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Evaluation of New or Worsening Lens Opacifications in Men With Non-metastatic Prostate Cancer Receiving Denosumab for Bone Loss

Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT00925600
Collaborator
(none)
769
Enrollment
172
Locations
2
Arms
77.4
Actual Duration (Months)
4.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase 3, randomized, double-blind, placebo-controlled study to evaluate new or worsening lens opacifications in men with non-metastatic prostate cancer receiving denosumab for bone loss due to androgen deprivation therapy.

Condition or Disease Intervention/Treatment Phase
  • Biological: Denosumab
  • Biological: Placebo
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
769 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Supportive Care
Official Title:
A Double-blind, Placebo-controlled Study to Evaluate New or Worsening Lens Opacifications in Subjects With Non-metastatic Prostate Cancer Receiving Denosumab for Bone Loss Due to Androgen-Deprivation Therapy
Actual Study Start Date :
Nov 30, 2009
Actual Primary Completion Date :
May 12, 2016
Actual Study Completion Date :
May 12, 2016

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

Participants received placebo administered by subcutaneous injection on Day 1 and at Month 6.

Biological: Placebo
Prefilled syringe for subcutaneous (SC) injection
Experimental: Denosumab

Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.

Biological: Denosumab
Prefilled syringe for subcutaneous (SC) injection administered at a dose of 60 mg
Other Names:
  • Prolia®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Lens Opacification Event Development or Progression by Month 12 [12 months]

      The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. Lens opacification event development or progression by month 12 was based on a change of ≥ 1.0 in P, ≥ 1.0 in C, or ≥ 0.7 in NO in the LOCS III score from baseline.

    Other Outcome Measures

    1. Percentage of Participant With Lens Opacification Event Development or Progression by Month 12 Based on a Change of ≥ 1.5 in P, ≥ 1.5 in C, or ≥ 1.5 in NO in the LOCS III Score [12 months]

      The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. Lens opacification event development or progression by month 12 was based on a change ≥ 1.5 in P, ≥ 1.5 in C, or ≥ 1.5 in NO in the LOCS III score from baseline.

    2. Percentage of Participants With Lens Opacification Event Development or Progression by Month 6 [6 months]

      The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. Lens opacification event development or progression by month 6 was based on a change of ≥ 1.0 in P, ≥ 1.0 in C, or ≥ 0.7 in NO in the LOCS III score from baseline.

    3. Percentage of Participants With Confirmed Lens Opacification Event Development or Progression by Month 12 [12 months]

      The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. Lens opacification event development or progression by month 12 was based on a change of ≥ 1.0 in P, ≥ 1.0 in C, or ≥ 0.7 in NO in the LOCS III score from baseline. A confirmed lens opacification event development or progression was defined as 2 directly subsequent events per protocol assessments at the same location (P, C, NO) using LOCS III as above.

    4. Percentage of Participants With a Decrease From Baseline in Best Corrected Visual Acuity (BCVA) of ≥ 10 Letters [Baseline and Months 3, 6, 9 and 12]

      The best corrected visual acuity (BCVA) is the best vision one can achieve with correction (such as eye glasses) as measured on an eye chart. BCVA was assessed by a trained ophthalmologist using the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart at 4 meters. The modified University of Crete ETDRS chart was used in Ukraine, Greece, Russia and Bulgaria, which do not use the Roman alphabet. The 2000 series revised ETDRS chart was used to assess the change in all other countries. The letter score was calculated based on the number of letters that were correctly identified; higher letter scores correspond to better visual acuity.

    5. Change From Baseline in Refraction Needed to Achieve BCVA [Baseline and months 3, 6, 9, and 12]

      Refraction error was measured using a phoropter. The change from baseline in spherical refraction error needed to achieve BCVA is reported.

    6. Number of Participants With Adverse Events [12 months]

      Adverse events (AEs) were assessed for severity by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) severity grading scale, version 3.0, where Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, Grade 4 =Life-threatening AE and Grade 5 = Death due to AE. Treatment-related AEs (TRAEs) include only events for which the investigator indicated there was a reasonable possibility they may have been caused by the study drug.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    30 Years to 120 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Men ≥ 30 years of age with non-metastatic prostate cancer, having undergone bilateral orchiectomy or initiated androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists and is expected to continue on ADT for at least 12 months

    • Adequate visual accuracy allowing eye testing

    • Bone Mineral Density (BMD) requirements: Osteopenia if under 70 years of age; Osteopenia or normal BMD if over 70 years of age

    • Signed informed consent

    Exclusion Criteria:

    • Previous surgery for cataracts in both eyes, current diagnosis of cataracts, cataracts surgery foreseen in the near future, or ocular disease leading to visual loss

    • Diagnosis of osteoporosis

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Anaheim California United States 92801
    2 Research Site Laguna Hills California United States 92653
    3 Research Site Murrieta California United States 92562
    4 Research Site San Diego California United States 92103
    5 Research Site San Diego California United States 92120
    6 Research Site San Diego California United States 92123
    7 Research Site San Luis Obispo California United States 93405
    8 Research Site Denver Colorado United States 80204
    9 Research Site Denver Colorado United States 80211
    10 Research Site Englewood Colorado United States 80113
    11 Research Site Middlebury Connecticut United States 06762
    12 Research Site New Britain Connecticut United States 06052
    13 Research Site Trinity Florida United States 34655
    14 Research Site Coeur d'Alene Idaho United States 83814
    15 Research Site Greenwood Indiana United States 46143
    16 Research Site West Des Moines Iowa United States 50266
    17 Research Site Kansas City Kansas United States 66160
    18 Research Site Shreveport Louisiana United States 71106
    19 Research Site Annapolis Maryland United States 21401
    20 Research Site Baltimore Maryland United States 21201
    21 Research Site Greenbelt Maryland United States 20770
    22 Research Site Grand Rapids Michigan United States 49546
    23 Research Site Sartell Minnesota United States 56377
    24 Research Site Saint Louis Missouri United States 63110
    25 Research Site Missoula Montana United States 59808
    26 Research Site Omaha Nebraska United States 68105-1850
    27 Research Site Omaha Nebraska United States 68130
    28 Research Site Berlin New Jersey United States 08009
    29 Research Site Bricktown New Jersey United States 08724
    30 Research Site Englewood New Jersey United States 07631
    31 Research Site Lawrenceville New Jersey United States 08648
    32 Research Site Mount Laurel New Jersey United States 08054
    33 Research Site Albany New York United States 12208
    34 Research Site Garden City New York United States 11530
    35 Research Site Kingston New York United States 12401
    36 Research Site New York New York United States 10021
    37 Research Site Poughkeepsie New York United States 12601
    38 Research Site Syracuse New York United States 13210
    39 Research Site Gastonia North Carolina United States 28054
    40 Research Site Greenville North Carolina United States 27834
    41 Research Site Cincinnati Ohio United States 45212
    42 Research Site Bala-Cynwyd Pennsylvania United States 19004
    43 Research Site Lancaster Pennsylvania United States 17604
    44 Research Site Philadelphia Pennsylvania United States 19107
    45 Research Site Myrtle Beach South Carolina United States 29572
    46 Research Site Knoxville Tennessee United States 37920
    47 Research Site Austin Texas United States 78759
    48 Research Site Dallas Texas United States 75231
    49 Research Site San Antonio Texas United States 78229
    50 Research Site Temple Texas United States 76508
    51 Research Site Richmond Virginia United States 23235
    52 Research Site Salem Virginia United States 24153
    53 Research Site Wahroonga New South Wales Australia 2076
    54 Research Site Herston Queensland Australia 4029
    55 Research Site Bentleigh East Victoria Australia 3165
    56 Research Site Ringwood East Victoria Australia 3135
    57 Research Site Pleven Bulgaria 5800
    58 Research Site Plovdiv Bulgaria 4004
    59 Research Site Sofia Bulgaria 1784
    60 Research Site Kelowna British Columbia Canada V1W 4V5
    61 Research Site Vancouver British Columbia Canada V5Z 1M9
    62 Research Site Victoria British Columbia Canada V8T 5G1
    63 Research Site Victoria British Columbia Canada V8V 3N1
    64 Research Site Halifax Nova Scotia Canada B3H 2Y9
    65 Research Site Barrie Ontario Canada L4M 7G1
    66 Research Site Brampton Ontario Canada L6T 4S5
    67 Research Site Brantford Ontario Canada N3S 6T6
    68 Research Site Burlington Ontario Canada L7N 3V2
    69 Research Site Guelph Ontario Canada N1H 5J1
    70 Research Site Kitchener Ontario Canada N2N 2B9
    71 Research Site London Ontario Canada N6A 4G5
    72 Research Site Newmarket Ontario Canada L3X 1W1
    73 Research Site North Bay Ontario Canada P1B 7K8
    74 Research Site North York Ontario Canada M3B 3S6
    75 Research Site Oakville Ontario Canada L6H 3P1
    76 Research Site Scarborough Ontario Canada M1P 2T7
    77 Research Site Toronto Ontario Canada M4N 3M5
    78 Research Site Toronto Ontario Canada M5G 2M9
    79 Research Site Toronto Ontario Canada M6A 3B5
    80 Research Site Laval Quebec Canada H7G 2E6
    81 Research Site Montreal Quebec Canada H2L 4M1
    82 Research Site Benesov Czechia 256 01
    83 Research Site Brno Czechia 612 00
    84 Research Site Hradec Kralove Czechia 500 05
    85 Research Site Jindrichuv Hradec Czechia 377 01
    86 Research Site Kromeriz Czechia 767 55
    87 Research Site Novy Jicin Czechia 741 01
    88 Research Site Olomouc Czechia 775 20
    89 Research Site Plzen Czechia 305 99
    90 Research Site Praha 2 Czechia 120 00
    91 Research Site Praha 4 Czechia 140 00
    92 Research Site Praha 6 Czechia 160 00
    93 Research Site Usti nad Labem Czechia 401 13
    94 Research Site Zlin Czechia 760 01
    95 Research Site Lyon Cédex 3 France 69437
    96 Research Site Paris Cedex 5 France 75248
    97 Research Site Alexandroupoli Greece 68100
    98 Research Site Athens Greece 11522
    99 Research Site Athens Greece 11526
    100 Research Site Athens Greece 11527
    101 Research Site Heraklion Greece 71110
    102 Research Site Larissa Greece 41110
    103 Research Site Patra Greece 26504
    104 Research Site Thessaloniki Greece 54622
    105 Research Site Thessaloniki Greece 56429
    106 Research Site Baja Hungary 6500
    107 Research Site Budapest Hungary 1036
    108 Research Site Budapest Hungary 1082
    109 Research Site Budapest Hungary 1204
    110 Research Site Gyor Hungary 9023
    111 Research Site Miskolc Hungary 3526
    112 Research Site Nyiregyhaza Hungary 4400
    113 Research Site Szeged Hungary 6722
    114 Research Site Ahmedabad Gujarat India 380 009
    115 Research Site Bangalore Karnataka India 560 027
    116 Research Site Aurangabad Maharashtra India 431 005
    117 Research Site Nashik Maharashtra India 422 004
    118 Research Site Ludhiana Punjab India 141 008
    119 Research Site Madurai Tamil Nadu India 625 107
    120 Research Site Kolkata West Bengal India 700 027
    121 Research Site Jelgava Latvia 3001
    122 Research Site Riga Latvia 1002
    123 Research Site Riga Latvia 1079
    124 Research Site Distrito Federal Mexico 01120
    125 Research Site Distrito Federal Mexico 11950
    126 Research Site Christchurch New Zealand 8013
    127 Research Site Takapuna, North Shore City New Zealand 0622
    128 Research Site Tauranga New Zealand 3112
    129 Research Site Whangarei New Zealand 0112
    130 Research Site Gdansk Poland 80-180
    131 Research Site Gdansk Poland 80-952
    132 Research Site Gdynia Poland 81-366
    133 Research Site Gdynia Poland 81-423
    134 Research Site Katowice Poland 40-857
    135 Research Site Myslowice Poland 41-400
    136 Research Site Opole Poland 45-086
    137 Research Site Poznan Poland 61-866
    138 Research Site Rzeszow Poland 35-021
    139 Research Site Siedlce Poland 08-110
    140 Research Site Slupsk Poland 76-200
    141 Research Site Szczecin Poland 70-111
    142 Research Site Warszawa Poland 00-631
    143 Research Site Warszawa Poland 02-005
    144 Research Site Warszawa Poland 02-781
    145 Research Site Wroclaw Poland 50-044
    146 Research Site Ivanovo Russian Federation 153013
    147 Research Site Moscow Russian Federation 105425
    148 Research Site Moscow Russian Federation 115478
    149 Research Site Moscow Russian Federation 125284
    150 Research Site Nizhny Novgorod Russian Federation 603126
    151 Research Site Rostov-na-Donu Russian Federation 344022
    152 Research Site Bratislava Slovakia 851 05
    153 Research Site Kosice Slovakia 040 01
    154 Research Site Kosice Slovakia 040 11
    155 Research Site Kosice Slovakia 040 23
    156 Research Site Martin Slovakia 036 59
    157 Research Site Nitra Slovakia 949 01
    158 Research Site Trencin Slovakia 911 01
    159 Research Site Celje Slovenia 3000
    160 Research Site Ljubljana Slovenia 1525
    161 Research Site Slovenj Gradec Slovenia 2380
    162 Research Site Paarl Western Cape South Africa 7646
    163 Research Site George South Africa 6530
    164 Research Site Kempton Park South Africa 1619
    165 Research Site Port Elizabeth South Africa 6001
    166 Research Site Tygerberg South Africa 7505
    167 Research Site Chernivtsi Ukraine 58002
    168 Research Site Dnipropetrovsk Ukraine 49005
    169 Research Site Kharkiv Ukraine 61037
    170 Research Site Kyiv Ukraine 02125
    171 Research Site Uzhgorod Ukraine 88000
    172 Research Site Zaporizhzhya Ukraine 69600

    Sponsors and Collaborators

    • Amgen

    Investigators

    • Study Director: MD, Amgen

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT00925600
    Other Study ID Numbers:
    • 20080560
    • 2009-012076-26
    First Posted:
    Jun 22, 2009
    Last Update Posted:
    May 30, 2017
    Last Verified:
    Apr 1, 2017
    Keywords provided by Amgen
    Lens Opacification
    Bone Loss
    Androgen Deprivation Therapy
    Non-metastatic prostate cancer
    Additional relevant MeSH terms:
    Prostatic Neoplasms
    Osteoporosis
    Bone Diseases, Metabolic
    Cataract
    Denosumab

    Study Results

    Participant Flow

    Recruitment Details This study was conducted at 125 centers in 18 countries: Australia, Bulgaria, Canada, the Czech Republic, France, Greece, Hungary, India, Latvia, Mexico, New Zealand, Poland, Russia, Slovakia, Slovenia, South Africa, Ukraine, and the United States. The first participant enrolled on 30 November 2009 and the last participant enrolled on 04 May 2015.
    Pre-assignment Detail Participants were randomly assigned to receive denosumab or placebo in a 1:1 allocation ratio. Randomization was stratified on the basis of screening Lens Opacities Classification System (LOCS) III status (< 3.0 at all sites versus ≥ 3.0 at any site); age group (< 75, ≥ 75 years), and patient-reported history of cataract (yes/no).
    Arm/Group Title Placebo Denosumab
    Arm/Group Description Participants randomized to receive placebo administered by subcutaneous injection on Day 1 and at Month 6. Participants randomized to receive denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
    Period Title: Overall Study
    STARTED 386 383
    Received Treatment 383 382
    COMPLETED 354 355
    NOT COMPLETED 32 28

    Baseline Characteristics

    Arm/Group Title Placebo Denosumab Total
    Arm/Group Description Participants randomized to receive placebo administered by subcutaneous injection on Day 1 and at Month 6. Participants randomized to receive denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6. Total of all reporting groups
    Overall Participants 386 383 769
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    71.0
    (7.0)
    71.1
    (7.2)
    71.0
    (7.1)
    Age, Customized (participants) [Number]
    18 - 64 years
    73
    18.9%
    66
    17.2%
    139
    18.1%
    65 - 74 years
    189
    49%
    194
    50.7%
    383
    49.8%
    75 - 84 years
    119
    30.8%
    116
    30.3%
    235
    30.6%
    ≥ 85 years
    5
    1.3%
    7
    1.8%
    12
    1.6%
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    Male
    386
    100%
    383
    100%
    769
    100%
    Race/Ethnicity, Customized (participants) [Number]
    White
    359
    93%
    346
    90.3%
    705
    91.7%
    Black (or African American)
    12
    3.1%
    11
    2.9%
    23
    3%
    Hispanic/Latino
    1
    0.3%
    9
    2.3%
    10
    1.3%
    Other
    7
    1.8%
    8
    2.1%
    15
    2%
    Asian
    7
    1.8%
    7
    1.8%
    14
    1.8%
    Japanese
    0
    0%
    1
    0.3%
    1
    0.1%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    1
    0.3%
    1
    0.1%
    Presence of Cataract(s) (participants) [Number]
    Yes
    59
    15.3%
    63
    16.4%
    122
    15.9%
    No
    327
    84.7%
    320
    83.6%
    647
    84.1%
    Presence of Diabetes (participants) [Number]
    Yes
    70
    18.1%
    61
    15.9%
    131
    17%
    No
    316
    81.9%
    322
    84.1%
    638
    83%
    Received Androgen-deprivation Therapy (ADT) (participants) [Number]
    Yes
    350
    90.7%
    353
    92.2%
    703
    91.4%
    No
    36
    9.3%
    30
    7.8%
    66
    8.6%
    Orchiectomy (Surgical Castration) (participants) [Number]
    Yes
    58
    15%
    51
    13.3%
    109
    14.2%
    No
    328
    85%
    332
    86.7%
    660
    85.8%
    Screening Lens Opacities Classification System (LOCS) III Status (participants) [Number]
    < 3.0 at all sites [P, C, and NO]
    299
    77.5%
    299
    78.1%
    598
    77.8%
    ≥ 3.0 at any of these sites
    87
    22.5%
    84
    21.9%
    171
    22.2%
    Participant-reported History of Cataract (participants) [Number]
    Yes
    35
    9.1%
    35
    9.1%
    70
    9.1%
    No
    351
    90.9%
    348
    90.9%
    699
    90.9%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With Lens Opacification Event Development or Progression by Month 12
    Description The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. Lens opacification event development or progression by month 12 was based on a change of ≥ 1.0 in P, ≥ 1.0 in C, or ≥ 0.7 in NO in the LOCS III score from baseline.
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    The lens opacification analysis set includes randomized participants who received ≥1 dose of study drug, had an evaluable baseline and at least 1 evaluable post-baseline LOCS III assessment at the corresponding lens site. Three participants randomized to placebo who received ≥ 1 dose of denosumab in error are analyzed in the denosumab group.
    Arm/Group Title Placebo Denosumab
    Arm/Group Description Participants received placebo administered by subcutaneous injection on Day 1 and at Month 6. Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
    Measure Participants 374 379
    Number [percentage of participants]
    33.2
    8.6%
    33.5
    8.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab
    Comments The primary endpoint was summarized with the point estimate of absolute risk difference (difference in incidence rates, denosumab minus placebo) and the corresponding 95% confidence interval using the Mantel-Haenszel method adjusting for the stratification factors: baseline LOCS III status (< 3.0 at all sites [P, C, and NO] vs. ≥ 3.0 at any of these sites), age group (< 75, ≥ 75 years), and patient-reported history of cataract (yes/no).
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Non-inferiority was demonstrated if the upper bound of the 97.5% one-sided confidence interval, or equivalently upper bound of two-sided 95% confidence interval was less than the pre-specified non-inferiority bound of 10%.
    Statistical Test of Hypothesis p-Value 0.0026
    Comments
    Method Mantel Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.4
    Confidence Interval (2-Sided) 95%
    -6.3 to 7.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.4
    Estimation Comments
    2. Other Pre-specified Outcome
    Title Percentage of Participant With Lens Opacification Event Development or Progression by Month 12 Based on a Change of ≥ 1.5 in P, ≥ 1.5 in C, or ≥ 1.5 in NO in the LOCS III Score
    Description The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. Lens opacification event development or progression by month 12 was based on a change ≥ 1.5 in P, ≥ 1.5 in C, or ≥ 1.5 in NO in the LOCS III score from baseline.
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    The lens opacification analysis set includes randomized participants who received ≥1 dose of study drug, had an evaluable baseline and at least 1 evaluable post-baseline LOCS III assessment at the corresponding lens site. Three participants randomized to placebo who eceived ≥ 1 dose of denosumab in error are analyzed in the denosumab group.
    Arm/Group Title Placebo Denosumab
    Arm/Group Description Participants received placebo administered by subcutaneous injection on Day 1 and at Month 6. Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
    Measure Participants 374 379
    Number [percentage of participants]
    10.7
    2.8%
    8.4
    2.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab
    Comments The point estimate of absolute risk difference (difference in incidence rates, denosumab minus placebo) and the corresponding 95% confidence interval was constructed using the Mantel-Haenszel method adjusting for the stratification factors: baseline LOCS III status (< 3.0 at all sites [P, C, and NO] vs. ≥ 3.0 at any of these sites), age group (< 75, ≥ 75 years), and patient-reported history of cataract (yes/no).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value -2.2
    Confidence Interval (2-Sided) 95%
    -6.4 to 2.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.1
    Estimation Comments
    3. Other Pre-specified Outcome
    Title Percentage of Participants With Lens Opacification Event Development or Progression by Month 6
    Description The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. Lens opacification event development or progression by month 6 was based on a change of ≥ 1.0 in P, ≥ 1.0 in C, or ≥ 0.7 in NO in the LOCS III score from baseline.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    Lens opacification analysis set includes randomized participants who received ≥1 dose of study drug, had an evaluable baseline and at least 1 evaluable post-baseline LOCS III assessment at the corresponding lens site at or before month 6. Three participants randomized to placebo who received denosumab in error are analyzed in the denosumab group.
    Arm/Group Title Placebo Denosumab
    Arm/Group Description Participants received placebo administered by subcutaneous injection on Day 1 and at Month 6. Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
    Measure Participants 374 379
    Number [percentage of participants]
    19.3
    5%
    19.0
    5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab
    Comments The point estimate of absolute risk difference (difference in incidence rates, denosumab minus placebo) and the corresponding 95% confidence interval was constructed using the Mantel-Haenszel method adjusting for the stratification factors: baseline LOCS III status (< 3.0 at all sites [P, C, and NO] vs. ≥ 3.0 at any of these sites), age group (< 75, ≥ 75 years), and patient-reported history of cataract (yes/no).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -5.9 to 5.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.9
    Estimation Comments
    4. Other Pre-specified Outcome
    Title Percentage of Participants With Confirmed Lens Opacification Event Development or Progression by Month 12
    Description The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. Lens opacification event development or progression by month 12 was based on a change of ≥ 1.0 in P, ≥ 1.0 in C, or ≥ 0.7 in NO in the LOCS III score from baseline. A confirmed lens opacification event development or progression was defined as 2 directly subsequent events per protocol assessments at the same location (P, C, NO) using LOCS III as above.
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    Lens opacification analysis set with at least two post-baseline LOCS III measurements by month 12. Three participants randomized to placebo who received at least 1 dose of denosumab in error are analyzed in the denosumab group.
    Arm/Group Title Placebo Denosumab
    Arm/Group Description Participants received placebo administered by subcutaneous injection on Day 1 and at Month 6. Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
    Measure Participants 361 367
    Number [percentage of participants]
    18.3
    4.7%
    16.1
    4.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab
    Comments The point estimate of absolute risk difference (difference in incidence rates, denosumab minus placebo) and the corresponding 95% confidence interval was constructed using the Mantel-Haenszel method adjusting for the stratification factors: baseline LOCS III status (< 3.0 at all sites [P, C, and NO] vs. ≥ 3.0 at any of these sites), age group (< 75, ≥ 75 years), and patient-reported history of cataract (yes/no).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value -2.2
    Confidence Interval (2-Sided) 95%
    -7.6 to 3.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.8
    Estimation Comments
    5. Other Pre-specified Outcome
    Title Percentage of Participants With a Decrease From Baseline in Best Corrected Visual Acuity (BCVA) of ≥ 10 Letters
    Description The best corrected visual acuity (BCVA) is the best vision one can achieve with correction (such as eye glasses) as measured on an eye chart. BCVA was assessed by a trained ophthalmologist using the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart at 4 meters. The modified University of Crete ETDRS chart was used in Ukraine, Greece, Russia and Bulgaria, which do not use the Roman alphabet. The 2000 series revised ETDRS chart was used to assess the change in all other countries. The letter score was calculated based on the number of letters that were correctly identified; higher letter scores correspond to better visual acuity.
    Time Frame Baseline and Months 3, 6, 9 and 12

    Outcome Measure Data

    Analysis Population Description
    Lens opacification analysis set with evaluable assessments at both baseline and the time point of interest in the same eye (as indicated by "n"). Three participants randomized to placebo who received at least 1 dose of denosumab in error are analyzed in the denosumab group.
    Arm/Group Title Placebo Denosumab
    Arm/Group Description Participants received placebo administered by subcutaneous injection on Day 1 and at Month 6. Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
    Measure Participants 374 379
    Month 3 (n = 372, 375)
    5.4
    1.4%
    6.1
    1.6%
    Month 6 (n = 355, 357)
    4.2
    1.1%
    6.4
    1.7%
    Month 9 (n = 350, 346)
    4.6
    1.2%
    6.6
    1.7%
    Month 12 (n = 343, 342)
    5.2
    1.3%
    7.3
    1.9%
    6. Other Pre-specified Outcome
    Title Change From Baseline in Refraction Needed to Achieve BCVA
    Description Refraction error was measured using a phoropter. The change from baseline in spherical refraction error needed to achieve BCVA is reported.
    Time Frame Baseline and months 3, 6, 9, and 12

    Outcome Measure Data

    Analysis Population Description
    Lens opacification analysis set with evaluable assessments at both baseline and each time point in the same eye. n=the number of evaluable eyes in the lens opacification analysis set at the corresponding time point; 3 participants randomized to placebo who received denosumab in error are analyzed in the denosumab group.
    Arm/Group Title Placebo - Left Eye Placebo - Right Eye Denosumab Denosumab - Right Eye
    Arm/Group Description Participants received placebo subcutaneous injection on Day 1 and at Month 6. Participants received placebo subcutaneous injection on Day 1 and at Month 6. Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6. Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
    Measure Participants 374 374 379 379
    Measure eyes 374 374 379 379
    Month 3 (n = 362, 358, 358, 359)
    0.01
    (0.60)
    0.01
    (0.49)
    0.05
    (0.73)
    0.04
    (0.51)
    Month 6 (n = 347, 343, 341, 344)
    -0.01
    (0.80)
    0.06
    (0.70)
    0.06
    (0.90)
    0.04
    (0.59)
    Month 9 (n = 341, 339, 332, 332)
    0.00
    (0.84)
    0.01
    (0.73)
    0.04
    (0.75)
    0.01
    (0.62)
    Month 12 (n = 336, 334, 328, 329)
    -0.03
    (0.70)
    -0.04
    (0.59)
    0.03
    (0.77)
    0.00
    (0.48)
    7. Other Pre-specified Outcome
    Title Number of Participants With Adverse Events
    Description Adverse events (AEs) were assessed for severity by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) severity grading scale, version 3.0, where Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, Grade 4 =Life-threatening AE and Grade 5 = Death due to AE. Treatment-related AEs (TRAEs) include only events for which the investigator indicated there was a reasonable possibility they may have been caused by the study drug.
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants who received at least one dose of study drug. Three participants randomized to the placebo group who received at least 1 dose of denosumab in error are analyzed in the denosumab group for safety.
    Arm/Group Title Placebo Denosumab
    Arm/Group Description Participants received placebo administered by subcutaneous injection on Day 1 and at Month 6. Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
    Measure Participants 380 385
    Any adverse event
    193
    50%
    191
    49.9%
    Serious adverse events
    52
    13.5%
    42
    11%
    AE leading to discontinuation of study drug
    5
    1.3%
    7
    1.8%
    AE leading to discontinuation from study
    2
    0.5%
    4
    1%
    Fatal adverse events
    4
    1%
    3
    0.8%
    AE grade 3, 4, or 5
    53
    13.7%
    46
    12%
    Treatment-related adverse events
    19
    4.9%
    21
    5.5%
    Serious treatment-related adverse events
    1
    0.3%
    2
    0.5%
    TRAE leading to discontinuation of study drug
    1
    0.3%
    3
    0.8%
    TRAE leading to discontinuation from study
    0
    0%
    1
    0.3%
    Fatal treatment-related adverse events
    0
    0%
    0
    0%
    TRAE grade 3, 4, or 5
    2
    0.5%
    2
    0.5%

    Adverse Events

    Time Frame 12 months
    Adverse Event Reporting Description All enrolled participants who received at least one dose of study drug. Three participants randomized to the placebo group received at least 1 dose of denosumab in error, and are included in the denosumab group for safety. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
    Arm/Group Title Placebo Denosumab
    Arm/Group Description Participants received placebo administered by subcutaneous injection on Day 1 and at Month 6. Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
    All Cause Mortality
    Placebo Denosumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Placebo Denosumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 52/380 (13.7%) 42/385 (10.9%)
    Blood and lymphatic system disorders
    Anaemia megaloblastic 1/380 (0.3%) 0/385 (0%)
    Cardiac disorders
    Angina pectoris 0/380 (0%) 2/385 (0.5%)
    Atrial fibrillation 1/380 (0.3%) 1/385 (0.3%)
    Cardiac failure 0/380 (0%) 1/385 (0.3%)
    Cardiac failure congestive 1/380 (0.3%) 0/385 (0%)
    Cardiac fibrillation 1/380 (0.3%) 0/385 (0%)
    Cardio-respiratory arrest 0/380 (0%) 1/385 (0.3%)
    Cardiogenic shock 1/380 (0.3%) 0/385 (0%)
    Coronary artery disease 2/380 (0.5%) 1/385 (0.3%)
    Coronary artery insufficiency 1/380 (0.3%) 0/385 (0%)
    Coronary artery stenosis 1/380 (0.3%) 0/385 (0%)
    Ischaemic cardiomyopathy 0/380 (0%) 1/385 (0.3%)
    Myocardial infarction 2/380 (0.5%) 1/385 (0.3%)
    Myocardial ischaemia 1/380 (0.3%) 3/385 (0.8%)
    Tachycardia paroxysmal 0/380 (0%) 1/385 (0.3%)
    Ventricular tachycardia 0/380 (0%) 1/385 (0.3%)
    Ear and labyrinth disorders
    Tinnitus 0/380 (0%) 1/385 (0.3%)
    Eye disorders
    Optic nerve disorder 0/380 (0%) 1/385 (0.3%)
    Uveitis 0/380 (0%) 1/385 (0.3%)
    Gastrointestinal disorders
    Abdominal pain 1/380 (0.3%) 0/385 (0%)
    Colitis ulcerative 0/380 (0%) 1/385 (0.3%)
    Diarrhoea 2/380 (0.5%) 0/385 (0%)
    Gastrointestinal haemorrhage 0/380 (0%) 1/385 (0.3%)
    Ileus 1/380 (0.3%) 0/385 (0%)
    Inguinal hernia 1/380 (0.3%) 1/385 (0.3%)
    Mechanical ileus 1/380 (0.3%) 0/385 (0%)
    Rectal haemorrhage 1/380 (0.3%) 1/385 (0.3%)
    Small intestinal stenosis 0/380 (0%) 1/385 (0.3%)
    General disorders
    Asthenia 1/380 (0.3%) 0/385 (0%)
    Cyst 1/380 (0.3%) 0/385 (0%)
    Peripheral swelling 1/380 (0.3%) 0/385 (0%)
    Pseudoangina 1/380 (0.3%) 0/385 (0%)
    Pyrexia 0/380 (0%) 1/385 (0.3%)
    Hepatobiliary disorders
    Bile duct stone 0/380 (0%) 1/385 (0.3%)
    Cholecystitis acute 1/380 (0.3%) 1/385 (0.3%)
    Cholelithiasis 1/380 (0.3%) 0/385 (0%)
    Infections and infestations
    Appendicitis perforated 1/380 (0.3%) 0/385 (0%)
    Arthritis bacterial 1/380 (0.3%) 0/385 (0%)
    Atypical pneumonia 1/380 (0.3%) 0/385 (0%)
    Diverticulitis 2/380 (0.5%) 0/385 (0%)
    Herpes zoster 1/380 (0.3%) 0/385 (0%)
    Kidney infection 0/380 (0%) 1/385 (0.3%)
    Liver abscess 0/380 (0%) 1/385 (0.3%)
    Pneumonia 2/380 (0.5%) 0/385 (0%)
    Pyelonephritis acute 1/380 (0.3%) 1/385 (0.3%)
    Injury, poisoning and procedural complications
    Cystitis radiation 0/380 (0%) 1/385 (0.3%)
    Foot fracture 1/380 (0.3%) 0/385 (0%)
    Fracture 0/380 (0%) 1/385 (0.3%)
    Hip fracture 1/380 (0.3%) 0/385 (0%)
    Lumbar vertebral fracture 1/380 (0.3%) 1/385 (0.3%)
    Multiple injuries 0/380 (0%) 1/385 (0.3%)
    Patella fracture 1/380 (0.3%) 0/385 (0%)
    Radiation proctitis 0/380 (0%) 1/385 (0.3%)
    Urethral stricture postoperative 1/380 (0.3%) 1/385 (0.3%)
    Metabolism and nutrition disorders
    Dehydration 0/380 (0%) 1/385 (0.3%)
    Diabetes mellitus inadequate control 0/380 (0%) 1/385 (0.3%)
    Hyponatraemia 1/380 (0.3%) 0/385 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/380 (0%) 1/385 (0.3%)
    Back pain 1/380 (0.3%) 0/385 (0%)
    Connective tissue inflammation 1/380 (0.3%) 0/385 (0%)
    Intervertebral disc compression 0/380 (0%) 1/385 (0.3%)
    Osteoarthritis 0/380 (0%) 2/385 (0.5%)
    Spinal osteoarthritis 0/380 (0%) 1/385 (0.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colon cancer 0/380 (0%) 1/385 (0.3%)
    Metastases to central nervous system 1/380 (0.3%) 0/385 (0%)
    Plasma cell myeloma 0/380 (0%) 1/385 (0.3%)
    Prostate cancer 0/380 (0%) 1/385 (0.3%)
    Squamous cell carcinoma of skin 1/380 (0.3%) 0/385 (0%)
    Nervous system disorders
    Aphasia 1/380 (0.3%) 0/385 (0%)
    Cerebrovascular accident 4/380 (1.1%) 1/385 (0.3%)
    Dementia 1/380 (0.3%) 0/385 (0%)
    Dizziness 2/380 (0.5%) 0/385 (0%)
    Encephalomalacia 1/380 (0.3%) 0/385 (0%)
    Epilepsy 1/380 (0.3%) 0/385 (0%)
    Haemorrhagic stroke 1/380 (0.3%) 0/385 (0%)
    Normal pressure hydrocephalus 0/380 (0%) 1/385 (0.3%)
    Syncope 1/380 (0.3%) 1/385 (0.3%)
    Transient ischaemic attack 1/380 (0.3%) 0/385 (0%)
    Product Issues
    Device dislocation 0/380 (0%) 1/385 (0.3%)
    Device malfunction 0/380 (0%) 1/385 (0.3%)
    Psychiatric disorders
    Depression 1/380 (0.3%) 0/385 (0%)
    Renal and urinary disorders
    Acute kidney injury 2/380 (0.5%) 0/385 (0%)
    Haematuria 1/380 (0.3%) 1/385 (0.3%)
    Pelvi-ureteric obstruction 1/380 (0.3%) 0/385 (0%)
    Stress urinary incontinence 1/380 (0.3%) 0/385 (0%)
    Urethral stenosis 1/380 (0.3%) 1/385 (0.3%)
    Urinary retention 2/380 (0.5%) 0/385 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 1/380 (0.3%) 0/385 (0%)
    Chronic obstructive pulmonary disease 1/380 (0.3%) 0/385 (0%)
    Chronic respiratory failure 1/380 (0.3%) 0/385 (0%)
    Epistaxis 0/380 (0%) 1/385 (0.3%)
    Pulmonary embolism 2/380 (0.5%) 2/385 (0.5%)
    Pulmonary fibrosis 1/380 (0.3%) 0/385 (0%)
    Skin and subcutaneous tissue disorders
    Diabetic foot 1/380 (0.3%) 0/385 (0%)
    Rash generalised 1/380 (0.3%) 0/385 (0%)
    Vascular disorders
    Deep vein thrombosis 1/380 (0.3%) 0/385 (0%)
    Peripheral ischaemia 1/380 (0.3%) 0/385 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo Denosumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 107/380 (28.2%) 121/385 (31.4%)
    Blood and lymphatic system disorders
    Anaemia 4/380 (1.1%) 2/385 (0.5%)
    Cardiac disorders
    Atrial fibrillation 3/380 (0.8%) 4/385 (1%)
    Ear and labyrinth disorders
    Vertigo 0/380 (0%) 6/385 (1.6%)
    Eye disorders
    Vision blurred 2/380 (0.5%) 5/385 (1.3%)
    Gastrointestinal disorders
    Constipation 16/380 (4.2%) 8/385 (2.1%)
    Diarrhoea 6/380 (1.6%) 2/385 (0.5%)
    General disorders
    Fatigue 2/380 (0.5%) 6/385 (1.6%)
    Oedema peripheral 1/380 (0.3%) 7/385 (1.8%)
    Infections and infestations
    Bronchitis 4/380 (1.1%) 6/385 (1.6%)
    Nasopharyngitis 7/380 (1.8%) 10/385 (2.6%)
    Sinusitis 3/380 (0.8%) 4/385 (1%)
    Upper respiratory tract infection 6/380 (1.6%) 5/385 (1.3%)
    Urinary tract infection 5/380 (1.3%) 5/385 (1.3%)
    Injury, poisoning and procedural complications
    Chest injury 4/380 (1.1%) 0/385 (0%)
    Investigations
    Prostatic specific antigen increased 0/380 (0%) 4/385 (1%)
    Metabolism and nutrition disorders
    Diabetes mellitus 5/380 (1.3%) 5/385 (1.3%)
    Type 2 diabetes mellitus 4/380 (1.1%) 1/385 (0.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 10/380 (2.6%) 12/385 (3.1%)
    Back pain 10/380 (2.6%) 11/385 (2.9%)
    Musculoskeletal pain 5/380 (1.3%) 3/385 (0.8%)
    Myalgia 2/380 (0.5%) 5/385 (1.3%)
    Osteoarthritis 2/380 (0.5%) 7/385 (1.8%)
    Pain in extremity 10/380 (2.6%) 6/385 (1.6%)
    Nervous system disorders
    Dizziness 4/380 (1.1%) 6/385 (1.6%)
    Headache 3/380 (0.8%) 6/385 (1.6%)
    Psychiatric disorders
    Insomnia 3/380 (0.8%) 6/385 (1.6%)
    Renal and urinary disorders
    Dysuria 4/380 (1.1%) 5/385 (1.3%)
    Haematuria 4/380 (1.1%) 3/385 (0.8%)
    Pollakiuria 6/380 (1.6%) 7/385 (1.8%)
    Urinary incontinence 4/380 (1.1%) 1/385 (0.3%)
    Urinary retention 4/380 (1.1%) 2/385 (0.5%)
    Respiratory, thoracic and mediastinal disorders
    Cough 6/380 (1.6%) 4/385 (1%)
    Dyspnoea 3/380 (0.8%) 4/385 (1%)
    Vascular disorders
    Hot flush 7/380 (1.8%) 7/385 (1.8%)
    Hypertension 16/380 (4.2%) 8/385 (2.1%)
    Hypotension 5/380 (1.3%) 1/385 (0.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.

    Results Point of Contact

    Name/Title Study Director
    Organization Amgen Inc.
    Phone 866-572-6436
    Email
    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT00925600
    Other Study ID Numbers:
    • 20080560
    • 2009-012076-26
    First Posted:
    Jun 22, 2009
    Last Update Posted:
    May 30, 2017
    Last Verified:
    Apr 1, 2017