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:
    A Multicenter, Randomized, Double-blind, Placebo-Controlled, Parallel-Group, Multiple-Dose Study to Evaluate the Effects of RLY5016 in Heart Failure Patients

    Summary
    EudraCT number
    		 2009-009983-29
    Trial protocol
    		 DE   CZ  
    Global end of trial date
    12 Nov 2009

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Aug 2016
    First version publication date
    06 Aug 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    RLY5016–202
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00868439
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Relypsa, Inc.
    Sponsor organisation address
    100 Cardinal Way, Redwood City, United States, 994063
    Public contact
    Medical Information, Relypsa, Inc., medinfo@relypsa.com
    Scientific contact
    Medical Information, Relypsa, Inc., medinfo@relypsa.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 Nov 2009
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    12 Nov 2009
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Nov 2009
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study was to assess the effects of patiromer on serum potassium participants with heart failure. This study also assessed the safety and tolerability of patiromer in participants with heart failure.
    Protection of trial subjects
    This study was conducted in accordance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 May 2009
    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
    Poland: 1
    Country: Number of subjects enrolled
    Czech Republic: 5
    Country: Number of subjects enrolled
    Germany: 5
    Country: Number of subjects enrolled
    United States: 19
    Country: Number of subjects enrolled
    Russian Federation: 35
    Country: Number of subjects enrolled
    Ukraine: 12
    Country: Number of subjects enrolled
    Georgia: 28
    Worldwide total number of subjects
    105
    EEA total number of subjects
    11
    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)
    31
    From 65 to 84 years
    72
    85 years and over
    2

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 120 subjects were randomized (60 to each treatment group). Of these, 120 randomized subjects, 105 received either patiromer (n = 56) or placebo (n = 49).

    Pre-assignment
    Screening details
    		 Eligible participants ≥ 18 y/o, had history of chronic HF, clinically initiated spironolactone therapy, serum K+ = 4.3 – 5.1 mEq/L at screening and baseline, and either had 1) CKD, w/ eGFR < 60 mL/min and receiving HF therapies or 2) documented history of hyperkalemia led to discontinuation w/ aldosterone antagonist w/in 6 months prior to baseline.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Patiromer
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Patiromer
    Investigational medicinal product code
    Other name
    RLY5016 for Oral Suspension
    Pharmaceutical forms
    Powder for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Patiromer, 15 g, orally, twice a day for up to 28 days. Spironolactone, 25 mg, orally, once a day for up to 28 days. Spironolactone was increased to 50 mg/day after 2 weeks if the participant’s serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant’s serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.

    Arm title
    		 Placebo
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo, orally, twice a day for up to 28 days. Spironolactone, 25 mg, orally, once a day for up to 28 days. Spironolactone was increased to 50 mg/day after 2 weeks if the participant’s serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant’s serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.

    Number of subjects in period 1 [1]
    		Patiromer Placebo
    Started
    55
    49
    Completed
    48
    40
    Not completed
    7
    9
         Adverse event, serious fatal
    -
    1
         Physician decision
    1
    -
         Consent withdrawn by subject
    -
    1
         Adverse event, non-fatal
    4
    3
         Prot-Specified W/D Criteria (Serum K+)
    2
    3
         Protocol deviation
    -
    1
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: One participant received one dose of patiromer and did not return to the clinic in a timely manner; the participant was terminated from the study for protocol noncompliance, and because the participant did not have post-treatment efficacy data, the participant was excluded from the Full Analysis Set but retained in the Safety Analysis Set.

    Baseline characteristics

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

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group values
    		 Patiromer Placebo Total
    Number of subjects
    		 55 49 104
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 16 14 30
        From 65-84 years
    		 37 35 72
        85 years and over
    		 2 0 2
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 68.3 ( 8.66 ) 68.2 ( 10.46 ) -
    Gender categorical
    Units: Subjects
        Female
    		 26 15 41
        Male
    		 29 34 63

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Patiromer
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Primary: Change From Baseline in Serum Potassium to the End of the 28-day Treatment Period

    		 Close Top of page
    End point title
    		 Change From Baseline in Serum Potassium to the End of the 28-day Treatment Period
    End point description
    Analysis was determined using Last Observation Carried Forward (LOCF).
    End point type
    Primary
    End point timeframe
    Baseline and Day 28
    End point values
    		 Patiromer Placebo
    Number of subjects analysed
    55
    49
    Units: milliequivalent(s)/litre
        least squares mean (standard error)
    -0.21 ( 0.066 )
    0.23 ( 0.072 )
    Statistical analysis title
    		 Statistical Analysis
    Comparison groups
    Patiromer v Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Proportion of Participants With a Serum Potassium Level During the 28-day Treatment Period That Was > 5.5 mEq/L.

    		 Close Top of page
    End point title
    		 Proportion of Participants With a Serum Potassium Level During the 28-day Treatment Period That Was > 5.5 mEq/L.
    End point description
    Analysis based on central laboratory data.
    End point type
    Secondary
    End point timeframe
    28 Days
    End point values
    		 Patiromer Placebo
    Number of subjects analysed
    55
    49
    Units: percent
        number (not applicable)
    7.3
    24.5
    Statistical analysis title
    		 Statistical Analysis
    Comparison groups
    Patiromer v Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.027
    Method
    		 Fisher exact
    Confidence interval

    Secondary: Proportion of Participants Discontinuing the Study Due to Serum Potassium Elevation (Serum K+ > 5.5 mEq/L).

    		 Close Top of page
    End point title
    		 Proportion of Participants Discontinuing the Study Due to Serum Potassium Elevation (Serum K+ > 5.5 mEq/L).
    End point description
    Analysis based on local laboratory data.
    End point type
    Secondary
    End point timeframe
    28 Days
    End point values
    		 Patiromer Placebo
    Number of subjects analysed
    55
    49
    Units: percent
        number (not applicable)
    0
    6.1
    Statistical analysis title
    		 Statistical Analysis
    Comparison groups
    Patiromer v Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.101
    Method
    		 Fisher exact
    Confidence interval

    Secondary: Proportion of Participants Whose Spironolactone Dose Was Increased.

    		 Close Top of page
    End point title
    		 Proportion of Participants Whose Spironolactone Dose Was Increased.
    End point description
    End point type
    Secondary
    End point timeframe
    28 Days
    End point values
    		 Patiromer Placebo
    Number of subjects analysed
    55
    49
    Units: percent
        number (not applicable)
    90.9
    73.5
    Statistical analysis title
    		 Statistical Analysis
    Comparison groups
    Patiromer v Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.022
    Method
    		 Fisher exact
    Confidence interval

    Secondary: Proportion of Participants With an Increase in Serum Potassium Level From Baseline to the End of the 28-day Treatment Period That Was ≥ 0.5 mEq/L

    		 Close Top of page
    End point title
    		 Proportion of Participants With an Increase in Serum Potassium Level From Baseline to the End of the 28-day Treatment Period That Was ≥ 0.5 mEq/L
    End point description
    Analysis was determined using LOCF.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 28
    End point values
    		 Patiromer Placebo
    Number of subjects analysed
    55
    49
    Units: percent
        number (not applicable)
    12.7
    24.5
    Statistical analysis title
    		 Statistical Analysis
    Comparison groups
    Patiromer v Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.136
    Method
    		 Fisher exact
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to 7 days after Day 28 or last patiromer dose, whichever was earlier.
    Adverse event reporting additional description
    Participants received at least one dose of trial medication.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    12.0
    Reporting groups
    Reporting group title
    Patiromer
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Serious adverse events
    		 Patiromer Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 56 (3.57%)
    2 / 49 (4.08%)
         number of deaths (all causes)
    0
    1
         number of deaths resulting from adverse events
    Cardiac disorders
    Coronary artery disease
         subjects affected / exposed
    2 / 56 (3.57%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Sudden cardiac death
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metabolism and nutrition disorders
    Gout
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Patiromer Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 56 (19.64%)
    1 / 49 (2.04%)
    Investigations
    Blood urea increased
         subjects affected / exposed
    3 / 56 (5.36%)
    0 / 49 (0.00%)
         occurrences all number
    3
    0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    3 / 56 (5.36%)
    0 / 49 (0.00%)
         occurrences all number
    3
    0
    Diarrhoea
         subjects affected / exposed
    3 / 56 (5.36%)
    1 / 49 (2.04%)
         occurrences all number
    3
    1
    Flatulence
         subjects affected / exposed
    4 / 56 (7.14%)
    0 / 49 (0.00%)
         occurrences all number
    4
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    23 Feb 2009
    RLY5016-202 Protocol Amendment 1: Substantial protocol amendment was in effect prior to actual start date of recruitment, 29 May 2009.
    07 Apr 2009
    RLY5016-202 Protocol Amendment 2: Substantial protocol amendment was in effect prior to actual start date of recruitment, 29 May 2009.

    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-Wed May 08 03:31:01 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA