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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   35348   clinical trials with a EudraCT protocol, of which   5785   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).
     
    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 Two Part Protocol Using Double Blind Placebo Control to Assess the Safety, Tolerability, and Pharmacokinetics of Single Escalating Intra-articular Doses Followed by Assessment of Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Intra-articular Dose of the TrkA Inhibitor, GZ389988A, in Patients With Painful Osteoarthritis of the Knee

    Summary
    EudraCT number
    2014-004805-34
    Trial protocol
    DE  
    Global end of trial date
    13 Sep 2017

    Results information
    Results version number
    v1(current)
    This version publication date
    27 Sep 2018
    First version publication date
    27 Sep 2018
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    TDU13828 – ACT13830
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02424942
    WHO universal trial number (UTN)
    U1111-1163-0806
    Other trial identifiers
    NCT Number for Part 2 Study (ACT13830): NCT02845271
    Sponsors
    Sponsor organisation name
    Genzyme, a Sanofi Company
    Sponsor organisation address
    500 Kendall Street, Cambridge, MA , United States, 02142
    Public contact
    Trial Transparency Team, Sanofi aventis recherche & développement , contact-US@sanofi.com
    Scientific contact
    Trial Transparency Team, Sanofi aventis recherche & développement, contact-US@sanofi.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
    21 Dec 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Sep 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess in subjects with painful osteoarthritis (OA) of the knee: - Part 1: The tolerability and safety of GZ389988A after ascending single intra-articular (IA) doses. - The pharmacokinetic (PK) parameters of GZ389988A after ascending single IA doses. - To obtain preliminary pharmacodynamics (PD) evaluation of GZ389988A after ascending single IA doses. - Part 2: The efficacy of a single IA dose of GZ389988A versus placebo. - The tolerability and safety of a single IA dose of GZ389988A. - The PK parameters of a single IA dose of GZ389988A.
    Protection of trial subjects
    Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    17 Apr 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    3 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 132
    Worldwide total number of subjects
    132
    EEA total number of subjects
    132
    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)
    81
    From 65 to 84 years
    51
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Study was conducted at a single center in Germany. A total of 28 subjects were randomized and treated between 17 April 2015 and 13 July 2016 in Part 1 and a total of 104 subjects were randomized and treated between 22 July 2016 and 13 September 2017 in Part 2 .

    Pre-assignment
    Screening details
    Part 1 consisted of 5 ascending dose levels of GZ389988A to determine maximum tolerated dose (MTD). For confirmation of MTD, the dose level of dose 3 and 4 were duplicated in 4 additional subjects with the same staggered dosing. Part 2 of the study was conducted at the MTD analyzed in Part 1.

    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
    Blinding implementation details
    For Part 2 of the study, GZ389988A and placebo were administered by a qualified orthopedic surgeon, supported by a nurse, both of whom were unblinded and not otherwise involved in the study (apart from identifying potential subjects for the study and taking synovial fluid samples).

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Part 1: Placebo
    Arm description
    Subjects received single dose of placebo (matched to GZ389988A) IA injection on Day 1. Data was pooled for all subjects who received placebo in Part1 and reported in this arm.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solvent for parenteral use
    Routes of administration
    Intraarticular use
    Dosage and administration details
    Subjects received single dose of placebo (matched to GZ389988A) IA injection in the knee joint on Day 1. To ensure safety conditions, dosing of each subject was staggered such that only one subject was dosed per day.

    Arm title
    Part 1: GZ389988A Dose 1
    Arm description
    Subjects received single dose of GZ389988A dose 1 IA injection on Day 1.
    Arm type
    Experimental

    Investigational medicinal product name
    GZ389988A
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intraarticular use
    Dosage and administration details
    Subjects received single dose of GZ389988A dose 1 IA injection in the knee joint on Day 1. To ensure safety conditions, dosing of each subject was staggered such that only one subject was dosed per day.

    Arm title
    Part 1: GZ389988A Dose 2
    Arm description
    Subjects received single dose of GZ389988A dose 2 injection on Day 1.
    Arm type
    Experimental

    Investigational medicinal product name
    GZ389988A
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intraarticular use
    Dosage and administration details
    Subjects received single dose of GZ389988A dose 2 IA injection in the knee joint on Day 1. To ensure safety conditions, dosing of each subject was staggered such that only one subject was dosed per day.

    Arm title
    Part 1: GZ389988A Dose 3
    Arm description
    Subjects received single dose of GZ389988A dose 3 IA injection on Day 1.
    Arm type
    Experimental

    Investigational medicinal product name
    GZ389988A
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intraarticular use
    Dosage and administration details
    Subjects received single dose of GZ389988A dose 3 IA injection in the knee joint on Day 1. To ensure safety conditions, dosing of each subject was staggered such that only one subject was dosed per day.

    Arm title
    Part 1: GZ389988A Dose 4
    Arm description
    Subjects received single dose of GZ389988A dose 4 IA injection on Day 1.
    Arm type
    Experimental

    Investigational medicinal product name
    GZ389988A
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intraarticular use
    Dosage and administration details
    Subjects received single dose of GZ389988A dose 4 IA injection in the knee joint on Day 1. To ensure safety conditions, dosing of each subject was staggered such that only one subject was dosed per day.

    Arm title
    Part 1: GZ389988A Dose 5
    Arm description
    Subjects received single dose of GZ389988A dose 5 IA injection on Day 1.
    Arm type
    Experimental

    Investigational medicinal product name
    GZ389988A
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intraarticular use
    Dosage and administration details
    Subjects received single dose of GZ389988A dose 5 IA injection in the knee joint on Day 1. To ensure safety conditions, dosing of each subject was staggered such that only one subject was dosed per day.

    Arm title
    Part 2: Placebo
    Arm description
    Subjects received single IA dose of placebo (matched to GZ389988A) injection on Day 1.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solvent for parenteral use
    Routes of administration
    Intraarticular use
    Dosage and administration details
    Subjects received single dose of placebo (matched to GZ389988A) IA injection in the knee joint on Day 1.

    Arm title
    Part 2: GZ389988A Dose 4 from Part 1
    Arm description
    Subjects received single IA dose of GZ389988A on Day 1 at dose 4 confirmed in Part 1.
    Arm type
    Experimental

    Investigational medicinal product name
    GZ389988A
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intraarticular use
    Dosage and administration details
    Subjects received single dose of GZ389988A at dose 4 IA injection in the knee joint on Day 1.

    Number of subjects in period 1
    Part 1: Placebo Part 1: GZ389988A Dose 1 Part 1: GZ389988A Dose 2 Part 1: GZ389988A Dose 3 Part 1: GZ389988A Dose 4 Part 1: GZ389988A Dose 5 Part 2: Placebo Part 2: GZ389988A Dose 4 from Part 1
    Started
    7
    3
    3
    6
    6
    3
    52
    52
    Completed
    7
    3
    3
    6
    6
    3
    52
    52

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Part 1: Placebo
    Reporting group description
    Subjects received single dose of placebo (matched to GZ389988A) IA injection on Day 1. Data was pooled for all subjects who received placebo in Part1 and reported in this arm.

    Reporting group title
    Part 1: GZ389988A Dose 1
    Reporting group description
    Subjects received single dose of GZ389988A dose 1 IA injection on Day 1.

    Reporting group title
    Part 1: GZ389988A Dose 2
    Reporting group description
    Subjects received single dose of GZ389988A dose 2 injection on Day 1.

    Reporting group title
    Part 1: GZ389988A Dose 3
    Reporting group description
    Subjects received single dose of GZ389988A dose 3 IA injection on Day 1.

    Reporting group title
    Part 1: GZ389988A Dose 4
    Reporting group description
    Subjects received single dose of GZ389988A dose 4 IA injection on Day 1.

    Reporting group title
    Part 1: GZ389988A Dose 5
    Reporting group description
    Subjects received single dose of GZ389988A dose 5 IA injection on Day 1.

    Reporting group title
    Part 2: Placebo
    Reporting group description
    Subjects received single IA dose of placebo (matched to GZ389988A) injection on Day 1.

    Reporting group title
    Part 2: GZ389988A Dose 4 from Part 1
    Reporting group description
    Subjects received single IA dose of GZ389988A on Day 1 at dose 4 confirmed in Part 1.

    Reporting group values
    Part 1: Placebo Part 1: GZ389988A Dose 1 Part 1: GZ389988A Dose 2 Part 1: GZ389988A Dose 3 Part 1: GZ389988A Dose 4 Part 1: GZ389988A Dose 5 Part 2: Placebo Part 2: GZ389988A Dose 4 from Part 1 Total
    Number of subjects
    7 3 3 6 6 3 52 52 132
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    51.9 ± 2.7 55.0 ± 2.6 53.3 ± 3.5 53.5 ± 4.4 53.7 ± 6.4 54.0 ± 6.0 64.1 ± 8.1 62.1 ± 9.4 -
    Gender categorical
    Units: Subjects
        Female
    4 1 1 3 3 1 25 26 64
        Male
    3 2 2 3 3 2 27 26 68
    Race
    Units: Subjects
        White
    7 3 3 6 6 3 50 52 130
        Asian
    0 0 0 0 0 0 1 0 1
        Other
    0 0 0 0 0 0 1 0 1

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Part 1: Placebo
    Reporting group description
    Subjects received single dose of placebo (matched to GZ389988A) IA injection on Day 1. Data was pooled for all subjects who received placebo in Part1 and reported in this arm.

    Reporting group title
    Part 1: GZ389988A Dose 1
    Reporting group description
    Subjects received single dose of GZ389988A dose 1 IA injection on Day 1.

    Reporting group title
    Part 1: GZ389988A Dose 2
    Reporting group description
    Subjects received single dose of GZ389988A dose 2 injection on Day 1.

    Reporting group title
    Part 1: GZ389988A Dose 3
    Reporting group description
    Subjects received single dose of GZ389988A dose 3 IA injection on Day 1.

    Reporting group title
    Part 1: GZ389988A Dose 4
    Reporting group description
    Subjects received single dose of GZ389988A dose 4 IA injection on Day 1.

    Reporting group title
    Part 1: GZ389988A Dose 5
    Reporting group description
    Subjects received single dose of GZ389988A dose 5 IA injection on Day 1.

    Reporting group title
    Part 2: Placebo
    Reporting group description
    Subjects received single IA dose of placebo (matched to GZ389988A) injection on Day 1.

    Reporting group title
    Part 2: GZ389988A Dose 4 from Part 1
    Reporting group description
    Subjects received single IA dose of GZ389988A on Day 1 at dose 4 confirmed in Part 1.

    Primary: Part 1: Number of Subjects With any Treatment-Emergent Adverse Events (TEAE)

    Close Top of page
    End point title
    Part 1: Number of Subjects With any Treatment-Emergent Adverse Events (TEAE) [1] [2]
    End point description
    Any untoward medical occurrence in a subject who received investigational medicinal product (IMP) was considered an adverse event (AE) without regard to possibility of causal relationship with this treatment. TEAEs: AEs that occurred or worsened during the on-treatment period (time from the first dose of study medication administration up to the end of study [EOS] visit). Analysis was performed on safety population which included all subjects who were exposed to study drug administration.
    End point type
    Primary
    End point timeframe
    From first dose of GZ389988A administration up to Day 84 (EOS)
    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: Since analysis is descriptive in nature, statistical data could not be provided.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was evaluated for Part 1 only.
    End point values
    Part 1: Placebo Part 1: GZ389988A Dose 1 Part 1: GZ389988A Dose 2 Part 1: GZ389988A Dose 3 Part 1: GZ389988A Dose 4 Part 1: GZ389988A Dose 5
    Number of subjects analysed
    7
    3
    3
    6
    6
    3
    Units: subjects
    6
    3
    3
    3
    5
    3
    No statistical analyses for this end point

    Primary: Part 2: Change From Baseline Average Over 4 Weeks (up to Day 28) in Weekly Mean score of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 Pain Subscore (Walking Pain) Collected Daily in the Target Knee

    Close Top of page
    End point title
    Part 2: Change From Baseline Average Over 4 Weeks (up to Day 28) in Weekly Mean score of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 Pain Subscore (Walking Pain) Collected Daily in the Target Knee [3]
    End point description
    WOMAC index(VAS 3.1):health status measure questionnaire:24questions(Q)of 3subscales:pain(5Q),stiffness(2Q),physical function(17Q).Each Q measured on 0(no pain)-100(maximal pain)visual analog scale(VAS).WOMAC A1(measure of pain during walking on flat surface)was part of pain sub-scale from WOMAC index.Weekly mean score of WOMAC A1,defined as average of daily measurements over the week was calculated for each week.Statistical analysis was done on the change from baseline in weekly mean score calculated for each week.Negative change=improvement.Analysis performed on Modified intent-to-treat(mITT)population included all randomized subjects exposed to study treatment,without any major/critical deviations related to diagnosis of primary knee OA or rescue medication other than those allowed,and for whom any WOMAC A1 pain sub-score from electronic Diary(eDiary)as measured by the VAS were considered evaluable at baseline,with atleast 1 post baseline assessment after single IA injection.
    End point type
    Primary
    End point timeframe
    Baseline, Day 1 to 28
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was evaluated for Part 2 only.
    End point values
    Part 2: Placebo Part 2: GZ389988A Dose 4 from Part 1
    Number of subjects analysed
    52
    52
    Units: Units on a Scale
        least squares mean (standard error)
    -15.7725 ± 3.0361
    -23.2590 ± 3.0346
    Statistical analysis title
    Over 4 weeks: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0441 [4]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least Squares Mean Difference
    Point estimate
    -7.4865
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.7065
         upper limit
    -0.2665
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.3476
    Notes
    [4] - Specified one-sided P-value.

    Secondary: Part 1: Maximum Plasma Concentration (Cmax) of GZ389988A

    Close Top of page
    End point title
    Part 1: Maximum Plasma Concentration (Cmax) of GZ389988A [5]
    End point description
    Cmax was defined as maximum plasma concentration of GZ389988A. Analysis was performed on PK population which included all subjects without any major deviations related to study drug administration, and for whom any PK parameters were available.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 144, 312, 480, 648, 984, 1320, 1656, and 1992 hours post-dose on Day 1
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Subjects treated with placebo were not included in the analysis of PK parameters.
    End point values
    Part 1: GZ389988A Dose 1 Part 1: GZ389988A Dose 2 Part 1: GZ389988A Dose 3 Part 1: GZ389988A Dose 4 Part 1: GZ389988A Dose 5
    Number of subjects analysed
    3
    3
    6
    6
    3
    Units: ng/mL
        arithmetic mean (standard deviation)
    1.65 ± 1.22
    0.224 ± 0.114
    4.56 ± 4.31
    10.8 ± 6.16
    17.7 ± 15.5
    No statistical analyses for this end point

    Secondary: Part 1: Area Under the Plasma-Drug-Concentration Versus Time Curve From Time Zero to Last Quantifiable -Concentration (AUClast) of GZ389988A

    Close Top of page
    End point title
    Part 1: Area Under the Plasma-Drug-Concentration Versus Time Curve From Time Zero to Last Quantifiable -Concentration (AUClast) of GZ389988A [6]
    End point description
    AUClast was defined as area under the plasma-drug-concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast where tlast was the time corresponding to the last concentration above the limit of quantification, Clast. Analysis was performed on PK population.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 144, 312, 480, 648, 984, 1320, 1656, and 1992 hours post-dose on Day 1
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Subjects treated with placebo were not included in the analysis of PK parameters.
    End point values
    Part 1: GZ389988A Dose 1 Part 1: GZ389988A Dose 2 Part 1: GZ389988A Dose 3 Part 1: GZ389988A Dose 4 Part 1: GZ389988A Dose 5
    Number of subjects analysed
    3
    3
    6
    6
    3
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    136 ± 22
    156 ± 105
    1230 ± 430
    2700 ± 827
    4340 ± 2300
    No statistical analyses for this end point

    Secondary: Part 1: Area Under the Plasma-Drug-Concentration Versus Time Curve From Time Zero to Infinity (AUCinf) of GZ389988A

    Close Top of page
    End point title
    Part 1: Area Under the Plasma-Drug-Concentration Versus Time Curve From Time Zero to Infinity (AUCinf) of GZ389988A [7]
    End point description
    AUCinf was defined as area under the plasma-drug-concentration versus time curve from time zero extrapolated to infinity. Values with percentage of extrapolation >30% were not reported. Analysis was performed on PK population. Number of subjects analyzed=subjects with available data for this endpoint. Here, 999 represents that SD was not calculated as data was available only for two subjects.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 144, 312, 480, 648, 984, 1320, 1656, and 1992 hours post-dose on Day 1
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Subjects treated with placebo were not included in the analysis of PK parameters.
    End point values
    Part 1: GZ389988A Dose 1 Part 1: GZ389988A Dose 2 Part 1: GZ389988A Dose 3 Part 1: GZ389988A Dose 4 Part 1: GZ389988A Dose 5
    Number of subjects analysed
    3
    0 [8]
    5
    6
    2
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    148 ± 15.6
    ±
    1530 ± 300
    2860 ± 724
    5640 ± 999
    Notes
    [8] - Since a log-linear terminal phase could not be determined and/or extrapolated area was >30%.
    No statistical analyses for this end point

    Secondary: Part 1: Terminal Half-Life (t1/2z) of GZ389988A

    Close Top of page
    End point title
    Part 1: Terminal Half-Life (t1/2z) of GZ389988A [9]
    End point description
    t1/2z was defined as time measured for the plasma concentration of GZ389988A to decrease by one half. Analysis was performed on PK population. Here, 999 represents that data was not calculated as data was available only for two subjects.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 144, 312, 480, 648, 984, 1320, 1656, and 1992 hours post-dose on Day 1
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Subjects treated with placebo were not included in the analysis of PK parameters.
    End point values
    Part 1: GZ389988A Dose 1 Part 1: GZ389988A Dose 2 Part 1: GZ389988A Dose 3 Part 1: GZ389988A Dose 4 Part 1: GZ389988A Dose 5
    Number of subjects analysed
    3
    3
    6
    6
    3
    Units: hours
        arithmetic mean (standard deviation)
    325 ± 283
    2000 ± 999
    692 ± 375
    439 ± 247
    647 ± 226
    No statistical analyses for this end point

    Secondary: Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of GZ389988A

    Close Top of page
    End point title
    Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of GZ389988A [10]
    End point description
    Tmax was defined as time to reach Cmax. Analysis was performed on PK population.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 144, 312, 480, 648, 984, 1320, 1656, and 1992 hours post-dose on Day 1
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Subjects treated with placebo were not included in the analysis of PK parameters.
    End point values
    Part 1: GZ389988A Dose 1 Part 1: GZ389988A Dose 2 Part 1: GZ389988A Dose 3 Part 1: GZ389988A Dose 4 Part 1: GZ389988A Dose 5
    Number of subjects analysed
    3
    3
    6
    6
    3
    Units: hours
        median (full range (min-max))
    12 (8 to 23.9)
    48 (24 to 1991)
    48.1 (8 to 143)
    36.2 (24 to 983)
    47.9 (36 to 48)
    No statistical analyses for this end point

    Secondary: Part 1: Apparent Volume of Distribution (Vz/F) of GZ389988A

    Close Top of page
    End point title
    Part 1: Apparent Volume of Distribution (Vz/F) of GZ389988A [11]
    End point description
    Vz/F was defined as apparent terminal phase plasma volume of distribution, and was calculated as: Dose/AUC*λz. Analysis was performed on PK population. Number of subjects analyzed=subjects with available data for this endpoint. Here, 999 represents that data was not calculated as data was available only for two subjects.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 144, 312, 480, 648, 984, 1320, 1656, and 1992 hours post-dose on Day 1
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Subjects treated with placebo were not included in the analysis of PK parameters.
    End point values
    Part 1: GZ389988A Dose 1 Part 1: GZ389988A Dose 2 Part 1: GZ389988A Dose 3 Part 1: GZ389988A Dose 4 Part 1: GZ389988A Dose 5
    Number of subjects analysed
    3
    0 [12]
    5
    6
    2
    Units: milliliter (mL)
        arithmetic mean (standard deviation)
    9830000 ± 9300000
    ±
    17200000 ± 10100000
    14400000 ± 9510000
    15200000 ± 999
    Notes
    [12] - Since log-linear terminal phase could not be determined &/or extrapolated area was >30%.
    No statistical analyses for this end point

    Secondary: Part 1: Apparent Total Body Clearance(CL/F) of GZ389988A

    Close Top of page
    End point title
    Part 1: Apparent Total Body Clearance(CL/F) of GZ389988A [13]
    End point description
    CL/F was defined as apparent total body clearance of a drug from the plasma, and was calculated as: Dose/AUC. Analysis was performed on PK population. Number of subjects analyzed=subjects with available data for this endpoint. Here, 999 represents that data was not calculated as data was available only for two subjects.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 144, 312, 480, 648, 984, 1320, 1656, and 1992 hours post-dose on Day 1
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Subjects treated with placebo were not included in the analysis of PK parameters.
    End point values
    Part 1: GZ389988A Dose 1 Part 1: GZ389988A Dose 2 Part 1: GZ389988A Dose 3 Part 1: GZ389988A Dose 4 Part 1: GZ389988A Dose 5
    Number of subjects analysed
    3
    0 [14]
    5
    6
    2
    Units: liters per hour (L/h)
        arithmetic mean (standard deviation)
    20.5 ± 2.11
    ±
    20.3 ± 4.2
    22.2 ± 6.19
    18.2 ± 999
    Notes
    [14] - Since log-linear terminal phase could not be determined &/or extrapolated area was >30%.
    No statistical analyses for this end point

    Secondary: Part 1: Synovial Fluid Concentrations of GZ389988A

    Close Top of page
    End point title
    Part 1: Synovial Fluid Concentrations of GZ389988A [15]
    End point description
    Analysis was performed on PK population. Number of subjects analyzed=subjects with available data for this endpoint. Here 'n' signifies number of subjects with available data for specified category for each arm respectively. 9999 represents that data was not calculated as data was below lower limit of quantification (0.1 ng/mL). 999 represents standard deviation could not be calculated due to single evaluable subject.
    End point type
    Secondary
    End point timeframe
    Pre-dose, at anytime on Day 28 and Day 84
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Synovial fluid concentrations were only collected for subjects who received placebo, GZ389988A Dose 4 and Dose 5.
    End point values
    Part 1: Placebo Part 1: GZ389988A Dose 4 Part 1: GZ389988A Dose 5
    Number of subjects analysed
    2
    1
    1
    Units: ng/mL
    arithmetic mean (standard deviation)
        Pre-dose (n= 2, 0, 1)
    9999 ± 999
    9999 ± 999
    9999 ± 999
        Day 28 (n= 1, 1, 0)
    9999 ± 999
    312 ± 999
    9999 ± 999
        Day 84 (n= 1, 0, 0)
    9999 ± 999
    9999 ± 999
    9999 ± 999
    No statistical analyses for this end point

    Secondary: Part 1: Change from Baseline in WOMAC Total Score at Day 7, 14, 21, 28, 42, 56, 70 and 84

    Close Top of page
    End point title
    Part 1: Change from Baseline in WOMAC Total Score at Day 7, 14, 21, 28, 42, 56, 70 and 84 [16]
    End point description
    WOMAC index is health status measure questionnaire of twenty-four questions comprising of 3 sub-scales: pain (5 questions), stiffness (2 questions) and physical function (17 questions). Each question was measured on a 100-millimeter (mm) visual analogue scale (VAS) ranging from 0=no pain to 100=maximal pain. Total score was sum of the 3 sub-scale scores, giving total score range of 0 to 2400 mm where higher scores indicated higher level of pain, stiffness and physical function. The change from baseline in WOMAC total score was calculated at each specified visit (Day 7, 14, 21, 28, 42, 56, 70, and 84). Analysis was performed on PD population which included all subjects without any major/critical deviations or AEs that would impact the PD response, and for whom any WOMAC sub-scores as measured by the 100-mm VAS were considered evaluable at baseline and at least 1 post-baseline measurements.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 7, 14, 21, 28, 42, 56, 70 and 84
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was evaluated for Part 1 only.
    End point values
    Part 1: Placebo Part 1: GZ389988A Dose 1 Part 1: GZ389988A Dose 2 Part 1: GZ389988A Dose 3 Part 1: GZ389988A Dose 4 Part 1: GZ389988A Dose 5
    Number of subjects analysed
    7
    3
    3
    6
    6
    2
    Units: millimeter
    arithmetic mean (standard deviation)
        Day 7
    -1008.7 ± 706.6
    -789.3 ± 786.4
    -17.3 ± 56.4
    -1160.8 ± 633.5
    -655.7 ± 617
    -1008.5 ± 901.6
        Day 14
    -880.6 ± 817.1
    -637.3 ± 758.2
    79 ± 341.6
    -1250.3 ± 542.1
    -777.3 ± 657.4
    -1205.5 ± 881.8
        Day 21
    -938.7 ± 774.7
    -554.3 ± 725.9
    -120 ± 156.5
    -1223.3 ± 663.7
    -769.3 ± 697.1
    -1215.5 ± 781.4
        Day 28
    -899.9 ± 783.4
    -480.3 ± 771.4
    -139 ± 125.7
    -1069.5 ± 831.7
    -789.2 ± 742.7
    -966.5 ± 779.9
        Day 42
    -1025.4 ± 681
    -499 ± 723.5
    -111.7 ± 125.4
    -1097.5 ± 867.8
    -755.8 ± 722
    -963.5 ± 1089.7
        Day 56
    -1006.4 ± 732.6
    -547.7 ± 791.1
    -222.3 ± 101.6
    -1083.2 ± 787.9
    -823.5 ± 707.1
    -901 ± 1130
        Day 70
    -1025.1 ± 680.3
    -476 ± 773.5
    -212 ± 137.4
    -1040.5 ± 780
    -840 ± 729.1
    -683 ± 933.4
        Day 84
    -1011.7 ± 698.2
    -503 ± 755.3
    -286.3 ± 210.7
    -805.2 ± 733.3
    -857 ± 711.2
    -502.5 ± 552.3
    No statistical analyses for this end point

    Secondary: Part 1: Change From Baseline in WOMAC Pain Sub-score at Day 7, 14, 21, 28, 42, 56, 70 and 84

    Close Top of page
    End point title
    Part 1: Change From Baseline in WOMAC Pain Sub-score at Day 7, 14, 21, 28, 42, 56, 70 and 84 [17]
    End point description
    WOMAC index is health status measure questionnaire of twenty-four questions comprising of 3 subscales: pain (5 questions), stiffness (2 questions) and physical function (17 questions). Each question was measured on a 100-mm VAS ranging from 0=no pain to 100=maximal pain. WOMAC pain sub-score was sum of 5 questions with score ranging from 0 to 500 mm, where higher score indicated higher level of pain. The change from baseline in WOMAC pain sub-score was calculated at each specified visit (Day 7, 14, 21, 28, 42, 56, 70, and 84). Analysis was performed on PD population.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 7, 14, 21, 28, 42, 56, 70 and 84
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was evaluated for Part 1 only.
    End point values
    Part 1: Placebo Part 1: GZ389988A Dose 1 Part 1: GZ389988A Dose 2 Part 1: GZ389988A Dose 3 Part 1: GZ389988A Dose 4 Part 1: GZ389988A Dose 5
    Number of subjects analysed
    7
    3
    3
    6
    6
    2
    Units: millimeter
    arithmetic mean (standard deviation)
        Day 7
    -208.9 ± 145.1
    -146.7 ± 158.7
    4.3 ± 38.1
    -265.8 ± 127.1
    -139 ± 119
    -205 ± 196.6
        Day 14
    -180.1 ± 162.3
    -121 ± 167.2
    27 ± 61
    -278.2 ± 99.9
    -154.3 ± 128
    -232.5 ± 210
        Day 21
    -193.3 ± 152.8
    -118.3 ± 161.3
    -23.7 ± 28.2
    -273.5 ± 120
    -160.8 ± 155.7
    -236.5 ± 174.7
        Day 28
    -193.6 ± 144.9
    -91.3 ± 183.4
    -22.3 ± 8.5
    -241.8 ± 161.3
    -165.7 ± 155.8
    -195 ± 169.7
        Day 42
    -215.7 ± 129
    -123.3 ± 151.1
    -11.3 ± 24.7
    -250.3 ± 175.5
    -152.7 ± 154
    -197 ± 236.2
        Day 56
    -203.9 ± 145.2
    -127 ± 167.4
    -23.3 ± 35.8
    -247.3 ± 154.4
    -177.8 ± 149.6
    -178 ± 246.1
        Day 70
    -210.3 ± 129.2
    -99.7 ± 162.5
    -37.7 ± 20.5
    -240.5 ± 153.1
    -162.2 ± 153.8
    -144 ± 200.8
        Day 84
    -210.6 ± 141.2
    -102.3 ± 152.9
    -40.3 ± 52.6
    -194.3 ± 146.3
    -182 ± 149.3
    -98.5 ± 129.4
    No statistical analyses for this end point

    Secondary: Part 1: Change From Baseline in WOMAC A1 Sub-score (Walking Pain) at Day 7, 14, 21, 28, 42, 56, 70 and 84

    Close Top of page
    End point title
    Part 1: Change From Baseline in WOMAC A1 Sub-score (Walking Pain) at Day 7, 14, 21, 28, 42, 56, 70 and 84 [18]
    End point description
    WOMAC A1 (measure of pain during walking on a flat surface) was part of the pain sub-scale (question 1) from the WOMAC index. WOMAC A1 was measured on a 100 mm VAS ranging from 0 to 100, where higher score indicated the higher level of pain. The change from baseline in WOMAC A1 sub-score was calculated at each specified visit (Day 7, 14, 21, 28, 42, 56, 70, and 84). Analysis was performed on PD population.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 7, 14, 21, 28, 42, 56, 70 and 84
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was evaluated for Part 1 only.
    End point values
    Part 1: Placebo Part 1: GZ389988A Dose 1 Part 1: GZ389988A Dose 2 Part 1: GZ389988A Dose 3 Part 1: GZ389988A Dose 4 Part 1: GZ389988A Dose 5
    Number of subjects analysed
    7
    3
    3
    6
    6
    2
    Units: millimeter
    arithmetic mean (standard deviation)
        Day 7
    -39.9 ± 28.2
    -30.7 ± 36.5
    -5 ± 12.5
    -54.3 ± 20.3
    -27 ± 21.6
    -39.5 ± 36.1
        Day 14
    -34.6 ± 32.6
    -25 ± 37.6
    -3.3 ± 3.8
    -57.7 ± 15.5
    -29.5 ± 25.3
    -46 ± 45.3
        Day 21
    -36.9 ± 30.2
    -24.7 ± 36.5
    -9.7 ± 3.2
    -54 ± 20.7
    -28.7 ± 35.3
    -44 ± 42.4
        Day 28
    -37.1 ± 29
    -20.7 ± 39.6
    -11.7 ± 3.1
    -50.3 ± 30.2
    -32.3 ± 29.9
    -39 ± 38.2
        Day 42
    -41.1 ± 25.9
    -26.7 ± 33.2
    -11.7 ± 4.2
    -52 ± 32.6
    -31.3 ± 30.7
    -39.5 ± 48.8
        Day 56
    -38.9 ± 28.8
    -28 ± 34.7
    -9 ± 8.7
    -52.2 ± 29.6
    -35.5 ± 31.2
    -34.5 ± 53
        Day 70
    -38.3 ± 27.1
    -19.3 ± 34.8
    -16.3 ± 0.6
    -49.2 ± 29.3
    -32.5 ± 32.5
    -31.5 ± 44.5
        Day 84
    -39.7 ± 29.1
    -24 ± 35.9
    -11.7 ± 12.1
    -44.5 ± 28.9
    -34.3 ± 31.9
    -15.5 ± 20.5
    Statistical analysis title
    Up to Day 28: GZ389988A Dose 1 vs Placebo
    Statistical analysis description
    Analysis was performed using linear mixed effect model with corresponding baseline as covariate and dose, week, week-by-dose interaction and gender as fixed effects.
    Comparison groups
    Part 1: GZ389988A Dose 1 v Part 1: Placebo
    Number of subjects included in analysis
    10
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Least squares mean difference
    Point estimate
    11.9984
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -22.6588
         upper limit
    46.6557
    Statistical analysis title
    Up to Day 28: GZ389988A Dose 2 vs Placebo
    Statistical analysis description
    Analysis was performed using linear mixed effect model with corresponding baseline as covariate and dose, week, week-by-dose interaction and gender as fixed effects.
    Comparison groups
    Part 1: GZ389988A Dose 2 v Part 1: Placebo
    Number of subjects included in analysis
    10
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Least squares mean difference
    Point estimate
    24.1031
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.8636
         upper limit
    60.0698
    Statistical analysis title
    Up to Day 28: GZ389988A Dose 3 vs Placebo
    Statistical analysis description
    Analysis was performed using linear mixed effect model with corresponding baseline as covariate and dose, week, week-by-dose interaction and gender as fixed effects.
    Comparison groups
    Part 1: GZ389988A Dose 3 v Part 1: Placebo
    Number of subjects included in analysis
    13
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Least squares mean difference
    Point estimate
    -19.0405
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -46.943
         upper limit
    8.8621
    Statistical analysis title
    Up to Day 28: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    Analysis was performed using linear mixed effect model with corresponding baseline as covariate and dose, week, week-by-dose interaction and gender as fixed effects.
    Comparison groups
    Part 1: GZ389988A Dose 4 v Part 1: Placebo
    Number of subjects included in analysis
    13
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Least squares mean difference
    Point estimate
    4.6515
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -23.6359
         upper limit
    32.939
    Statistical analysis title
    Up to Day 28: GZ389988A Dose 5 vs Placebo
    Statistical analysis description
    Analysis was performed using linear mixed effect model with corresponding baseline as covariate and dose, week, week-by-dose interaction and gender as fixed effects.
    Comparison groups
    Part 1: GZ389988A Dose 5 v Part 1: Placebo
    Number of subjects included in analysis
    9
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Least squares mean difference
    Point estimate
    -4.069
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -46.0989
         upper limit
    37.9609
    Statistical analysis title
    Up to Day 84: GZ389988A Dose 1 vs Placebo
    Statistical analysis description
    Analysis was performed using linear mixed effect model with corresponding baseline as covariate and dose, week, week-by-dose interaction and gender as fixed effects.
    Comparison groups
    Part 1: GZ389988A Dose 1 v Part 1: Placebo
    Number of subjects included in analysis
    10
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Least squares mean difference
    Point estimate
    13.5698
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -20.9287
         upper limit
    48.0684
    Statistical analysis title
    Up to Day 84: GZ389988A Dose 2 vs Placebo
    Statistical analysis description
    Analysis was performed using linear mixed effect model with corresponding baseline as covariate and dose, week, week-by-dose interaction and gender as fixed effects.
    Comparison groups
    Part 1: GZ389988A Dose 2 v Part 1: Placebo
    Number of subjects included in analysis
    10
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Least squares mean difference
    Point estimate
    22.9246
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -12.8893
         upper limit
    58.7384
    Statistical analysis title
    Up to Day 84: GZ389988A Dose 3 vs Placebo
    Statistical analysis description
    Analysis was performed using linear mixed effect model with corresponding baseline as covariate and dose, week, week-by-dose interaction and gender as fixed effects.
    Comparison groups
    Part 1: GZ389988A Dose 3 v Part 1: Placebo
    Number of subjects included in analysis
    13
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Least squares mean difference
    Point estimate
    -15.5315
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -43.306
         upper limit
    12.2429
    Statistical analysis title
    Up to Day 84: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    Analysis was performed using linear mixed effect model with corresponding baseline as covariate and dose, week, week-by-dose interaction and gender as fixed effects.
    Comparison groups
    Part 1: GZ389988A Dose 4 v Part 1: Placebo
    Number of subjects included in analysis
    13
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Least squares mean difference
    Point estimate
    3.8271
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -24.334
         upper limit
    31.9882
    Statistical analysis title
    Up to Day 84: GZ389988A Dose 5 vs Placebo
    Statistical analysis description
    Analysis was performed using linear mixed effect model with corresponding baseline as covariate and dose, week, week-by-dose interaction and gender as fixed effects.
    Comparison groups
    Part 1: GZ389988A Dose 5 v Part 1: Placebo
    Number of subjects included in analysis
    9
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Least squares mean difference
    Point estimate
    3.0649
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -38.7884
         upper limit
    44.9183

    Secondary: Part 1: Change From Baseline in WOMAC Stiffness Sub-score at Day 7, 14, 21, 28, 42, 56, 70 and 84

    Close Top of page
    End point title
    Part 1: Change From Baseline in WOMAC Stiffness Sub-score at Day 7, 14, 21, 28, 42, 56, 70 and 84 [19]
    End point description
    WOMAC index is health status measure questionnaire of twenty-four questions comprising 3 sub-scales: pain (5 questions), stiffness (2 questions) and physical function (17 questions). Each question was measured on a 100-mm VAS ranging from 0=no pain to 100=maximal pain. Stiffness was defined as a sensation of decreased ease of movement in the index joint. WOMAC stiffness sub-score was sum of 2 questions with score ranging from 0 to 200 mm, where higher score indicated higher level of stiffness. The change from baseline in WOMAC stiffness sub-score was calculated at each specified visit (Day 7, 14, 21, 28, 42, 56, 70, and 84). Analysis was performed on PD population.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 7, 14, 21, 28, 42, 56, 70 and 84
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was evaluated for Part 1 only.
    End point values
    Part 1: Placebo Part 1: GZ389988A Dose 1 Part 1: GZ389988A Dose 2 Part 1: GZ389988A Dose 3 Part 1: GZ389988A Dose 4 Part 1: GZ389988A Dose 5
    Number of subjects analysed
    7
    3
    3
    6
    6
    2
    Units: millimeter
    arithmetic mean (standard deviation)
        Day 7
    -79.7 ± 58.9
    -55.3 ± 54
    2.7 ± 14.2
    -87.7 ± 46.2
    -56.5 ± 57.1
    -78 ± 70.7
        Day 14
    -72 ± 69.1
    -56 ± 70.4
    16.7 ± 26
    -96.3 ± 43.2
    -62 ± 56.9
    -97 ± 75
        Day 21
    -73.3 ± 61.2
    -48.3 ± 69.3
    6.3 ± 17.5
    -96 ± 56.5
    -56 ± 59.6
    -98.5 ± 67.2
        Day 28
    -74.4 ± 67.9
    -46.7 ± 73.2
    -6.7 ± 1.5
    -90.8 ± 74.9
    -58.2 ± 65.1
    -86.5 ± 62.9
        Day 42
    -79 ± 60.4
    -39 ± 63.5
    0.7 ± 15.3
    -87.7 ± 67.4
    -62.2 ± 65.5
    -75.5 ± 85.6
        Day 56
    -77 ± 63.9
    -44 ± 66.7
    -19.3 ± 9.9
    -87.8 ± 66.1
    -66 ± 64.3
    -77.5 ± 98.3
        Day 70
    -84.6 ± 57.7
    -44.3 ± 70.8
    -13 ± 12.5
    -81.5 ± 66.5
    -71 ± 65.5
    -60 ± 86.3
        Day 84
    -82.3 ± 57.4
    -43.7 ± 67.2
    -19.3 ± 15.3
    -63.2 ± 64.6
    -69.7 ± 67
    -46.5 ± 68.6
    No statistical analyses for this end point

    Secondary: Part 1: Change From Baseline in WOMAC Physical Function Sub-score at Day 7, 14, 21, 28, 42, 56, 70 and 84

    Close Top of page
    End point title
    Part 1: Change From Baseline in WOMAC Physical Function Sub-score at Day 7, 14, 21, 28, 42, 56, 70 and 84 [20]
    End point description
    WOMAC index is health status measure questionnaire of twenty-four questions comprising of 3 sub-scales: pain (5 questions), stiffness (2 questions) and physical function (17 questions). Each question was measured on a 100-mm VAS ranging from 0=no pain to 100=maximal pain. WOMAC physical function sub-score was sum of 17 questions with score ranging from 0 to 1700 mm, where higher score indicated higher level of physical function. The change from baseline in WOMAC physical sub-score was calculated at each specified visit (Day 7, 14, 21, 28, 42, 56, 70, and 84). Analysis was performed on PD population.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 7, 14, 21, 28, 42, 56, 70 and 84
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was evaluated for Part 1 only.
    End point values
    Part 1: Placebo Part 1: GZ389988A Dose 1 Part 1: GZ389988A Dose 2 Part 1: GZ389988A Dose 3 Part 1: GZ389988A Dose 4 Part 1: GZ389988A Dose 5
    Number of subjects analysed
    7
    3
    3
    6
    6
    2
    Units: millimeter
    arithmetic mean (standard deviation)
        Day 7
    -720.1 ± 503.8
    -587.3 ± 577.3
    -24.3 ± 16.8
    -807.3 ± 469
    -460.2 ± 444.4
    -725.5 ± 634.3
        Day 14
    -628.4 ± 586.4
    -460.3 ± 521.4
    35.3 ± 258
    -875.8 ± 411.2
    -561 ± 474.5
    -876 ± 596.8
        Day 21
    -672.1 ± 561.9
    -387.7 ± 495.9
    -102.7 ± 138.4
    -853.8 ± 496.9
    -552.5 ± 484.3
    -880.5 ± 539.5
        Day 28
    -631.9 ± 573.5
    -342.3 ± 515.4
    -110 ± 118.6
    -736.8 ± 605.6
    -565.3 ± 523.8
    -685 ± 547.3
        Day 42
    -730.7 ± 493.2
    -336.7 ± 511.7
    -101 ± 91.1
    -759.5 ± 632.4
    -541 ± 504.5
    -691 ± 767.9
        Day 56
    -725.6 ± 524.9
    -376.7 ± 557.5
    -179.7 ± 105
    -748 ± 575.3
    -579.7 ± 495.5
    -645.5 ± 785.6
        Day 70
    -730.3 ± 495.2
    -332 ± 540.7
    -161.3 ± 115.7
    -718.5 ± 569.4
    -606.8 ± 512.5
    -479 ± 646.3
        Day 84
    -718.9 ± 500.5
    -357 ± 535.5
    -226.7 ± 153.4
    -547.7 ± 531.4
    -605.3 ± 498
    -357.5 ± 354.3
    No statistical analyses for this end point

    Secondary: Part 2: Change From Baseline Average Over 12 Weeks (up to Day 84) in Weekly Mean score of WOMAC A1 Pain Subscore (Walking Pain) Collected Daily in the Target Knee

    Close Top of page
    End point title
    Part 2: Change From Baseline Average Over 12 Weeks (up to Day 84) in Weekly Mean score of WOMAC A1 Pain Subscore (Walking Pain) Collected Daily in the Target Knee [21]
    End point description
    WOMAC A1 (Question 1 of the pain sub-scale of WOMAC index) was used to measure the amount of pain in the target knee while walking on a flat surface during last 24 hours. It was measured daily on a 0-100 VAS ranging from 0=no pain to 100=maximal pain, where higher score indicated the higher intensity of pain. The weekly mean score of WOMAC A1 pain subscore, defined as average of daily measurements over the week were calculated for each week. The statistical analysis was done on the change from baseline score calculated at each week. Analysis was performed on mITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Days 1 to 84
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was evaluated for Part 2 only.
    End point values
    Part 2: Placebo Part 2: GZ389988A Dose 4 from Part 1
    Number of subjects analysed
    52
    52
    Units: Units on a Scale
        least squares mean (standard error)
    -20.6174 ± 3.0805
    -27.3981 ± 3.0790
    Statistical analysis title
    Over 12 weeks: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0636 [22]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.7807
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.1019
         upper limit
    0.5405
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.4096
    Notes
    [22] - Specified one-sided P-value.

    Secondary: Part2:Change From Baseline Average Over Days 1to7(1 Week),1to14(2 Weeks),1to21(3 Weeks),1to42(6 Weeks),1to56(8 Weeks), and 1to70(10 Weeks) in Weekly Mean Score of WOMAC A1 Pain Subscore (Walking Pain) Collected Daily in the Target Knee

    Close Top of page
    End point title
    Part2:Change From Baseline Average Over Days 1to7(1 Week),1to14(2 Weeks),1to21(3 Weeks),1to42(6 Weeks),1to56(8 Weeks), and 1to70(10 Weeks) in Weekly Mean Score of WOMAC A1 Pain Subscore (Walking Pain) Collected Daily in the Target Knee [23]
    End point description
    WOMAC A1 (Question 1 of the pain sub-scale of WOMAC index) was used to measure the amount of pain in the target knee while walking on a flat surface during last 24 hours. It was measured daily on a 0-100 VAS ranging from 0=no pain to 100=maximal pain, where higher score indicated the higher intensity of pain. The weekly mean score of WOMAC A1 pain subscore, defined as average of daily measurements over the week were calculated for each week. The statistical analysis was done on the change from baseline score calculated at each week. Analysis was performed on mITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Days 1 to 7, 1 to 14, 1 to 21, 1 to 42, 1 to 56, and 1 to 70
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was evaluated for Part 2 only.
    End point values
    Part 2: Placebo Part 2: GZ389988A Dose 4 from Part 1
    Number of subjects analysed
    52
    52
    Units: Units on a Scale
    least squares mean (standard error)
        Days 1 to 7
    -8.8568 ± 3.3391
    -9.9056 ± 3.3378
        Days 1 to 14
    -12.3714 ± 3.2149
    -18.1451 ± 3.2135
        Days 1 to 21
    -14.4834 ± 3.0802
    -21.2600 ± 3.0787
        Days 1 to 42
    -17.6864 ± 3.0139
    -25.2616 ± 3.0125
        Days 1 to 56
    -19.0908 ± 3.0223
    -26.3236 ± 3.0208
        Days 1 to 70
    -19.9442 ± 3.0493
    -27.0007 ± 3.0478
    Statistical analysis title
    Over Days 1 to 7: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4133 [24]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -1.0488
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -8.9906
         upper limit
    6.8929
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.7714
    Notes
    [24] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 14: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1062 [25]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.7737
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.4134
         upper limit
    1.866
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.5975
    Notes
    [25] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 21: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0638 [26]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.7766
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.1001
         upper limit
    0.5469
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.4092
    Notes
    [26] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 42: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0412 [27]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -7.5751
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.7424
         upper limit
    -0.4079
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.3167
    Notes
    [27] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 56: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0489 [28]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -7.2329
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.4193
         upper limit
    -0.0464
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.3284
    Notes
    [28] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 70: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0546 [29]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -7.0565
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.3054
         upper limit
    0.1923
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.366
    Notes
    [29] - Specified one-sided P-value.

    Secondary: Part2:Change From Baseline at Day 7(Week 1),14(Week 2),21(Week 3),28(Week 4),35(Week 5),42(Week 6),49(Week 7),56(Week 8),63(Week 9),70(Week 10),77(Week 11) and 84(Week 12) in Weekly Mean WOMAC A1 Pain Subscore (Walking Pain) Collected Daily in Target Knee

    Close Top of page
    End point title
    Part2:Change From Baseline at Day 7(Week 1),14(Week 2),21(Week 3),28(Week 4),35(Week 5),42(Week 6),49(Week 7),56(Week 8),63(Week 9),70(Week 10),77(Week 11) and 84(Week 12) in Weekly Mean WOMAC A1 Pain Subscore (Walking Pain) Collected Daily in Target Knee [30]
    End point description
    WOMAC A1 (Question 1 of the pain sub-scale of WOMAC index) was used to measure the amount of pain in the target knee while walking on a flat surface during last 24 hours. It was measured daily on a 0-100 VAS ranging from 0=no pain to 100=maximal pain, where higher score indicated the higher intensity of pain. The weekly mean score of WOMAC A1 pain subscore, defined as average of daily measurements over the week were calculated for each week. The statistical analysis was done on the change from baseline score calculated at each week. Analysis was performed on mITT population. Here, “Number analyzed”(n)=number of subjects with available data at specified time point for each dose respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, and 84
    Notes
    [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was evaluated for Part 2 only.
    End point values
    Part 2: Placebo Part 2: GZ389988A Dose 4 from Part 1
    Number of subjects analysed
    52
    52
    Units: Units on a Scale
    least squares mean (standard error)
        Day 7 (n= 52, 52)
    -8.8568 ± 3.3391
    -9.9056 ± 3.3378
        Day 14 (n= 52, 52)
    -15.8860 ± 3.3768
    -26.3846 ± 3.3755
        Day 21 (n= 52, 52)
    -18.7074 ± 3.0849
    -27.4899 ± 3.0835
        Day 28 (n= 52, 52)
    -19.6397 ± 3.1821
    -29.2558 ± 3.1807
        Day 35 (n= 52, 52)
    -20.5792 ± 3.1606
    -29.1186 ± 3.1591
        Day 42 (n= 52, 52)
    -22.4494 ± 3.3453
    -29.4149 ± 3.3440
        Day 49 (n= 52, 52)
    -23.1269 ± 3.3366
    -29.5587 ± 3.3353
        Day 56 (n= 52, 52)
    -23.4806 ± 3.3393
    -29.4609 ± 3.3380
        Day 63 (n= 52, 52)
    -23.9254 ± 3.4491
    -29.9304 ± 3.4478
        Day 70 (n= 52, 52)
    -22.7903 ± 3.4670
    -29.4876 ± 3.4657
        Day 77 (n= 52, 52)
    -24.0650 ± 3.4885
    -29.8836 ± 3.4872
        Day 84 (n= 52, 51)
    -23.9020 ± 3.6026
    -28.8869 ± 3.6072
    Statistical analysis title
    At Day 7: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4133 [31]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -1.0488
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -8.9906
         upper limit
    6.8929
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.7714
    Notes
    [31] - Specified one-sided P-value.
    Statistical analysis title
    At Day 14: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.016 [32]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -10.4986
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -18.5104
         upper limit
    -2.4867
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.8241
    Notes
    [32] - Specified one-sided P-value.
    Statistical analysis title
    At Day 21: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0247 [33]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -8.7824
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -16.1122
         upper limit
    -1.4527
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.4159
    Notes
    [33] - Specified one-sided P-value.
    Statistical analysis title
    At Day 28: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0185 [34]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -9.6161
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -17.1703
         upper limit
    -2.062
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.5517
    Notes
    [34] - Specified one-sided P-value.
    Statistical analysis title
    At Day 35: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0308 [35]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -8.5393
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -16.0423
         upper limit
    -1.0363
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.5216
    Notes
    [35] - Specified one-sided P-value.
    Statistical analysis title
    At Day 42: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.074 [36]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.9655
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.8971
         upper limit
    0.9661
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.78
    Notes
    [36] - Specified one-sided P-value.
    Statistical analysis title
    At Day 49: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0901 [37]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.4318
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.3434
         upper limit
    1.4798
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.7678
    Notes
    [37] - Specified one-sided P-value.
    Statistical analysis title
    At Day 56: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1064 [38]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.9804
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.8986
         upper limit
    1.9379
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.7717
    Notes
    [38] - Specified one-sided P-value.
    Statistical analysis title
    At Day 63: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1127 [39]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.005
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.1785
         upper limit
    2.1685
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.9253
    Notes
    [39] - Specified one-sided P-value.
    Statistical analysis title
    At Day 70: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0895 [40]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.6973
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.9124
         upper limit
    1.5179
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.9504
    Notes
    [40] - Specified one-sided P-value.
    Statistical analysis title
    At Day 77: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1227 [41]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.8185
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.0838
         upper limit
    2.4468
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.9805
    Notes
    [41] - Specified one-sided P-value.
    Statistical analysis title
    At Day 84: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1674 [42]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.9849
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.5217
         upper limit
    3.5519
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.144
    Notes
    [42] - Specified one-sided P-value.

    Secondary: Part2:Change From Baseline Average Over Days 1to7(1 Week),1to14(2 Weeks),1to21(3 Weeks), 1to28(4 Weeks),1to42(6 Weeks),1to56(8 Weeks),1to70(10 Weeks) and 1to84(12 Weeks) in Weekly Mean Overall Knee Pain Scores Collected Daily in Target Knee

    Close Top of page
    End point title
    Part2:Change From Baseline Average Over Days 1to7(1 Week),1to14(2 Weeks),1to21(3 Weeks), 1to28(4 Weeks),1to42(6 Weeks),1to56(8 Weeks),1to70(10 Weeks) and 1to84(12 Weeks) in Weekly Mean Overall Knee Pain Scores Collected Daily in Target Knee [43]
    End point description
    Overall knee pain was measured daily in target knee on a 0-100 VAS ranging from 0=no pain to 100=maximal pain, where higher score indicated the higher level of pain. The weekly mean score of overall Knee pain score, defined as average of daily measurements over the week were calculated for each week. The statistical analysis was done on the change from baseline score calculated at each week. Analysis was performed on mITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Days 1 to 7, 1 to 14, 1 to 21, 1 to 28, 1 to 42, 1 to 56, 1 to 70, and 1 to 84
    Notes
    [43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was evaluated for Part 2 only.
    End point values
    Part 2: Placebo Part 2: GZ389988A Dose 4 from Part 1
    Number of subjects analysed
    52
    52
    Units: Units on a Scale
    least squares mean (standard error)
        Days 1 to 7
    -9.9274 ± 3.3127
    -10.7946 ± 3.3118
        Days 1 to 14
    -13.2629 ± 3.2686
    -18.4167 ± 3.2676
        Days 1 to 21
    -15.1501 ± 3.1853
    -21.1158 ± 3.1843
        Days 1 to 28
    -16.0917 ± 3.1581
    -22.9558 ± 3.1570
        Days 1 to 42
    -17.7356 ± 3.1494
    -24.8351 ± 3.1484
        Days 1 to 56
    -19.0673 ± 3.1611
    -25.6929 ± 3.1601
        Days 1 to 70
    -19.9019 ± 3.1966
    -26.2116 ± 3.1955
        Days 1 to 84
    -20.4833 ± 3.2299
    -26.5761 ± 3.2289
    Statistical analysis title
    Over Days 1 to 7: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4278 [44]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -0.8672
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -8.7645
         upper limit
    7.0301
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.7477
    Notes
    [44] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 14: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1371 [45]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.1538
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -12.9374
         upper limit
    2.6299
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.686
    Notes
    [45] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 21: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0974 [46]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.9658
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.554
         upper limit
    1.6224
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.5699
    Notes
    [46] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 28: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0665 [47]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.8641
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.3885
         upper limit
    0.6603
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.5319
    Notes
    [47] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 42: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0597 [48]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -7.0995
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.6032
         upper limit
    0.4041
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.5199
    Notes
    [48] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 56: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0736 [49]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.6255
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.1561
         upper limit
    0.9051
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.5362
    Notes
    [49] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 70: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0859 [50]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.3097
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.9222
         upper limit
    1.3027
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.5856
    Notes
    [50] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 84: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0957 [51]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.0927
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.7823
         upper limit
    1.5969
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.6321
    Notes
    [51] - Specified one-sided P-value.

    Secondary: Part2:Change From Baseline at Day 7(Week 1),14(Week 2),21(Week 3),28(Week 4),35(Week 5),42(Week 6),49(Week 7),56(Week 8),63(Week 9),70(Week 10),77(Week 11) and 84(Week 12) in Weekly Mean Score of Overall Knee Pain Collected Daily

    Close Top of page
    End point title
    Part2:Change From Baseline at Day 7(Week 1),14(Week 2),21(Week 3),28(Week 4),35(Week 5),42(Week 6),49(Week 7),56(Week 8),63(Week 9),70(Week 10),77(Week 11) and 84(Week 12) in Weekly Mean Score of Overall Knee Pain Collected Daily [52]
    End point description
    Overall knee pain was measured daily on a 0-100 VAS ranging from 0=no pain to 100=maximal pain, where higher score indicated the higher level of pain. The weekly mean score of Overall knee pain, defined as average of daily measurements over the week were calculated for each week. The statistical analysis was done on the change from baseline score calculated at each week. Analysis was performed on mITT population. Here, “n”= number of subjects with available data at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, and 84
    Notes
    [52] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was evaluated for Part 2 only.
    End point values
    Part 2: Placebo Part 2: GZ389988A Dose 4 from Part 1
    Number of subjects analysed
    52
    52
    Units: Units on a Scale
    least squares mean (standard error)
        Day 7 (n= 52, 52)
    -9.9274 ± 3.3127
    -10.7946 ± 3.3118
        Day 14 (n= 52, 52)
    -16.5985 ± 3.5081
    -26.0388 ± 3.5072
        Day 21 (n= 52, 52)
    -18.9243 ± 3.3007
    -26.5141 ± 3.2997
        Day 28 (n= 52, 52)
    -18.9167 ± 3.3622
    -28.4757 ± 3.3612
        Day 35 (n= 52, 52)
    -19.9309 ± 3.3408
    -28.6657 ± 3.3399
        Day 42 (n= 52, 52)
    -22.1158 ± 3.5050
    -28.5219 ± 3.5041
        Day 49 (n= 52, 52)
    -22.6754 ± 3.4793
    -28.2430 ± 3.4784
        Day 56 (n= 52, 52)
    -23.4499 ± 3.5077
    -28.2891 ± 3.5068
        Day 63 (n= 52, 52)
    -23.6896 ± 3.6526
    -28.3854 ± 3.6517
        Day 70 (n= 52, 52)
    -22.7903 ± 3.6445
    -28.1876 ± 3.6437
        Day 77 (n= 52, 52)
    -23.5177 ± 3.6836
    -28.7047 ± 3.6827
        Day 84 (n= 52, 51)
    -23.2638 ± 3.7426
    -28.0923 ± 3.7481
    Statistical analysis title
    At Day 7: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4278 [53]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -0.8672
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -8.7645
         upper limit
    7.0301
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.7477
    Notes
    [53] - Specified one-sided P-value.
    Statistical analysis title
    At Day 14: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0315 [54]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -9.4404
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -17.7768
         upper limit
    -1.1039
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.0205
    Notes
    [54] - Specified one-sided P-value.
    Statistical analysis title
    At Day 21: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0559 [55]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -7.5898
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -15.442
         upper limit
    0.2623
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.7309
    Notes
    [55] - Specified one-sided P-value.
    Statistical analysis title
    At Day 28: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0249 [56]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -9.559
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -17.5526
         upper limit
    -1.5655
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.8167
    Notes
    [56] - Specified one-sided P-value.
    Statistical analysis title
    At Day 35: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0354 [57]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -8.7348
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -16.6783
         upper limit
    -0.7912
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.7869
    Notes
    [57] - Specified one-sided P-value.
    Statistical analysis title
    At Day 42: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1022 [58]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.4061
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.7298
         upper limit
    1.9176
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.0162
    Notes
    [58] - Specified one-sided P-value.
    Statistical analysis title
    At Day 49: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1331 [59]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.5676
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.8315
         upper limit
    2.6962
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.9802
    Notes
    [59] - Specified one-sided P-value.
    Statistical analysis title
    At Day 56: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1686 [60]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.8392
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.169
         upper limit
    3.4906
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.02
    Notes
    [60] - Specified one-sided P-value.
    Statistical analysis title
    At Day 63: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1853 [61]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.6959
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.3618
         upper limit
    3.9701
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.2226
    Notes
    [61] - Specified one-sided P-value.
    Statistical analysis title
    At Day 70: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1514 [62]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.3973
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.0448
         upper limit
    3.2501
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.2113
    Notes
    [62] - Specified one-sided P-value.
    Statistical analysis title
    At Day 77: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1634 [63]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.187
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.925
         upper limit
    3.551
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.2659
    Notes
    [63] - Specified one-sided P-value.
    Statistical analysis title
    At Day 84: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1845 [64]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.8286
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.7105
         upper limit
    4.0534
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.3526
    Notes
    [64] - Specified one-sided P-value.

    Secondary: Part 2: Change From Baseline Average Over Days 1to7(1 Week),1to14(2 Weeks),1to21(3 Weeks), 1to28(4 Weeks),1to42(6 Weeks),1to56(8 Weeks),1to70(10 Weeks) and 1to84(12 Weeks) in WOMAC A1 Pain Subscore (Walking Pain) Over Last 48 Hours (hrs) at Each Visit

    Close Top of page
    End point title
    Part 2: Change From Baseline Average Over Days 1to7(1 Week),1to14(2 Weeks),1to21(3 Weeks), 1to28(4 Weeks),1to42(6 Weeks),1to56(8 Weeks),1to70(10 Weeks) and 1to84(12 Weeks) in WOMAC A1 Pain Subscore (Walking Pain) Over Last 48 Hours (hrs) at Each Visit [65]
    End point description
    WOMAC A1 (Question 1 of the pain sub-scale of WOMAC index) was used to measure the amount of pain in the target knee while walking on a flat surface during last 48 hours. It was measured daily on a 0-100 VAS ranging from 0=no pain to 100=maximal pain, where higher score indicated the higher intensity of pain. The statistical analysis was done on the change from baseline score (calculated as average of daily measurements over the week) for each week. Analysis was performed on mITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Days 1 to 7, 1 to 14, 1 to 21, 1 to 28, 1 to 42, 1 to 56, 1 to 70, and 1 to 84
    Notes
    [65] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was evaluated for Part 2 only.
    End point values
    Part 2: Placebo Part 2: GZ389988A Dose 4 from Part 1
    Number of subjects analysed
    52
    52
    Units: Units on Scale
    least squares mean (standard error)
        Days 1 to 7
    -15.4217 ± 3.4624
    -20.4256 ± 3.4613
        Days 1 to 14
    -18.0488 ± 3.3113
    -23.7308 ± 3.3103
        Days 1 to 21
    -19.5463 ± 3.2320
    -25.6484 ± 3.2323
        Days 1 to 28
    -20.4634 ± 3.2113
    -26.6924 ± 3.2113
        Days 1 to 42
    -21.5405 ± 3.2292
    -27.3880 ± 3.2289
        Days 1 to 56
    -22.4092 ± 3.2288
    -27.8870 ± 3.2284
        Days 1 to 70
    -22.9995 ± 3.2364
    -28.3369 ± 3.2360
        Days 1 to 84
    -23.6827 ± 3.2759
    -28.8040 ± 3.2754
    Statistical analysis title
    Over Days 1 to 7: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1572 [66]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.0039
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.2235
         upper limit
    3.2156
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.9481
    Notes
    [66] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 14: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1166 [67]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.6819
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.5459
         upper limit
    2.1821
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.7369
    Notes
    [67] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 21: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0951 [68]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.1021
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.7836
         upper limit
    1.5795
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.6273
    Notes
    [68] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 28: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0893 [69]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.229
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.8622
         upper limit
    1.4042
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.5981
    Notes
    [69] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 42: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1044 [70]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.8475
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.5218
         upper limit
    1.8268
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.6229
    Notes
    [70] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 56: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1194 [71]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.4778
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.1512
         upper limit
    2.1956
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.6222
    Notes
    [71] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 70: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.126 [72]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.3373
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.0285
         upper limit
    2.3538
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.6328
    Notes
    [72] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 84: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1386 [73]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.1214
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -12.9041
         upper limit
    2.6613
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.6879
    Notes
    [73] - Specified one-sided P-value.

    Secondary: Part2:Change From Baseline in WOMAC A1 Pain Subscore (Walking Pain) at Days 7(Week 1),14(Week 2),21(Week 3),28(Week 4),42(Week 6),56(Week 8),70(Week 10) and 84(Week 12) as Measured by the VAS 0-100 Over the Last 48 Hours at Each Visit

    Close Top of page
    End point title
    Part2:Change From Baseline in WOMAC A1 Pain Subscore (Walking Pain) at Days 7(Week 1),14(Week 2),21(Week 3),28(Week 4),42(Week 6),56(Week 8),70(Week 10) and 84(Week 12) as Measured by the VAS 0-100 Over the Last 48 Hours at Each Visit [74]
    End point description
    WOMAC A1 (Question 1 of the pain sub-scale of WOMAC index) was used to measure the amount of pain in the target knee while walking on a flat surface during last 48 hours. It was measured daily on a 0-100 VAS ranging from 0=no pain to 100=maximal pain, where higher score indicated the higher intensity of pain. The change from baseline in WOMAC A1 Pain sub-score was calculated at each specified visit (Day 7, 14, 21, 28, 42, 56, 70, and 84). Analysis was performed on mITT population. Here, “n” = number of subjects with available data at specified time-points.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 7, 14, 21, 28, 42, 56, 70, and 84
    Notes
    [74] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was evaluated for Part 2 only.
    End point values
    Part 2: Placebo Part 2: GZ389988A Dose 4 from Part 1
    Number of subjects analysed
    52
    52
    Units: Units on a Scale
    least squares mean (standard error)
        Day 7 (n= 51, 51)
    -15.4217 ± 3.4624
    -20.4256 ± 3.4613
        Day 14 (n= 52, 52)
    -20.6760 ± 3.5315
    -27.0359 ± 3.5308
        Day 21 (n= 52, 51)
    -22.5414 ± 3.4460
    -29.4838 ± 3.4541
        Day 28 (n= 52, 52)
    -23.2144 ± 3.5295
    -29.8243 ± 3.5289
        Day 42 (n= 52, 52)
    -25.8491 ± 3.6966
    -30.1705 ± 3.6960
        Day 56 (n= 52, 52)
    -26.7529 ± 3.6175
    -30.3820 ± 3.6169
        Day 70 (n= 52, 52)
    -26.5414 ± 3.6795
    -31.0359 ± 3.6789
        Day 84 (n= 52, 52)
    -28.4644 ± 3.9791
    -32.0743 ± 3.9785
    Statistical analysis title
    At Day 7: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1572 [75]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.0039
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.2235
         upper limit
    3.2156
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.9481
    Notes
    [75] - Specified one-sided P-value.
    Statistical analysis title
    At Day 14: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1052 [76]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.3599
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.7348
         upper limit
    2.015
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.0453
    Notes
    [76] - Specified one-sided P-value.
    Statistical analysis title
    At Day 21: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0811 [77]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.9424
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -15.1275
         upper limit
    1.2426
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.9325
    Notes
    [77] - Specified one-sided P-value.
    Statistical analysis title
    At Day 28: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0964 [78]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.6099
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.9774
         upper limit
    1.7575
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.0425
    Notes
    [78] - Specified one-sided P-value.
    Statistical analysis title
    At Day 42: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2073 [79]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.3214
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.0767
         upper limit
    4.4338
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.2765
    Notes
    [79] - Specified one-sided P-value.
    Statistical analysis title
    At Day 56: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2419 [80]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -3.6291
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -12.201
         upper limit
    4.9428
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.1657
    Notes
    [80] - Specified one-sided P-value.
    Statistical analysis title
    At Day 70: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1971 [81]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.4945
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.2108
         upper limit
    4.2217
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.2526
    Notes
    [81] - Specified one-sided P-value.
    Statistical analysis title
    At Day 84: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.263 [82]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -3.6099
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.0243
         upper limit
    5.8045
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.6726
    Notes
    [82] - Specified one-sided P-value.

    Secondary: Part2:Change From Baseline Average Over Days1to7(1Week),1to14(2Weeks),1to21(3Weeks), 1to28(4Weeks),1to42(6Weeks),1to56(8Weeks),1to70(10Weeks),1to84(12Weeks)in WOMAC Index total,Pain,Stiffness,Physical Function Subscale Scores Over Last 48hrs at Each Visit

    Close Top of page
    End point title
    Part2:Change From Baseline Average Over Days1to7(1Week),1to14(2Weeks),1to21(3Weeks), 1to28(4Weeks),1to42(6Weeks),1to56(8Weeks),1to70(10Weeks),1to84(12Weeks)in WOMAC Index total,Pain,Stiffness,Physical Function Subscale Scores Over Last 48hrs at Each Visit [83]
    End point description
    WOMAC index is health status measure questionnaire of twenty-four questions comprising of 3 subscales: pain (5 questions), stiffness (2 questions) and physical function (17 questions). Each question was measured on a 0-100 VAS ranging from 0=minimum to 100=maximum during last 48 hours. Higher score= higher intensity of pain, worse physical function and higher level of stiffness respectively. A total WOMAC index score and a WOMAC sub-score for each dimension were calculated as an average of each item concerned. The statistical analysis was done on the change from baseline score (calculated as average of daily measurements over the week), for each week. Analysis was performed on mITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Days 1 to 7, 1 to 14, 1 to 21 , 1 to 28, 1 to 42, 1 to 56, 1 to 70, and 1 to 84
    Notes
    [83] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was evaluated for Part 2 only.
    End point values
    Part 2: Placebo Part 2: GZ389988A Dose 4 from Part 1
    Number of subjects analysed
    52
    52
    Units: Units on a Scale
    least squares mean (standard error)
        WOMAC index total score: Days 1 to 7
    -13.9536 ± 3.2157
    -16.2722 ± 3.2156
        WOMAC index total score: Days 1 to 14
    -14.6039 ± 2.8898
    -18.4564 ± 2.8897
        WOMAC index total score: Days 1 to 21
    -15.0071 ± 2.7805
    -19.8222 ± 2.7811
        WOMAC index total score: Days 1 to 28
    -15.4475 ± 2.7629
    -20.6935 ± 2.7632
        WOMAC index total score: Days 1 to 42
    -16.0557 ± 2.7745
    -21.2131 ± 2.7747
        WOMAC index total score: Days 1 to 56
    -16.5502 ± 2.7821
    -21.5489 ± 2.7822
        WOMAC index total score: Days 1 to 70
    -16.9351 ± 2.7917
    -21.8778 ± 2.7917
        WOMAC index total score: Days 1 to 84
    -17.3448 ± 2.8144
    -22.1534 ± 2.8145
        WOMAC pain: Days 1 to 7
    -13.5225 ± 3.2676
    -18.4672 ± 3.2677
        WOMAC pain: Days 1 to 14
    -15.1259 ± 2.9754
    -21.4359 ± 2.9755
        WOMAC pain: Days 1 to 21
    -15.9809 ± 2.9200
    -22.8014 ± 2.9208
        WOMAC pain: Days 1 to 28
    -16.6680 ± 2.9075
    -23.8205 ± 2.9079
        WOMAC pain: Days 1 to 42
    -17.4526 ± 2.9282
    -24.2865 ± 2.9285
        WOMAC pain: Days 1 to 56
    -18.1224 ± 2.9414
    -24.6728 ± 2.9416
        WOMAC pain: Days 1 to 70
    -18.5926 ± 2.9533
    -25.0136 ± 2.9534
        WOMAC pain: Days 1 to 84
    -19.1073 ± 2.9844
    -25.4106 ± 2.9846
        WOMAC stiffness: Days 1 to 7
    -12.5795 ± 3.1733
    -15.2077 ± 3.1730
        WOMAC stiffness: Days 1 to 14
    -12.7060 ± 2.8869
    -16.6392 ± 2.8865
        WOMAC stiffness: Days 1 to 21
    -13.0431 ± 2.8011
    -17.3458 ± 2.8016
        WOMAC stiffness: Days 1 to 28
    -13.6227 ± 2.7517
    -17.8996 ± 2.7518
        WOMAC stiffness: Days 1 to 42
    -14.3493 ± 2.7603
    -18.3973 ± 2.7602
        WOMAC stiffness: Days 1 to 56
    -14.9539 ± 2.7693
    -18.6249 ± 2.7691
        WOMAC stiffness: Days 1 to 70
    -15.4091 ± 2.7859
    -18.8163 ± 2.7857
        WOMAC stiffness: Days 1 to 84
    -15.7973 ± 2.8181
    -19.1306 ± 2.8178
        WOMAC physical function: Days 1 to 7
    -14.3938 ± 3.3808
    -15.6007 ± 3.3805
        WOMAC physical function: Days 1 to 14
    -14.8167 ± 3.0225
    -17.6462 ± 3.0222
        WOMAC physical function: Days 1 to 21
    -15.0919 ± 2.8798
    -19.0910 ± 2.8802
        WOMAC physical function: Days 1 to 28
    -15.4419 ± 2.8524
    -19.9566 ± 2.8525
        WOMAC physical function: Days 1 to 42
    -15.9833 ± 2.8539
    -20.4948 ± 2.8538
        WOMAC physical function: Days 1 to 56
    -16.4127 ± 2.8536
    -20.8287 ± 2.8534
        WOMAC physical function: Days 1 to 70
    -16.7638 ± 2.8571
    -21.1705 ± 2.8568
        WOMAC physical function: Days 1 to 84
    -17.1449 ± 2.8742
    -21.4059 ± 2.8740
    Statistical analysis title
    Days1 to 7:WOMAC index-GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3059 [84]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -2.3186
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -9.8826
         upper limit
    5.2454
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.5517
    Notes
    [84] - Specified one-sided P-value.
    Statistical analysis title
    Days1to14:WOMAC index-GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1743 [85]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -3.8525
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -10.6463
         upper limit
    2.9413
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.0913
    Notes
    [85] - Specified one-sided P-value.
    Statistical analysis title
    Days1to21:WOMAC index-GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1121 [86]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.8151
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.3523
         upper limit
    1.7221
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.9374
    Notes
    [86] - Specified one-sided P-value.
    Statistical analysis title
    Days1to28:WOMAC index-GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0915 [87]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.246
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.7414
         upper limit
    1.2494
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.9124
    Notes
    [87] - Specified one-sided P-value.
    Statistical analysis title
    Days1to42:WOMAC index-GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0961 [88]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.1574
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.6798
         upper limit
    1.365
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.9286
    Notes
    [88] - Specified one-sided P-value.
    Statistical analysis title
    Days1to56:WOMAC index-GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1037 [89]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.9987
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.5389
         upper limit
    1.5414
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.9393
    Notes
    [89] - Specified one-sided P-value.
    Statistical analysis title
    Days1to70:WOMAC index-GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.107 [90]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.9427
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.5054
         upper limit
    1.62
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.9528
    Notes
    [90] - Specified one-sided P-value.
    Statistical analysis title
    Days1to84:WOMAC index-GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1152 [91]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.8086
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.4247
         upper limit
    1.8076
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.9849
    Notes
    [91] - Specified one-sided P-value.
    Statistical analysis title
    Days1to7:WOMAC pain-GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1446 [92]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.9447
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -12.6514
         upper limit
    2.762
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.6389
    Notes
    [92] - Specified one-sided P-value.
    Statistical analysis title
    Days1to14:WOMAC pain-GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0694 [93]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.31
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.3288
         upper limit
    0.7089
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.2274
    Notes
    [93] - Specified one-sided P-value.
    Statistical analysis title
    Days1to21:WOMAC pain-GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0517 [94]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.8205
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.7103
         upper limit
    0.0692
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.15
    Notes
    [94] - Specified one-sided P-value.
    Statistical analysis title
    Days1to28:WOMAC pain-GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0433 [95]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -7.1525
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.0125
         upper limit
    -0.2924
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.1321
    Notes
    [95] - Specified one-sided P-value.
    Statistical analysis title
    Days1to42:WOMAC pain-GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0518 [96]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.8339
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.7423
         upper limit
    0.0745
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.1612
    Notes
    [96] - Specified one-sided P-value.
    Statistical analysis title
    Days1to56:WOMAC pain-GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0601 [97]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.5504
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.4896
         upper limit
    0.3888
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.1796
    Notes
    [97] - Specified one-sided P-value.
    Statistical analysis title
    Days1to70:WOMAC pain-GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0646 [98]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.421
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.3882
         upper limit
    0.5461
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.1964
    Notes
    [98] - Specified one-sided P-value.
    Statistical analysis title
    Days1to84:WOMAC pain-GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0701 [99]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.3033
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.3433
         upper limit
    0.7368
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.2402
    Notes
    [99] - Specified one-sided P-value.
    Statistical analysis title
    Days1to7:WOMAC stiffness-GZ389988A Dose4vsPlacebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2799
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -2.6283
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -10.0893
         upper limit
    4.8328
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.4902
    Statistical analysis title
    Day1to14:WOMAC stiffness-GZ389988A Dose4vsPlacebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.169 [100]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -3.9332
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -10.7165
         upper limit
    2.8502
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.0855
    Notes
    [100] - Specified one-sided P-value.
    Statistical analysis title
    Day1to21:WOMAC stiffness-GZ389988A Dose4vsPlacebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1402 [101]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.3027
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -10.8849
         upper limit
    2.2795
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.9648
    Notes
    [101] - Specified one-sided P-value.
    Statistical analysis title
    Day1to28:WOMAC stiffness-GZ389988A Dose4vsPlacebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1374 [102]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.277
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -10.7429
         upper limit
    2.189
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.8948
    Notes
    [102] - Specified one-sided P-value.
    Statistical analysis title
    Day1to42:WOMAC stiffness-GZ389988A Dose4vsPlacebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1513 [103]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.048
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -10.5339
         upper limit
    2.4379
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.9068
    Notes
    [103] - Specified one-sided P-value.
    Statistical analysis title
    Day1to56:WOMAC stiffness-GZ389988A Dose4vsPlacebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1756 [104]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -3.6711
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -10.1782
         upper limit
    2.8361
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.9195
    Notes
    [104] - Specified one-sided P-value.
    Statistical analysis title
    Day1to70:WOMAC stiffness-GZ389988A Dose4vsPlacebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1948 [105]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -3.4073
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -9.9535
         upper limit
    3.139
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.9429
    Notes
    [105] - Specified one-sided P-value.
    Statistical analysis title
    Day1to84:WOMAC stiffness-GZ389988A Dose4vsPlacebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2026 [106]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -3.3333
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -9.9551
         upper limit
    3.2886
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.9883
    Notes
    [106] - Specified one-sided P-value.
    Statistical analysis title
    Day1to7:WOMAC physical function-GZ389988A/Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4007 [107]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -1.2069
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -9.1559
         upper limit
    6.742
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.7829
    Notes
    [107] - Specified one-sided P-value.
    Statistical analysis title
    Day1to14:WOMAC physical function-GZ389988A/Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2549 [108]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -2.8295
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -9.9312
         upper limit
    4.2721
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.2764
    Notes
    [108] - Specified one-sided P-value.
    Statistical analysis title
    Day1to21:WOMAC physical function-GZ389988A/Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1644 [109]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -3.9991
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -10.7655
         upper limit
    2.7673
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.0753
    Notes
    [109] - Specified one-sided P-value.
    Statistical analysis title
    Day1to28:WOMAC physical function-GZ389988A/Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.133 [110]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.5148
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.2162
         upper limit
    2.1867
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.0364
    Notes
    [110] - Specified one-sided P-value.
    Statistical analysis title
    Day1to42:WOMAC physical function-GZ389988A/Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1333 [111]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.5115
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.2161
         upper limit
    2.1931
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.0383
    Notes
    [111] - Specified one-sided P-value.
    Statistical analysis title
    Day1to56:WOMAC physical function-GZ389988A/Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1384 [112]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.416
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.12
         upper limit
    2.2879
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.0379
    Notes
    [112] - Specified one-sided P-value.
    Statistical analysis title
    Day1to70:WOMAC physical function-GZ389988A/Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1392 [113]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.4066
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.1187
         upper limit
    2.3054
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.0427
    Notes
    [113] - Specified one-sided P-value.
    Statistical analysis title
    Day1to84:WOMAC physical function-GZ389988A/Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1487 [114]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.261
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.0134
         upper limit
    2.4914
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.067
    Notes
    [114] - Specified one-sided P-value.

    Secondary: Part2:Change From Baseline at Days 7(Week 1),14(Week 2),21(Week 3),28(Week 4),42(Week 6),56(Week 8),70(Week 10) and 84(Week 12) in WOMAC Index Total, Pain, Stiffness, and Physical Function Subscores Over the Last 48 Hours at Each Visit

    Close Top of page
    End point title
    Part2:Change From Baseline at Days 7(Week 1),14(Week 2),21(Week 3),28(Week 4),42(Week 6),56(Week 8),70(Week 10) and 84(Week 12) in WOMAC Index Total, Pain, Stiffness, and Physical Function Subscores Over the Last 48 Hours at Each Visit [115]
    End point description
    WOMAC index is health status measure questionnaire of twenty-four questions comprising of 3 subscales: pain (5 questions), stiffness (2 questions) and physical function (17 questions). Each question was measured on a 0-100 VAS ranging from 0=minimum to 100=maximum over last 48 hours. A total WOMAC index score and a WOMAC sub-score for each dimension were calculated as an average of each item concerned. The change from baseline in all sub-scores were calculated at each specified visit (Day 7, 14, 21, 28, 42, 56, 70, and 84). Analysis was performed on mITT population. Here, “n” = number of subjects with available data at specified time-points.
    End point type
    Secondary
    End point timeframe
    Baseline, Days 7, 14, 21, 28, 42, 56, 70, and 84
    Notes
    [115] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was evaluated for Part 2 only.
    End point values
    Part 2: Placebo Part 2: GZ389988A Dose 4 from Part 1
    Number of subjects analysed
    52
    52
    Units: Units on a Scale
    least squares mean (standard error)
        WOMAC index total score: Day 7 (n= 51, 51)
    -13.9536 ± 3.2157
    -16.2722 ± 3.2156
        WOMAC index total score: Day 14 (n= 52, 52)
    -15.2543 ± 2.8562
    -20.6406 ± 2.8561
        WOMAC index total score: Day 21 (n= 52, 51)
    -15.8136 ± 2.8464
    -22.5539 ± 2.8524
        WOMAC index total score: Day 28 (n= 52, 52)
    -16.7687 ± 3.0042
    -23.3073 ± 3.0041
        WOMAC index total score: Day 42 (n= 52, 52)
    -18.4882 ± 3.1248
    -23.2913 ± 3.1247
        WOMAC index total score: Day 56 (n= 52, 52)
    -19.0227 ± 3.1251
    -23.2280 ± 3.1251
        WOMAC index total score: Day 70 (n= 52, 52)
    -19.2446 ± 3.1578
    -23.8514 ± 3.1578
        WOMAC index total score: Day 84 (n= 52, 52)
    -20.2126 ± 3.2945
    -24.0822 ± 3.2944
        WOMAC pain: Day 7 (n= 51, 51)
    -13.5225 ± 3.2676
    -18.4672 ± 3.2677
        WOMAC pain: Day 14 (n= 52, 52)
    -16.7293 ± 2.9820
    -24.4045 ± 2.9820
        WOMAC pain: Day 21 (n= 52, 51)
    -17.6908 ± 3.1114
    -25.5325 ± 3.1180
        WOMAC pain: Day 28 (n= 52, 52)
    -18.7293 ± 3.1775
    -26.8776 ± 3.1775
        WOMAC pain: Day 42 (n= 52, 52)
    -20.5908 ± 3.3318
    -26.1507 ± 3.3318
        WOMAC pain: Day 56 (n= 52, 52)
    -21.4716 ± 3.3291
    -26.6045 ± 3.3291
        WOMAC pain: Day 70 (n= 52, 52)
    -21.4139 ± 3.3493
    -27.0584 ± 3.3493
        WOMAC pain: Day 84 (n= 52, 52)
    -22.7101 ± 3.5443
    -28.1891 ± 3.5443
        WOMAC stiffness: Day 7 (n= 51, 51)
    -12.5795 ± 3.1733
    -15.2077 ± 3.1730
        WOMAC stiffness: Day 14 (n= 52, 52)
    -12.8326 ± 2.9546
    -18.0707 ± 2.9542
        WOMAC stiffness: Day 21 (n= 52, 51)
    -13.7172 ± 2.9834
    -18.7590 ± 2.9905
        WOMAC stiffness: Day 28 (n= 52, 52)
    -15.3614 ± 2.9550
    -19.5611 ± 2.9546
        WOMAC stiffness: Day 42 (n= 52, 52)
    -17.2557 ± 3.1652
    -20.3880 ± 3.1648
        WOMAC stiffness: Day 56 (n= 52, 52)
    -17.9768 ± 3.1887
    -19.7630 ± 3.1884
        WOMAC stiffness: Day 70 (n= 52, 52)
    -18.1403 ± 3.2690
    -19.9649 ± 3.2686
        WOMAC stiffness: Day 84 (n= 52, 52)
    -18.5153 ± 3.4455
    -21.3303 ± 3.4452
        WOMAC physical function: Day 7 (n= 51, 51)
    -14.3938 ± 3.3808
    -15.6007 ± 3.3805
        WOMAC physical function: Day 14 (n= 52, 52)
    -15.2395 ± 2.9659
    -19.6916 ± 2.9656
        WOMAC physical function: Day 21 (n= 52, 51)
    -15.6423 ± 2.8821
    -21.9805 ± 2.8879
        WOMAC physical function: Day 28 (n= 52, 52)
    -16.4918 ± 3.0682
    -22.5536 ± 3.0678
        WOMAC physical function: Day 42 (n= 52, 52)
    -18.1491 ± 3.1651
    -22.6475 ± 3.1648
        WOMAC physical function: Day 56 (n= 52, 52)
    -18.5597 ± 3.1579
    -22.4982 ± 3.1576
        WOMAC physical function: Day 70 (n= 52, 52)
    -18.8708 ± 3.1861
    -23.2211 ± 3.1858
        WOMAC physical function: Day 84 (n= 52, 52)
    -19.8119 ± 3.3138
    -23.0536 ± 3.3135
    Statistical analysis title
    At Day 7: WOMAC index- GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3059
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -2.3186
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -9.8826
         upper limit
    5.2454
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.5517
    Statistical analysis title
    At Day 14:WOMAC index- GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0929
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.3864
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -12.1001
         upper limit
    1.3274
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.0438
    Statistical analysis title
    At Day 21:WOMAC index- GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0489
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.7403
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.4366
         upper limit
    -0.044
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.0344
    Statistical analysis title
    At Day 28:WOMAC index- GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0636
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.5386
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.5968
         upper limit
    0.5195
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.2529
    Statistical analysis title
    At Day 42:WOMAC index- GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.14
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.8031
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -12.1439
         upper limit
    2.5378
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.4233
    Statistical analysis title
    At Day 56:WOMAC index- GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.172
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.2053
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.5475
         upper limit
    3.1369
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.4238
    Statistical analysis title
    At Day 70:WOMAC index- GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1526
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.6067
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -12.0255
         upper limit
    2.8121
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.47
    Statistical analysis title
    At Day 84:WOMAC index- GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2043
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -3.8696
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.6091
         upper limit
    3.87
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.663
    Statistical analysis title
    At Day 7:WOMAC pain-GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1446
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.9447
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -12.6514
         upper limit
    2.762
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.6389
    Statistical analysis title
    At Day 14:WOMAC pain-GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0365
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -7.6752
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.7089
         upper limit
    -0.6415
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.2368
    Statistical analysis title
    At Day 21:WOMAC pain-GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0396
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -7.8417
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -15.1836
         upper limit
    -0.4998
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.4236
    Statistical analysis title
    At Day 28:WOMAC pain-GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0369
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -8.1483
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -15.6366
         upper limit
    -0.6601
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.512
    Statistical analysis title
    At Day 42:WOMAC pain-GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1212
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.5599
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.4087
         upper limit
    2.289
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.7293
    Statistical analysis title
    At Day 56:WOMAC pain-GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.14
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.1329
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -12.9761
         upper limit
    2.7103
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.7255
    Statistical analysis title
    At Day 70:WOMAC pain-GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1189
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.6445
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.5353
         upper limit
    2.2464
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.7541
    Statistical analysis title
    At Day 84:WOMAC pain-GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1392
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.4791
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.826
         upper limit
    2.8679
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.0288
    Statistical analysis title
    At Day7:WOMAC stiffness-GZ389988A Dose4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2799
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -2.6283
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -10.0893
         upper limit
    4.8328
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.4902
    Statistical analysis title
    At Day14:WOMAC stiffness-GZ389988A Dose4vsPlacebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1066
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.2381
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -12.1806
         upper limit
    1.7044
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.1812
    Statistical analysis title
    At Day21:WOMAC stiffness-GZ389988A Dose4vsPlacebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1179
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.0418
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -12.0581
         upper limit
    1.9744
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.2272
    Statistical analysis title
    At Day28:WOMAC stiffness-GZ389988A Dose4vsPlacebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1588
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.1996
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.1391
         upper limit
    2.7398
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.1817
    Statistical analysis title
    At Day42:WOMAC stiffness-GZ389988A Dose4vsPlacebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: Placebo v Part 2: GZ389988A Dose 4 from Part 1
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2429
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -3.1323
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -10.5647
         upper limit
    4.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.4787
    Statistical analysis title
    At Day56:WOMAC stiffness-GZ389988A Dose4vsPlacebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3465
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -1.7862
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -9.2753
         upper limit
    5.7029
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.5121
    Statistical analysis title
    At Day70:WOMAC stiffness-GZ389988A Dose4vsPlacebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.347
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -1.8246
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -9.5019
         upper limit
    5.8526
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.6255
    Statistical analysis title
    At Day84:WOMAC stiffness-GZ389988A Dose4vsPlacebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2825
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -2.815
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -10.9068
         upper limit
    5.2767
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.875
    Statistical analysis title
    At Day7:WOMAC physical function-GZ389988A/Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4007
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -1.2069
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -9.1559
         upper limit
    6.742
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.7829
    Statistical analysis title
    Day14:WOMAC physical function-GZ389988A/Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1456
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.4521
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.4195
         upper limit
    2.5153
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.1965
    Statistical analysis title
    Day21:WOMAC physical function-GZ389988A/Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0618
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.3382
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.1144
         upper limit
    0.4379
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.0825
    Statistical analysis title
    Day28:WOMAC physical function-GZ389988A/Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0828
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.0618
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.2662
         upper limit
    1.1425
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.341
    Statistical analysis title
    Day42:WOMAC physical function-GZ389988A/Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1587
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.4985
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.9303
         upper limit
    2.9334
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.4781
    Statistical analysis title
    Day56:WOMAC physical function-GZ389988A/Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.19
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -3.9385
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.3538
         upper limit
    3.4768
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.4678
    Statistical analysis title
    Day70:WOMAC physical function-GZ389988A/Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1684
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.3503
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.8315
         upper limit
    3.131
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.5077
    Statistical analysis title
    Day84:WOMAC physical function-GZ389988A/Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2454
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -3.2417
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.0232
         upper limit
    4.5398
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.6883

    Secondary: Part 2: Change From Baseline in Patient Global Assessment (PGA) of Disease Status Average Over Days 1 to 7 (1 Week), 1 to 14 (2 Weeks), 1 to 21 (3 Weeks), 1 to 28 (4 Weeks), 1 to 42 (6 Weeks), 1 to 56 (8 Weeks), 1 to 70 (10 Weeks) and 1 to 84 (12 Weeks)

    Close Top of page
    End point title
    Part 2: Change From Baseline in Patient Global Assessment (PGA) of Disease Status Average Over Days 1 to 7 (1 Week), 1 to 14 (2 Weeks), 1 to 21 (3 Weeks), 1 to 28 (4 Weeks), 1 to 42 (6 Weeks), 1 to 56 (8 Weeks), 1 to 70 (10 Weeks) and 1 to 84 (12 Weeks) [116]
    End point description
    The PGA was used by subjects to rate the disease (osteoarthritis) status of the target knee. Subjects provided their response on a 0-100 VAS ranging from 0 (very well) to 100 (very poor), where higher scores indicated very poor condition of the knee. The statistical analysis was done on the change from baseline score (calculated as average of daily measurements over the week) for each week. Analysis was performed on mITT population. Here, "number of subjects analysed"= subjects with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Days 1 to 7, 1 to 14, 1 to 21, 1 to 28, 1 to 42, 1 to 56, 1 to 70, and 1 to 84
    Notes
    [116] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was evaluated for Part 2 only.
    End point values
    Part 2: Placebo Part 2: GZ389988A Dose 4 from Part 1
    Number of subjects analysed
    51
    50
    Units: Units on a Scale
    least squares mean (standard error)
        Days 1 to 7
    -14.1316 ± 3.3297
    -15.2721 ± 3.3621
        Days 1 to 14
    -13.8982 ± 2.9877
    -17.0106 ± 3.0163
        Days 1 to 21
    -14.3368 ± 2.8826
    -18.7073 ± 2.9113
        Days 1 to 28
    -14.7325 ± 2.8647
    -19.7327 ± 2.8927
        Days 1 to 42
    -15.6194 ± 2.8508
    -20.0680 ± 2.8780
        Days 1 to 56
    -15.9930 ± 2.8412
    -20.1116 ± 2.8683
        Days 1 to 70
    -16.0358 ± 2.8573
    -20.2284 ± 2.8846
        Days 1 to 84
    -16.3448 ± 2.8734
    -20.5685 ± 2.9008
    Statistical analysis title
    Over Days 1 to 7: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4051 [117]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -1.1405
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -9.0084
         upper limit
    6.7274
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.7344
    Notes
    [117] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 14: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2328 [118]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -3.1124
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -10.1667
         upper limit
    3.9419
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.2484
    Notes
    [118] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 21: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1445 [119]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.3705
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.178
         upper limit
    2.437
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.0999
    Notes
    [119] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 28: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1113 [120]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.0002
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.7651
         upper limit
    1.7647
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.0742
    Notes
    [120] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 42: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1376 [121]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.4486
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.1802
         upper limit
    2.283
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.0539
    Notes
    [121] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 56: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1553 [122]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.1185
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -10.8277
         upper limit
    2.5906
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.0402
    Notes
    [122] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 70: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1523 [123]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.1926
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -10.94
         upper limit
    2.5549
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.0631
    Notes
    [123] - Specified one-sided P-value.
    Statistical analysis title
    Over Days 1 to 84: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1519 [124]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.2237
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.0094
         upper limit
    2.5621
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.086
    Notes
    [124] - Specified one-sided P-value.

    Secondary: Part 2: Change From Baseline in PGA of Disease Status at Each Visit (Days 7, 14, 21, 28, 42, 56, 70 and 84)

    Close Top of page
    End point title
    Part 2: Change From Baseline in PGA of Disease Status at Each Visit (Days 7, 14, 21, 28, 42, 56, 70 and 84) [125]
    End point description
    The PGA was used by subjects to rate the disease (osteoarthritis) status of the target knee. Subjects provided their response on a 0-100 VAS ranging from 0 (very well) to 100 (very poor), where higher scores indicated very poor condition of the knee. The change from baseline in all sub-scores were calculated at each specified visit (Day 7, 14, 21, 28, 42, 56, 70, and 84). Analysis was performed on mITT population. Here, “n” = number of subjects with available data at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 7, 14, 21, 28, 42, 56, 70, and 84
    Notes
    [125] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was evaluated for Part 2 only.
    End point values
    Part 2: Placebo Part 2: GZ389988A Dose 4 from Part 1
    Number of subjects analysed
    52
    52
    Units: Units on a Scale
    least squares mean (standard error)
        Day 7 (n= 50, 49)
    -14.1316 ± 3.3297
    -15.2721 ± 3.3621
        Day 14 (n= 51, 50)
    -13.6649 ± 3.0777
    -18.7492 ± 3.1072
        Day 21 (n= 51, 49)
    -15.2139 ± 3.1048
    -22.1005 ± 3.1442
        Day 28 (n= 51, 50)
    -15.9198 ± 3.2593
    -22.8092 ± 3.2907
        Day 42 (n= 50, 50)
    -19.1669 ± 3.2510
    -21.4092 ± 3.2726
        Day 56 (n= 51, 50)
    -17.8610 ± 3.2428
    -20.3292 ± 3.2740
        Day 70 (n= 51, 50)
    -16.2923 ± 3.4257
    -20.9292 ± 3.4588
        Day 84 (n= 51, 50)
    -18.5080 ± 3.4637
    -22.9492 ± 3.4972
    Statistical analysis title
    At Day 7: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4051 [126]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -1.1405
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -9.0084
         upper limit
    6.7274
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.7344
    Notes
    [126] - Specified one-sided P-value.
    Statistical analysis title
    At Day 14: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1241 [127]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -5.0843
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -12.3511
         upper limit
    2.1825
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.3762
    Notes
    [127] - Specified one-sided P-value.
    Statistical analysis title
    At Day 21: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0612 [128]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.8866
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.2264
         upper limit
    0.4532
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.4216
    Notes
    [128] - Specified one-sided P-value.
    Statistical analysis title
    At Day 28: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0701 [129]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -6.8894
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -14.581
         upper limit
    0.8022
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.6342
    Notes
    [129] - Specified one-sided P-value.
    Statistical analysis title
    At Day 42: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3141 [130]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -2.2422
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -9.9037
         upper limit
    5.4192
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.6156
    Notes
    [130] - Specified one-sided P-value.
    Statistical analysis title
    At Day 56: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2968 [131]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -2.4682
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -10.1217
         upper limit
    5.1853
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.6108
    Notes
    [131] - Specified one-sided P-value.
    Statistical analysis title
    At Day 70: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1717 [132]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.6369
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -12.7232
         upper limit
    3.4495
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.8706
    Notes
    [132] - Specified one-sided P-value.
    Statistical analysis title
    At Day 84: GZ389988A Dose 4 vs Placebo
    Statistical analysis description
    The linear mixed effect model included the corresponding baseline as covariate and treatment, week, week-by-treatment interaction and gender as fixed effects.
    Comparison groups
    Part 2: GZ389988A Dose 4 from Part 1 v Part 2: Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1847 [133]
    Method
    Linear Mixed Effect Model
    Parameter type
    Least squares mean difference
    Point estimate
    -4.4412
    Confidence interval
         level
    90%
         sides