Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A placebo-controlled, double-blinded, randomized, trial using a combination of apocynin and paeonol (APPA) for the treatment of knee osteoarthritis

    Summary
    EudraCT number
    		 2020-000249-14
    Trial protocol
    		 DK  
    Global end of trial date
    16 Apr 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Jul 2022
    First version publication date
    07 Jul 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    APPA-P2-1
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04657926
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AKL Research and Development Ltd
    Sponsor organisation address
    Stevenage Bioscience Catalyst, Gunnels Wood Road Stevenage Herts, Stevenage, United Kingdom, SG1 2FX
    Public contact
    Research and Development, AKL Research and Development Ltd, +44 (1438) 906906,
    Scientific contact
    Research and Development, AKL Research and Development Ltd, +44 (1438) 906906,
    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
    16 Nov 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    16 Apr 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Apr 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the change in pain, in terms of the WOMAC pain score of the target knee.
    Protection of trial subjects
    Patient protection was ensured by following high medical and ethical standards in accordance with the principles laid down in the Declaration of Helsinki, and that are consistent with Good Clinical Practice and applicable regulations. To manage pain, subject were provided with rescue pain medication in the form of paracetamol tablets 500 mg. The dosage of paracetamol that the subjects was allowed to take per day was defined according to the standard of care in the countries where the trial was carried out; however, the maximum dose should not exceed 1 gram per dose and 4 grams per day.
    Background therapy
    		 NA
    Evidence for comparator
    		 NA
    Actual start date of recruitment
    16 Sep 2020
    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
    Denmark: 152
    Worldwide total number of subjects
    152
    EEA total number of subjects
    152
    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)
    95
    From 65 to 84 years
    57
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 First Subject First Visit was on 16 September 2020 Last Subject Fist Visit was on 05 March 2021

    Pre-assignment
    Screening details
    		 Overall 334 subjects were screened in this study. Out of which 152 subjects were randomized and received the study treatment into the study.

    Period 1
    Period 1 title
    Overall Study (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
    		 APPA
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    APPA
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    27.5 days of treatment with two capsules of IMP twice daily

    Arm title
    		 Placebo
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    27.5 days of treatment with two capsules of IMP twice daily

    Number of subjects in period 1
    		APPA Placebo
    Started
    75
    77
    Completed
    73
    76
    Not completed
    2
    1
         Physician decision
    -
    1
         Adverse event, non-fatal
    1
    -
         Lost to follow-up
    1
    -

    Baseline characteristics

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

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group values
    		 APPA Placebo Total
    Number of subjects
    		 75 77 152
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 42 53 95
        From 65-84 years
    		 33 24 57
    Gender categorical
    Units: Subjects
        Female
    		 30 45 75
        Male
    		 45 32 77
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 0 0 0
        Black or African American
    		 1 0 1
        Native Hawaiian or other Pacific Islander
    		 0 0 0
        White
    		 73 77 150
        Other
    		 1 0 1
    Ethnicity
    Units: Subjects
        Hispanic or latino
    		 0 1 1
        Not hispanic or latino
    		 74 76 150
        Not reported
    		 0 0 0
        Unknown
    		 1 0 1

    End points

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

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Subject analysis set title
    PainDETECT-subgroup APPA
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    A pre-defined subgroup analysis with a baseline PainDETECT score >12.

    Subject analysis set title
    PainDETECT-subgroup Placebo
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    A pre-defined subgroup analysis with a baseline PainDETECT score >12.

    Primary: Change from baseline in WOMAC pain sub-score (questions 1 to 5) in the target knee as evaluated at week 4.

    		 Close Top of page
    End point title
    		 Change from baseline in WOMAC pain sub-score (questions 1 to 5) in the target knee as evaluated at week 4.
    End point description
    The primary endpoint of this trial was the change from baseline in WOMAC pain sub-score (questions 1 to 5) in the target knee as evaluated at week 4.
    End point type
    Primary
    End point timeframe
    From baseline to week 4.
    End point values
    		 APPA Placebo
    Number of subjects analysed
    75
    77
    Units: Score
        least squares mean (confidence interval 95%)
    -16.40 (-19.74 to -13.05)
    -15.51 (-18.80 to -12.21)
    Statistical analysis title
    		 Change in WOMAC pain sub-score at week 4
    Statistical analysis description
    The treatment effect on the primary endpoint was assessed using a repeated measurement analysis of variance (MMRM) on absolute change from baseline, including baseline value, the treatment group, the time point, sex, country, the subject characteristic of unilateral/bilateral knee OA at baseline as factors, and including treatment by time as interaction.
    Comparison groups
    Placebo v APPA
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 < 0.05
    Method
    		 Mixed models analysis
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [1] - For the treatment effect testing of APPA versus placebo, the null and the alternative hypothesis was: H0: Mean(Placebo) = Mean(APPA) H1: Mean(Placebo) ≠ Mean(APPA), If the null hypothesis was rejected, the alternative hypothesis was accepted, and it was concluded that the treatment effect of APPA differs from placebo. The primary endpoint was analyzed in one step thus no adjustment for multiplicity was performed in the primary endpoint analysis.

    Secondary: Changes from baseline in WOMAC total score at week 4

    		 Close Top of page
    End point title
    		 Changes from baseline in WOMAC total score at week 4
    End point description
    End point type
    Secondary
    End point timeframe
    From baseline to 4 weeks
    End point values
    		 APPA Placebo
    Number of subjects analysed
    75
    77
    Units: points
        least squares mean (confidence interval 95%)
    -13.89 (-17.20 to -10.58)
    -11.61 (-14.87 to -8.35)
    No statistical analyses for this end point

    Secondary: Changes from baseline in WOMAC function scores at week 4

    		 Close Top of page
    End point title
    		 Changes from baseline in WOMAC function scores at week 4
    End point description
    End point type
    Secondary
    End point timeframe
    From baseline to 4 weeks.
    End point values
    		 APPA Placebo
    Number of subjects analysed
    75
    77
    Units: Points
        least squares mean (confidence interval 95%)
    -13.19 (-16.69 to -9.69)
    -10.19 (-13.64 to -6.74)
    No statistical analyses for this end point

    Secondary: Changes from baseline in total OA pain assessed by ICOAP scores at week 4

    		 Close Top of page
    End point title
    		 Changes from baseline in total OA pain assessed by ICOAP scores at week 4
    End point description
    End point type
    Secondary
    End point timeframe
    from baseline to week 4
    End point values
    		 APPA Placebo
    Number of subjects analysed
    75
    77
    Units: points
        least squares mean (confidence interval 95%)
    -14.36 (-17.92 to -10.79)
    -11.70 (-15.21 to -8.19)
    No statistical analyses for this end point

    Secondary: Change from baseline in the weekly mean of the average daily pain intensity at Week 4

    		 Close Top of page
    End point title
    		 Change from baseline in the weekly mean of the average daily pain intensity at Week 4
    End point description
    End point type
    Secondary
    End point timeframe
    From baseline to Week 4.
    End point values
    		 APPA Placebo
    Number of subjects analysed
    75
    77
    Units: Points
        least squares mean (confidence interval 95%)
    -1.2118 (-1.5512 to -0.8724)
    -1.0397 (-1.3573 to -0.7221)
    No statistical analyses for this end point

    Secondary: Change from baseline in WOMAC pain score in PainDETECT >12 subgroup

    		 Close Top of page
    End point title
    		 Change from baseline in WOMAC pain score in PainDETECT >12 subgroup
    End point description
    Change from baseline in WOMAC pain score in PainDETECT >12 subgroup
    End point type
    Secondary
    End point timeframe
    from baseline to week 4.
    End point values
    		 PainDETECT-subgroup APPA PainDETECT-subgroup Placebo
    Number of subjects analysed
    20
    25
    Units: points
        least squares mean (confidence interval 95%)
    -25.48 (-32.07 to -18.89)
    -14.28 (-20.15 to -8.42)
    Statistical analysis title
    		 Subgroup analysis
    Statistical analysis description
    Difference in change from baseline in WOMAC pain score in PainDETECT >12 subgroup.
    Comparison groups
    PainDETECT-subgroup APPA v PainDETECT-subgroup Placebo
    Number of subjects included in analysis
    45
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Mixed models analysis
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -
         upper limit
    		 -
    Statistical analysis title
    		 Subgroup analysis
    Statistical analysis description
    Difference in change from baseline in WOMAC pain score in PainDETECT >12 subgroup.
    Comparison groups
    PainDETECT-subgroup APPA v PainDETECT-subgroup Placebo
    Number of subjects included in analysis
    45
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Mixed models analysis
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -
         upper limit
    		 -

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    The AE reporting period for safety surveillance begins when the subject is initially included in the trial (date of first signature of informed consent/date of first signature of first informed consent) and continues until the up to 14-day follow-up phone
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    APPA
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Serious adverse events
    		 APPA Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 77 (1.30%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Prostate cancer
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 77 (1.30%)
         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: 4%
    Non-serious adverse events
    		 APPA Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    13 / 75 (17.33%)
    2 / 77 (2.60%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 75 (4.00%)
    2 / 77 (2.60%)
         occurrences all number
    4
    2
    General disorders and administration site conditions
    Feeling hot
         subjects affected / exposed
    3 / 75 (4.00%)
    0 / 77 (0.00%)
         occurrences all number
    3
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    3 / 75 (4.00%)
    0 / 77 (0.00%)
         occurrences all number
    4
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    4 / 75 (5.33%)
    0 / 77 (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? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None
    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 26 21:24:23 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA