Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

    The EU Clinical Trials Register currently displays   44020   clinical trials with a EudraCT protocol, of which   7318   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Optimising Vitamin D Status in Older People: A Randomised Controlled Trial of Vitamin D Supplementation

    Summary
    EudraCT number
    		 2011-004890-10
    Trial protocol
    		 GB  
    Global end of trial date
    05 Jun 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    05 Aug 2016
    First version publication date
    05 Aug 2016
    Other versions
    Summary report(s)
    		 test

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    5907
    Additional study identifiers
    ISRCTN number
    		 ISRCTN35648481
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 REC Reference: 12/NE/0050
    Sponsors
    Sponsor organisation name
    The Newcastle upon Tyne Hospitals NHS Foundation Trust
    Sponsor organisation address
    Level 1, Regent Point, Regent Farm Road , Gosforth, Newcastle Upon Tyne,, United Kingdom, NE3 3HD
    Public contact
    Newcastle University , Dr Terry J. Aspray , 0044 191 223 1160, t.j.aspray@newcastle.ac.uk
    Scientific contact
    Newcastle University , Dr Terry J. Aspray , 0044 191 223 1160, t.j.aspray@newcastle.ac.uk
    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
    19 May 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    05 Jun 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Jun 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Primary Objective: We aim to establish the effects of three doses of vitamin D supplement, given for 12 months on the change in bone mineral density (BMD) to indicate a beneficial effect on bone health.
    Protection of trial subjects
    No actions required
    Background therapy
    		 No background therapy, ambulant, community dwelling men and women aged 70 years and above
    Evidence for comparator
    		 N/A
    Actual start date of recruitment
    08 Nov 2012
    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
    United Kingdom: 379
    Worldwide total number of subjects
    379
    EEA total number of subjects
    379
    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)
    0
    From 65 to 84 years
    367
    85 years and over
    12

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were recruited through General Practices participating in the Primary Care Research Network – Northern and Yorkshire (PCRN-NY). Invitation letters were sent to potential recruits, identified from the GP age-sex registers.

    Pre-assignment
    Screening details
    		 A member of the research team contacted the participant by telephone to ensured that the participant understood the study, answered any questions the participant had and confirmed eligibility. Subsequently scheduled a first study visit to provide informed consent, a screening safety blood sample to confirm eligibility and safety to take part.

    Pre-assignment period milestones
    Number of subjects started
    		 379
    Number of subjects completed
    		 374

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Protocol deviation: 5
    Period 1
    Period 1 title
    Baseline
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    Randomisation was conducted by the Newcastle Clinical Trials Unit (NCTU) web based system. Patients were randomised in a 1:1:1 ratio to vitamin D 12,000 IU, 24,000 IU or 48,000 IU (Figure 1).A computer-generated allocation list of random permuted blocks was used to appropriate allocation. No unblinding was required during the study, and all code break envelopes were present at the study pharmacy close-out visit.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 12,000 IU
    Arm description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 12,000 IU of vitamin D
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vigantol®
    Investigational medicinal product code
    200106 or EMD 28162
    Other name
    Vigantol Oel
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    The vitamin D3 preparation was a liquid, containing 20,000 IU/ml of vitamin D3 (Vigantol) which was mixed with Miglyol oil, which contains no vitamin D3. Both will be provided by MODE Pharma, UK. Participants in this arm received 0.6 ml Vigantol and 1.8 ml Miglyol oil once a month over the 12 month period.

    Arm title
    		 24,000 IU
    Arm description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 24,000 IU of vitamin D
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vigantol®
    Investigational medicinal product code
    200106 or EMD 28162
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    The vitamin D3 preparation was a liquid, containing 20,000 IU/ml of vitamin D3 (Vigantol) which was mixed with Miglyol oil, which contains no vitamin D3. Both will be provided by MODE Pharma, UK. Participants in this arm received 0.6 ml Vigantol and 1.8 ml Miglyol oil once a month over the 12 month period.

    Arm title
    		 48,000 IU
    Arm description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 48,000 IU of vitamin D
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vigantol®
    Investigational medicinal product code
    200106 or EMD 28162
    Other name
    Vigantol Oel
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    The vitamin D3 preparation was a liquid, containing 20,000 IU/ml of vitamin D3 (Vigantol) which was mixed with Miglyol oil, which contains no vitamin D3. Both will be provided by MODE Pharma, UK. Participants in this arm received 2.4 ml Vigantol oil once a month over the 12 month period.

    Number of subjects in period 1 [1]
    		12,000 IU 24,000 IU 48,000 IU
    Started
    122
    124
    128
    Completed
    122
    124
    128
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: 2 participants were randomised at screening visit but were found to be ineligible later during the visit and thus were withdrawn. 3 Participants changed their mind during baseline visit and withdrew
    Period 2
    Period 2 title
    0 - 3 months
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    Randomisation was conducted by the Newcastle Clinical Trials Unit (NCTU) web based system. Patients were randomised in a 1:1:1 ratio to vitamin D 12,000 IU, 24,000 IU or 48,000 IU (Figure 1).A computer-generated allocation list of random permuted blocks was used to appropriate allocation. No unblinding was required during the study, and all code break envelopes were present at the study pharmacy close-out visit.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 12,000 IU
    Arm description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 12,000 IU of vitamin D
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vigantol®
    Investigational medicinal product code
    200106 or EMD 28162
    Other name
    Vigantol Oel
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    The vitamin D3 preparation was a liquid, containing 20,000 IU/ml of vitamin D3 (Vigantol) which was mixed with Miglyol oil, which contains no vitamin D3. Both will be provided by MODE Pharma, UK. Participants in this arm received 0.6 ml Vigantol and 1.8 ml Miglyol oil once a month over the 12 month period.

    Arm title
    		 24,000 IU
    Arm description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 24,000 IU of vitamin D
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vigantol®
    Investigational medicinal product code
    200106 or EMD 28162
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    The vitamin D3 preparation was a liquid, containing 20,000 IU/ml of vitamin D3 (Vigantol) which was mixed with Miglyol oil, which contains no vitamin D3. Both will be provided by MODE Pharma, UK. Participants in this arm received 0.6 ml Vigantol and 1.8 ml Miglyol oil once a month over the 12 month period.

    Arm title
    		 48,000 IU
    Arm description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 48,000 IU of vitamin D
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vigantol®
    Investigational medicinal product code
    200106 or EMD 28162
    Other name
    Vigantol Oel
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    The vitamin D3 preparation was a liquid, containing 20,000 IU/ml of vitamin D3 (Vigantol) which was mixed with Miglyol oil, which contains no vitamin D3. Both will be provided by MODE Pharma, UK. Participants in this arm received 2.4 ml Vigantol oil once a month over the 12 month period.

    Number of subjects in period 2
    		12,000 IU 24,000 IU 48,000 IU
    Started
    122
    124
    128
    Completed
    121
    122
    124
    Not completed
    1
    2
    4
         Consent withdrawn by subject
    -
    2
    1
         Adverse event, non-fatal
    1
    -
    1
         Lost to follow-up
    -
    -
    1
         Protocol deviation
    -
    -
    1
    Period 3
    Period 3 title
    3 - 6 months
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    Randomisation was conducted by the Newcastle Clinical Trials Unit (NCTU) web based system. Patients were randomised in a 1:1:1 ratio to vitamin D 12,000 IU, 24,000 IU or 48,000 IU (Figure 1).A computer-generated allocation list of random permuted blocks was used to appropriate allocation. No unblinding was required during the study, and all code break envelopes were present at the study pharmacy close-out visit.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 12,000 IU
    Arm description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 12,000 IU of vitamin D
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vigantol®
    Investigational medicinal product code
    200106 or EMD 28162
    Other name
    Vigantol Oel
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    The vitamin D3 preparation was a liquid, containing 20,000 IU/ml of vitamin D3 (Vigantol) which was mixed with Miglyol oil, which contains no vitamin D3. Both will be provided by MODE Pharma, UK. Participants in this arm received 0.6 ml Vigantol and 1.8 ml Miglyol oil once a month over the 12 month period.

    Arm title
    		 24,000 IU
    Arm description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 24,000 IU of vitamin D
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vigantol®
    Investigational medicinal product code
    200106 or EMD 28162
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    The vitamin D3 preparation was a liquid, containing 20,000 IU/ml of vitamin D3 (Vigantol) which was mixed with Miglyol oil, which contains no vitamin D3. Both will be provided by MODE Pharma, UK. Participants in this arm received 0.6 ml Vigantol and 1.8 ml Miglyol oil once a month over the 12 month period.

    Arm title
    		 48,000 IU
    Arm description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 48,000 IU of vitamin D
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vigantol®
    Investigational medicinal product code
    200106 or EMD 28162
    Other name
    Vigantol Oel
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    The vitamin D3 preparation was a liquid, containing 20,000 IU/ml of vitamin D3 (Vigantol) which was mixed with Miglyol oil, which contains no vitamin D3. Both will be provided by MODE Pharma, UK. Participants in this arm received 2.4 ml Vigantol oil once a month over the 12 month period.

    Number of subjects in period 3
    		12,000 IU 24,000 IU 48,000 IU
    Started
    121
    122
    124
    Completed
    118
    117
    121
    Not completed
    3
    5
    3
         Adverse event, serious fatal
    1
    1
    -
         Consent withdrawn by subject
    1
    1
    2
         Adverse event, non-fatal
    1
    2
    1
         Protocol deviation
    -
    1
    -
    Period 4
    Period 4 title
    6 - 9 months
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    Randomisation was conducted by the Newcastle Clinical Trials Unit (NCTU) web based system. Patients were randomised in a 1:1:1 ratio to vitamin D 12,000 IU, 24,000 IU or 48,000 IU (Figure 1).A computer-generated allocation list of random permuted blocks was used to appropriate allocation. No unblinding was required during the study, and all code break envelopes were present at the study pharmacy close-out visit.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 12,000 IU
    Arm description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 12,000 IU of vitamin D
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vigantol®
    Investigational medicinal product code
    200106 or EMD 28162
    Other name
    Vigantol Oel
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    The vitamin D3 preparation was a liquid, containing 20,000 IU/ml of vitamin D3 (Vigantol) which was mixed with Miglyol oil, which contains no vitamin D3. Both will be provided by MODE Pharma, UK. Participants in this arm received 0.6 ml Vigantol and 1.8 ml Miglyol oil once a month over the 12 month period.

    Arm title
    		 24,000 IU
    Arm description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 24,000 IU of vitamin D
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vigantol®
    Investigational medicinal product code
    200106 or EMD 28162
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    The vitamin D3 preparation was a liquid, containing 20,000 IU/ml of vitamin D3 (Vigantol) which was mixed with Miglyol oil, which contains no vitamin D3. Both will be provided by MODE Pharma, UK. Participants in this arm received 0.6 ml Vigantol and 1.8 ml Miglyol oil once a month over the 12 month period.

    Arm title
    		 48,000 IU
    Arm description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 48,000 IU of vitamin D
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vigantol®
    Investigational medicinal product code
    200106 or EMD 28162
    Other name
    Vigantol Oel
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    The vitamin D3 preparation was a liquid, containing 20,000 IU/ml of vitamin D3 (Vigantol) which was mixed with Miglyol oil, which contains no vitamin D3. Both will be provided by MODE Pharma, UK. Participants in this arm received 2.4 ml Vigantol oil once a month over the 12 month period.

    Number of subjects in period 4
    		12,000 IU 24,000 IU 48,000 IU
    Started
    118
    117
    121
    Completed
    113
    116
    117
    Not completed
    5
    1
    4
         Consent withdrawn by subject
    2
    -
    3
         Adverse event, non-fatal
    3
    1
    1
    Period 5
    Period 5 title
    9 - 12 months
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    Randomisation was conducted by the Newcastle Clinical Trials Unit (NCTU) web based system. Patients were randomised in a 1:1:1 ratio to vitamin D 12,000 IU, 24,000 IU or 48,000 IU (Figure 1).A computer-generated allocation list of random permuted blocks was used to appropriate allocation. No unblinding was required during the study, and all code break envelopes were present at the study pharmacy close-out visit.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 12,000 IU
    Arm description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 12,000 IU of vitamin D
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vigantol®
    Investigational medicinal product code
    200106 or EMD 28162
    Other name
    Vigantol Oel
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    The vitamin D3 preparation was a liquid, containing 20,000 IU/ml of vitamin D3 (Vigantol) which was mixed with Miglyol oil, which contains no vitamin D3. Both will be provided by MODE Pharma, UK. Participants in this arm received 0.6 ml Vigantol and 1.8 ml Miglyol oil once a month over the 12 month period.

    Arm title
    		 24,000 IU
    Arm description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 24,000 IU of vitamin D
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vigantol®
    Investigational medicinal product code
    200106 or EMD 28162
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    The vitamin D3 preparation was a liquid, containing 20,000 IU/ml of vitamin D3 (Vigantol) which was mixed with Miglyol oil, which contains no vitamin D3. Both will be provided by MODE Pharma, UK. Participants in this arm received 0.6 ml Vigantol and 1.8 ml Miglyol oil once a month over the 12 month period.

    Arm title
    		 48,000 IU
    Arm description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 48,000 IU of vitamin D
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vigantol®
    Investigational medicinal product code
    200106 or EMD 28162
    Other name
    Vigantol Oel
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    The vitamin D3 preparation was a liquid, containing 20,000 IU/ml of vitamin D3 (Vigantol) which was mixed with Miglyol oil, which contains no vitamin D3. Both will be provided by MODE Pharma, UK. Participants in this arm received 2.4 ml Vigantol oil once a month over the 12 month period.

    Number of subjects in period 5
    		12,000 IU 24,000 IU 48,000 IU
    Started
    113
    116
    117
    Completed
    113
    114
    116
    Not completed
    0
    2
    1
         Adverse event, serious fatal
    -
    1
    -
         Consent withdrawn by subject
    -
    -
    1
         Adverse event, non-fatal
    -
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    12,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 12,000 IU of vitamin D

    Reporting group title
    24,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 24,000 IU of vitamin D

    Reporting group title
    48,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 48,000 IU of vitamin D

    Reporting group values
    		 12,000 IU 24,000 IU 48,000 IU Total
    Number of subjects
    		 122 124 128 374
    Age categorical
    Units: Subjects
        From 65-84 years
    		 118 119 122 359
        85 years and over
    		 4 5 6 15
    Age continuous
    Averga
    Units: years
        arithmetic mean (standard deviation)
    		 74.6 ± 3.9 75 ± 4.3 75.4 ± 4.4 -
    Gender categorical
    Units: Subjects
        Male
    		 57 59 65 181
        Female
    		 65 65 63 193
    BMD
    Bone Mineral Density at HIP (DEXA Scan)
    Units: g/cm2
        arithmetic mean (standard deviation)
    		 0.98 ± 0.155 0.987 ± 0.179 0.973 ± 0.187 -
    250HD
    Vitamin D as plasma 25OHD
    Units: nm/L
        arithmetic mean (standard deviation)
    		 41.38 ± 19.99 39.67 ± 20.64 38.87 ± 19.72 -
    fnBMD
    Femoral neck bone mineral density
    Units: g/cm2
        arithmetic mean (standard deviation)
    		 0.898 ± 0.138 0.915 ± 0.154 0.892 ± 0.163 -
    PTH
    Parathyroid hormone
    Units: g/ml
        arithmetic mean (standard deviation)
    		 48.28 ± 25.66 47.49 ± 23.38 49.96 ± 21.27 -
    CTX
    C-terminal telopeptide (CTX),
    Units: ng/ml
        arithmetic mean (standard deviation)
    		 0.41 ± 0.17 0.41 ± 0.19 0.4 ± 0.19 -
    bone ALP
    bone specific alkaline phosphatase (bone ALP)
    Units: g/L
        arithmetic mean (standard deviation)
    		 10.28 ± 3.72 10.82 ± 3.79 9.99 ± 3.19 -
    P1NP
    N-terminal propeptide of procollagen type I (P1NP)
    Units: ug/L
        arithmetic mean (standard deviation)
    		 41.15 ± 18.22 39.26 ± 15.55 39.37 ± 16.16 -
    Weight
    in Kg
    Units: kg
        arithmetic mean (standard deviation)
    		 73.87 ± 11.93 77.21 ± 14.53 76.11 ± 14.23 -
    Height
    measures in cm
    Units: cm
        arithmetic mean (standard deviation)
    		 167.22 ± 8.07 167.09 ± 9.86 167.39 ± 10.01 -
    BMI
    derrived
    Units: kg/m2
        arithmetic mean (standard deviation)
    		 26.4 ± 3.66 27.56 ± 4.12 27.08 ± 3.97 -
    Fat mass
    Units: kg
        arithmetic mean (standard deviation)
    		 23.94 ± 8.48 25.49 ± 8.24 24.91 ± 8.31 -
    Free fat mass
    Units: kg
        arithmetic mean (standard deviation)
    		 49.87 ± 8.96 51.66 ± 10.71 50.67 ± 10.86 -
    Subject analysis sets

    Subject analysis set title
    End of Study
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    See protocol for details http://www.ncbi.nlm.nih.gov/pubmed/24041337

    Subject analysis sets values
    		 End of Study
    Number of subjects
    374
    Age categorical
    Units: Subjects
        From 65-84 years
        85 years and over
    Age continuous
    Averga
    Units: years
        arithmetic mean (standard deviation)
    ±
    Gender categorical
    Units: Subjects
        Male
    181
        Female
    193
    BMD
    Bone Mineral Density at HIP (DEXA Scan)
    Units: g/cm2
        arithmetic mean (standard deviation)
    ±
    250HD
    Vitamin D as plasma 25OHD
    Units: nm/L
        arithmetic mean (standard deviation)
    ±
    fnBMD
    Femoral neck bone mineral density
    Units: g/cm2
        arithmetic mean (standard deviation)
    ±
    PTH
    Parathyroid hormone
    Units: g/ml
        arithmetic mean (standard deviation)
    ±
    CTX
    C-terminal telopeptide (CTX),
    Units: ng/ml
        arithmetic mean (standard deviation)
    ±
    bone ALP
    bone specific alkaline phosphatase (bone ALP)
    Units: g/L
        arithmetic mean (standard deviation)
    ±
    P1NP
    N-terminal propeptide of procollagen type I (P1NP)
    Units: ug/L
        arithmetic mean (standard deviation)
    ±
    Weight
    in Kg
    Units: kg
        arithmetic mean (standard deviation)
    ±
    Height
    measures in cm
    Units: cm
        arithmetic mean (standard deviation)
    ±
    BMI
    derrived
    Units: kg/m2
        arithmetic mean (standard deviation)
    ±
    Fat mass
    Units: kg
        arithmetic mean (standard deviation)
    ±
    Free fat mass
    Units: kg
        arithmetic mean (standard deviation)
    ±

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    12,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 12,000 IU of vitamin D

    Reporting group title
    24,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 24,000 IU of vitamin D

    Reporting group title
    48,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 48,000 IU of vitamin D
    Reporting group title
    12,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 12,000 IU of vitamin D

    Reporting group title
    24,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 24,000 IU of vitamin D

    Reporting group title
    48,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 48,000 IU of vitamin D
    Reporting group title
    12,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 12,000 IU of vitamin D

    Reporting group title
    24,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 24,000 IU of vitamin D

    Reporting group title
    48,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 48,000 IU of vitamin D
    Reporting group title
    12,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 12,000 IU of vitamin D

    Reporting group title
    24,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 24,000 IU of vitamin D

    Reporting group title
    48,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 48,000 IU of vitamin D
    Reporting group title
    12,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 12,000 IU of vitamin D

    Reporting group title
    24,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 24,000 IU of vitamin D

    Reporting group title
    48,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 48,000 IU of vitamin D

    Subject analysis set title
    End of Study
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    See protocol for details http://www.ncbi.nlm.nih.gov/pubmed/24041337

    Primary: Change in BMD

    		 Close Top of page
    End point title
    		 Change in BMD
    End point description
    Bone Minderal Density at HIP (DEXA Scan) The difference in BMD between baseline and 12 months derived by subtracting baseline from 12m value per individual
    End point type
    Primary
    End point timeframe
    12 months
    End point values
    		 12,000 IU 24,000 IU 48,000 IU
    Number of subjects analysed
    109 [1]
    106 [2]
    112 [3]
    Units: g/cm2
        arithmetic mean (standard deviation)
    -0.001 ± 0.013
    -0.003 ± 0.018
    -0.005 ± 0.016
    Notes
    [1] - Data not available for all subjects
    [2] - Data not available for all subjects
    [3] - Data not available for all subjects
    Statistical analysis title
    		 Change in BMD from baseline to 12 months
    Statistical analysis description
    To compare the response in the three treatment groups while allowing for the effects of baseline covariates. Baseline BMD at hip, parathyroid hormone in plasma and plasma concentration of 25OHD, lean mass, fat mass estimated glomerular filtration rate (GFR) will be included amongst those under consideration in addition to baseline FRAX score, measures of kidney function, weight and height, gender and age. The inclusion of interaction terms will also be explored.
    Comparison groups
    12,000 IU v 24,000 IU v 48,000 IU
    Number of subjects included in analysis
    327
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.0535 [4]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [4] - Final model adjusted for baseline bmd, gender, age, weight and height

    Secondary: Change in 250HD

    		 Close Top of page
    End point title
    		 Change in 250HD
    End point description
    Vitamin D as plasma 25OHD The difference in 25OHD between baseline and 12 months derived by subtracting baseline from 12m value per individual
    End point type
    Secondary
    End point timeframe
    12 Months
    End point values
    		 12,000 IU 24,000 IU 48,000 IU
    Number of subjects analysed
    112 [5]
    113 [6]
    113 [7]
    Units: nm/L
        arithmetic mean (standard deviation)
    14.27 ± 12.63
    25.32 ± 18.02
    40.58 ± 19.88
    Notes
    [5] - Data not available for all subjects
    [6] - Data not available for all subjects
    [7] - Data not available for all subjects
    Statistical analysis title
    		 Change in 25OHD from baseline to 12 months
    Statistical analysis description
    The ANCOVA model derived for the primary outcome analysis will be used. Consideration will be given to the inclusion of baseline 25OHD in addition if this was not included in the final model for the primary outcome. Significance of this term for inclusion in the final model will be assessed as described previously.
    Comparison groups
    12,000 IU v 24,000 IU v 48,000 IU
    Number of subjects included in analysis
    338
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [8]
    P-value
    		 > 0.001
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [8] - Final model adjusted for baseline 25OHD, gender, age, weight and height

    Secondary: Change in fnBMD

    		 Close Top of page
    End point title
    		 Change in fnBMD
    End point description
    Femoral-neck bone mineral density The difference fnBMD between baseline and 12 months derived by subtracting baseline from 12m value per individual
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 12,000 IU 24,000 IU 48,000 IU
    Number of subjects analysed
    110 [9]
    110 [10]
    111 [11]
    Units: g/cm2
        arithmetic mean (standard deviation)
    0.002 ± 0.02
    0 ± 0.023
    0.001 ± 0.021
    Notes
    [9] - Data not available for all subjects
    [10] - Data not available for all subjects
    [11] - Data not available for all subjects
    Statistical analysis title
    		 Change in fnBMD
    Statistical analysis description
    The ANCOVA model derived for the primary outcome analysis will be used. Consideration will be given to the inclusion of baseline fnBMD in addition if this was not included in the final model for the primary outcome. Significance of this term for inclusion in the final model will be assessed as described previously.
    Comparison groups
    12,000 IU v 24,000 IU v 48,000 IU
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [12]
    P-value
    		 > 0.02
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [12] - Final model adjusted for baseline fnBMD, baseline PTH, gender, age, weight and height

    Secondary: Change in PTH

    		 Close Top of page
    End point title
    		 Change in PTH
    End point description
    Parathyroid hormone The difference in PTH between baseline and 12 months derived by subtracting baseline from 12m value per individual
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 12,000 IU 24,000 IU 48,000 IU
    Number of subjects analysed
    112 [13]
    113 [14]
    113 [15]
    Units: pg/ml
        arithmetic mean (standard deviation)
    -2.92 ± 18.39
    -2.92 ± 18.14
    -10.56 ± 15.4
    Notes
    [13] - Data not available for all subjects
    [14] - Data not available for all subjects
    [15] - Data not available for all subjects
    Statistical analysis title
    		 Change in PTH
    Statistical analysis description
    The ANCOVA model derived for the primary outcome analysis will be used. Consideration will be given to the inclusion of baseline PTH in addition if this was not included in the final model for the primary outcome. Significance of this term for inclusion in the final model will be assessed as described previously.
    Comparison groups
    24,000 IU v 48,000 IU v 12,000 IU
    Number of subjects included in analysis
    338
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [16]
    P-value
    		 > 0.001
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [16] - Final model adjusted for baseline PTH, gender, age, weight and height.

    Secondary: Change in CTX

    		 Close Top of page
    End point title
    		 Change in CTX
    End point description
    Change in C-terminal telopeptide The difference in CTX between baseline and 12 months derived by subtracting baseline from 12m value per individual
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 12,000 IU 24,000 IU 48,000 IU
    Number of subjects analysed
    112 [17]
    113 [18]
    114 [19]
    Units: ng/ml
        arithmetic mean (standard deviation)
    -0.046 ± 0.125
    -0.055 ± 124
    -0.031 ± 0.142
    Notes
    [17] - Data not available for all subjects
    [18] - Data not available for all subjects
    [19] - Data not available for all subjects
    Statistical analysis title
    		 Change in CTX
    Statistical analysis description
    An ANCOVA model with change in CTX as dependent variable, independent variables considered, 25OHD, PTH and kidney function at baseline and dietary calcium and vitamin D intake at baseline. Other covariates considered as for primary outcome analysis.
    Comparison groups
    12,000 IU v 24,000 IU v 48,000 IU
    Number of subjects included in analysis
    339
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [20]
    P-value
    		 > 0.001
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [20] - Final model adjusted for baseline CTX, gender, age, weight and height.

    Secondary: Change in bone BAP

    		 Close Top of page
    End point title
    		 Change in bone BAP
    End point description
    Change in Bone Alkaline Phosphatase The difference in BAP between baseline and 12 months derived by subtracting baseline from 12m value per individual
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 12,000 IU 24,000 IU 48,000 IU
    Number of subjects analysed
    111 [21]
    113 [22]
    114 [23]
    Units: ug /L
        arithmetic mean (standard deviation)
    0.96 ± 3.398
    0.682 ± 3.761
    0.792 ± 3.82
    Notes
    [21] - Data not available for all subjects
    [22] - Data not available for all subjects
    [23] - Data not available for all subjects
    Statistical analysis title
    		 Change in bone BAP
    Statistical analysis description
    An ANCOVA model with change in BAP as dependent variable, independent variables considered, 25OHD, PTH and kidney function at baseline and dietary calcium and vitamin D intake at baseline. Other covariates considered as for primary outcome analysis.
    Comparison groups
    12,000 IU v 24,000 IU v 48,000 IU
    Number of subjects included in analysis
    338
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [24]
    P-value
    		 > 0.194
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [24] - Final model adjusted for baseline BAP, baseline urinary calcium, gender, age, weight and height.

    Secondary: Change in P1NP

    		 Close Top of page
    End point title
    		 Change in P1NP
    End point description
    Terminal propeptide of procollagen type 1 The difference in P1NP between baseline and 12 months derived by subtracting baseline from 12m value per individual
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 12,000 IU 24,000 IU 48,000 IU
    Number of subjects analysed
    112 [25]
    113 [26]
    114 [27]
    Units: ug/L
        arithmetic mean (standard deviation)
    1.129 ± 14.853
    3.367 ± 13.301
    4.031 ± 13.259
    Notes
    [25] - Data not available for all subjects
    [26] - Data not available for all subjects
    [27] - Data not available for all subjects
    Statistical analysis title
    		 Change in P1NP
    Statistical analysis description
    An ANCOVA model with change in P1NP as dependent variable, independent variables considered, 25OHD, PTH and kidney function at baseline and dietary calcium and vitamin D intake at baseline. Other covariates considered as for primary outcome analysis.
    Comparison groups
    12,000 IU v 24,000 IU v 48,000 IU
    Number of subjects included in analysis
    339
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [28]
    P-value
    		 > 0.001
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [28] - Final model adjusted for baseline P1NP, baseline urinary calcium/creatinine ratio, gender, age, weight and height.

    Secondary: Adverse Evemts

    		 Close Top of page
    End point title
    		 Adverse Evemts
    End point description
    End point type
    Secondary
    End point timeframe
    12 Months
    End point values
    		 12,000 IU 24,000 IU 48,000 IU
    Number of subjects analysed
    122
    124
    128
    Units: Adverse Event Occurance
        Mild
    296
    283
    283
        Moderate
    131
    149
    145
        Severe
    0
    6
    3
        Missing
    8
    2
    5
    Attachments
    		 Untitled (Filename: Adverse Events Summary.pdf)
    No statistical analyses for this end point

    Secondary: Falls

    		 Close Top of page
    End point title
    		 Falls
    End point description
    The number of falls experienced during the study. Expressed as fall rate per 12 months in order to take into account differing durations of study involvement.
    End point type
    Secondary
    End point timeframe
    12 Months
    End point values
    		 12,000 IU 24,000 IU 48,000 IU
    Number of subjects analysed
    100 [29]
    95 [30]
    97 [31]
    Units: Falls per 12 months per patient
        number (not applicable)
    48
    43
    54
    Notes
    [29] - Number of participants with fall data
    [30] - Number of participants with fall data
    [31] - Number of participants with fall data
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information [1]
    Timeframe for reporting adverse events
    Adverse events were reported from first visit until final visit
    Adverse event reporting additional description
    Throughout the study adverse events were recorded as free text in the medical notes. The adverse events were retrospectively transcribed into the eCRF with best intention for accuracy and completeness. During the transcription no medical dictionary was used in order to avoid bias by retrospectively coding and categorizing these events
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 Free Text
    Dictionary version
    NA
    Reporting groups
    Reporting group title
    12,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 12,000 IU of vitamin D

    Reporting group title
    24,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 24,000 IU of vitamin D

    Reporting group title
    48,000 IU
    Reporting group description
    		 Once a month participant received an oral dose of Vigantol® equivalent to 48,000 IU of vitamin D

    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: Adverse events were reported as secondary outcome and a list off all adverse events is provided there
    Serious adverse events
    		 12,000 IU 24,000 IU 48,000 IU
    Total subjects affected by serious adverse events
         subjects affected / exposed
    14 / 122 (11.48%)
    9 / 124 (7.26%)
    6 / 128 (4.69%)
         number of deaths (all causes)
    1
    2
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Prostate cancer
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 124 (0.81%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Recurrence of melanoma and cerebral metasteses
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 124 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Hepatitis E infection
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 124 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrilation
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 124 (0.81%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congestive cardiac faliure
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 124 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congestive heart falure
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 124 (0.81%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Left total anterior circulation infarct with intrecerebral haemorrage post thyromoblysis
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 124 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mild posterior circulation stroke
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 124 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischemic attack
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 124 (0.81%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    2 / 122 (1.64%)
    0 / 124 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chest pain/breathlessness
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 124 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache and facial swelling
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 124 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache, postural hypotension and migraine
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 124 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Trauma
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 124 (0.81%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    White cell count reduced
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 124 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Death Traffic Accident
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 124 (0.81%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Death
    Additional description: Unknown cause
         subjects affected / exposed
    1 / 122 (0.82%)
    1 / 124 (0.81%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Ischemic colitis
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 124 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Paracolic abcess
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 124 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Exacerbation of asthma
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 124 (0.81%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Possible pulmonary oedema
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 124 (0.81%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Right basal pneumonia with pluritis
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 124 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tightness in chest
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 124 (0.81%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Fractured femur
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 124 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fractured rib
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 124 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Right hip joint effusion
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 124 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Broncietctasis and lower respiratory tract infection
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 124 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 124 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 12,000 IU 24,000 IU 48,000 IU
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 124 (0.00%)
    0 / 128 (0.00%)

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Oct 2012
    - Peanut allergy removed from exclusion criteria - An optional statement has been added to the informed consent form to allow potential approach of subject for other studies in the future. - Correction to inconsistencies between table and text format of study procedures had been made.

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/24041337
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA