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    Clinical Trial Results:
    A Phase 3, Randomized, Double-blind, Parallel-group, Active-controlled Study to Compare the Efficacy, Safety, Pharmacodynamics, Pharmacokinetics and Immunogenicity of Enzene Denosumab (ENZ215) and Prolia®in Postmenopausal Women with Osteoporosis

    Summary
    EudraCT number
    		 2021-004811-26
    Trial protocol
    		 LT   DK   ES   BG   PL  
    Global end of trial date
    18 Jul 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    23 Oct 2025
    First version publication date
    23 Oct 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ALK22/ENZ215-DEN2
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05405725
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Alkem Laboratories Ltd.
    Sponsor organisation address
    ALKEM HOUSE, "Devashish", Adjacent to Matulya centre, Senapati Bapat Marg, Lower Parel, Mumbai, India, 400013
    Public contact
    Sharma Akhilesh, Alkem Laboratories Ltd, Mumbai, India, +91 22-39829999, Akhilesh.Sharma@alkem.com
    Scientific contact
    Sharma Akhilesh, Alkem Laboratories Ltd, Mumbai, India, +91 22-39829999, Akhilesh.Sharma@alkem.com
    Sponsor organisation name
    Enzene Biosciences Ltd.
    Sponsor organisation address
    Plot No. A-22/A/1/2,MIDC Chakan Industrial Area, Phase II, Vill-Khalumbre, Taluka Khed, Maharashtra, India, 410501
    Public contact
    Sharma Akhilesh, Alkem Laboratories Ltd., Mumbai, India, +91 20-30674622, Akhilesh.Sharma@alkem.com
    Scientific contact
    Sharma Akhilesh, Alkem Laboratories Ltd, Mumbai, India, +91 20-30674622, Akhilesh.Sharma@alkem.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
    28 Oct 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Jul 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    • To evaluate the efficacy of ENZ215 when compared to Prolia® in patients with postmenopausal osteoporosis, in terms of change in BMD at the lumbar spine from baseline to Month 12 • To compare the AUEC of sCTX levels from baseline to Month 6
    Protection of trial subjects
    Safety & Efficacy data reviewed by DMC at predefined timepoints
    Background therapy
    		 Calcium and Vitamin D supplements
    Evidence for comparator
    		 Prolia® (denosumab) to be used as an active comparator; 60 mg/mL solution for injections in PFS for SC administration. EU marketing authorization holder: Amgen Europe B.V. Minervum 7061, 4817 ZK Breda, The Netherlands
    Actual start date of recruitment
    21 Feb 2022
    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
    Serbia: 39
    Country: Number of subjects enrolled
    Poland: 230
    Country: Number of subjects enrolled
    Spain: 2
    Country: Number of subjects enrolled
    Czechia: 134
    Country: Number of subjects enrolled
    Lithuania: 45
    Country: Number of subjects enrolled
    Bulgaria: 54
    Worldwide total number of subjects
    504
    EEA total number of subjects
    465
    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)
    204
    From 65 to 84 years
    300
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Of the 1,061 participants screened for the study, 504 were randomized (253 to ENZ215 and 251 to Prolia®); all these participants were treated. 469 participants overall (93.1%) completed the double-blind treatment period (233 participants [92.1%] in the ENZ215 group and 236 participants [94.0%] in the Prolia group) and 35 participants discontinued.

    Pre-assignment
    Screening details
    		 1) Postmenopausal women aged ≥ 55 and ≤ 85 years; 2) Body weight ≥ 50 kg and ≤ 90 kg; 3) Diagnosed with osteoporosis, with absolute BMD consistent with T-scores of ≤-2.5 and ≥- 4.0 at the lumbar spine (L1-L4 region) as measured by dual-energy X ray absorptiometry (DXA) at screening; 4) At least 5 years of postmenopausal status confirmed by FSH.

    Pre-assignment period milestones
    Number of subjects started
    		 1061 [1]
    Intermediate milestone: Number of subjects
    Participants who failed screening: 557
    Intermediate milestone: Number of subjects
    Participants randomized: 504
    Number of subjects completed
    		 504

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Not meeting criteria: 527
    Reason: Number of subjects
    		 other: 30
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Indicated number of patients is a total of patients from screened group, 557 doesn't qualify the Inclusion/exclusion criteria and 504 patients were randomized for participation in the trial.
    Period 1
    Period 1 title
    Double-blind treatment period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Assessor
    Blinding implementation details
    This is a double-blind study (till Month 12) in which patients and Investigators are blinded to study intervention. The IRT has been programmed with blind-breaking instructions. After double-blind part (first 12 months) study analysis were carried out.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Biosimilar Denosumab (ENZ215)
    Arm description
    		 Participants received 60 mg ENZ215 on Day 1 and Month 6 as a subcutaneous injection during the double blind treatment period
    Arm type
    		 Experimental

    Investigational medicinal product name
    Biosimilar Denosumab (ENZ215)
    Investigational medicinal product code
    Other name
    Enzene Denosumab
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    60 mg/mL PFS, solution for injections, for SC administration

    Arm title
    		 Prolia®
    Arm description
    		 Participants received 60 mg Prolia® on Day 1 and Month 6 as a subcutaneous injection during the double blind treatment period.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Prolia®
    Investigational medicinal product code
    Other name
    Denosumab
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    60 mg/mL solution for injection in PFS; for SC administration

    Number of subjects in period 1
    		Biosimilar Denosumab (ENZ215) Prolia®
    Started
    253
    251
    FPFV
    253
    251
    LPLV
    239
    236
    Data Base Lock
    253
    251
    CSR Finalization
    253
    251
    Completed
    233
    236
    Not completed
    20
    15
         Consent withdrawn by subject
    14
    10
         personal reason
    2
    1
         Physician decision
    -
    1
         death
    -
    1
         Adverse event, non-fatal
    1
    2
         Protocol deviation
    3
    -
    Period 2
    Period 2 title
    Open-label extension period
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Biosimilar Denosumab (ENZ215)
    Arm description
    		 A subset of participants in Prolia® arm who completed the double-blind treatment period, were randomized to receive 60 mg ENZ215 at Month 12 as a subcutaneous injection during the open-label, switch-over period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Biosimilar Denosumab (ENZ215)
    Investigational medicinal product code
    Other name
    Enzene Denosumab
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    60 mg/mL solutions for injection in PFS; for SC administration

    Arm title
    		 Prolia®
    Arm description
    		 A subset of participants in Prolia® arm who completed the double-blind treatment period, were randomized to receive 60 mg Prolia® at Month 12 as a subcutaneous injection during the open-label, switch-over period.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Prolia®
    Investigational medicinal product code
    Other name
    Denosumab
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    60 mg/mL solution for injection in PFS; for SC administration

    Number of subjects in period 2 [2]
    		Biosimilar Denosumab (ENZ215) Prolia®
    Started
    60
    60
    Completed
    60
    60
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Open label extension planned for 120 Patients from Prolia group, 60 in ENZ215 arm and 60 in Prolia Arm

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Biosimilar Denosumab (ENZ215)
    Reporting group description
    		 Participants received 60 mg ENZ215 on Day 1 and Month 6 as a subcutaneous injection during the double blind treatment period

    Reporting group title
    Prolia®
    Reporting group description
    		 Participants received 60 mg Prolia® on Day 1 and Month 6 as a subcutaneous injection during the double blind treatment period.

    Reporting group values
    		 Biosimilar Denosumab (ENZ215) Prolia® Total
    Number of subjects
    		 253 251 504
    Age categorical
    Units: Subjects
        ≥55 to < 70 years
    		 171 171 342
        ≥70 to ≤ 85 years
    		 82 80 162
    Age continuous
    Units: years
        median (full range (min-max))
    		 66.0 (55 to 84) 66.0 (55 to 82) -
    Gender categorical
    only female
    Units: Subjects
        Female
    		 253 251 504
    Prior use of Bisphosphonate
    Units: Subjects
        yes
    		 44 43 87
        no
    		 209 208 417
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 0 1 1
        Not Hispanic or Latino
    		 253 250 503
        Not stated
    		 0 0 0
    Race
    Units: Subjects
        White
    		 253 251 504
        Black or African American
    		 0 0 0
    Years since menopause
    Units: number
        median (full range (min-max))
    		 17.0 (5 to 40) 17.0 (5 to 42) -
    Subject analysis sets

    Subject analysis set title
    ITT Set
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The ITT analysis set consisted of all randomized participants who received at least one dose of study intervention in the double-blind treatment period. In the ITT analysis set, treatment was assigned based on the study intervention to which participants were randomized, regardless of which treatment they actually received.

    Subject analysis sets values
    		 ITT Set
    Number of subjects
    504
    Age categorical
    Units: Subjects
        ≥55 to < 70 years
    342
        ≥70 to ≤ 85 years
    162
    Age continuous
    Units: years
        median (full range (min-max))
    66.0 (55 to 84)
    Gender categorical
    only female
    Units: Subjects
        Female
    504
    Prior use of Bisphosphonate
    Units: Subjects
        yes
    87
        no
    417
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    1
        Not Hispanic or Latino
    503
        Not stated
    0
    Race
    Units: Subjects
        White
    504
        Black or African American
    0
    Years since menopause
    Units: number
        median (full range (min-max))
    17.0 (5 to 42)

    End points

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    End points reporting groups
    Reporting group title
    Biosimilar Denosumab (ENZ215)
    Reporting group description
    		 Participants received 60 mg ENZ215 on Day 1 and Month 6 as a subcutaneous injection during the double blind treatment period

    Reporting group title
    Prolia®
    Reporting group description
    		 Participants received 60 mg Prolia® on Day 1 and Month 6 as a subcutaneous injection during the double blind treatment period.
    Reporting group title
    Biosimilar Denosumab (ENZ215)
    Reporting group description
    		 A subset of participants in Prolia® arm who completed the double-blind treatment period, were randomized to receive 60 mg ENZ215 at Month 12 as a subcutaneous injection during the open-label, switch-over period.

    Reporting group title
    Prolia®
    Reporting group description
    		 A subset of participants in Prolia® arm who completed the double-blind treatment period, were randomized to receive 60 mg Prolia® at Month 12 as a subcutaneous injection during the open-label, switch-over period.

    Subject analysis set title
    ITT Set
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The ITT analysis set consisted of all randomized participants who received at least one dose of study intervention in the double-blind treatment period. In the ITT analysis set, treatment was assigned based on the study intervention to which participants were randomized, regardless of which treatment they actually received.

    Primary: AUEC of sCTX over the initial 6 months (from Day 1 pre-dose to Month 6 pre-dose)

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    End point title
    		 AUEC of sCTX over the initial 6 months (from Day 1 pre-dose to Month 6 pre-dose)
    End point description
    AUEC of sCTX over the initial 6 months (from Day 1 pre-dose to Month 6 pre-dose)
    End point type
    Primary
    End point timeframe
    6 month
    End point values
    		 Biosimilar Denosumab (ENZ215) Prolia®
    Number of subjects analysed
    234
    237
    Units: percentage change
        geometric mean (confidence interval 95%)
    347382.787 (340087.2488 to 354834.8289)
    345858.423 (338640.7259 to 353229.9557)
    Statistical analysis title
    		 Double-blind treatment period Analysis Set
    Comparison groups
    Biosimilar Denosumab (ENZ215) v Prolia®
    Number of subjects included in analysis
    471
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 ≥ 0.05
    Method
    		 ANCOVA
    Parameter type
    		 Ratio of Geometric Means
    Point estimate
    1.004
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9748
         upper limit
    		 1.0349

    Primary: Percentage change in BMD at lumbar spine (L1-L4 region) measured by DXA from baseline to Month 12

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    End point title
    		 Percentage change in BMD at lumbar spine (L1-L4 region) measured by DXA from baseline to Month 12
    End point description
    The primary endpoint analysis (using a treatment policy estimand in the ITT set) demonstrated equivalence of ENZ215 compared to Prolia® for the percentage change in BMD at lumbar spine (L1-L4 region) measured by DXA from baseline to Month 12: adjusted LS mean (95% CI) of 5.350 (4.7306; 5.9695) in the ENZ215 group and 5.533 (4.9225; 6.1440) in the Prolia group; LS mean difference (95% CI) of -0.183 (-0.9044; 0.5380). Overall, 12 participants (2.4%) experienced ICE1 (defined as “significant BMD assessment delays for > 35 days at Visit 9 [Month 12]”): six participants (2.4%) in each treatment group. Overall, nine participants (1.8%) experienced ICE2 (defined as “participant received other medication alongside the IP, which affected the primary variable [prohibited medications]”): six participants (2.4%) in the ENZ215 group and three participants (1.2%) in the Prolia group.
    End point type
    Primary
    End point timeframe
    from start of baseline double-blind treatment period (therapy) to Month 12
    End point values
    		 Biosimilar Denosumab (ENZ215) Prolia®
    Number of subjects analysed
    231
    235
    Units: mean
        least squares mean (confidence interval 95%)
    5.530 (4.7306 to 5.9695)
    5.533 (4.9225 to 6.1440)
    Statistical analysis title
    		 Mixed Model Repeated Measures
    Statistical analysis description
    Analysis was performed with a mixed model repeated measures model with observed %CfB in lumbar spine BMD as the dependent variable model including treatment, age strata, previous treatment with bisphosphonate, visit*treatment interaction and baseline BMD value as covariates.
    Comparison groups
    Prolia® v Biosimilar Denosumab (ENZ215)
    Number of subjects included in analysis
    466
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    Parameter type
    		 LS mean difference
    Point estimate
    -0.183
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9044
         upper limit
    		 0.538

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the signing of informed consent until the end of the study. Overall, 321 participants (63.7%) experienced 834 TEAEs during the double-blind treatment period. Overall, 46 participants (38.3%) experienced 66 TEAEs during the open-label extension.
    Adverse event reporting additional description
    There was a similar percentage of participants in ENZ215 group and Prolia group who experienced TEAEs, severe TEAEs, study treatment-related TEAEs, TESAEs, treatment-emergent AESIs and TEAEs leading to treatment withdrawal -mild or moderate in severity. There was one SUSAR and one AE/TEAE leading to death, both of which were reported in Prolia.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    ENZ215 Double-blind Treatment Period
    Reporting group description
    		 Participants received 60 mg ENZ215 on Day 1 and Month 6 as a subcutaneous injection during the double blind treatment period.

    Reporting group title
    Prolia® Double-Blind Treatment period
    Reporting group description
    		 Participants received 60 mg Prolia® on Day 1 and Month 6 as a subcutaneous injection during the double blind treatment period.

    Reporting group title
    ENZ215 Open Label Treatment Period
    Reporting group description
    		 A subset of participants in Prolia® arm who completed the double-blind treatment period, were randomised to receive 60 mg ENZ215 at Month 12 as a subcutaneous injection during the open-label, switch-over period.

    Reporting group title
    Prolia® Open Label treatment Period
    Reporting group description
    		 A subset of participants in Prolia® arm who completed the double-blind treatment period, were randomised to receive 60 mg Prolia® at Month 12 as a subcutaneous injection during the open-label, switch-over period.

    Serious adverse events
    		 ENZ215 Double-blind Treatment Period Prolia® Double-Blind Treatment period ENZ215 Open Label Treatment Period Prolia® Open Label treatment Period
    Total subjects affected by serious adverse events
         subjects affected / exposed
    16 / 253 (6.32%)
    15 / 251 (5.98%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         number of deaths (all causes)
    0
    1
    0
    0
         number of deaths resulting from adverse events
    0
    1
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (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 / 253 (0.00%)
    1 / 251 (0.40%)
    0 / 60 (0.00%)
    0 / 60 (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
    Breast cancer
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 251 (0.40%)
    0 / 60 (0.00%)
    0 / 60 (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
    Chromophobe renal cell carcinoma
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 251 (0.40%)
    0 / 60 (0.00%)
    0 / 60 (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
    Meningioma benign
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 251 (0.40%)
    0 / 60 (0.00%)
    0 / 60 (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
    Investigations
    Red blood cells urine positive
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 251 (0.40%)
    0 / 60 (0.00%)
    0 / 60 (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
    Injury, poisoning and procedural complications
    Radius fracture
         subjects affected / exposed
    3 / 253 (1.19%)
    1 / 251 (0.40%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    1 / 253 (0.40%)
    1 / 251 (0.40%)
    0 / 60 (0.00%)
    0 / 60 (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
    Wrist fracture
         subjects affected / exposed
    2 / 253 (0.79%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Craniofacial fracture
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 251 (0.40%)
    0 / 60 (0.00%)
    0 / 60 (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
    Foot fracture
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 251 (0.40%)
    0 / 60 (0.00%)
    0 / 60 (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
    Forearm fracture
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 251 (0.40%)
    0 / 60 (0.00%)
    0 / 60 (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
    Fracture displacement
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (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
    Humerus fracture
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (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
    Lower limb fracture
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 251 (0.40%)
    0 / 60 (0.00%)
    0 / 60 (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
    Meniscus injury
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (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
    Ulna fracture
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (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
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 251 (0.40%)
    0 / 60 (0.00%)
    0 / 60 (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
    Aortic valve stenosis
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (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
    Myocardial infarction
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 251 (0.40%)
    0 / 60 (0.00%)
    0 / 60 (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
    Pericarditis
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (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
    Nervous system disorders
    Ischaemic cerebral infarction
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (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
    Myasthenia gravis
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (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
    Thoracic radiculopathy
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 251 (0.40%)
    0 / 60 (0.00%)
    0 / 60 (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
    Gastrointestinal disorders
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (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
    Reproductive system and breast disorders
    Genital prolapse
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (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
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 251 (0.40%)
    0 / 60 (0.00%)
    0 / 60 (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
    SAPHO syndrome
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (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
    Infections and infestations
    COVID-19
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 251 (0.40%)
    0 / 60 (0.00%)
    0 / 60 (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 / 1
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 251 (0.40%)
    0 / 60 (0.00%)
    0 / 60 (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
    Diverticulitis
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (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
    Influenza
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (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
    Pneumonia
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (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
    Staphylococcal bacteraemia
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (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
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 ENZ215 Double-blind Treatment Period Prolia® Double-Blind Treatment period ENZ215 Open Label Treatment Period Prolia® Open Label treatment Period
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    115 / 253 (45.45%)
    122 / 251 (48.61%)
    23 / 60 (38.33%)
    23 / 60 (38.33%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign neoplasm
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Uterine leiomyoma
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    9 / 253 (3.56%)
    12 / 251 (4.78%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    9
    14
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    3 / 253 (1.19%)
    2 / 251 (0.80%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    3
    2
    0
    0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    Dyspnoea
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    Upper respiratory tract inflammation
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    Vitamin D decreased
         subjects affected / exposed
    6 / 253 (2.37%)
    6 / 251 (2.39%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    6
    6
    0
    0
    Injury, poisoning and procedural complications
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    Meniscus injury
         subjects affected / exposed
    3 / 253 (1.19%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    3
    0
    1
    0
    Thoracic vertebral fracture
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    Tooth fracture
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    Cardiac disorders
    Atrioventricular block first degree
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    Headache
         subjects affected / exposed
    6 / 253 (2.37%)
    13 / 251 (5.18%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    9
    16
    0
    0
    Radiculopathy
         subjects affected / exposed
    3 / 253 (1.19%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Neutropenia
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    3 / 253 (1.19%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Eye disorders
    Blepharochalasis
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Chalazion
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Glaucoma
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Diarrhoea
         subjects affected / exposed
    6 / 253 (2.37%)
    6 / 251 (2.39%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    6
    6
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    2 / 253 (0.79%)
    5 / 251 (1.99%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    2
    6
    0
    0
    Chronic gastritis
         subjects affected / exposed
    2 / 253 (0.79%)
    3 / 251 (1.20%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    2
    3
    0
    0
    Constipation
         subjects affected / exposed
    3 / 253 (1.19%)
    2 / 251 (0.80%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    3
    3
    0
    0
    Toothache
         subjects affected / exposed
    3 / 253 (1.19%)
    2 / 251 (0.80%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    3
    2
    0
    0
    Gastritis
         subjects affected / exposed
    5 / 253 (1.98%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    6
    0
    0
    0
    Nausea
         subjects affected / exposed
    0 / 253 (0.00%)
    3 / 251 (1.20%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Hepatobiliary disorders
    Hepatic steatosis
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Endocrine disorders
    Autoimmune thyroiditis
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    1
    1
    Osteoarthritis
         subjects affected / exposed
    8 / 253 (3.16%)
    4 / 251 (1.59%)
    1 / 60 (1.67%)
    1 / 60 (1.67%)
         occurrences all number
    9
    4
    1
    1
    Spinal pain
         subjects affected / exposed
    5 / 253 (1.98%)
    4 / 251 (1.59%)
    2 / 60 (3.33%)
    0 / 60 (0.00%)
         occurrences all number
    7
    4
    2
    0
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Shoulder girdle pain
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    Arthralgia
         subjects affected / exposed
    9 / 253 (3.56%)
    9 / 251 (3.59%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    9
    13
    0
    0
    Back pain
         subjects affected / exposed
    6 / 253 (2.37%)
    6 / 251 (2.39%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    9
    6
    0
    0
    Muscle spasms
         subjects affected / exposed
    2 / 253 (0.79%)
    3 / 251 (1.20%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    3
    3
    0
    0
    Pain in extremity
         subjects affected / exposed
    3 / 253 (1.19%)
    2 / 251 (0.80%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    3
    2
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    18 / 253 (7.11%)
    22 / 251 (8.76%)
    5 / 60 (8.33%)
    5 / 60 (8.33%)
         occurrences all number
    21
    24
    6
    5
    Bronchitis
         subjects affected / exposed
    11 / 253 (4.35%)
    6 / 251 (2.39%)
    0 / 60 (0.00%)
    2 / 60 (3.33%)
         occurrences all number
    12
    6
    0
    2
    COVID-19
         subjects affected / exposed
    5 / 253 (1.98%)
    12 / 251 (4.78%)
    1 / 60 (1.67%)
    1 / 60 (1.67%)
         occurrences all number
    5
    12
    1
    1
    Pharyngitis
         subjects affected / exposed
    6 / 253 (2.37%)
    3 / 251 (1.20%)
    2 / 60 (3.33%)
    0 / 60 (0.00%)
         occurrences all number
    7
    3
    2
    0
    Upper respiratory tract infection
         subjects affected / exposed
    11 / 253 (4.35%)
    16 / 251 (6.37%)
    2 / 60 (3.33%)
    0 / 60 (0.00%)
         occurrences all number
    13
    19
    2
    0
    Gastroenteritis
         subjects affected / exposed
    5 / 253 (1.98%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    6
    0
    0
    1
    Herpes zoster
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Influenza
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    Lyme disease
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pneumonia
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Sinusitis
         subjects affected / exposed
    3 / 253 (1.19%)
    4 / 251 (1.59%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    3
    4
    1
    0
    Tracheobronchitis
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    Viral infection
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    8 / 253 (3.16%)
    8 / 251 (3.19%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    8
    9
    0
    0
    Cystitis
         subjects affected / exposed
    5 / 253 (1.98%)
    6 / 251 (2.39%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    5
    6
    0
    0
    Urinary tract infection bacterial
         subjects affected / exposed
    3 / 253 (1.19%)
    5 / 251 (1.99%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    4
    5
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    1 / 253 (0.40%)
    5 / 251 (1.99%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    6
    0
    0
    Oral herpes
         subjects affected / exposed
    2 / 253 (0.79%)
    3 / 251 (1.20%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    2
    3
    0
    0
    Pulpitis dental
         subjects affected / exposed
    1 / 253 (0.40%)
    3 / 251 (1.20%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    3
    0
    0
    Bronchitis bacterial
         subjects affected / exposed
    3 / 253 (1.19%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Respiratory tract infection viral
         subjects affected / exposed
    3 / 253 (1.19%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    4
    0
    0
    0
    Metabolism and nutrition disorders
    Hypomagnesaemia
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    1
    1
    Dyslipidaemia
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 251 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    Hypocalcaemia
         subjects affected / exposed
    7 / 253 (2.77%)
    6 / 251 (2.39%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    7
    6
    0
    0
    Vitamin D deficiency
         subjects affected / exposed
    6 / 253 (2.37%)
    4 / 251 (1.59%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    6
    4
    0
    0
    Hypercalcaemia
         subjects affected / exposed
    2 / 253 (0.79%)
    4 / 251 (1.59%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    2
    4
    0
    0
    Hyperlipidaemia
         subjects affected / exposed
    3 / 253 (1.19%)
    1 / 251 (0.40%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    3
    1
    0
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Dec 2021
    Global Protocol Amendment 1 dated 16 December 2021 [Protocol version1.1] - NS: 1) Change in address of the Co Sponsor; 2) Clarifications in section 5.2 Exclusion Criteria: Exclusion criteria #13 was changed from “Total hip or femoral neck T-score <4.0” to “Total hip or femoral neck T score <−4.0”
    08 Apr 2022
    Global Protocol Amendment 2 dated 08 April 2022 [Protocol version 2.0] - NS: This amendment is considered to be non-substantial based on the criteria set forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the European Union because it neither significantly impacts the safety or physical/mental integrity of participants nor the scientific value of the study. The Global clinical study protocol (CSP) Amendment 2 was prepared in response to queries from the regulatory authority in Czech Republic.
    27 Jul 2022
    Country Specific (SPAIN) Protocol Amendment 2.1 dated 27 July 2022 - SM: has been prepared for resubmission after study rejection by Spanish Regulatory Authorities: 1) Section 5.1 Inclusion Criteria: Inclusion criteria #2 for Spain: a) Postmenopausal women aged ≥ 70 years with LS T-score is ≤-2.5 and ≥ 4.0 or b) Postmenopausal women aged ≥ 55 and < 70 years with either i) LS T-score ≤ -3.0 and ≥ 4.0 or ii) LS T-score is ≤ -2.5 and > 3.0 and they have a prior fragility fracture (except for hip fracture), including non-exclusionary vertebral fractures. 2) Section 8.2.2 Vital Signs: The following text: “Oral temperature, heart rate, respiratory rate, and blood pressure will be assessed” has been updated to “Body temperature, heart rate, respiratory rate, and blood pressure will be assessed.” 3)
    19 Oct 2022
    Country Specific (SPAIN) Protocol Amendment 2.2 dated 19 October 2022 [Protocol Version 2.2]: SM This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the European Union. The clinical study protocol (CSP) Amendment 2.2 was prepared in response to queries from the regulatory authority in Spain. 1) Section 5.1 Inclusion Criteria: Inclusion criteria #2: Postmenopausal women aged ≥ 55 and ≤ 85 years globally, except for Spain. In Spain specifically refer to the below criteria: a. Postmenopausal women aged ≥ 75 and ≤ 85 years with LS T-score ≤ -2.5 or b. Postmenopausal women aged ≥ 65 and < 75 years with LS T-score is ≤ -2.5 and a prior fragility fracture (except for hip fracture), including non-exclusionary vertebral fractures c. In both cases (i.e. criteria a and b), it must also be that these are women who present a contraindication for the use of bisphosphonates or who do not tolerate the oral route.
    16 Feb 2023
    Global Protocol Amendment 3 dated 16 February 2023 - NS: This amendment is non-substantial based on the criteria set forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the European Union because it neither significantly impacts the safety or physical/mental integrity of participants nor the scientific value of the study. The Global clinical study protocol (CSP) Amendment 3.0 was prepared to add clarifications and update typo errors noted in earlier version of the document.

    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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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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