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   43845   clinical trials with a EudraCT protocol, of which   7282   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:
    Randomised, double-blind, placebo-controlled, parallel-group, multi-centre, phase III trial to investigate the efficacy, safety and tolerability of Naloxone HCl PR Tablets in patients with opioid induced constipation.

    Summary
    EudraCT number
    		 2017-000657-39
    Trial protocol
    		 DE   CZ   SK   ES   BG   PT   GB   HU  
    Global end of trial date
    02 May 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    20 May 2020
    First version publication date
    20 May 2020
    Other versions
    Summary report(s)
    		 CTR Synopsis

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    0217/DEV
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Develco Pharma Schweiz AG
    Sponsor organisation address
    Hohenrainstr. 12 D, Pratteln, Switzerland, 4133
    Public contact
    Sponsor Clinical Team, Develco Pharma Schweiz AG, +41 614255020, info@develco.ch
    Scientific contact
    Sponsor Clinical Team, Develco Pharma Schweiz AG, +41 614255020, info@develco.ch
    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
    14 Aug 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    02 May 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    02 May 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the efficacy of Naloxone HCl PR Tablets administered twice daily at TDD of 24 mg and 48 mg over placebo in the treatment of opioid induced constipation (OIC) in terms of overall complete spontaneous bowel movement (CSBM) responder rates
    Protection of trial subjects
    The trial was conducted in compliance with the protocol, by trial personnel, who are qualified by education, training, and experience in their roles, with adherence to Good Clinical Practice (GCP), the applicable regulatory requirements and ethical principles based on the Declaration of Helsinki.
    Background therapy
    		 Laxative rescue medication: Bisacodyl 5 mg gastro-resistant tablets, oral administration, single dose: 1-4 tablets (5-20 mg).
    Evidence for comparator
    		 -
    Actual start date of recruitment
    31 Jul 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 112
    Country: Number of subjects enrolled
    Portugal: 22
    Country: Number of subjects enrolled
    Slovakia: 49
    Country: Number of subjects enrolled
    Spain: 22
    Country: Number of subjects enrolled
    United Kingdom: 149
    Country: Number of subjects enrolled
    Bulgaria: 75
    Country: Number of subjects enrolled
    Czech Republic: 59
    Country: Number of subjects enrolled
    Germany: 53
    Country: Number of subjects enrolled
    Serbia: 22
    Worldwide total number of subjects
    563
    EEA total number of subjects
    541
    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)
    403
    From 65 to 84 years
    153
    85 years and over
    7

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Subjects of ≥ 18 years of age with opioid induced constipation

    Pre-assignment
    Screening details
    		 A total of 897 subjects were screened, out of these, 563 subjects were randomized. 75 and 259 subjects were screening and confirmation failures respectively.

    Period 1
    Period 1 title
    Overall (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
    		 NLX 48
    Arm description
    		 Subjects receive Naloxone HCl PR tablets blinded using double-dummy technique, total daily dose 48 mg, oral administration, twice daily.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Naloxone hydrochloride
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Prolonged-release tablet
    Routes of administration
    Oral use
    Dosage and administration details
    All patients will take two tablets of the trial medication in the morning and two tablets of the trial medication in the evening, i.e. at each intake • Naloxone HCl 24 mg PR Tablet plus Naloxone HCl 12 mg PR Placebo Tablet

    Arm title
    		 NLX 24
    Arm description
    		 Subjects receive Naloxone HCl PR tablets blinded using double-dummy technique, total daily dose 24 mg, oral administration, twice daily
    Arm type
    		 Experimental

    Investigational medicinal product name
    Naloxone hydrochloride
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Prolonged-release tablet
    Routes of administration
    Oral use
    Dosage and administration details
    All patients will take two tablets of the trial medication in the morning and two tablets of the trial medication in the evening, i.e. at each intake • Naloxone HCl 12 mg PR Tablet plus Naloxone HCl 24 mg PR Placebo Tablet

    Arm title
    		 Placebo
    Arm description
    		 Subjects receive corresponding placebo tablets, total daily dose: 24 or 48 mg, oral administration, twice daily
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    All patients will take two tablets of the trial medication in the morning and two tablets of the trial medication in the evening, i.e. at each intake •Naloxone HCl 24 mg PR Placebo Tablet plus Naloxone HCl 12 mg PR Placebo Tablet.

    Number of subjects in period 1
    		NLX 48 NLX 24 Placebo
    Started
    190
    187
    186
    Completed
    165
    164
    167
    Not completed
    25
    23
    19
         Consent withdrawn by subject
    3
    2
    3
         Physician decision
    -
    -
    1
         Adverse event, non-fatal
    20
    18
    10
         Other
    1
    1
    2
         Lost to follow-up
    -
    1
    -
         Lack of efficacy
    1
    1
    3

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    NLX 48
    Reporting group description
    		 Subjects receive Naloxone HCl PR tablets blinded using double-dummy technique, total daily dose 48 mg, oral administration, twice daily.

    Reporting group title
    NLX 24
    Reporting group description
    		 Subjects receive Naloxone HCl PR tablets blinded using double-dummy technique, total daily dose 24 mg, oral administration, twice daily

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects receive corresponding placebo tablets, total daily dose: 24 or 48 mg, oral administration, twice daily

    Reporting group values
    		 NLX 48 NLX 24 Placebo Total
    Number of subjects
    		 190 187 186 563
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 142 126 135 403
        85 years and over
    		 45 60 48 153
        From 18 - 64 years
    		 3 1 3 7
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 54.7 ± 11.55 58.4 ± 11.88 57.1 ± 12.17 -
    Gender categorical
    Units: Subjects
        Female
    		 117 116 116 349
        Male
    		 73 71 70 214

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    NLX 48
    Reporting group description
    		 Subjects receive Naloxone HCl PR tablets blinded using double-dummy technique, total daily dose 48 mg, oral administration, twice daily.

    Reporting group title
    NLX 24
    Reporting group description
    		 Subjects receive Naloxone HCl PR tablets blinded using double-dummy technique, total daily dose 24 mg, oral administration, twice daily

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects receive corresponding placebo tablets, total daily dose: 24 or 48 mg, oral administration, twice daily

    Subject analysis set title
    NLX 48 Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomised patients who received at least one dose of the double-blind trial medication.

    Subject analysis set title
    NLX 24 Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomised patients who received at least one dose of the double-blind trial medication.

    Subject analysis set title
    Placebo Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomised patients who received at least one dose of the double-blind trial medication.

    Subject analysis set title
    NLX 48 FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All randomised patients

    Subject analysis set title
    NLX 24 FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All randomised patients

    Subject analysis set title
    Placebo FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All randomised patients

    Primary: Overall CSBM response rate

    		 Close Top of page
    End point title
    		 Overall CSBM response rate
    End point description
    Overall CSBM response rate of Weeks 1 to 12 of Naloxone HCl 24 mg PR Tablets twice daily vs placebo and Naloxone HCl 12 mg PR Tablets twice daily vs placebo will be compared.
    End point type
    Primary
    End point timeframe
    Week 1 up to Week 12
    End point values
    		 NLX 48 FAS NLX 24 FAS Placebo FAS
    Number of subjects analysed
    190
    187
    186
    Units: subjects
    29
    25
    19
    Statistical analysis title
    		 Overall CSBM response rate NLX 48 vs Placebo
    Statistical analysis description
    Statistical Analysis of Overall CSBM response rate
    Comparison groups
    NLX 48 FAS v Placebo FAS
    Number of subjects included in analysis
    376
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1648
    Method
    		 Regression, Linear
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 2.89
    Statistical analysis title
    		 Overall CSBM response rate NLX 24 vs Placebo
    Statistical analysis description
    Statistical Analysis of Overall CSBM response rate
    Comparison groups
    NLX 24 FAS v Placebo FAS
    Number of subjects included in analysis
    373
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3725
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 2.53

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From first intake of IMP and not more than 14 days after last administration of IMP
    Adverse event reporting additional description
    Only numbers of TEAEs are reported.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    NLX 48 Safety
    Reporting group description
    		 -

    Reporting group title
    NLX 24 Safety
    Reporting group description
    		 -

    Reporting group title
    Placebo Safety
    Reporting group description
    		 -

    Serious adverse events
    		 NLX 48 Safety NLX 24 Safety Placebo Safety
    Total subjects affected by serious adverse events
         subjects affected / exposed
    8 / 191 (4.19%)
    3 / 186 (1.61%)
    6 / 185 (3.24%)
         number of deaths (all causes)
    0
    0
    1
         number of deaths resulting from adverse events
    0
    0
    1
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    0 / 191 (0.00%)
    0 / 186 (0.00%)
    1 / 185 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Nervous system disorders
    Cervicobrachial syndrome
         subjects affected / exposed
    1 / 191 (0.52%)
    0 / 186 (0.00%)
    0 / 185 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Faecaloma
         subjects affected / exposed
    0 / 191 (0.00%)
    0 / 186 (0.00%)
    1 / 185 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 191 (0.52%)
    0 / 186 (0.00%)
    0 / 185 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal infarction
         subjects affected / exposed
    0 / 191 (0.00%)
    0 / 186 (0.00%)
    1 / 185 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    1 / 191 (0.52%)
    0 / 186 (0.00%)
    0 / 185 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 191 (0.00%)
    1 / 186 (0.54%)
    0 / 185 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 191 (0.00%)
    0 / 186 (0.00%)
    1 / 185 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    1 / 191 (0.52%)
    0 / 186 (0.00%)
    0 / 185 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    1 / 191 (0.52%)
    0 / 186 (0.00%)
    0 / 185 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    0 / 191 (0.00%)
    0 / 186 (0.00%)
    1 / 185 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Chondrocalcinosis
         subjects affected / exposed
    1 / 191 (0.52%)
    0 / 186 (0.00%)
    0 / 185 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vertebral osteophyte
         subjects affected / exposed
    0 / 191 (0.00%)
    1 / 186 (0.54%)
    0 / 185 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Influenza
         subjects affected / exposed
    1 / 191 (0.52%)
    0 / 186 (0.00%)
    0 / 185 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 191 (0.00%)
    1 / 186 (0.54%)
    0 / 185 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 191 (0.52%)
    0 / 186 (0.00%)
    0 / 185 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 191 (0.00%)
    0 / 186 (0.00%)
    1 / 185 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypoglycaemia
         subjects affected / exposed
    1 / 191 (0.52%)
    0 / 186 (0.00%)
    0 / 185 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 3%
    Non-serious adverse events
    		 NLX 48 Safety NLX 24 Safety Placebo Safety
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    98 / 191 (51.31%)
    107 / 186 (57.53%)
    95 / 185 (51.35%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    5 / 191 (2.62%)
    10 / 186 (5.38%)
    4 / 185 (2.16%)
         occurrences all number
    5
    10
    6
    General disorders and administration site conditions
    Drug withdrawal syndrome
         subjects affected / exposed
    8 / 191 (4.19%)
    9 / 186 (4.84%)
    3 / 185 (1.62%)
         occurrences all number
    8
    9
    3
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    12 / 191 (6.28%)
    11 / 186 (5.91%)
    6 / 185 (3.24%)
         occurrences all number
    14
    12
    7
    Abdominal pain
         subjects affected / exposed
    6 / 191 (3.14%)
    6 / 186 (3.23%)
    5 / 185 (2.70%)
         occurrences all number
    7
    6
    5
    Nausea
         subjects affected / exposed
    9 / 191 (4.71%)
    5 / 186 (2.69%)
    3 / 185 (1.62%)
         occurrences all number
    10
    5
    3
    Constipation
         subjects affected / exposed
    8 / 191 (4.19%)
    3 / 186 (1.61%)
    3 / 185 (1.62%)
         occurrences all number
    10
    3
    3
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    7 / 191 (3.66%)
    9 / 186 (4.84%)
    9 / 185 (4.86%)
         occurrences all number
    8
    9
    10

    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.
    NA
    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-Fri Apr 19 06:39:55 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA