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    Clinical Trial Results:
    A Phase 2a Study Evaluating the Safety, Efficacy, and Pharmacodynamic Effects of ABT-981 in Patients with Knee Osteoarthritis

    Summary
    EudraCT number
    		 2013-003467-60
    Trial protocol
    		 DK   GB   NL   ES   IT  
    Global end of trial date
    13 Dec 2016

    Results information
    Results version number
    		 v3(current)
    This version publication date
    08 Nov 2019
    First version publication date
    06 Dec 2017
    Other versions
    		 v1 , v2
    Version creation reason
    • Correction of full data set
    correct the unit of measure in some secondary endpoints

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    M13-741
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02087904
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AbbVie Deutschland GmbH & Co.KG
    Sponsor organisation address
    AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6-4UB
    Public contact
    Marc Levesque, MD, Abbvie, 1 847-936-7855, marc.levesque@abbvie.com
    Scientific contact
    Marc Levesque, MD, Abbvie, 1 847-936-7855, marc.levesque@abbvie.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
    13 Dec 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Dec 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the effect of ABT-981 on osteoarthritis (OA) knee pain using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at Week 16 and synovitis/effusion volume of the index knee using quantitative measures and semi-quantitative magnetic resonance imaging (MRI) scoring at Week 26 in subjects with knee osteoarthritis.
    Protection of trial subjects
    Participant and/or legal guardian read and understood the information provided about the study and gave written permission.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    04 Jun 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 58
    Country: Number of subjects enrolled
    Netherlands: 2
    Country: Number of subjects enrolled
    United Kingdom: 1
    Country: Number of subjects enrolled
    Denmark: 61
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Italy: 3
    Country: Number of subjects enrolled
    Australia: 3
    Country: Number of subjects enrolled
    Canada: 33
    Country: Number of subjects enrolled
    Puerto Rico: 5
    Country: Number of subjects enrolled
    United States: 150
    Country: Number of subjects enrolled
    Mexico: 31
    Worldwide total number of subjects
    350
    EEA total number of subjects
    128
    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)
    219
    From 65 to 84 years
    131
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 The study included a screening period (approximately 45 days prior to first study drug dose) and a washout period (5 half-lives of the longest acting analgesic used, or 48 hours, whichever was longer, in which all standard of care analgesic medications were discontinued prior to the first study drug dose).

    Pre-assignment period milestones
    Number of subjects started
    		 350
    Number of subjects completed
    		 347

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 did not receive study drug: 3
    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, Carer, Assessor
    Blinding implementation details
    The study was conducted in a double-blind manner such that the investigator and subjects were blinded to the treatment assignments. All clinical site personnel, except for the unblinded licensed pharmacist or unblinded, qualified pharmacy technician and an unblinded monitor, remained blinded to the treatment.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Matching placebo SC E2W
    Arm type
    		 Placebo

    Investigational medicinal product name
    placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Study drug (placebo) was provided as a lyophilized powder in vials that were reconstituted to a solution for injection at the clinical site by the unblinded pharmacist or unblinded, qualified designees as permitted by local/state law.

    Arm title
    		 ABT-981 25 mg
    Arm description
    		 25 mg ABT-981 SC E2W
    Arm type
    		 Experimental

    Investigational medicinal product name
    ABT-981
    Investigational medicinal product code
    Other name
    lutikizumab
    Pharmaceutical forms
    Powder for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Study drug (ABT-981) was provided as a lyophilized powder in vials that were reconstituted to a solution for injection at the clinical site by the unblinded pharmacist or unblinded, qualified designees as permitted by local/state law.

    Arm title
    		 ABT-981 100 mg
    Arm description
    		 100 mg ABT-981 SC E2W
    Arm type
    		 Experimental

    Investigational medicinal product name
    ABT-981
    Investigational medicinal product code
    Other name
    lutikizumab
    Pharmaceutical forms
    Powder for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Study drug (ABT-981) was provided as a lyophilized powder in vials that were reconstituted to a solution for injection at the clinical site by the unblinded pharmacist or unblinded, qualified designees as permitted by local/state law.

    Arm title
    		 ABT-981 200 mg
    Arm description
    		 200 mg ABT-981 SC E2W
    Arm type
    		 Experimental

    Investigational medicinal product name
    ABT-981
    Investigational medicinal product code
    Other name
    lutikizumab
    Pharmaceutical forms
    Powder for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Study drug (ABT-981) was provided as a lyophilized powder in vials that were reconstituted to a solution for injection at the clinical site by the unblinded pharmacist or unblinded, qualified designees as permitted by local/state law.

    Number of subjects in period 1 [1]
    		Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Started
    85
    89
    85
    88
    Completed
    60
    70
    65
    64
    Not completed
    25
    19
    20
    24
         Consent withdrawn by subject
    8
    3
    7
    4
         Not specified
    6
    2
    4
    4
         Adverse event
    8
    4
    4
    12
         Lost to follow-up
    -
    4
    2
    2
         Lack of efficacy
    3
    6
    3
    2
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: 3 subjects did not receive study drug and are not included in the subject disposition.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Matching placebo SC E2W

    Reporting group title
    ABT-981 25 mg
    Reporting group description
    		 25 mg ABT-981 SC E2W

    Reporting group title
    ABT-981 100 mg
    Reporting group description
    		 100 mg ABT-981 SC E2W

    Reporting group title
    ABT-981 200 mg
    Reporting group description
    		 200 mg ABT-981 SC E2W

    Reporting group values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg Total
    Number of subjects
    		 85 89 85 88 347
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 59.53 ± 8.850 61.63 ± 7.546 60.21 ± 8.194 59.05 ± 10.273 -
    Gender categorical
    Units: Subjects
        Female
    		 52 63 53 57 225
        Male
    		 33 26 32 31 122

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Matching placebo SC E2W

    Reporting group title
    ABT-981 25 mg
    Reporting group description
    		 25 mg ABT-981 SC E2W

    Reporting group title
    ABT-981 100 mg
    Reporting group description
    		 100 mg ABT-981 SC E2W

    Reporting group title
    ABT-981 200 mg
    Reporting group description
    		 200 mg ABT-981 SC E2W

    Primary: Change from Baseline in WOMAC Pain Scores of the Index Knee at Week 16

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    End point title
    		 Change from Baseline in WOMAC Pain Scores of the Index Knee at Week 16
    End point description
    The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) numerical rating scale (NRS). The pain sub-score has a range of 0 (no pain) to 50 (maximum pain). A negative change from baseline indicates improvement. Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, LOCF (missing responses were imputed by calculation based on the last non-missing post-baseline component values).
    End point type
    Primary
    End point timeframe
    Baseline, Week 16
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    85
    88
    84
    88
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -8.9 (-10.96 to -6.90)
    -9.2 (-11.23 to -7.23)
    -11.8 (-13.84 to -9.75)
    -10.1 (-12.10 to -8.10)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.834 [1]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.13
         upper limit
    		 2.53
    Notes
    [1] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and Kellgren-Lawrence (K-L) grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    169
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.05 [2]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.73
         upper limit
    		 0.01
    Notes
    [2] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.415 [3]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4
         upper limit
    		 1.66
    Notes
    [3] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.

    Primary: Change from Baseline in Quantitative Synovitis of the Index Knee at Week 26

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    End point title
    		 Change from Baseline in Quantitative Synovitis of the Index Knee at Week 26
    End point description
    Change in synovitis of the index knee was evaluated using quantitative magnetic resonance imaging (MRI) measurements. MRI quantitative synovitis of the index knee was defined by mean synovial membrane thickness. Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.
    End point type
    Primary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    59
    65
    59
    63
    Units: mm
        least squares mean (confidence interval 95%)
    -0.05 (-0.107 to 0.011)
    0.01 (-0.045 to 0.068)
    -0.08 (-0.134 to -0.016)
    0.01 (-0.047 to 0.067)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.145 [4]
    Method
    		 ANCOVA
    Parameter type
    		 LS
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.021
         upper limit
    		 0.141
    Notes
    [4] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.52 [5]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.11
         upper limit
    		 0.056
    Notes
    [5] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.159 [6]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.023
         upper limit
    		 0.139
    Notes
    [6] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.

    Primary: Change from Baseline in Effusion Volume of the Index Knee at Week 26

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    End point title
    		 Change from Baseline in Effusion Volume of the Index Knee at Week 26
    End point description
    Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.
    End point type
    Primary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    60
    69
    67
    68
    Units: mL
        least squares mean (confidence interval 95%)
    0.03 (-2.498 to 2.562)
    0.26 (-2.113 to 2.624)
    -1.04 (-3.421 to 1.347)
    -1.49 (-3.868 to 0.898)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.897 [7]
    Method
    		 ANCOVA
    Parameter type
    		 LS mean Difference
    Point estimate
    0.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.193
         upper limit
    		 3.642
    Notes
    [7] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.542 [8]
    Method
    		 ANCOVA
    Parameter type
    		 LS mean Difference
    Point estimate
    -1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.515
         upper limit
    		 2.377
    Notes
    [8] - P-value for test of difference between ABT-981 100 dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    128
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.385 [9]
    Method
    		 ANCOVA
    Parameter type
    		 LS mean Difference
    Point estimate
    -1.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.95
         upper limit
    		 1.916
    Notes
    [9] - P-value for test of difference between ABT-981 200 dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.

    Primary: Change from Baseline in Whole-Organ Magnetic Resonance Imaging Score (WORMS) Semi-Quantitative Synovitis/Effusion Score of the Index Knee at Week 26

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    End point title
    		 Change from Baseline in Whole-Organ Magnetic Resonance Imaging Score (WORMS) Semi-Quantitative Synovitis/Effusion Score of the Index Knee at Week 26
    End point description
    Semi-quantitative synovitis/effusion volume WORMS scores were scored as normal (0), < 33% of maximum estimated distention (1), 33% – 66% of maximum estimated distention (2), or > 66% of maximum estimated distention (3). Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.
    End point type
    Primary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    70
    76
    70
    75
    Units: units on a scale
        least squares mean (confidence interval 95%)
    0.07 (-0.057 to 0.193)
    -0.01 (-0.130 to 0.113)
    -0.08 (-0.205 to 0.043)
    -0.07 (-0.196 to 0.048)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    146
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.384 [10]
    Method
    		 ANCOVA
    Parameter type
    		 LS mean Difference
    Point estimate
    -0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.249
         upper limit
    		 0.096
    Notes
    [10] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.095 [11]
    Method
    		 ANCOVA
    Parameter type
    		 LS mean Difference
    Point estimate
    -0.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.324
         upper limit
    		 0.026
    Notes
    [11] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.106 [12]
    Method
    		 ANCOVA
    Parameter type
    		 LS mean Difference
    Point estimate
    -0.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.314
         upper limit
    		 0.03
    Notes
    [12] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.

    Secondary: Change From Baseline in WOMAC Physical Function Scores of the Index Knee at Week 16

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    End point title
    		 Change From Baseline in WOMAC Physical Function Scores of the Index Knee at Week 16
    End point description
    The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) NRS. The WOMAC physical function subscale score was 0 (normal) to 170 (least physical function). A negative change from baseline indicates improvement. Modified intent to Treat population: all subjects who received at least 1 dose of study drug, LOCF (missing responses were imputed by calculation based on the last non-missing post-baseline component values).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 16
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    85
    88
    84
    87
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -28.7 (-35.30 to -22.15)
    -29.8 (-36.27 to -23.32)
    -36.3 (-42.90 to -29.69)
    -32.1 (-38.64 to -25.63)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.818 [13]
    Method
    		 ANCOVA
    Parameter type
    		 LS mean Difference
    Point estimate
    -1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.22
         upper limit
    		 8.08
    Notes
    [13] - P-value for test of difference between ABT-981 25 mg dose group and placebo at each post-baseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    169
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.109 [14]
    Method
    		 ANCOVA
    Parameter type
    		 LS mean Difference
    Point estimate
    -7.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.83
         upper limit
    		 1.69
    Notes
    [14] - P-value for test of difference between ABT-981 100 mg dose group and placebo at each post-baseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.465 [15]
    Method
    		 ANCOVA
    Parameter type
    		 LS mean Difference
    Point estimate
    -3.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.58
         upper limit
    		 5.76
    Notes
    [15] - P-value for test of difference between ABT-981 200 mg dose group and placebo at each post-baseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.

    Secondary: Change From Baseline in WOMAC Physical Function Scores of the Index Knee at Week 26

    		 Close Top of page
    End point title
    		 Change From Baseline in WOMAC Physical Function Scores of the Index Knee at Week 26
    End point description
    The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) NRS. The WOMAC physical function subscale score was 0 (normal) to 170 (least physical function). A negative change from baseline indicates improvement. Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, LOCF (missing responses were imputed by calculation based on the last non-missing post-baseline component values).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    85
    88
    84
    87
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -29.7 (-36.61 to -22.75)
    -31.8 (-38.62 to -24.98)
    -38.9 (-45.83 to -31.92)
    -36.9 (-43.71 to -30.00)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.666 [16]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.76
         upper limit
    		 7.52
    Notes
    [16] - P-value for test of difference between ABT-981 25 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    169
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.065 [17]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -9.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.95
         upper limit
    		 0.56
    Notes
    [17] - P-value for test of difference between ABT-981 100 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.145 [18]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -7.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.84
         upper limit
    		 2.49
    Notes
    [18] - P-value for test of difference between ABT-981 200 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.

    Secondary: Change From Baseline in WOMAC Physical Function Scores of the Index Knee at Week 52

    		 Close Top of page
    End point title
    		 Change From Baseline in WOMAC Physical Function Scores of the Index Knee at Week 52
    End point description
    The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) NRS. The WOMAC physical function subscale score was 0 (normal) to 170 (least physical function). A negative change from baseline indicates improvement. Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, LOCF (missing responses were imputed by calculation based on the last non-missing post-baseline component values).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    85
    88
    84
    87
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -32.9 (-40.66 to -25.12)
    -36.1 (-43.76 to -28.46)
    -38.7 (-46.52 to -30.92)
    -39.7 (-47.37 to -32.00)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.558 [19]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -3.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.03
         upper limit
    		 7.59
    Notes
    [19] - P-value for test of difference between ABT-981 25 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    169
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.295 [20]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -5.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.77
         upper limit
    		 5.11
    Notes
    [20] - P-value for test of difference between ABT-981 100 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.218 [21]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -6.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.63
         upper limit
    		 4.04
    Notes
    [21] - P-value for test of difference between ABT-981 200 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.

    Secondary: Change From Baseline in WOMAC Pain Scores of the Index Knee at Week 26

    		 Close Top of page
    End point title
    		 Change From Baseline in WOMAC Pain Scores of the Index Knee at Week 26
    End point description
    The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) numerical rating scale (NRS). The pain sub-score has a range of 0 (no pain) to 50 (maximum pain). A negative change from baseline indicates improvement. Modified intent to Treat population: all subjects who received at least 1 dose of study drug, LOCF (missing responses were imputed by calculation based on the last non-missing post-baseline component values).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    85
    88
    84
    88
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -9.2 (-11.29 to -7.07)
    -9.8 (-11.90 to -7.75)
    -11.9 (-13.99 to -9.76)
    -11.6 (-13.65 to -9.51)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.664 [22]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.58
         upper limit
    		 2.28
    Notes
    [22] - P-value for test of difference between ABT-981 25 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    169
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.075 [23]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.67
         upper limit
    		 0.28
    Notes
    [23] - P-value for test of difference between ABT-981 100 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.107 [24]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.33
         upper limit
    		 0.52
    Notes
    [24] - P-value for test of difference between ABT-981 200 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.

    Secondary: Change From Baseline in WOMAC Pain Scores of the Index Knee at Week 52

    		 Close Top of page
    End point title
    		 Change From Baseline in WOMAC Pain Scores of the Index Knee at Week 52
    End point description
    The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) numerical rating scale (NRS). The pain sub-score has a range of 0 (no pain) to 50 (maximum pain). A negative change from baseline indicates improvement. Modified intent to Treat population: all subjects who received at least 1 dose of study drug, LOCF (missing responses were imputed by calculation based on the last non-missing post-baseline component values).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    85
    88
    84
    88
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -10.0 (-12.24 to -7.68)
    -11.0 (-13.29 to -8.80)
    -12.1 (-14.42 to -9.84)
    -12.2 (-14.49 to -10.00)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5 [25]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.26
         upper limit
    		 2.08
    Notes
    [25] - P-value for test of difference between ABT-981 25 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    169
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.186 [26]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.39
         upper limit
    		 1.05
    Notes
    [26] - P-value for test of difference between ABT-981 100 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.157 [27]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.46
         upper limit
    		 0.88
    Notes
    [27] - P-value for test of difference between ABT-981 200 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.

    Secondary: Change from Baseline in Global Total Bone Marrow Lesion (BML) Score of the Index Knee Magnetic Resonance Imaging (MRI) at Week 26

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    End point title
    		 Change from Baseline in Global Total Bone Marrow Lesion (BML) Score of the Index Knee Magnetic Resonance Imaging (MRI) at Week 26
    End point description
    BMLs in 15 regions were measured with MRI, and graded as 0 (normal), 1 (mild; < 25% of region), 2 (moderate; 25% – 50% of region), or 3 (severe; > 50% of region). The global total BML score was the sum of the 15 component scores, and ranged from 0 (normal) to 45 (severe). Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    69
    76
    69
    75
    Units: units on a scale
        least squares mean (confidence interval 95%)
    0.1 (-0.24 to 0.43)
    0.3 (0.01 to 0.65)
    -0.0 (-0.37 to 0.29)
    0.1 (-0.22 to 0.43)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    ABT-981 25 mg v Placebo
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.319 [28]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.23
         upper limit
    		 0.69
    Notes
    [28] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.564 [29]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 0.33
    Notes
    [29] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.966 [30]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.45
         upper limit
    		 0.47
    Notes
    [30] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.

    Secondary: Change from Baseline in Global Total BML Score of the Index Knee MRI at Week 52

    		 Close Top of page
    End point title
    		 Change from Baseline in Global Total BML Score of the Index Knee MRI at Week 52
    End point description
    BMLs in 15 regions were measured with MRI, and graded as 0 (normal), 1 (mild; < 25% of region), 2 (moderate; 25% – 50% of region), or 3 (severe; > 50% of region). The global total BML score was the sum of the 15 component scores, and ranged from 0 (normal) to 45 (severe). Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    56
    66
    61
    66
    Units: units on a scale
        least squares mean (confidence interval 95%)
    0.1 (-0.34 to 0.48)
    0.2 (-0.16 to 0.60)
    0.1 (-0.30 to 0.48)
    0.0 (-0.36 to 0.39)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.602 [31]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.41
         upper limit
    		 0.7
    Notes
    [31] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.953 [32]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.55
         upper limit
    		 0.58
    Notes
    [32] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.83 [33]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.61
         upper limit
    		 0.49
    Notes
    [33] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.

    Secondary: Change from Baseline in Index Knee Intermittent and Constant Osteoarthritis Pain (ICOAP) Scores at Week 16

    		 Close Top of page
    End point title
    		 Change from Baseline in Index Knee Intermittent and Constant Osteoarthritis Pain (ICOAP) Scores at Week 16
    End point description
    The ICOAP is a multidimensional osteoarthritis-specific measure designed to comprehensively evaluate the pain experience in patients with hip or knee osteoarthritis. The ICOAP includes 11 items (5 constant pain items; 6 intermittent pain items). Each item is rated on a 0 to 4 point scale with a 7-day recall period. The raw maximum intermittent pain score ranges from 0 to 24, transformed to a reported scale of 0 (no pain) to 100 (worst pain). The raw maximum constant pain score ranges from 0 to 20, transformed to a reported scale of 0 (no pain) to 100 (worst pain). Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 16
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    75
    84
    76
    77
    Units: units on a scale
    least squares mean (confidence interval 95%)
        Intermittent pain
    -20.2 (-24.32 to -16.08)
    -19.5 (-23.40 to -15.58)
    -21.3 (-25.40 to -17.26)
    -18.8 (-22.92 to -14.71)
        Constant pain
    -18.6 (-22.88 to -14.33)
    -17.7 (-21.73 to -13.62)
    -24.2 (-28.39 to -19.94)
    -20.0 (-24.24 to -15.72)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Intermittent pain
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    159
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.804 [34]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.91
         upper limit
    		 6.33
    Notes
    [34] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Intermittent pain
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    151
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.699 [35]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.9
         upper limit
    		 4.63
    Notes
    [35] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Intermittent pain
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.636 [36]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.37
         upper limit
    		 7.14
    Notes
    [36] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Constant pain
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    159
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.756 [37]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.91
         upper limit
    		 6.76
    Notes
    [37] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    Constant pain
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    151
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.068 [38]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -5.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.55
         upper limit
    		 0.42
    Notes
    [38] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Constant pain
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.649 [39]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.34
         upper limit
    		 4.58
    Notes
    [39] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.

    Secondary: Change from Baseline in ICOAP Scores at Week 26

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    End point title
    		 Change from Baseline in ICOAP Scores at Week 26
    End point description
    The ICOAP is a multidimensional osteoarthritis-specific measure designed to comprehensively evaluate the pain experience in patients with hip or knee osteoarthritis. The ICOAP includes 11 items (5 constant pain items; 6 intermittent pain items). Each item is rated on a 0 to 4 point scale with a 7-day recall period. The raw maximum intermittent pain score ranges from 0 to 24, transformed to a reported scale of 0 (no pain) to 100 (worst pain). The raw maximum constant pain score ranges from 0 to 20, transformed to a reported scale of 0 (no pain) to 100 (worst pain). Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    68
    75
    72
    73
    Units: units on a scale
    least squares mean (confidence interval 95%)
        Intermittent pain
    -18.7 (-23.21 to -14.21)
    -19.7 (-23.99 to -15.42)
    -21.3 (-25.66 to -16.98)
    -21.7 (-26.11 to -17.38)
        Constant pain
    -19.6 (-24.22 to -14.96)
    -18.8 (-23.26 to -14.42)
    -21.6 (-26.05 to -17.08)
    -22.1 (-26.61 to -17.61)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Intermittent pain
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.75 [40]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.14
         upper limit
    		 5.14
    Notes
    [40] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Intermittent pain
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.409 [41]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.82
         upper limit
    		 3.6
    Notes
    [41] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Intermittent pain
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.338 [42]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.24
         upper limit
    		 3.18
    Notes
    [42] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Constant pain
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.817 [43]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.59
         upper limit
    		 7.08
    Notes
    [43] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    Constant pain
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.544 [44]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.37
         upper limit
    		 4.43
    Notes
    [44] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Constant pain
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.437 [45]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.91
         upper limit
    		 3.86
    Notes
    [45] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.

    Secondary: Change from Baseline in ICOAP Scores at Week 52

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    End point title
    		 Change from Baseline in ICOAP Scores at Week 52
    End point description
    The ICOAP is a multidimensional osteoarthritis-specific measure designed to comprehensively evaluate the pain experience in patients with hip or knee osteoarthritis. The ICOAP includes 11 items (5 constant pain items; 6 intermittent pain items). Each item is rated on a 0 to 4 point scale with a 7-day recall period. The raw maximum intermittent pain score ranges from 0 to 24, transformed to a reported scale of 0 (no pain) to 100 (worst pain). The raw maximum constant pain score ranges from 0 to 20, transformed to a reported scale of 0 (no pain) to 100 (worst pain). Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    58
    70
    66
    66
    Units: units on a scale
    least squares mean (confidence interval 95%)
        Intermittent pain
    -23.2 (-28.51 to -17.83)
    -25.4 (-30.21 to -20.51)
    -23.6 (-28.53 to -18.64)
    -27.2 (-32.19 to -22.14)
        Constant pain
    -20.6 (-25.93 to -15.21)
    -21.8 (-26.70 to -16.94)
    -25.2 (-30.14 to -20.17)
    -29.7 (-34.78 to -24.66)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Intermittent pain
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    128
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.545 [46]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.31
         upper limit
    		 4.92
    Notes
    [46] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Intermittent pain
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.909 [47]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.65
         upper limit
    		 6.81
    Notes
    [47] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Intermittent pain
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.278 [48]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.23
         upper limit
    		 3.25
    Notes
    [48] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Constant pain
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    128
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.732 [49]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.42
         upper limit
    		 5.92
    Notes
    [49] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    Constant pain
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.216 [50]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -4.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.86
         upper limit
    		 2.69
    Notes
    [50] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Constant pain
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.014 [51]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -9.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.42
         upper limit
    		 -1.88
    Notes
    [51] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.

    Secondary: Change From Baseline In Index Knee Pain Intensity at Week 16

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    End point title
    		 Change From Baseline In Index Knee Pain Intensity at Week 16
    End point description
    The index knee pain intensity was assessed in 3 different ways using an 11 -point NRS (0 to 10 points representing 'no pain' to 'worst possible pain'). Subjects were asked to enter: 1) average pain intensity during the past week (7-day recall period); 2) the worst pain during activity over the past 24 hours; 3) pain intensity before and after a 40 meter walk (performance pain, before and after). The 40 meter fast-paced walk test is a test of short distance walking activity, walking speed over short distances and changing direction during walking. Individuals taking the test should walk as quickly but as safely as possible, without running, along a walkway and then turn around, and repeat again for a total distance of 40 m (132 feet). The total time taken to walk the 40 meters is recorded. Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 16
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    75
    84
    77
    77
    Units: units on a scale
    least squares mean (confidence interval 95%)
        7-Day Recall Period
    -2.4 (-2.86 to -1.97)
    -2.4 (-2.79 to -1.95)
    -2.7 (-3.09 to -2.22)
    -2.1 (-2.55 to -1.67)
        Activity Pain
    -2.3 (-2.85 to -1.82)
    -2.4 (-2.85 to -1.87)
    -2.7 (-3.19 to -2.17)
    -2.1 (-2.59 to -1.56)
        Performance Pain (Before)
    -2.4 (-2.82 to -1.89)
    -2.1 (-2.58 to -1.70)
    -2.5 (-2.97 to -2.06)
    -2.1 (-2.52 to -1.60)
        Performance Pain (After)
    -2.6 (-3.07 to -2.11)
    -2.4 (-2.90 to -2.00)
    -2.7 (-3.16 to -2.22)
    -2.3 (-2.77 to -1.82)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    7-day recall period
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    159
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.874 [52]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.56
         upper limit
    		 0.66
    Notes
    [52] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    7-day recall period
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.451 [53]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.86
         upper limit
    		 0.38
    Notes
    [53] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    7-day recall period
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.331 [54]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.31
         upper limit
    		 0.93
    Notes
    [54] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Activity pain
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    159
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.932 [55]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.73
         upper limit
    		 0.67
    Notes
    [55] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    Activity pain
    Comparison groups
    ABT-981 100 mg v Placebo
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.344 [56]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.07
         upper limit
    		 0.37
    Notes
    [56] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Activity pain
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.489 [57]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.47
         upper limit
    		 0.97
    Notes
    [57] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 7
    Statistical analysis description
    Performance pain (before)
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    159
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.498 [58]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.42
         upper limit
    		 0.85
    Notes
    [58] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 8
    Statistical analysis description
    Performance pain (before)
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.637 [59]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 0.49
    Notes
    [59] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 9
    Statistical analysis description
    Performance pain (before)
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.367 [60]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.35
         upper limit
    		 0.94
    Notes
    [60] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 10
    Statistical analysis description
    Performance pain (after)
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    159
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.67 [61]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.51
         upper limit
    		 0.79
    Notes
    [61] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 11
    Statistical analysis description
    Performance pain (after)
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.776 [62]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.76
         upper limit
    		 0.57
    Notes
    [62] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 12
    Statistical analysis description
    Performance pain (after)
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.387 [63]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.37
         upper limit
    		 0.96
    Notes
    [63] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.

    Secondary: Change From Baseline In Index Knee Pain Intensity at Week 26

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    End point title
    		 Change From Baseline In Index Knee Pain Intensity at Week 26
    End point description
    The index knee pain intensity was assessed in 3 different ways using an 11 -point NRS (0 to 10 points representing 'no pain' to 'worst possible pain'). Subjects were asked to enter: 1) average pain intensity during the past week (7-day recall period); 2) the worst pain during activity over the past 24 hours; 3) pain intensity before and after a 40 meter walk (performance pain, before and after). The 40 meter fast-paced walk test is a test of short distance walking activity, walking speed over short distances and changing direction during walking. Individuals taking the test should walk as quickly but as safely as possible, without running, along a walkway and then turn around, and repeat again for a total distance of 40 m (132 feet). The total time taken to walk the 40 meters is recorded. Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    68 [64]
    75
    73 [65]
    73
    Units: units on a scale
    least squares mean (confidence interval 95%)
        7-Day Recall Period
    -2.2 (-2.76 to -1.73)
    -2.4 (-2.89 to -1.91)
    -2.8 (-3.29 to -2.31)
    -2.5 (-2.98 to -1.99)
        Activity Pain
    -2.5 (-3.07 to -1.91)
    -2.5 (-3.10 to -1.99)
    -2.8 (-3.37 to -2.25)
    -2.5 (-3.10 to -1.97)
        Performance Pain (Before)
    -2.2 (-2.72 to -1.70)
    -2.2 (-2.68 to -1.71)
    -2.6 (-3.13 to -2.16)
    -2.7 (-3.15 to -2.17)
        Performance Pain (After)
    -2.5 (-3.01 to -1.98)
    -2.4 (-2.90 to -1.92)
    -3.0 (-3.53 to -2.54)
    -2.6 (-3.13 to -2.13)
    Notes
    [64] - n=67 for Performance Pain (After)
    [65] - n=72 for Performance Pain (After)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    7-day recall period
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.661 [66]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.86
         upper limit
    		 0.54
    Notes
    [66] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    7-day recall period
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.122 [67]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.26
         upper limit
    		 0.15
    Notes
    [67] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    7-day recall period
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.507 [68]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.94
         upper limit
    		 0.47
    Notes
    [68] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Activity pain
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.892 [69]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.85
         upper limit
    		 0.74
    Notes
    [69] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    Activity pain
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.433 [70]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.12
         upper limit
    		 0.48
    Notes
    [70] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Activity pain
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.92 [71]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.84
         upper limit
    		 0.76
    Notes
    [71] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 7
    Statistical analysis description
    Performance pain (before)
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.957 [72]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.68
         upper limit
    		 0.71
    Notes
    [72] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 8
    Statistical analysis description
    Performance pain (before)
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.222 [73]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.13
         upper limit
    		 0.26
    Notes
    [73] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 9
    Statistical analysis description
    Performance pain (before)
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.209 [74]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.15
         upper limit
    		 0.25
    Notes
    [74] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 10
    Statistical analysis description
    Performance pain (after); n=67 for placebo group (subjects in this analysis =142, not the auto-calculated 143)
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.813 [75]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.62
         upper limit
    		 0.79
    Notes
    [75] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 11
    Statistical analysis description
    Performance pain (after); n=67 for placebo group and n=72 for ABT-981 100 mg (subjects in this analysis =139, not the auto-calculated 141)
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.135 [76]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.25
         upper limit
    		 0.17
    Notes
    [76] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 12
    Statistical analysis description
    Performance pain (after); n=67 for placebo group (subjects in this analysis =140, not the auto-calculated 141)
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.697 [77]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.85
         upper limit
    		 0.57
    Notes
    [77] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.

    Secondary: Change From Baseline In Index Knee Pain Intensity at Week 52

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    End point title
    		 Change From Baseline In Index Knee Pain Intensity at Week 52
    End point description
    The index knee pain intensity was assessed in 3 different ways using an 11 -point NRS (0 to 10 points representing 'no pain' to 'worst possible pain'). Subjects were asked to enter: 1) average pain intensity during the past week (7-day recall period); 2) the worst pain during activity over the past 24 hours; 3) pain intensity before and after a 40 meter walk (performance pain, before and after). The 40 meter fast-paced walk test is a test of short distance walking activity, walking speed over short distances and changing direction during walking. Individuals taking the test should walk as quickly but as safely as possible, without running, along a walkway and then turn around, and repeat again for a total distance of 40 m (132 feet). The total time taken to walk the 40 meters is recorded. Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    58
    70
    67
    66
    Units: units on a scale
    least squares mean (confidence interval 95%)
        7-Day Recall Period
    -2.9 (-3.51 to -2.35)
    -2.9 (-3.45 to -2.39)
    -2.9 (-3.43 to -2.35)
    -3.1 (-3.65 to -2.56)
        Activity Pain
    -2.8 (-3.48 to -2.16)
    -3.0 (-3.64 to -2.43)
    -3.2 (-3.77 to -2.55)
    -3.0 (-3.65 to -2.40)
        Performance Pain (Before)
    -2.6 (-3.14 to -2.03)
    -2.7 (-3.24 to -2.23)
    -3.0 (-3.51 to -2.49)
    -2.9 (-3.46 to -2.41)
        Performance Pain (After)
    -2.9 (-3.47 to -2.33)
    -3.0 (-3.53 to -2.50)
    -3.4 (-3.90 to -2.86)
    -3.2 (-3.69 to -2.62)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    7-day recall period
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    128
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.978 [78]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.76
         upper limit
    		 0.79
    Notes
    [78] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    7-day recall period
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.925 [79]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.75
         upper limit
    		 0.82
    Notes
    [79] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    7-day recall period
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.659 [80]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.96
         upper limit
    		 0.61
    Notes
    [80] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Activity pain
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    128
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.633 [81]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 0.67
    Notes
    [81] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    Activity pain
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.46 [82]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.23
         upper limit
    		 0.56
    Notes
    [82] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Activity pain
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.663 [83]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 0.7
    Notes
    [83] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 7
    Statistical analysis description
    Performance pain (before)
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    128
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.696 [84]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.89
         upper limit
    		 0.59
    Notes
    [84] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 8
    Statistical analysis description
    Performance pain (before)
    Comparison groups
    ABT-981 100 mg v Placebo
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.278 [85]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.16
         upper limit
    		 0.34
    Notes
    [85] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 9
    Statistical analysis description
    Performance pain (before)
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.357 [86]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 0.4
    Notes
    [86] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 10
    Statistical analysis description
    Performance pain (after)
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    128
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.761 [87]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.87
         upper limit
    		 0.64
    Notes
    [87] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 11
    Statistical analysis description
    Performance pain (after)
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.218 [88]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.25
         upper limit
    		 0.29
    Notes
    [88] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 12
    Statistical analysis description
    Performance pain (after)
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.513 [89]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.02
         upper limit
    		 0.51
    Notes
    [89] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.

    Secondary: Change From Baseline in Patient Global Assessment (PGA) of Arthritis of the Index Knee at Week 16

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    End point title
    		 Change From Baseline in Patient Global Assessment (PGA) of Arthritis of the Index Knee at Week 16
    End point description
    The PGA is a single item for evaluating overall osteoarthritis disease activity. PGA is assessed using an 11-point NRS of 0 to 10 points (representing best to worst disease status, respectively), with a 7-day recall period. Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 16
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    75
    84
    77
    77
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -2.5 (-2.94 to -2.01)
    -2.4 (-2.80 to -1.92)
    -2.9 (-3.34 to -2.42)
    -2.6 (-3.08 to -2.15)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    ABT-981 25 mg v Placebo
    Number of subjects included in analysis
    159
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.728 [90]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.52
         upper limit
    		 0.75
    Notes
    [90] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.219 [91]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.06
         upper limit
    		 0.24
    Notes
    [91] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.673 [92]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.79
         upper limit
    		 0.51
    Notes
    [92] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.

    Secondary: Change From Baseline in PGA of Arthritis of the Index Knee at Week 26

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    End point title
    		 Change From Baseline in PGA of Arthritis of the Index Knee at Week 26
    End point description
    The PGA is a single item for evaluating overall osteoarthritis disease activity. PGA is assessed using an 11-point NRS of 0 to 10 points (representing best to worst disease status, respectively), with a 7-day recall period. Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    68
    75
    73
    73
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -2.4 (-2.96 to -1.91)
    -2.4 (-2.94 to -1.94)
    -3.0 (-3.48 to -2.47)
    -2.7 (-3.18 to -2.16)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.984 [93]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.73
         upper limit
    		 0.71
    Notes
    [93] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.145 [94]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.26
         upper limit
    		 0.19
    Notes
    [94] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.527 [95]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.96
         upper limit
    		 0.49
    Notes
    [95] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.

    Secondary: Change From Baseline in PGA of Arthritis of the Index Knee at Week 52

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    End point title
    		 Change From Baseline in PGA of Arthritis of the Index Knee at Week 52
    End point description
    The PGA is a single item for evaluating overall osteoarthritis disease activity. PGA is assessed using an 11-point NRS of 0 to 10 points (representing best to worst disease status, respectively), with a 7-day recall period. Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    58
    70
    67
    66
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -3.0 (-3.62 to -2.44)
    -2.9 (-3.48 to -2.41)
    -3.2 (-3.71 to -2.62)
    -3.5 (-4.01 to -2.89)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    128
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.836 [96]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.71
         upper limit
    		 0.87
    Notes
    [96] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.738 [97]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.94
         upper limit
    		 0.66
    Notes
    [97] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3 [98]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.22
         upper limit
    		 0.38
    Notes
    [98] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.

    Secondary: Change From Baseline in Cartilage Volume of the Index Knee at Week 26

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    End point title
    		 Change From Baseline in Cartilage Volume of the Index Knee at Week 26
    End point description
    Cartilage volume of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI. Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    58
    65
    53
    66
    Units: mm^3
    least squares mean (confidence interval 95%)
        Global knee
    -326.0 (-400.83 to -251.13)
    -325.5 (-397.10 to -253.83)
    -322.4 (-400.20 to -244.61)
    -359.0 (-429.72 to -288.35)
        Medial central condyle + plateau
    -59.1 (-83.12 to -35.10)
    -54.9 (-77.83 to -31.90)
    -50.1 (-75.13 to -25.07)
    -57.5 (-80.12 to -34.88)
        Medial condyle + plateau
    -128.6 (-166.76 to -90.50)
    -126.5 (-163.03 to -90.02)
    -124.5 (-164.13 to -84.86)
    -114.9 (-150.86 to -78.90)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Global knee
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    123
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.992 [99]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -101.59
         upper limit
    		 102.62
    Notes
    [99] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Global knee
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.948 [100]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    3.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -103.95
         upper limit
    		 111.1
    Notes
    [100] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Global knee
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.523 [101]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -33.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -134.76
         upper limit
    		 68.65
    Notes
    [101] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Medial central condyle + plateau
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    123
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.799 [102]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    4.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.47
         upper limit
    		 36.95
    Notes
    [102] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    Medial central condyle + plateau
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.609 [103]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -25.62
         upper limit
    		 43.64
    Notes
    [103] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Medial central condyle + plateau
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.923 [104]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -30.97
         upper limit
    		 34.19
    Notes
    [104] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 7
    Statistical analysis description
    Medial condyle + plateau
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    123
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.937 [105]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -49.88
         upper limit
    		 54.08
    Notes
    [105] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 8
    Statistical analysis description
    Medial condyle + plateau
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.882 [106]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    4.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -50.68
         upper limit
    		 58.95
    Notes
    [106] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 9
    Statistical analysis description
    Medial condyle + plateau
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.602 [107]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    13.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -38.05
         upper limit
    		 65.55
    Notes
    [107] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.

    Secondary: Change From Baseline in Cartilage Volume of the Index Knee at Week 52

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    End point title
    		 Change From Baseline in Cartilage Volume of the Index Knee at Week 52
    End point description
    Cartilage volume of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI. Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    49
    57
    50
    56
    Units: mm^3
    least squares mean (confidence interval 95%)
        Global knee
    -557.0 (-659.86 to -454.10)
    -598.7 (-694.66 to -502.76)
    -554.3 (-654.92 to -453.60)
    -583.1 (-678.88 to -487.23)
        Medial central condyle + plateau
    -101.2 (-134.56 to -67.79)
    -126.3 (-157.5 to -95.09)
    -90.1 (-122.89 to -57.29)
    -113.0 (-144.08 to -81.84)
        Medial condyle + plateau
    -214.7 (-273.77 to -155.64)
    -255.0 (-310.03 to -199.97)
    -190.3 (-248.05 to -132.51)
    -242.8 (-297.71 to -187.86)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Global knee
    Comparison groups
    ABT-981 25 mg v Placebo
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.554 [108]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -41.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -180.49
         upper limit
    		 97.04
    Notes
    [108] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Global knee
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.97 [109]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    2.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -140.86
         upper limit
    		 146.31
    Notes
    [109] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Global knee
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.713 [110]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -26.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -165.47
         upper limit
    		 113.32
    Notes
    [110] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Medial central condyle + plateau
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.272 [111]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -25.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -70.12
         upper limit
    		 19.88
    Notes
    [111] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    Medial central condyle + plateau
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.64 [112]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    11.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -35.63
         upper limit
    		 57.8
    Notes
    [112] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Medial central condyle + plateau
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.608 [113]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -11.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -56.94
         upper limit
    		 33.38
    Notes
    [113] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 7
    Statistical analysis description
    Medial condyle + plateau
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.319 [114]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -40.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -119.88
         upper limit
    		 39.3
    Notes
    [114] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 8
    Statistical analysis description
    Medial condyle + plateau
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.56 [115]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    24.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -58.05
         upper limit
    		 106.91
    Notes
    [115] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 9
    Statistical analysis description
    Medial condyle + plateau
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.489 [116]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -28.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -107.97
         upper limit
    		 51.82
    Notes
    [116] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.

    Secondary: Change From Baseline in Cartilage Thickness of the Index Knee at Week 26

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    End point title
    		 Change From Baseline in Cartilage Thickness of the Index Knee at Week 26
    End point description
    Cartilage thickness of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI. Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    58
    65
    53
    66
    Units: mm
    least squares mean (confidence interval 95%)
        Global knee
    -0.047 (-0.058 to -0.036)
    -0.047 (-0.058 to -0.037)
    -0.048 (-0.059 to -0.037)
    -0.052 (-0.062 to -0.041)
        Medial central condyle + plateau
    -0.085 (-0.122 to -0.048)
    -0.077 (-0.113 to -0.042)
    -0.074 (-0.113 to -0.036)
    -0.076 (-0.111 to -0.041)
        Medial condyle + plateau
    -0.046 (-0.060 to -0.031)
    -0.045 (-0.059 to -0.031)
    -0.047 (-0.062 to -0.032)
    -0.044 (-0.058 to -0.031)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Global knee
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    123
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.972 [117]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.015
         upper limit
    		 0.015
    Notes
    [117] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Global knee
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.929 [118]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.001
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.017
         upper limit
    		 0.015
    Notes
    [118] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Global knee
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.543 [119]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.005
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.02
         upper limit
    		 0.01
    Notes
    [119] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Medial central condyle + plateau
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    123
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.752 [120]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.008
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.043
         upper limit
    		 0.059
    Notes
    [120] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    Medial central condyle + plateau
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.691 [121]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.011
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.042
         upper limit
    		 0.064
    Notes
    [121] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Medial central condyle + plateau
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.71 [122]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.041
         upper limit
    		 0.06
    Notes
    [122] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 7
    Statistical analysis description
    Medial condyle + plateau
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    123
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.965 [123]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.019
         upper limit
    		 0.02
    Notes
    [123] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 8
    Statistical analysis description
    Medial condyle + plateau
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.885 [124]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.002
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.022
         upper limit
    		 0.019
    Notes
    [124] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 9
    Statistical analysis description
    Medial condyle + plateau
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.887 [125]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.001
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.018
         upper limit
    		 0.021
    Notes
    [125] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.

    Secondary: Change From Baseline in Cartilage Thickness of the Index Knee at Week 52

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    End point title
    		 Change From Baseline in Cartilage Thickness of the Index Knee at Week 52
    End point description
    Cartilage thickness of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI. Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    49
    57
    50
    56
    Units: mm
    least squares mean (confidence interval 95%)
        Global knee
    -0.081 (-0.095 to -0.066)
    -0.085 (-0.099 to -0.072)
    -0.081 (-0.095 to -0.067)
    -0.083 (-0.097 to -0.070)
        Medial central condyle + plateau
    -0.136 (-0.187 to -0.084)
    -0.176 (-0.224 to -0.127)
    -0.113 (-0.163 to -0.062)
    -0.141 (-0.190 to -0.093)
        Medial condyle + plateau
    -0.084 (-0.106 to -0.063)
    -0.096 (-0.117 to -0.076)
    -0.073 (-0.094 to -0.052)
    -0.087 (-0.107 to -0.067)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Global knee
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.619 [126]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.005
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.024
         upper limit
    		 0.014
    Notes
    [126] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Global knee
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.952 [127]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.001
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.02
         upper limit
    		 0.019
    Notes
    [127] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Global knee
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.765 [128]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.003
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.022
         upper limit
    		 0.016
    Notes
    [128] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Medial central condyle + plateau
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.258 [129]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.11
         upper limit
    		 0.03
    Notes
    [129] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    Medial central condyle + plateau
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.535 [130]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.023
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.049
         upper limit
    		 0.094
    Notes
    [130] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Medial central condyle + plateau
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.866 [131]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.006
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.076
         upper limit
    		 0.064
    Notes
    [131] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 7
    Statistical analysis description
    Medial condyle + plateau
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.413 [132]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.012
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.041
         upper limit
    		 0.017
    Notes
    [132] - P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 8
    Statistical analysis description
    Medial condyle + plateau
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.445 [133]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.012
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.018
         upper limit
    		 0.042
    Notes
    [133] - P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 9
    Statistical analysis description
    Medial condyle + plateau
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.835 [134]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.003
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.032
         upper limit
    		 0.026
    Notes
    [134] - P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.

    Secondary: Outcome Measures in Rheumatology Clinical Trials/Osteoarthritis Research Society International (OMERACT/OARSI) Response Rate at Week 16

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    End point title
    		 Outcome Measures in Rheumatology Clinical Trials/Osteoarthritis Research Society International (OMERACT/OARSI) Response Rate at Week 16
    End point description
    Percentage of subjects classified as OMERACT-OARSI responders at Week 16. A subject was considered an OMERACT-OARSI responder if any of the following 3 criteria were met: 1. WOMAC Pain (in 0 – 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 2. WOMAC Function (in normalized 0 – 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 3. At least 2 of the following 3 are met: WOMAC Pain improvement ≥ 20% and absolute reduction (in normalized 0 – 100 scale) ≥ 10 as compared to the baseline; WOMAC Function improvement ≥ 20% and absolute reduction (in normalized 0 – 100 scale) ≥ 10 as compared to the baseline; PGA improvement ≥ 20% and absolute change (in normalized 0 – 100 scale) ≥ 10 as compared to the baseline. Response rate 95% confidence interval based on normal approximation. Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, LOCF.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    85
    88
    84
    87
    Units: percentage of subjects
        number (confidence interval 95%)
    60.0 (49.6 to 70.4)
    67.0 (57.2 to 76.9)
    72.6 (63.1 to 82.2)
    65.5 (55.5 to 75.5)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    ABT-981 25 mg v Placebo
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.311 [135]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Response Rate Difference
    Point estimate
    7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.3
         upper limit
    		 21.4
    Notes
    [135] - P-value for test of difference between each ABT-981 dose group and Placebo was from a Cochran-Mantel-Haenszel test using age group and K-L grade as stratification factors.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    169
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.08 [136]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Response Rate Difference
    Point estimate
    12.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 26.7
    Notes
    [136] - P-value for test of difference between each ABT-981 dose group and Placebo was from a Cochran-Mantel-Haenszel test using age group and K-L grade as stratification factors.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    ABT-981 200 mg v Placebo
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.435 [137]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Response Rate Difference
    Point estimate
    5.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.9
         upper limit
    		 19.9
    Notes
    [137] - P-value for test of difference between each ABT-981 dose group and Placebo was from a Cochran-Mantel-Haenszel test using age group and K-L grade as stratification factors.

    Secondary: OMERACT/OARSI Response Rate at Week 26

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    End point title
    		 OMERACT/OARSI Response Rate at Week 26
    End point description
    Percentage of subjects classified as OMERACT-OARSI responders at Week 26. A subject was considered an OMERACT-OARSI responder if any of the following 3 criteria were met: 1. WOMAC Pain (in 0 – 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 2. WOMAC Function (in normalized 0 – 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 3. At least 2 of the following 3 are met: WOMAC Pain improvement ≥ 20% and absolute reduction (in normalized 0 – 100 scale) ≥ 10 as compared to the baseline; WOMAC Function improvement ≥ 20% and absolute reduction (in normalized 0 – 100 scale) ≥ 10 as compared to the baseline; PGA improvement ≥ 20% and absolute change (in normalized 0 – 100 scale) ≥ 10 as compared to the baseline. Response rate 95% confidence interval based on normal approximation. Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, LOCF.
    End point type
    Secondary
    End point timeframe
    Week 26
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    85
    88
    84
    88
    Units: percentage of subjects
        number (confidence interval 95%)
    62.4 (52.1 to 72.7)
    64.8 (54.8 to 74.8)
    66.7 (56.6 to 76.7)
    72.7 (63.4 to 82.0)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ABT-981 25 mg
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.744 [138]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Response Rate Difference
    Point estimate
    2.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.9
         upper limit
    		 16.8
    Notes
    [138] - P-value for test of difference between each ABT-981 dose group and Placebo was from a Cochran-Mantel-Haenszel test using age group and K-L grade as stratification factors.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    169
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.581 [139]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Response Rate Difference
    Point estimate
    4.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.1
         upper limit
    		 18.7
    Notes
    [139] - P-value for test of difference between each ABT-981 dose group and Placebo was from a Cochran-Mantel-Haenszel test using age group and K-L grade as stratification factors.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.146 [140]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Response Rate Difference
    Point estimate
    10.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.5
         upper limit
    		 24.3
    Notes
    [140] - P-value for test of difference between each ABT-981 dose group and Placebo was from a Cochran-Mantel-Haenszel test using age group and K-L grade as stratification factors.

    Secondary: OMERACT/OARSI Response Rate at Week 52

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    End point title
    		 OMERACT/OARSI Response Rate at Week 52
    End point description
    Percentage of subjects classified as OMERACT-OARSI responders at Week 52. A subject was considered an OMERACT-OARSI responder if any of the following 3 criteria were met: 1. WOMAC Pain (in 0 – 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 2. WOMAC Function (in normalized 0 – 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 3. At least 2 of the following 3 are met: WOMAC Pain improvement ≥ 20% and absolute reduction (in normalized 0 – 100 scale) ≥ 10 as compared to the baseline; WOMAC Function improvement ≥ 20% and absolute reduction (in normalized 0 – 100 scale) ≥ 10 as compared to the baseline; PGA improvement ≥ 20% and absolute change (in normalized 0 – 100 scale) ≥ 10 as compared to the baseline. Response rate 95% confidence interval based on normal approximation. Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, LOCF.
    End point type
    Secondary
    End point timeframe
    Week 52
    End point values
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Number of subjects analysed
    85
    88
    84
    88
    Units: percentage of subjects
        number (confidence interval 95%)
    70.6 (60.9 to 80.3)
    69.3 (59.7 to 79.0)
    71.4 (61.8 to 81.1)
    72.7 (63.4 to 82.0)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    ABT-981 25 mg v Placebo
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.824 [141]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Response Rate Difference
    Point estimate
    -1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.9
         upper limit
    		 12.4
    Notes
    [141] - P-value for test of difference between each ABT-981 dose group and Placebo was from a Cochran-Mantel-Haenszel test using age group and K-L grade as stratification factors.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ABT-981 100 mg
    Number of subjects included in analysis
    169
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.964 [142]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Response Rate Difference
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.8
         upper limit
    		 14.5
    Notes
    [142] - P-value for test of difference between each ABT-981 dose group and Placebo was from a Cochran-Mantel-Haenszel test using age group and K-L grade as stratification factors.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ABT-981 200 mg
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.763 [143]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Response Rate Difference
    Point estimate
    2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.3
         upper limit
    		 15.6
    Notes
    [143] - P-value for test of difference between each ABT-981 dose group and Placebo was from a Cochran-Mantel-Haenszel test using age group and K-L grade as stratification factors.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    up to Week 52 (or last dose of study drug) plus 70 days
    Adverse event reporting additional description
    Safety Population: all subjects who took at least one dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Matching placebo subcutaneously (SC) every 2 weeks (E2W)

    Reporting group title
    ABT-981 25 mg
    Reporting group description
    		 25 mg ABT-981 SC E2W

    Reporting group title
    ABT-981 100 mg
    Reporting group description
    		 100 mg ABT-981 SC E2W

    Reporting group title
    ABT-981 200 mg
    Reporting group description
    		 200 mg ABT-981 SC E2W

    Serious adverse events
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    8 / 85 (9.41%)
    11 / 89 (12.36%)
    8 / 85 (9.41%)
    4 / 88 (4.55%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    BASAL CELL CARCINOMA
    Additional description: In addition to this one subject with an SAE of basal cell carcinoma, two other subjects developed basal cell carcinomas that were considered AEs but not SAEs, by the site investigator.
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 89 (1.12%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COLON ADENOMA
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 89 (1.12%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INVASIVE DUCTAL BREAST CARCINOMA
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 89 (0.00%)
    0 / 85 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LUNG CANCER METASTATIC
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 89 (0.00%)
    0 / 85 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    ANKLE FRACTURE
         subjects affected / exposed
    1 / 85 (1.18%)
    1 / 89 (1.12%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CERVICAL VERTEBRAL FRACTURE
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 89 (0.00%)
    1 / 85 (1.18%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CONCUSSION
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 89 (1.12%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FALL
         subjects affected / exposed
    2 / 85 (2.35%)
    0 / 89 (0.00%)
    1 / 85 (1.18%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HIP FRACTURE
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 89 (0.00%)
    1 / 85 (1.18%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HUMERUS FRACTURE
         subjects affected / exposed
    1 / 85 (1.18%)
    0 / 89 (0.00%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    JOINT INJURY
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 89 (0.00%)
    1 / 85 (1.18%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LACERATION
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 89 (0.00%)
    1 / 85 (1.18%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PROCEDURAL INTESTINAL PERFORATION
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 89 (1.12%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RADIUS FRACTURE
         subjects affected / exposed
    1 / 85 (1.18%)
    0 / 89 (0.00%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ROAD TRAFFIC ACCIDENT
         subjects affected / exposed
    1 / 85 (1.18%)
    0 / 89 (0.00%)
    0 / 85 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SKULL FRACTURE
         subjects affected / exposed
    1 / 85 (1.18%)
    0 / 89 (0.00%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TIBIA FRACTURE
         subjects affected / exposed
    1 / 85 (1.18%)
    0 / 89 (0.00%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    UPPER LIMB FRACTURE
         subjects affected / exposed
    1 / 85 (1.18%)
    0 / 89 (0.00%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    HYPERTENSION
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 89 (1.12%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    AQUEDUCTAL STENOSIS
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 89 (0.00%)
    1 / 85 (1.18%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BRAIN OEDEMA
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 89 (0.00%)
    1 / 85 (1.18%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CEREBRAL HAEMORRHAGE
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 89 (1.12%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYDROCEPHALUS
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 89 (0.00%)
    1 / 85 (1.18%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PARKINSON'S DISEASE
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 89 (0.00%)
    1 / 85 (1.18%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SEIZURE
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 89 (1.12%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SYNCOPE
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 89 (0.00%)
    0 / 85 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    COLITIS
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 89 (1.12%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ENTERITIS
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 89 (1.12%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ENTEROCOLITIS
         subjects affected / exposed
    1 / 85 (1.18%)
    0 / 89 (0.00%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PANCREATITIS
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 89 (0.00%)
    0 / 85 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SMALL INTESTINAL OBSTRUCTION
         subjects affected / exposed
    1 / 85 (1.18%)
    0 / 89 (0.00%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    CHOLECYSTITIS
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 89 (1.12%)
    1 / 85 (1.18%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LIVER DISORDER
         subjects affected / exposed
    1 / 85 (1.18%)
    0 / 89 (0.00%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    ALVEOLITIS ALLERGIC
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 89 (0.00%)
    1 / 85 (1.18%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ASTHMA
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 89 (0.00%)
    1 / 85 (1.18%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 89 (0.00%)
    1 / 85 (1.18%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    NEPHROLITHIASIS
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 89 (1.12%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    ADRENAL HAEMORRHAGE
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 89 (1.12%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    BACK PAIN
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 89 (1.12%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OSTEOARTHRITIS
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 89 (0.00%)
    1 / 85 (1.18%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    APPENDICITIS
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 89 (1.12%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIVERTICULITIS
         subjects affected / exposed
    1 / 85 (1.18%)
    0 / 89 (0.00%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PERITONITIS
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 89 (1.12%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 89 (0.00%)
    1 / 85 (1.18%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    1 / 85 (1.18%)
    0 / 89 (0.00%)
    0 / 85 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo ABT-981 25 mg ABT-981 100 mg ABT-981 200 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    66 / 85 (77.65%)
    63 / 89 (70.79%)
    65 / 85 (76.47%)
    75 / 88 (85.23%)
    Investigations
    NEUTROPHIL COUNT DECREASED
         subjects affected / exposed
    1 / 85 (1.18%)
    3 / 89 (3.37%)
    13 / 85 (15.29%)
    13 / 88 (14.77%)
         occurrences all number
    2
    12
    53
    43
    Injury, poisoning and procedural complications
    CONTUSION
         subjects affected / exposed
    3 / 85 (3.53%)
    9 / 89 (10.11%)
    2 / 85 (2.35%)
    5 / 88 (5.68%)
         occurrences all number
    3
    9
    2
    8
    FALL
         subjects affected / exposed
    3 / 85 (3.53%)
    5 / 89 (5.62%)
    3 / 85 (3.53%)
    8 / 88 (9.09%)
         occurrences all number
    3
    6
    4
    9
    LIGAMENT SPRAIN
         subjects affected / exposed
    3 / 85 (3.53%)
    6 / 89 (6.74%)
    2 / 85 (2.35%)
    2 / 88 (2.27%)
         occurrences all number
    3
    6
    2
    2
    Vascular disorders
    HYPERTENSION
         subjects affected / exposed
    6 / 85 (7.06%)
    7 / 89 (7.87%)
    5 / 85 (5.88%)
    1 / 88 (1.14%)
         occurrences all number
    9
    8
    7
    1
    Nervous system disorders
    DIZZINESS
         subjects affected / exposed
    1 / 85 (1.18%)
    3 / 89 (3.37%)
    6 / 85 (7.06%)
    3 / 88 (3.41%)
         occurrences all number
    1
    3
    8
    3
    HEADACHE
         subjects affected / exposed
    22 / 85 (25.88%)
    14 / 89 (15.73%)
    14 / 85 (16.47%)
    21 / 88 (23.86%)
         occurrences all number
    48
    37
    29
    34
    Blood and lymphatic system disorders
    NEUTROPENIA
         subjects affected / exposed
    1 / 85 (1.18%)
    12 / 89 (13.48%)
    12 / 85 (14.12%)
    21 / 88 (23.86%)
         occurrences all number
    1
    22
    21
    41
    General disorders and administration site conditions
    FATIGUE
         subjects affected / exposed
    12 / 85 (14.12%)
    4 / 89 (4.49%)
    5 / 85 (5.88%)
    7 / 88 (7.95%)
         occurrences all number
    15
    4
    5
    8
    INJECTION SITE ERYTHEMA
         subjects affected / exposed
    1 / 85 (1.18%)
    4 / 89 (4.49%)
    7 / 85 (8.24%)
    5 / 88 (5.68%)
         occurrences all number
    1
    11
    36
    12
    INJECTION SITE PAIN
         subjects affected / exposed
    7 / 85 (8.24%)
    2 / 89 (2.25%)
    2 / 85 (2.35%)
    1 / 88 (1.14%)
         occurrences all number
    15
    2
    3
    1
    INJECTION SITE RASH
         subjects affected / exposed
    3 / 85 (3.53%)
    3 / 89 (3.37%)
    7 / 85 (8.24%)
    8 / 88 (9.09%)
         occurrences all number
    28
    26
    24
    86
    INJECTION SITE REACTION
         subjects affected / exposed
    0 / 85 (0.00%)
    6 / 89 (6.74%)
    8 / 85 (9.41%)
    12 / 88 (13.64%)
         occurrences all number
    0
    15
    10
    30
    PAIN
         subjects affected / exposed
    6 / 85 (7.06%)
    3 / 89 (3.37%)
    4 / 85 (4.71%)
    4 / 88 (4.55%)
         occurrences all number
    8
    3
    7
    4
    Gastrointestinal disorders
    DIARRHOEA
         subjects affected / exposed
    7 / 85 (8.24%)
    6 / 89 (6.74%)
    5 / 85 (5.88%)
    9 / 88 (10.23%)
         occurrences all number
    9
    7
    5
    12
    NAUSEA
         subjects affected / exposed
    3 / 85 (3.53%)
    4 / 89 (4.49%)
    6 / 85 (7.06%)
    6 / 88 (6.82%)
         occurrences all number
    3
    7
    6
    6
    Respiratory, thoracic and mediastinal disorders
    COUGH
         subjects affected / exposed
    5 / 85 (5.88%)
    7 / 89 (7.87%)
    5 / 85 (5.88%)
    5 / 88 (5.68%)
         occurrences all number
    6
    7
    5
    5
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    2 / 85 (2.35%)
    4 / 89 (4.49%)
    5 / 85 (5.88%)
    7 / 88 (7.95%)
         occurrences all number
    2
    7
    5
    8
    Skin and subcutaneous tissue disorders
    PRURITUS
         subjects affected / exposed
    0 / 85 (0.00%)
    6 / 89 (6.74%)
    5 / 85 (5.88%)
    4 / 88 (4.55%)
         occurrences all number
    0
    7
    6
    5
    RASH
         subjects affected / exposed
    3 / 85 (3.53%)
    2 / 89 (2.25%)
    6 / 85 (7.06%)
    4 / 88 (4.55%)
         occurrences all number
    3
    2
    7
    4
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    16 / 85 (18.82%)
    16 / 89 (17.98%)
    19 / 85 (22.35%)
    14 / 88 (15.91%)
         occurrences all number
    20
    24
    37
    26
    BACK PAIN
         subjects affected / exposed
    14 / 85 (16.47%)
    8 / 89 (8.99%)
    11 / 85 (12.94%)
    14 / 88 (15.91%)
         occurrences all number
    15
    9
    16
    17
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    5 / 85 (5.88%)
    5 / 89 (5.62%)
    4 / 85 (4.71%)
    4 / 88 (4.55%)
         occurrences all number
    7
    6
    6
    4
    MYALGIA
         subjects affected / exposed
    1 / 85 (1.18%)
    2 / 89 (2.25%)
    3 / 85 (3.53%)
    9 / 88 (10.23%)
         occurrences all number
    1
    2
    4
    11
    PAIN IN EXTREMITY
         subjects affected / exposed
    6 / 85 (7.06%)
    5 / 89 (5.62%)
    7 / 85 (8.24%)
    5 / 88 (5.68%)
         occurrences all number
    8
    14
    7
    7
    Infections and infestations
    BRONCHITIS
         subjects affected / exposed
    2 / 85 (2.35%)
    5 / 89 (5.62%)
    1 / 85 (1.18%)
    4 / 88 (4.55%)
         occurrences all number
    2
    6
    1
    4
    INFLUENZA
         subjects affected / exposed
    10 / 85 (11.76%)
    2 / 89 (2.25%)
    5 / 85 (5.88%)
    4 / 88 (4.55%)
         occurrences all number
    17
    2
    5
    5
    NASOPHARYNGITIS
         subjects affected / exposed
    16 / 85 (18.82%)
    9 / 89 (10.11%)
    13 / 85 (15.29%)
    17 / 88 (19.32%)
         occurrences all number
    18
    10
    16
    22
    SINUSITIS
         subjects affected / exposed
    1 / 85 (1.18%)
    5 / 89 (5.62%)
    3 / 85 (3.53%)
    3 / 88 (3.41%)
         occurrences all number
    1
    5
    5
    3
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    8 / 85 (9.41%)
    8 / 89 (8.99%)
    7 / 85 (8.24%)
    12 / 88 (13.64%)
         occurrences all number
    12
    8
    8
    16
    URINARY TRACT INFECTION
         subjects affected / exposed
    4 / 85 (4.71%)
    3 / 89 (3.37%)
    5 / 85 (5.88%)
    8 / 88 (9.09%)
         occurrences all number
    5
    3
    5
    9

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Oct 2013
    Added secondary objective of safety and tolerability.
    28 Jan 2014
    Added additional questions to increase sensitivity of knee pain intensity measure and changed AE grading to CTCAE grading scale.
    01 Apr 2014
    Extended minimal post-dosing observational period to 1 hour, extended the assessment period of knee pain intensity prior to screening to 14 days to enhance selection of appropriate subjects, allowed for the use of low dose ibuprofen as an add-on rescue medication, and added subject discontinuation criteria due to lack of efficacy based on the subject's assessment of knee pain intensity scores.
    02 Oct 2014
    Expanded screening and washout periods to accommodate scheduling/assessment of screening imaging procedures, gave sites the option to use ultrasound or MRI imaging to detect synovitis during screening, clarified pregnancy testing requirements, included previous exposure to drugs of an immunosuppressive nature as exclusion criterion, allowed subjects with widened degree of moderate knee mal-alignment to be enrolled, further defined several abnormal laboratory values which were considered exclusionary, revised knee pain intensity to provide instructions for 40 meter fast-paced walk test, modified section for the collection and handling of PK and ADA samples, and added Appendix D to list various TB test scenarios.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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