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    Clinical Trial Results:
    A Phase 3 Multicenter, Multinational, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ALN TTRSC in Patients With Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)

    Summary
    EudraCT number
    2014-003835-20
    Trial protocol
    GB   SE   DE   ES   BE   IT  
    Global end of trial date
    30 Mar 2017

    Results information
    Results version number
    v1(current)
    This version publication date
    12 Apr 2018
    First version publication date
    12 Apr 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    ALN-TTRSC-004
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02319005
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Alnylam Pharmaceuticals, Inc.
    Sponsor organisation address
    300 Third Street, Cambridge, MA, United States, 02142
    Public contact
    Investor Relations and Corporate Communications, Alnylam Pharmaceuticals, Inc., Investors@alnylam.com
    Scientific contact
    Chief Medical Officer, Alnylam Pharmaceuticals, Inc. , Clinicaltrials@alnylam.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
    12 May 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 Mar 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Mar 2017
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To determine the efficacy and safety of ALN-TTRSC (revusiran) in patients with familial amyloidotic cardiomyopathy (FAC), hereafter referred to as hereditary transthyretin (TTR)-mediated cardiac amyloidosis (hATTR cardiac amyloidosis).
    Protection of trial subjects
    An independent Data Monitoring Committee (DMC) was implemented for the study and operated under a prespecified charter.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    10 Dec 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 3
    Country: Number of subjects enrolled
    Sweden: 4
    Country: Number of subjects enrolled
    United Kingdom: 22
    Country: Number of subjects enrolled
    United States: 136
    Country: Number of subjects enrolled
    Belgium: 1
    Country: Number of subjects enrolled
    Canada: 5
    Country: Number of subjects enrolled
    France: 7
    Country: Number of subjects enrolled
    Germany: 22
    Country: Number of subjects enrolled
    Italy: 6
    Worldwide total number of subjects
    206
    EEA total number of subjects
    65
    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)
    66
    From 65 to 84 years
    139
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 206 patients with hATTR cardiac amyloidosis were enrolled and randomized in the study.

    Pre-assignment period milestones
    Number of subjects started
    206
    Number of subjects completed
    206

    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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Revusiran
    Arm description
    All patients who received at least 1 dose of revusiran
    Arm type
    Experimental

    Investigational medicinal product name
    Revusiran
    Investigational medicinal product code
    ALN-TTRSC
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Patients received 500 mg revusiran or placebo daily for 5 days during the first week, a single dose on Day 7, and then once weekly for up to 18 months.

    Arm title
    Placebo
    Arm description
    All patients who received at least 1 dose of placebo.
    Arm type
    Placebo

    Investigational medicinal product name
    Normal Saline
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Patients received placebo daily for 5 days during the first week, a single dose on Day 7, and then once weekly for up to 18 months.

    Number of subjects in period 1
    Revusiran Placebo
    Started
    140
    66
    Completed
    92
    51
    Not completed
    48
    15
         Adverse event, serious fatal
    20
    7
         Consent withdrawn by subject
    9
    7
         Physician decision
    2
    -
         Adverse event, non-fatal
    9
    -
         Other
    5
    1
         Due to Study Termination
    2
    -
         Lost to follow-up
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Revusiran
    Reporting group description
    All patients who received at least 1 dose of revusiran

    Reporting group title
    Placebo
    Reporting group description
    All patients who received at least 1 dose of placebo.

    Reporting group values
    Revusiran Placebo Total
    Number of subjects
    140 66 206
    Age categorical
    Units: Subjects
        In utero
    0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    41 25 66
        From 65-84 years
    98 41 139
        85 years and over
    1 0 1
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    68.6 ( 9.28 ) 66.2 ( 9.54 ) -
    Gender categorical
    Units: Subjects
        Female
    35 13 48
        Male
    105 53 158
    New York Heart Association Class
    Units: Subjects
        Class I
    13 4 17
        Class II
    83 42 125
        Class III
    44 20 64
    Subject analysis sets

    Subject analysis set title
    Safety
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    All randomized patients that were treated and received at least 1 dose of the study drug.

    Subject analysis sets values
    Safety
    Number of subjects
    206
    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)
    66
        From 65-84 years
    139
        85 years and over
    1
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    67.8 ( 9.40 )
    Gender categorical
    Units: Subjects
        Female
    48
        Male
    158
    New York Heart Association Class
    Units: Subjects
        Class I
    17
        Class II
    125
        Class III
    64

    End points

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    End points reporting groups
    Reporting group title
    Revusiran
    Reporting group description
    All patients who received at least 1 dose of revusiran

    Reporting group title
    Placebo
    Reporting group description
    All patients who received at least 1 dose of placebo.

    Subject analysis set title
    Safety
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    All randomized patients that were treated and received at least 1 dose of the study drug.

    Primary: 6-Minute Walk Test

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    End point title
    6-Minute Walk Test [1]
    End point description
    The difference between the revusiran and placebo group in change from baseline to 18 months in the total distance walked in 6 minutes
    End point type
    Primary
    End point timeframe
    From baseline to 18 months
    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: Limited collection of data due to the Sponsor's decision to terminate the study
    End point values
    Safety
    Number of subjects analysed
    0 [2]
    Units: meter
        arithmetic mean (standard error)
    ( )
    Notes
    [2] - Limited collection of data due to the Sponsor's decision to terminate the study
    No statistical analyses for this end point

    Primary: Serum TTR Reduction

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    End point title
    Serum TTR Reduction [3]
    End point description
    The difference between revusiran (ALN-TTRSC) and placebo group in the percent reduction in serum TTR levels over 18 months
    End point type
    Primary
    End point timeframe
    From baseline to 18 months
    Notes
    [3] - 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: Limited collection of data due to the Sponsor's decision to terminate the study
    End point values
    Safety
    Number of subjects analysed
    0 [4]
    Units: meter
        arithmetic mean (standard error)
    ( )
    Notes
    [4] - Limited collection of data due to the Sponsor's decision to terminate the study
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All AEs that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study)
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Revusiran
    Reporting group description
    All patients who received at least 1 dose of revusiran

    Reporting group title
    Placebo
    Reporting group description
    All patients who received at least 1 dose of placebo.

    Serious adverse events
    Revusiran Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    83 / 140 (59.29%)
    34 / 66 (51.52%)
         number of deaths (all causes)
    23
    7
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Prostate cancer
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuroendocrine tumour
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangiocarcinoma
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to lung
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gallbladder cancer
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to biliary tract
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clear cell renal cell carcinoma
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    3 / 140 (2.14%)
    2 / 66 (3.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery aneurysm
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Lipoma excision
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    1 / 140 (0.71%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Asthenia
         subjects affected / exposed
    1 / 140 (0.71%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypothermia
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral swelling
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Medical device complication
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    1 / 140 (0.71%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    2 / 140 (1.43%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Mental status changes
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Weight decreased
         subjects affected / exposed
    2 / 140 (1.43%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test abnormal
         subjects affected / exposed
    2 / 140 (1.43%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme abnormal
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Craniocerebral injury
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug administration error
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    25 / 140 (17.86%)
    9 / 66 (13.64%)
         occurrences causally related to treatment / all
    2 / 35
    0 / 13
         deaths causally related to treatment / all
    2 / 5
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    15 / 140 (10.71%)
    9 / 66 (13.64%)
         occurrences causally related to treatment / all
    1 / 20
    0 / 12
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    9 / 140 (6.43%)
    4 / 66 (6.06%)
         occurrences causally related to treatment / all
    4 / 12
    0 / 6
         deaths causally related to treatment / all
    1 / 4
    0 / 2
    Atrial fibrillation
         subjects affected / exposed
    7 / 140 (5.00%)
    2 / 66 (3.03%)
         occurrences causally related to treatment / all
    1 / 8
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    2 / 140 (1.43%)
    4 / 66 (6.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    4 / 140 (2.86%)
    2 / 66 (3.03%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Cardiac arrest
         subjects affected / exposed
    3 / 140 (2.14%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Ventricular tachycardia
         subjects affected / exposed
    2 / 140 (1.43%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    1 / 140 (0.71%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    2 / 140 (1.43%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Cardiac amyloidosis
         subjects affected / exposed
    1 / 140 (0.71%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia supraventricular
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiorenal syndrome
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pericardial effusion
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Low cardiac output syndrome
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nervous system disorders
    Neuropathy peripheral
         subjects affected / exposed
    7 / 140 (5.00%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    7 / 7
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    4 / 140 (2.86%)
    3 / 66 (4.55%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 140 (0.00%)
    2 / 66 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    2 / 140 (1.43%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    2 / 140 (1.43%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Amnesia
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Central nervous system lesion
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Convulsion
         subjects affected / exposed
    2 / 140 (1.43%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Pancytopenia
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heparin-induced thrombocytopenia
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spleen disorder
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo positional
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Impaired gastric emptying
         subjects affected / exposed
    3 / 140 (2.14%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    2 / 140 (1.43%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 140 (1.43%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    2 / 140 (1.43%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal amyloidosis
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumobilia
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis cholestatic
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Cutaneous vasculitis
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure acute
         subjects affected / exposed
    5 / 140 (3.57%)
    2 / 66 (3.03%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Renal failure
         subjects affected / exposed
    3 / 140 (2.14%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 140 (0.71%)
    2 / 66 (3.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstructive uropathy
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal Failure Chronic
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    2 / 140 (1.43%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot deformity
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    3 / 140 (2.14%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 140 (1.43%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nocardiosis
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective tenosynovitis
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 140 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia infection
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    3 / 140 (2.14%)
    3 / 66 (4.55%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    4 / 140 (2.86%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    2 / 140 (1.43%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    2 / 140 (1.43%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 140 (0.71%)
    2 / 66 (3.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cachexia
         subjects affected / exposed
    2 / 140 (1.43%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hyperglycaemic hyperosmolar nonketotic syndrome
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lactic acidosis
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypervolaemia
         subjects affected / exposed
    1 / 140 (0.71%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Revusiran Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    134 / 140 (95.71%)
    61 / 66 (92.42%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    11 / 140 (7.86%)
    4 / 66 (6.06%)
         occurrences all number
    15
    4
    General disorders and administration site conditions
    Injection site pain
         subjects affected / exposed
    23 / 140 (16.43%)
    4 / 66 (6.06%)
         occurrences all number
    101
    13
    Injection site erythema
         subjects affected / exposed
    16 / 140 (11.43%)
    0 / 66 (0.00%)
         occurrences all number
    64
    0
    Fatigue
         subjects affected / exposed
    14 / 140 (10.00%)
    8 / 66 (12.12%)
         occurrences all number
    16
    32
    Oedema peripheral
         subjects affected / exposed
    25 / 140 (17.86%)
    12 / 66 (18.18%)
         occurrences all number
    30
    16
    Asthenia
         subjects affected / exposed
    15 / 140 (10.71%)
    2 / 66 (3.03%)
         occurrences all number
    18
    2
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    25 / 140 (17.86%)
    10 / 66 (15.15%)
         occurrences all number
    29
    14
    Dyspnoea
         subjects affected / exposed
    16 / 140 (11.43%)
    9 / 66 (13.64%)
         occurrences all number
    22
    9
    Productive cough
         subjects affected / exposed
    9 / 140 (6.43%)
    1 / 66 (1.52%)
         occurrences all number
    9
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    8 / 140 (5.71%)
    2 / 66 (3.03%)
         occurrences all number
    8
    2
    Investigations
    Weight decreased
         subjects affected / exposed
    12 / 140 (8.57%)
    4 / 66 (6.06%)
         occurrences all number
    14
    5
    Blood lactic acid increased
         subjects affected / exposed
    15 / 140 (10.71%)
    3 / 66 (4.55%)
         occurrences all number
    16
    3
    Blood bilirubin increased
         subjects affected / exposed
    10 / 140 (7.14%)
    4 / 66 (6.06%)
         occurrences all number
    11
    4
    Liver function test abnormal
         subjects affected / exposed
    12 / 140 (8.57%)
    1 / 66 (1.52%)
         occurrences all number
    12
    1
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    10 / 140 (7.14%)
    5 / 66 (7.58%)
         occurrences all number
    16
    9
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    10 / 140 (7.14%)
    3 / 66 (4.55%)
         occurrences all number
    14
    3
    Atrial fibrillation
         subjects affected / exposed
    16 / 140 (11.43%)
    2 / 66 (3.03%)
         occurrences all number
    20
    3
    Cardiac failure congestive
         subjects affected / exposed
    4 / 140 (2.86%)
    6 / 66 (9.09%)
         occurrences all number
    4
    9
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    18 / 140 (12.86%)
    13 / 66 (19.70%)
         occurrences all number
    19
    15
    Neuropathy peripheral
         subjects affected / exposed
    20 / 140 (14.29%)
    6 / 66 (9.09%)
         occurrences all number
    21
    6
    Hypoaesthesia
         subjects affected / exposed
    12 / 140 (8.57%)
    4 / 66 (6.06%)
         occurrences all number
    21
    5
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    20 / 140 (14.29%)
    11 / 66 (16.67%)
         occurrences all number
    23
    13
    Nausea
         subjects affected / exposed
    20 / 140 (14.29%)
    5 / 66 (7.58%)
         occurrences all number
    28
    7
    Vomiting
         subjects affected / exposed
    9 / 140 (6.43%)
    5 / 66 (7.58%)
         occurrences all number
    18
    7
    Abdominal pain
         subjects affected / exposed
    7 / 140 (5.00%)
    3 / 66 (4.55%)
         occurrences all number
    10
    5
    Diarrhoea
         subjects affected / exposed
    9 / 140 (6.43%)
    5 / 66 (7.58%)
         occurrences all number
    9
    5
    Abdominal pain upper
         subjects affected / exposed
    9 / 140 (6.43%)
    1 / 66 (1.52%)
         occurrences all number
    9
    1
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    9 / 140 (6.43%)
    2 / 66 (3.03%)
         occurrences all number
    9
    2
    Renal and urinary disorders
    Renal failure acute
         subjects affected / exposed
    9 / 140 (6.43%)
    1 / 66 (1.52%)
         occurrences all number
    9
    3
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    14 / 140 (10.00%)
    8 / 66 (12.12%)
         occurrences all number
    19
    9
    Arthralgia
         subjects affected / exposed
    9 / 140 (6.43%)
    6 / 66 (9.09%)
         occurrences all number
    10
    8
    Muscle spasms
         subjects affected / exposed
    9 / 140 (6.43%)
    2 / 66 (3.03%)
         occurrences all number
    11
    3
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    11 / 140 (7.86%)
    5 / 66 (7.58%)
         occurrences all number
    11
    5
    Bronchitis
         subjects affected / exposed
    10 / 140 (7.14%)
    3 / 66 (4.55%)
         occurrences all number
    11
    3
    Sinusitis
         subjects affected / exposed
    7 / 140 (5.00%)
    3 / 66 (4.55%)
         occurrences all number
    8
    4
    Upper respiratory tract infection
         subjects affected / exposed
    8 / 140 (5.71%)
    4 / 66 (6.06%)
         occurrences all number
    8
    4
    Urinary tract infection
         subjects affected / exposed
    8 / 140 (5.71%)
    2 / 66 (3.03%)
         occurrences all number
    8
    4
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    6 / 140 (4.29%)
    8 / 66 (12.12%)
         occurrences all number
    10
    12
    Decreased appetite
         subjects affected / exposed
    13 / 140 (9.29%)
    6 / 66 (9.09%)
         occurrences all number
    16
    6
    Gout
         subjects affected / exposed
    3 / 140 (2.14%)
    7 / 66 (10.61%)
         occurrences all number
    4
    16
    Fluid overload
         subjects affected / exposed
    6 / 140 (4.29%)
    4 / 66 (6.06%)
         occurrences all number
    6
    6

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Feb 2016
    The primary purpose for the protocol amendment is to update eligibility criteria related to confirmation of amyloid tissue deposition and liver function. These changes do not alter the originally intended patient population. Additionally, in response to adverse events (AEs) observed during the study, more intensive monitoring of liver function is incorporated into the protocol. A dose reduction allowance for significant injection site reactions (ISRs) and liver function test (LFT) abnormalities is also included.
    11 Oct 2016
    Provided guidance for follow-up of patients enrolled in the study following the Sponsor’s decision to discontinue study drug dosing in all ongoing revusiran studies

    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.
    Study drug was discontinued early due to an imbalance in mortality observed between patients treated with revusiran and placebo. Given the limited exposure to study drug, clinical efficacy conclusions cannot be drawn.
    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.

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