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    Clinical Trial Results:
    A Multicenter, Randomized, Multiple-dose Phase 3 Study to Evaluate the Noninferiority of Romosozumab at a 90 mg/mL Concentration Compared With a 70 mg/mL Concentration in Postmenopausal Women With Osteoporosis

    Summary
    EudraCT number
    		 2013-000434-35
    Trial protocol
    		 PL   CZ  
    Global end of trial date
    08 Dec 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    17 Jul 2016
    First version publication date
    17 Jul 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    20120156
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02016716
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Amgen, Inc.
    Sponsor organisation address
    One Amgen Center Drive, Thousand Oaks, CA, United States, 91320
    Public contact
    IHQ-Medical Info - Clinical Trials, Amgen (Europe) GmbH, MedinfoInternational@amgen.com
    Scientific contact
    IHQ-Medical Info - Clinical Trials, Amgen (Europe) GmbH, MedinfoInternational@amgen.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
    08 Dec 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    08 Dec 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the non-inferiority of a 6-month treatment with 210 mg romosozumab administered every month (QM) using a 90 mg/mL concentration compared with 210 mg romosozumab QM using a 70 mg/mL concentration on percent change from baseline in bone mineral density (BMD) at the lumbar spine as assessed by dual-energy x-ray absorptiometry (DXA) in postmenopausal women with osteoporosis.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) and applicable country regulations/guidelines. The protocol, informed consent form (ICF), other written subject information were submitted to the applicable Independent Ethics Committee (IEC) or Institutional Review Board (IRB) for written approval , which was received by Amgen before recruitment of subjects into the study and shipment of Amgen investigational product. All subjects provided written informed consent after the aims, methods, and potential risks of the study were adequately explained. Informed consent was obtained before any protocol-specific screening procedures or any investigational products were administered.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    03 Dec 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 250
    Country: Number of subjects enrolled
    Czech Republic: 15
    Country: Number of subjects enrolled
    United States: 29
    Worldwide total number of subjects
    294
    EEA total number of subjects
    265
    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)
    115
    From 65 to 84 years
    175
    85 years and over
    4

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study was conducted at 11 centers: 7 in Poland, 2 in the Czech Republic, and 2 in the United States. The First subject enrolled on 03 December 2013 and the last subject enrolled on 07 March 2014.

    Pre-assignment
    Screening details
    		 After signing informed consent subjects entered a screening period to complete eligibility assessments. Eligible subjects were randomized in a 22:5:22:5 ratio to •romosozumab 90 mg/mL •placebo 90 mg/mL •romosozumab 70 mg/mL •placebo 70 mg/mL For efficacy analyses the 2 placebo groups were combined, for safety the data are reported separately.

    Period 1
    Period 1 title
    Overall study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    Randomization was double-blind within the concentrations (romosozumab 90 mg/mL and placebo 90 mg/mL; romosozumab 70 mg/mL and placebo 70 mg/mL).

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received matching placebo (either administered as 2 subcutaneous (SC) injections of 1.17 mL or 3 SC injections of 1.0 mL) every month for 6 months.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection once a month

    Arm title
    		 Romosozumab 70 mg/mL
    Arm description
    		 Participants received 210 mg romosozumab monthly, administered as 3 subcutaneous 1 mL injections of a 70 mg/mL solution, for 6 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Romosozumab
    Investigational medicinal product code
    AMG 785
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered as 3 SC injections of a 70 mg/mL concentration in a 1.0 mL glass prefilled syringe.

    Arm title
    		 Romosozumab 90 mg/mL
    Arm description
    		 Participants received 210 mg romosozumab monthly, administered as 2 subcutaneous 1.17 mL injections of a 90 mg/mL solution, for 6 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Romosozumab
    Investigational medicinal product code
    AMG 785
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered as 2 SC injections of a 90 mg/mL concentration in a 1.17 mL crystal zenith resin prefilled syringe.

    Number of subjects in period 1
    		Placebo Romosozumab 70 mg/mL Romosozumab 90 mg/mL
    Started
    53
    118
    123
    Completed
    47
    110
    117
    Not completed
    6
    8
    6
         Consent withdrawn by subject
    5
    5
    5
         Lost to follow-up
    1
    2
    1
         Protocol-specified criteria
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received matching placebo (either administered as 2 subcutaneous (SC) injections of 1.17 mL or 3 SC injections of 1.0 mL) every month for 6 months.

    Reporting group title
    Romosozumab 70 mg/mL
    Reporting group description
    		 Participants received 210 mg romosozumab monthly, administered as 3 subcutaneous 1 mL injections of a 70 mg/mL solution, for 6 months.

    Reporting group title
    Romosozumab 90 mg/mL
    Reporting group description
    		 Participants received 210 mg romosozumab monthly, administered as 2 subcutaneous 1.17 mL injections of a 90 mg/mL solution, for 6 months.

    Reporting group values
    		 Placebo Romosozumab 70 mg/mL Romosozumab 90 mg/mL Total
    Number of subjects
    		 53 118 123 294
    Age categorical
    Units: Subjects
        < 65 years
    		 23 46 46 115
        ≥ 65 years
    		 30 72 77 179
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 68.4 ( 8 ) 67.4 ( 7.1 ) 67.7 ( 7.6 ) -
    Gender categorical
    Units: Subjects
        Female
    		 53 118 123 294
        Male
    		 0 0 0 0
    Race
    Units: Subjects
        Asian
    		 0 2 0 2
        Black (or African American)
    		 0 1 0 1
        White
    		 53 115 123 291
    Lumbar Spine Bone Mineral Density (BMD) T-score
    The T-score is the bone mineral density (BMD) at the site when compared to that of a healthy thirty-year-old. Normal is a T-score of −1.0 or higher; Osteopenia is defined as between −1.0 and −2.5; Osteoporosis is defined as −2.5 or lower, meaning a bone density that is two and a half standard deviations below the mean of a thirty-year-old man/woman.
    Units: T-score
        arithmetic mean (standard deviation)
    		 -2.842 ( 1.033 ) -2.965 ( 0.96 ) -3.029 ( 0.687 ) -
    Total Hip BMD T-score
    Units: T-score
        arithmetic mean (standard deviation)
    		 -2.057 ( 0.634 ) -1.819 ( 0.673 ) -1.828 ( 0.649 ) -
    Femoral Neck BMD T-score
    Units: T-score
        arithmetic mean (standard deviation)
    		 -2.304 ( 0.517 ) -2.139 ( 0.611 ) -2.018 ( 0.593 ) -
    Serum Procollagen Type 1 N-telopeptide (P1NP)
    Units: µg/L
        median (inter-quartile range (Q1-Q3))
    		 49 (38 to 61) 53 (40 to 61) 50 (40 to 64) -
    Serum Type 1 Collagen C-telopeptide (CTX)
    Units: ng/L
        median (inter-quartile range (Q1-Q3))
    		 426.5 (296.5 to 560.5) 440 (288 to 613) 402 (299 to 530) -

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received matching placebo (either administered as 2 subcutaneous (SC) injections of 1.17 mL or 3 SC injections of 1.0 mL) every month for 6 months.

    Reporting group title
    Romosozumab 70 mg/mL
    Reporting group description
    		 Participants received 210 mg romosozumab monthly, administered as 3 subcutaneous 1 mL injections of a 70 mg/mL solution, for 6 months.

    Reporting group title
    Romosozumab 90 mg/mL
    Reporting group description
    		 Participants received 210 mg romosozumab monthly, administered as 2 subcutaneous 1.17 mL injections of a 90 mg/mL solution, for 6 months.

    Primary: Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine

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    End point title
    		 Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine
    End point description
    Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA).
    End point type
    Primary
    End point timeframe
    Baseline and month 6
    End point values
    		 Placebo Romosozumab 70 mg/mL Romosozumab 90 mg/mL
    Number of subjects analysed
    46 [1]
    110 [2]
    117 [3]
    Units: percent change
        least squares mean (confidence interval 95%)
    0.8 (-0.4 to 2.1)
    9.6 (8.8 to 10.4)
    9.2 (8.4 to 10)
    Notes
    [1] - Subjects with values at baseline and at month 6
    [2] - Subjects with values at baseline and at month 6
    [3] - Subjects with values at baseline and at month 6
    Statistical analysis title
    		 Non-inferiority Analysis
    Statistical analysis description
    For the evaluation of the non-inferiority hypothesis, the least squares mean of the treatment difference for romosozumab treatment groups only (romosozumab 90 mg/mL - romosozumab 70 mg/mL) and the corresponding lower 1-sided 97.5% CI was estimated using an ANCOVA model adjusting for treatment, and baseline lumbar spine BMD T-score.
    Comparison groups
    Romosozumab 70 mg/mL v Romosozumab 90 mg/mL
    Number of subjects included in analysis
    227
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [4]
    Method
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 0.7
    Notes
    [4] - The primary hypothesis was that the mean percent change from baseline in lumbar spine BMD at month 6 in subjects receiving romosozumab 210 mg QM using the 90 mg/mL concentration would not be inferior to that in subjects receiving romosozumab 210 mg QM using the 70 mg/mL concentration using a margin of -2.0%.

    Secondary: Percent Change From Baseline in Total Hip BMD

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    End point title
    		 Percent Change From Baseline in Total Hip BMD
    End point description
    Total hip BMD was measured using DXA. Analysis was based on ANCOVA model adjusting for treatment, and baseline total hip BMD T score.
    End point type
    Secondary
    End point timeframe
    Baseline and month 6
    End point values
    		 Placebo Romosozumab 70 mg/mL Romosozumab 90 mg/mL
    Number of subjects analysed
    46 [5]
    110 [6]
    116 [7]
    Units: percent change
        least squares mean (confidence interval 95%)
    0 (-0.9 to 0.8)
    3.9 (3.4 to 4.4)
    3.4 (2.9 to 4)
    Notes
    [5] - Subjects with values at baseline and at month 6
    [6] - Subjects with values at baseline and at month 6
    [7] - Subjects with values at baseline and at month 6
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Femoral Neck BMD

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    End point title
    		 Percent Change From Baseline in Femoral Neck BMD
    End point description
    Femoral neck BMD was measured using DXA. The analysis was based on ANCOVA model adjusting for treatment, and baseline femoral neck BMD T score.
    End point type
    Secondary
    End point timeframe
    Baseline and month 6
    End point values
    		 Placebo Romosozumab 70 mg/mL Romosozumab 90 mg/mL
    Number of subjects analysed
    46 [8]
    110 [9]
    116 [10]
    Units: percent change
        least squares mean (confidence interval 95%)
    -0.5 (-1.5 to 0.5)
    3.1 (2.5 to 3.8)
    2.6 (2 to 3.3)
    Notes
    [8] - Subjects with values at baseline and month 6
    [9] - Subjects with values at baseline and month 6
    [10] - Subjects with values at baseline and month 6
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in N-Terminal Propeptide Type 1 Procollagen (P1NP)

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    End point title
    		 Percent Change From Baseline in N-Terminal Propeptide Type 1 Procollagen (P1NP)
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, month 1, month 3 and month 6
    End point values
    		 Placebo Romosozumab 70 mg/mL Romosozumab 90 mg/mL
    Number of subjects analysed
    51 [11]
    115 [12]
    120 [13]
    Units: percent change
    median (inter-quartile range (Q1-Q3))
        Month 1 (n = 51, 111, 116)
    2 (-5.797 to 16.129)
    96.296 (67.143 to 159.341)
    97.435 (69.259 to 126.179)
        Month 3 (n = 48, 110, 115)
    -9.601 (-21.503 to 2.922)
    23.96 (-1.587 to 46.667)
    16.216 (-10.39 to 50)
        Month 6 (n = 45, 102, 110)
    -12.5 (-27.5 to 14.286)
    -2.885 (-28.07 to 18.421)
    -3.604 (-22.222 to 27.273)
    Notes
    [11] - Subjects with values at baseline and at ≥ 1 post-baseline visit
    [12] - Subjects with values at baseline and at ≥ 1 post-baseline visit
    [13] - Subjects with values at baseline and at ≥ 1 post-baseline visit
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Serum C-Telopeptide (CTX)

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    End point title
    		 Percent Change From Baseline in Serum C-Telopeptide (CTX)
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, month 1, month 3 and month 6
    End point values
    		 Placebo Romosozumab 70 mg/mL Romosozumab 90 mg/mL
    Number of subjects analysed
    51 [14]
    115 [15]
    120 [16]
    Units: percent change
    median (inter-quartile range (Q1-Q3))
        Month 1 (n = 51, 111, 117)
    0.282 (-16.183 to 12.874)
    -23.158 (-42.943 to -9.967)
    -21.456 (-35.602 to -7.246)
        Month 3 (n = 48, 110, 116)
    -5.687 (-20.666 to 15.566)
    -11.219 (-35.206 to 9.484)
    -5.473 (-24.139 to 26.386)
        Month 6 (n = 45, 108, 114)
    -8.12 (-26.935 to 10.059)
    -25.78 (-43.573 to -8.216)
    -17.305 (-37.566 to 6.405)
    Notes
    [14] - Subjects with values at baseline and at ≥ 1 post-baseline visit.
    [15] - Subjects with values at baseline and at ≥ 1 post-baseline visit.
    [16] - Subjects with values at baseline and at ≥ 1 post-baseline visit.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events are reported from the first dose of study drug until 90 days after last dose (9 months overall).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Placebo 70 mg/mL
    Reporting group description
    		 Participants received matching placebo administered as 3 SC injections of 1.0 mL every month for 6 months.

    Reporting group title
    Placebo 90 mg/mL
    Reporting group description
    		 Participants received matching placebo administered as 2 subcutaneous (SC) injections of 1.17 mL every month for 6 months.

    Reporting group title
    Romosozumab 70 mg/mL
    Reporting group description
    		 Participants received 210 mg romosozumab monthly, administered as 3 subcutaneous 1 mL injections of a 70 mg/mL solution, for 6 months

    Reporting group title
    Romosozumab 90 mg/mL
    Reporting group description
    		 Participants received 210 mg romosozumab monthly, administered as 2 subcutaneous 1.17 mL injections of a 90 mg/mL solution, for 6 months.

    Serious adverse events
    		 Placebo 70 mg/mL Placebo 90 mg/mL Romosozumab 70 mg/mL Romosozumab 90 mg/mL
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 26 (15.38%)
    2 / 26 (7.69%)
    7 / 119 (5.88%)
    3 / 123 (2.44%)
         number of deaths (all causes)
    1
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    0 / 123 (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
    Basal cell carcinoma
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         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
    Medullary thyroid cancer
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    0 / 123 (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
    Uterine cancer
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (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
    Injury, poisoning and procedural complications
    Carbon monoxide poisoning
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (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
    Femoral neck fracture
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (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
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 119 (0.00%)
    0 / 123 (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
    Overdose
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (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
    Patella fracture
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    0 / 123 (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
    Arterial rupture
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         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
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (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
    Cardiac failure
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (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
    Surgical and medical procedures
    Umbilical hernia repair
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (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
    Nervous system disorders
    Ischaemic stroke
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (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
    Polyneuropathy
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 119 (0.00%)
    0 / 123 (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
    Retrograde amnesia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    0 / 123 (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
    Blood and lymphatic system disorders
    Coagulopathy
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (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
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (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
    Appendicitis noninfective
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (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
    Gastritis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (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
    Mesenteric artery embolism
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    0 / 123 (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
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         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
    Musculoskeletal and connective tissue disorders
    Spinal deformity
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 119 (0.00%)
    0 / 123 (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
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 119 (0.00%)
    0 / 123 (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
    Vertebral lesion
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 119 (0.00%)
    0 / 123 (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
    Infections and infestations
    Appendicitis perforated
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (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
    Sepsis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (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
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Placebo 70 mg/mL Placebo 90 mg/mL Romosozumab 70 mg/mL Romosozumab 90 mg/mL
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    17 / 26 (65.38%)
    11 / 26 (42.31%)
    62 / 119 (52.10%)
    71 / 123 (57.72%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Thyroid neoplasm
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    1
    2
    Basal cell carcinoma
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    2 / 123 (1.63%)
         occurrences all number
    0
    0
    0
    2
    Vascular disorders
    Arteriosclerosis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hot flush
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypertension
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    3 / 119 (2.52%)
    3 / 123 (2.44%)
         occurrences all number
    1
    0
    3
    3
    Hypertensive angiopathy
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Phlebitis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    2
    Varicose vein
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Surgical and medical procedures
    Tooth extraction
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    1
    0
    1
    0
    General disorders and administration site conditions
    Administration site erythema
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    2 / 123 (1.63%)
         occurrences all number
    0
    0
    0
    4
    Administration site reaction
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Asthenia
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    4 / 119 (3.36%)
    4 / 123 (3.25%)
         occurrences all number
    0
    5
    4
    5
    Chest pain
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    0 / 123 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cyst
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Fatigue
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Generalised oedema
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Influenza like illness
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Injection site erythema
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 119 (1.68%)
    7 / 123 (5.69%)
         occurrences all number
    0
    0
    3
    23
    Injection site hypersensitivity
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    2 / 123 (1.63%)
         occurrences all number
    0
    0
    2
    2
    Injection site inflammation
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    2 / 123 (1.63%)
         occurrences all number
    0
    0
    1
    2
    Injection site pain
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    7 / 119 (5.88%)
    3 / 123 (2.44%)
         occurrences all number
    0
    0
    16
    15
    Injection site swelling
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    4 / 123 (3.25%)
         occurrences all number
    0
    0
    0
    5
    Local swelling
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Malaise
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Polyp
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pyrexia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Hypersensitivity
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    0 / 123 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Seasonal allergy
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Reproductive system and breast disorders
    Breast mass
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Breast swelling
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    1
    1
    Cough
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    1 / 119 (0.84%)
    1 / 123 (0.81%)
         occurrences all number
    0
    2
    1
    1
    Emphysema
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Respiratory tract congestion
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Rhinitis allergic
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    1
    0
    1
    Sinus congestion
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    0 / 123 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Neurosis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 119 (0.00%)
    0 / 123 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Investigations
    Blood glucose abnormal
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Blood potassium increased
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Blood thyroid stimulating hormone decreased
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Smear cervix abnormal
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Thyroid gland scan abnormal
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    0 / 123 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Thyroxine increased
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Tri-iodothyronine free increased
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Weight increased
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Ultrasound thyroid abnormal
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    2 / 119 (1.68%)
    2 / 123 (1.63%)
         occurrences all number
    2
    0
    2
    4
    Contusion
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    3 / 119 (2.52%)
    3 / 123 (2.44%)
         occurrences all number
    0
    0
    6
    6
    Forearm fracture
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Foot fracture
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Hand fracture
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Head injury
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Ligament injury
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Ligament sprain
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    2 / 123 (1.63%)
         occurrences all number
    1
    0
    1
    2
    Meniscus injury
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Neck injury
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Patella fracture
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Procedural pain
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Radius fracture
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    1 / 123 (0.81%)
         occurrences all number
    1
    0
    1
    1
    Spinal fracture
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Tooth fracture
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cardiac disorders
    Arrhythmia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 119 (1.68%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Arrhythmia supraventricular
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Mitral valve incompetence
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Atrial fibrillation
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Palpitations
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Tricuspid valve incompetence
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    1
    1
    Ventricular arrhythmia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nervous system disorders
    Balance disorder
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Cerebrovascular disorder
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Cerebrovascular insufficiency
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Dizziness
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 26 (3.85%)
    3 / 119 (2.52%)
    1 / 123 (0.81%)
         occurrences all number
    1
    1
    3
    1
    Headache
         subjects affected / exposed
    3 / 26 (11.54%)
    0 / 26 (0.00%)
    2 / 119 (1.68%)
    2 / 123 (1.63%)
         occurrences all number
    3
    0
    2
    2
    Hypoaesthesia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    1
    0
    0
    1
    Paraesthesia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Migraine
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 119 (0.00%)
    0 / 123 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Sciatica
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    3 / 123 (2.44%)
         occurrences all number
    0
    0
    0
    3
    Tremor
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Vertebrobasilar insufficiency
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    0 / 123 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Leukopenia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    0 / 123 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Lymphadenopathy
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Ear and labyrinth disorders
    Ear discomfort
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Ear disorder
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    0 / 123 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Tinnitus
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    0 / 123 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Vertigo
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Abdominal pain
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    1 / 119 (0.84%)
    1 / 123 (0.81%)
         occurrences all number
    0
    1
    2
    1
    Abdominal pain upper
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    2 / 119 (1.68%)
    1 / 123 (0.81%)
         occurrences all number
    1
    0
    2
    1
    Aphthous stomatitis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Chronic gastritis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Constipation
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    1 / 123 (0.81%)
         occurrences all number
    1
    0
    1
    1
    Diarrhoea
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    3 / 119 (2.52%)
    0 / 123 (0.00%)
         occurrences all number
    0
    1
    3
    0
    Diverticulum intestinal
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dyspepsia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Erosive oesophagitis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Faeces discoloured
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Gastric ulcer
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    1
    1
    Gastritis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    1 / 119 (0.84%)
    1 / 123 (0.81%)
         occurrences all number
    0
    1
    1
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 119 (1.68%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    2
    1
    Gingival swelling
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    2
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Haemorrhoids
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    1
    0
    0
    1
    Inguinal hernia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Large intestine polyp
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 119 (1.68%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Nausea
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    2 / 119 (1.68%)
    1 / 123 (0.81%)
         occurrences all number
    1
    0
    2
    1
    Pancreatitis chronic
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 119 (0.00%)
    0 / 123 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Peptic ulcer
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Periodontal disease
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Proctitis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Salivary gland calculus
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Toothache
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Vomiting
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hepatic steatosis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Angioedema
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Dermatitis allergic
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    1 / 119 (0.84%)
    3 / 123 (2.44%)
         occurrences all number
    0
    1
    1
    3
    Eczema
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    12
    Erythema
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Hyperhidrosis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pruritus
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    10
    Pruritus generalised
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    2
    Rash
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    6
    Rash macular
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    2
    Rash pruritic
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Skin lesion
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    2 / 123 (1.63%)
         occurrences all number
    0
    0
    0
    11
    Urticaria
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 119 (0.00%)
    0 / 123 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Nephrolithiasis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 119 (1.68%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    2
    1
    Renal colic
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Renal cyst
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Renal pain
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 119 (0.00%)
    0 / 123 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Urinary tract inflammation
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Hypothyroidism
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 119 (1.68%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Thyroiditis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 26 (3.85%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Arthralgia
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    4 / 119 (3.36%)
    6 / 123 (4.88%)
         occurrences all number
    0
    2
    4
    10
    Bone pain
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    2 / 119 (1.68%)
    2 / 123 (1.63%)
         occurrences all number
    0
    2
    2
    2
    Exostosis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    1
    1
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Joint stiffness
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 119 (0.00%)
    0 / 123 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Lordosis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 119 (0.00%)
    0 / 123 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Muscle contracture
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Musculoskeletal pain
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    2 / 123 (1.63%)
         occurrences all number
    1
    0
    1
    2
    Muscular weakness
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Myalgia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    3 / 119 (2.52%)
    3 / 123 (2.44%)
         occurrences all number
    0
    0
    3
    4
    Osteoarthritis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    2 / 119 (1.68%)
    6 / 123 (4.88%)
         occurrences all number
    0
    1
    2
    6
    Pain in extremity
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    2 / 119 (1.68%)
    4 / 123 (3.25%)
         occurrences all number
    1
    0
    3
    8
    Spinal deformity
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Spinal pain
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Spinal osteoarthritis
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    4 / 119 (3.36%)
    2 / 123 (1.63%)
         occurrences all number
    1
    0
    4
    2
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    2 / 119 (1.68%)
    3 / 123 (2.44%)
         occurrences all number
    1
    0
    2
    3
    Ear infection bacterial
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Ear infection viral
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Genitourinary chlamydia infection
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    0 / 123 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gingivitis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Helicobacter infection
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    2 / 123 (1.63%)
         occurrences all number
    0
    0
    0
    2
    Herpes zoster
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Infection
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Influenza
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    3 / 26 (11.54%)
    0 / 26 (0.00%)
    9 / 119 (7.56%)
    19 / 123 (15.45%)
         occurrences all number
    4
    0
    10
    21
    Laryngitis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Onychomycosis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Oral herpes
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Pharyngitis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    2 / 123 (1.63%)
         occurrences all number
    0
    0
    0
    2
    Pharyngitis bacterial
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pneumonia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pulpitis dental
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Respiratory tract infection
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Rhinitis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    1
    0
    1
    Sinusitis
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    4 / 123 (3.25%)
         occurrences all number
    1
    0
    0
    4
    Tonsillitis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    1
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 26 (3.85%)
    2 / 26 (7.69%)
    1 / 119 (0.84%)
    2 / 123 (1.63%)
         occurrences all number
    1
    2
    1
    2
    Upper respiratory tract infection bacterial
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    1 / 119 (0.84%)
    7 / 123 (5.69%)
         occurrences all number
    0
    2
    2
    7
    Urinary tract infection bacterial
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Vaginal infection
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 119 (1.68%)
    3 / 123 (2.44%)
         occurrences all number
    0
    0
    2
    3
    Metabolism and nutrition disorders
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    0 / 123 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hyperlipidaemia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Increased appetite
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Obesity
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 119 (0.00%)
    1 / 123 (0.81%)
         occurrences all number
    0
    0
    0
    1
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 119 (0.84%)
    0 / 123 (0.00%)
         occurrences all number
    0
    0
    1
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Sep 2013
    The protocol was amended to include the following changes: - To include an additional assessment for formation of antiromosozumab antibodies at the month 1 study visit. This additional assessment allowed a more comprehensive characterization of the antiromosozumab antibody response. - The eligibility criteria were modified to allow participation of a wider range of subjects. Specifically, the minimal age was lowered from 60 to 55 years and for exclusionary medications, the protocol-mandated off-treatment times were revised. Similarly, the use of vitamin K (and analogs) for the treatment of osteoporosis, and the use of activated vitamin D were added to the on-study excluded treatments list. - To account for the imprecision of serum calcium laboratory measurements, retesting of serum calcium was permitted within the screening window if the initial test indicated an elevated level of serum calcium within 1.1x the upper limit of normal set by the central laboratory. - It was clarified that if a subject was rescreened for serum 25-hydroxyvitamin D level, they were not required to reconsent for the rescreening period. - Expectations for serious adverse event reporting were defined for the time after the protocol-mandated reporting period ended. - Analysis detail pertaining to the assessment of antiromosozumab antibodies was modified to reflect the statistical analysis plan.

    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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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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