    Scientific contact
    Martin Sustr, Krka ČR, s.r.o. Sokolovská 192/79 180 00 Prague, 00420 602 486846, martin.sustr@krka.biz
    Sponsor organisation name
    KRKA Magyarország Kereskedelmi Kft.
    Sponsor organisation address
    Dunavirág u. 2-6. 3.torony, 3.em., Budapest, Hungary, 1138
    Public contact
    Ágota Mészáros, KRKA Magyarország Kereskedelmi Kft. Dunavirág u. 2-6. 3.torony, 3.em. 1138 Budapest Hungary, +362 0 8012549, agota.meszaros@krka.biz
    Scientific contact
    Ágota Mészáros, KRKA Magyarország Kereskedelmi Kft. Dunavirág u. 2-6. 3.torony, 3.em. 1138 Budapest Hungary, +362 0 8012549, agota.meszaros@krka.biz
    Sponsor organisation name
    KRKA-RUS LLC
    Sponsor organisation address
    Vodny Business Center, 22nd floor, 5/1 Golovinskoye Highway, Moscow, Russian Federation, 125212
    Public contact
    Anna Zakharova, KRKA-RUS LLC Vodny Business Center, 22nd floor, 5/1 Golovinskoye Highway 125212 Moscow Russia, anna.zakharova@krka.biz
    Scientific contact
    Anna Zakharova, KRKA-RUS LLC Vodny Business Center, 22nd floor, 5/1 Golovinskoye Highway 125212 Moscow Russia, anna.zakharova@krka.biz
    Sponsor organisation name
    KRKA Romania S.R.L.
    Sponsor organisation address
    Sema Parc, etaj 10, Sector 6, Bucharest, Romania, 060032
    Public contact
    Cristina Boeriu, KRKA Romania S.R.L. Sema Parc, etaj 10, Sector 6 060032 Bucharest Romania, 0040 72 9990907, cristina.boeriu@krka.biz
    Scientific contact
    Cristina Boeriu, KRKA Romania S.R.L. Sema Parc, etaj 10, Sector 6 060032 Bucharest Romania, 0040 72 9990907, cristina.boeriu@krka.biz
    Sponsor organisation name
    KRKA UKRAINE LLC
    Sponsor organisation address
    Ul. Staronavodnitskaya 13, of. 127, PB 42, Kiev, Ukraine, 01015
    Public contact
    Pavlo Radchuk, KRKA UKRAINE LLC Ul. Staronavodnitskaya 13, of. 127, PB 42 01015 Kiev Ukraine, pavlo.radchuk@krka.biz
    Scientific contact
    Pavlo Radchuk, KRKA UKRAINE LLC Ul. Staronavodnitskaya 13, of. 127, PB 42 01015 Kiev Ukraine, pavlo.radchuk@krka.biz
    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
    29 Jan 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 Jul 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Jul 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The aim of the study is to establish the efficacy and safety of Roswera® in wide populations of patients with primary hypercholesterolemia and mixed dyslipidemia (type IIb) (patients with high absolute risk for cardiovascular diseases in primary and secondary prevention) with emphasis on placement of additional strengths 15 mg and 30 mg in clinical practice.
    Protection of trial subjects
    The study was conducted in accordance with the ethical principles that are based on the Declaration of Helsinki. In general patients aged 18-75 years of both genders with primary hypercholesterolemia or mixed dyslipidemia (type IIb) were eligible for the inclusion in the study. Prior to any study activities patients needed to sign written informed consent form. The dose of Rosuvastatin was adjusted on V2 (4 weeks) and on V3 (8 weeks) according to trial scheme and target lipid values.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Mar 2013
    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
    Croatia: 50
    Country: Number of subjects enrolled
    Ukraine: 52
    Country: Number of subjects enrolled
    Russian Federation: 122
    Country: Number of subjects enrolled
    Romania: 54
    Country: Number of subjects enrolled
    Slovenia: 67
    Country: Number of subjects enrolled
    Czech Republic: 65
    Country: Number of subjects enrolled
    Hungary: 62
    Worldwide total number of subjects
    472
    EEA total number of subjects
    298
    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)
    367
    From 65 to 84 years
    105
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 There were 472 patients enrolled in the study.

    Pre-assignment
    Screening details
    		 In general patients aged 18-75 years of both genders with primary hypercholesterolemia or mixed dyslipidemia (type IIb) were eligible for the inclusion in the study. Prior to any study activities patients needed to sign written informed consent form.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Group 10
    Arm description
    		 All patients meeting inclusion criteria were randomized at the start of the trial course (Visit 1) into two groups to receive either 10 mg/day or 15 mg/day of rosuvastatin. On V2 (after 4 weeks) and V3 (after 8 weeks) the dose was adjusted according to achievement of target LDL-c goals. If the patient did not achieve target LDL-c goal, the dose was increased according to the trial scheme. Patients starting the treatment with 10 mg/day of Roswera® were titrated according to the regimen 10 mg – 20 mg – 40 mg. Patients starting the treatment with 15 mg/day of Roswera® were titrated according to the regimen 15 mg – 30 mg – 40 mg.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Roswera® 10
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 tablet per day at any time during the day, throughout the trial at the same time. Roswera® 10 contains 10 mg of rosuvastatin per tablet.

    Investigational medicinal product name
    Roswera® 20
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 tablet per day at any time during the day, throughout the trial at the same time. Roswera® 20 contains 20 mg of rosuvastatin per tablet.

    Investigational medicinal product name
    Roswera® 40
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 tablet per day at any time during the day, throughout the trial at the same time. Roswera® 40 contains 40 mg of rosuvastatin per tablet.

    Arm title
    		 Group 15
    Arm description
    		 All patients meeting inclusion criteria were randomized at the start of the trial course (Visit 1) into two groups to receive either 10 mg/day or 15 mg/day of rosuvastatin. On V2 (after 4 weeks) and V3 (after 8 weeks) the dose was adjusted according to achievement of target LDL-c goals. If the patient did not achieve target LDL-c goal, the dose was increased according to the trial scheme. Patients starting the treatment with 10 mg/day of Roswera® were titrated according to the regimen 10 mg – 20 mg – 40 mg. Patients starting the treatment with 15 mg/day of Roswera® were titrated according to the regimen 15 mg – 30 mg – 40 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Roswera® 15
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 tablet per day at any time during the day, throughout the trial at the same time. Roswera® 15 contains 15 mg of rosuvastatin per tablet.

    Investigational medicinal product name
    Roswera® 30
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 tablet per day at any time during the day, throughout the trial at the same time. Roswera® 30 contains 30 mg of rosuvastatin per tablet.

    Investigational medicinal product name
    Roswera® 40
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 tablet per day at any time during the day, throughout the trial at the same time. Roswera® 40 contains 40 mg of rosuvastatin per tablet.

    Number of subjects in period 1
    		Group 10 Group 15
    Started
    239
    233
    Completed
    215
    212
    Not completed
    24
    21
         Physician decision
    1
    1
         Consent withdrawn by subject
    6
    3
         Adverse event, non-fatal
    13
    15
         Lost to follow-up
    1
    -
         Protocol deviation
    3
    2

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall Trial
    Reporting group description
    		 -

    Reporting group values
    		 Overall Trial Total
    Number of subjects
    		 472 472
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 56.9 ( 9.81 ) -
    Gender categorical
    Units: Subjects
        Female
    		 225 225
        Male
    		 246 246
        NA
    		 1 1

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Group 10
    Reporting group description
    		 All patients meeting inclusion criteria were randomized at the start of the trial course (Visit 1) into two groups to receive either 10 mg/day or 15 mg/day of rosuvastatin. On V2 (after 4 weeks) and V3 (after 8 weeks) the dose was adjusted according to achievement of target LDL-c goals. If the patient did not achieve target LDL-c goal, the dose was increased according to the trial scheme. Patients starting the treatment with 10 mg/day of Roswera® were titrated according to the regimen 10 mg – 20 mg – 40 mg. Patients starting the treatment with 15 mg/day of Roswera® were titrated according to the regimen 15 mg – 30 mg – 40 mg.

    Reporting group title
    Group 15
    Reporting group description
    		 All patients meeting inclusion criteria were randomized at the start of the trial course (Visit 1) into two groups to receive either 10 mg/day or 15 mg/day of rosuvastatin. On V2 (after 4 weeks) and V3 (after 8 weeks) the dose was adjusted according to achievement of target LDL-c goals. If the patient did not achieve target LDL-c goal, the dose was increased according to the trial scheme. Patients starting the treatment with 10 mg/day of Roswera® were titrated according to the regimen 10 mg – 20 mg – 40 mg. Patients starting the treatment with 15 mg/day of Roswera® were titrated according to the regimen 15 mg – 30 mg – 40 mg.

    Primary: Efficacy of Roswera® in achieving target LDL-c levels

    		 Close Top of page
    End point title
    		 Efficacy of Roswera® in achieving target LDL-c levels
    End point description
    The primary efficacy endpoint was to evaluate efficacy of Roswera® in achieving 2011 ESC/EAS guidelines target LDL-c levels in patients with hyperlipidemia. At each control visit, the serum lipids were measured and according to results, the achievement of target lipid levels was obtained. During the trial, the proportion of patients achieving target LDL-c values was steadily increasing. At the end of the trial, 62% of patients in Group 10 and 73% of patients in Group 15 achieved target LDL-c levels.
    End point type
    Primary
    End point timeframe
    12 weeks for one patient and was the same for the whole duration of the study (FPI 14.3.2013 - LPO 31.7.2015).
    End point values
    		 Group 10 Group 15
    Number of subjects analysed
    234
    228
    Units: % of patients reaching target LDL-c
    number (not applicable)
        Visit 2 (4 weeks)
    50
    59
        Visit 3 (8 weeks)
    59
    74
        Visit 4 (12 weeks)
    62
    73
    Statistical analysis title
    		 Difference between groups
    Statistical analysis description
    Because of the reasonably large sample, the asymptotic z-test was employed to assess the difference between means of two variables measured in the same population. Asymptotic 95%-confidence interval for the difference between means was used for interval estimation. The difference in proportion of patients achieving target LDL-c levels was statistically significant between Group 10 and Group 15 on each control visit (p < 0.0001 on V3 and V4; p < 0.05 on V2) and was in favour of Group 15.
    Comparison groups
    Group 10 v Group 15
    Number of subjects included in analysis
    462
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.05
    Method
    		 asymptotic z-test
    Confidence interval

    Primary: LDL-c values across visits

    		 Close Top of page
    End point title
    		 LDL-c values across visits
    End point description
    The primary efficacy endpoint was to evaluate efficacy of Roswera® in achieving 2011 ESC/EAS guidelines target LDL-c levels in patients with hyperlipidemia. At each control visit, the serum lipids were measured and according to results, the achievement of target lipid levels was obtained. Group 10: The mean LDL-c values at the beginning and at the end of the trial were 4.33 ± 1.11 mmol/l and 2.36 ± 0.72 mmol/l, respectively. The mean LDL-c decreased statistically significantly from the V1 to V2 (p < 0.0001) and from V2 to V3 (p < 0.0001). Group 15: The mean LDL-c values at the beginning and at the end of the trial were 4.44 ± 1.02 mmol/l and 2.28 ± 0.66 mmol/l, respectively. The mean LDL-c decreased statistically significantly from the V1 to V2 (p < 0.0001) and from V2 to V3 (p < 0.0001).
    End point type
    Primary
    End point timeframe
    12 weeks for one patient and was the same for the whole duration of the study ( FPI 14.3.2013 - LPO 31.7.2015).
    End point values
    		 Group 10 Group 15
    Number of subjects analysed
    237
    232
    Units: mmol/l
    arithmetic mean (standard deviation)
        Visit 1 (baseline)
    4.33 ( 1.11 )
    4.44 ( 1.02 )
        Visit 2 (4 weeks)
    2.64 ( 0.93 )
    2.52 ( 0.80 )
        Visit 3 (8 weeks)
    2.38 ( 0.76 )
    2.28 ( 0.71 )
        Visit 4 (12 weeks)
    2.36 ( 0.72 )
    2.28 ( 0.66 )
    Statistical analysis title
    		 comparison between two visits
    Statistical analysis description
    Because of the reasonably large sample, the asymptotic z-test was employed to assess the difference between means of two variables measured in the same population. Asymptotic 95%-confidence interval for the difference between means was used for interval estimation.
    Comparison groups
    Group 10 v Group 15
    Number of subjects included in analysis
    469
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.05
    Method
    		 Asymptotic z-test
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    12 weeks for one patient and was the same for the whole duration of the study (FPI 14.3.2013 - LPO 31.7.2015).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    All patients
    Reporting group description
    		 All 472 patients that were included in the ITT analysis.

    Serious adverse events
    		 All patients
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 472 (0.00%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 All patients
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    91 / 472 (19.28%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    11 / 472 (2.33%)
         occurrences all number
    13
    Blood and lymphatic system disorders
    Blood creatine phosphokinase increased
         subjects affected / exposed
    9 / 472 (1.91%)
         occurrences all number
    9
    General disorders and administration site conditions
    Insomnia
         subjects affected / exposed
    5 / 472 (1.06%)
         occurrences all number
    6
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    16 / 472 (3.39%)
         occurrences all number
    17
    Nausea
         subjects affected / exposed
    12 / 472 (2.54%)
         occurrences all number
    12
    Diarrhoea
         subjects affected / exposed
    10 / 472 (2.12%)
         occurrences all number
    12
    Flatulence
         subjects affected / exposed
    10 / 472 (2.12%)
         occurrences all number
    13
    Constipation
         subjects affected / exposed
    7 / 472 (1.48%)
         occurrences all number
    10
    Dyspepsia
         subjects affected / exposed
    6 / 472 (1.27%)
         occurrences all number
    7
    Hepatobiliary disorders
    Hepatic enzyme increased
         subjects affected / exposed
    6 / 472 (1.27%)
         occurrences all number
    6
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    14 / 472 (2.97%)
         occurrences all number
    16
    Muscular weakness
         subjects affected / exposed
    7 / 472 (1.48%)
         occurrences all number
    7
    Muscle spasms
         subjects affected / exposed
    6 / 472 (1.27%)
         occurrences all number
    7

    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-Mon Apr 29 02:35:47 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA