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STARTT: Study of Romosozumab (AMG 785) in Tibial Diaphyseal Fractures Status Post Intramedullary Nailing

Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT00907296
Collaborator
UCB Pharma (Industry)
402
Enrollment
103
Locations
10
Arms
44.2
Actual Duration (Months)
3.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to investigate the effect of romosozumab compared with placebo on time to radiographic healing of fresh tibial diaphyseal fractures (fractures in the midsection of the shinbone).

Condition or Disease Intervention/Treatment Phase
  • Biological: Romosozumab
  • Drug: Placebo
 Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
402 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multi-center, Randomized, Double Blind, Placebo-controlled Study of AMG 785 in Skeletally Mature Adults With a Fresh Unilateral Tibial Diaphyseal Fracture Status Post Definitive Fracture Fixation With an Intramedullary Nail
Actual Study Start Date :
Sep 2, 2009
Actual Primary Completion Date :
Mar 6, 2012
Actual Study Completion Date :
May 10, 2013

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

Participants received subcutaneous injections of matching placebo on day 1 and at weeks 2, 6, and 12.

Drug: Placebo
Administered by subcutaneous injection
Experimental: Romosozumab 70 mg: 2 Doses

Participants received subcutaneous injections of 70 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12.

Biological: Romosozumab
Administered by subcutaneous injection
Other Names:
  • AMG 785
  • Evenity

    		•
    Experimental: Romosozumab 70 mg: 3 Doses

    Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12.

    Biological: Romosozumab
    Administered by subcutaneous injection
    Other Names:
  • AMG 785
  • Evenity

    		•
    Experimental: Romosozumab 70 mg: 4 Doses

    Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2, 6, and 12.

    Biological: Romosozumab
    Administered by subcutaneous injection
    Other Names:
  • AMG 785
  • Evenity

    		•
    Experimental: Romosozumab 140 mg: 2 Doses

    Participants received subcutaneous injections of 140 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12.

    Biological: Romosozumab
    Administered by subcutaneous injection
    Other Names:
  • AMG 785
  • Evenity

    		•
    Experimental: Romosozumab 140 mg: 3 Doses

    Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12.

    Biological: Romosozumab
    Administered by subcutaneous injection
    Other Names:
  • AMG 785
  • Evenity

    		•
    Experimental: Romosozumab 140 mg: 4 Doses

    Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2, 6, and 12.

    Biological: Romosozumab
    Administered by subcutaneous injection
    Other Names:
  • AMG 785
  • Evenity

    		•
    Experimental: Romosozumab 210 mg: 2 Doses

    Participants received subcutaneous injections of 210 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12.

    Biological: Romosozumab
    Administered by subcutaneous injection
    Other Names:
  • AMG 785
  • Evenity

    		•
    Experimental: Romosozumab 210 mg: 3 Doses

    Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12.

    Biological: Romosozumab
    Administered by subcutaneous injection
    Other Names:
  • AMG 785
  • Evenity

    		•
    Experimental: Romosozumab 210 mg: 4 Doses

    Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2, 6, and 12.

    Biological: Romosozumab
    Administered by subcutaneous injection
    Other Names:
  • AMG 785
  • Evenity

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Time to Radiographic Healing [52 weeks]

      Time to radiographic healing was defined as the time from intramedullary (IM) nailing to the first occurrence of bridging of 3 out of 4 cortices. Radiographic fracture healing was determined by a panel of independent reviewers (orthopedic/trauma surgeons and radiologists) blinded to treatment. The cumulative incidence function (CIF) method was used to estimate the median time to radiographic healing and the confidence intervals. Unplanned revision surgery to promote healing was considered a competing risk in CIF estimate.

    Secondary Outcome Measures

    1. Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain [Week 8 and weeks 12, 16, 20, 24, 36, and 52]

      The Medical Outcome Study Short Form 36-Item Health Survey (SF-36), Version 2, is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical functioning domain includes 10 questions that assess limitations in physical activities because of health problems. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. The range of SF-36 physical functioning is 14.94 - 57.03. Higher scores indicate a higher level of functioning. A positive change from baseline score indicates an improvement in physical functioning.

    2. Number of Participants With Unplanned Revision Surgeries [52 weeks]

    3. Time to Clinical Healing [52 weeks]

      Time to clinical healing was defined as the time from the IM nailing surgery date to the first date that both the score for ability to bear weight on the fractured limb and the score for absence of pain at the fracture site were equal to 6. The score for the ability to bear weight on the fractured limb was based on the ability to stand on affected leg without assistive device and the ability to walk without assistive device. The score ranges from 0 (unable to bear full body weight on the fractured limb) to 6 (able to bear full body weight on the fractured limb). Absence of pain at the fracture site was based on the absence of pain at the fracture site when applying direct pressure to the fracture site and applying a stress to the fracture site. The score ranges from 0 (pain without palpation at fracture site) to 6 (total absence of pain at fracture site). Time to clinical healing was estimated using CIF; unplanned revision surgery was considered a competing risk in CIF estimate.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Skeletally mature adults, age 18 to 85 years with radiographically closed growth plates

    • Fresh unilateral closed or Gustilo type I or type II open tibial fracture

    • Definitive fracture fixation with reamed (closed and open fractures) or unreamed (open fractures only) intramedullary nailing

    Exclusion Criteria:

    • Major polytrauma or significant axial trauma

    • Associated lower extremity fracture that will delay subject's ability to bear weight beyond the normal time expected for a tibial shaft fracture

    • Use of bone grafts at the time of fracture fixation

    • Pathological fracture or metabolic or bone disease

    • History of symptomatic spinal stenosis or facial nerve paralysis

    • Malignancy within the last 5 years

    • Evidence of the following (currently or within the past 5 years): elevated transaminases, significantly impaired renal function, current hyper- or hypocalcaemia

    • Use of agents affecting bone metabolism

    • Subject refuses to use appropriate methods of contraception

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Birmingham Alabama United States 35294
    2 Research Site Orange California United States 92868
    3 Research Site Aurora Colorado United States 80012
    4 Research Site Denver Colorado United States 80204
    5 Research Site Jacksonville Florida United States 32209
    6 Research Site Indianapolis Indiana United States 46202
    7 Research Site Detroit Michigan United States 48202
    8 Research Site Saint Louis Missouri United States 63110
    9 Research Site Brooklyn New York United States 11220
    10 Research Site Rochester New York United States 14642
    11 Research Site Altoona Pennsylvania United States 16602
    12 Research Site Philadelphia Pennsylvania United States 19104
    13 Research Site Columbia South Carolina United States 29203
    14 Research Site Sandy Utah United States 84070
    15 Research Site Geelong Victoria Australia 3220
    16 Research Site Parkville Victoria Australia 3050
    17 Research Site Blagoevgrad Bulgaria 2700
    18 Research Site Pleven Bulgaria 5800
    19 Research Site Plovdiv Bulgaria 4002
    20 Research Site Ruse Bulgaria 7000
    21 Research Site Sofia Bulgaria 1527
    22 Research Site Red Deer Alberta Canada T4N 6V7
    23 Research Site Ajax Ontario Canada L1S 2J5
    24 Research Site Thunder Bay Ontario Canada P7B 7C7
    25 Research Site Toronto Ontario Canada M5C 1R6
    26 Research Site Waterloo Ontario Canada N2J 1C4
    27 Research Site Windsor Ontario Canada N9A 1E1
    28 Research Site Montreal Quebec Canada H3G 1A4
    29 Research Site Montreal Quebec Canada H4J 1C5
    30 Research Site Hvidovre Denmark 2650
    31 Research Site København NV Denmark 2400
    32 Research Site Ã…rhus C Denmark 8000
    33 Research Site Tallinn Estonia 11312
    34 Research Site Tartu Estonia 50410
    35 Research Site Lille France 59000
    36 Research Site Marseille France 13009
    37 Research Site Nantes Cedex 1 France 44035
    38 Research Site Paris Cedex 12 France 75571
    39 Research Site Aachen Germany 52074
    40 Research Site Hamburg Germany 20246
    41 Research Site Hannover Germany 30625
    42 Research Site Mannheim Germany 68165
    43 Research Site Muenster Germany 48149
    44 Research Site Athens Greece 12462
    45 Research Site Athens Greece 14561
    46 Research Site Larissa Greece 41110
    47 Research Site Patra Greece 26500
    48 Research Site Thessaloniki Greece 56429
    49 Research Site Hong Kong Hong Kong
    50 Research Site New Territories Hong Kong
    51 Research Site Budapest Hungary 1081
    52 Research Site Miskolc Hungary 3526
    53 Research Site Nyiregyhaza Hungary 4400
    54 Research Site Szeged Hungary 6725
    55 Research Site Bangalore Karnataka India 560 034
    56 Research Site Bangalore Karnataka India 560 054
    57 Research Site Mangalore Karnataka India 575 002
    58 Research Site Pune Maharashtra India 411 005
    59 Research Site Jaipur Rajasthan India 302 022
    60 Research Site Madurai Tamil Nadu India 625 020
    61 Research Site Gandhinagar India 382 428
    62 Research Site Mangalore India 575 001
    63 Research Site Nashik India 422 009
    64 Research Site Firenze Italy 50139
    65 Research Site Milano Italy 20122
    66 Research Site Milano Italy 20142
    67 Research Site Pisa Italy 56126
    68 Research Site Roma (RM) Italy 00133
    69 Research Site Verona Italy 37126
    70 Research Site Liepaja Latvia 3400
    71 Research Site Riga Latvia 1004
    72 Research Site Riga Latvia 1005
    73 Research Site Valmiera Latvia 4201
    74 Research Site Kaunas Lithuania 44320
    75 Research Site Vilnius Lithuania 04130
    76 Research Site Monterrey Nuevo León Mexico 64040
    77 Research Site Christchurch New Zealand 8022
    78 Research Site Tauranga New Zealand 3143
    79 Research Site Kongsvinger Norway 2226
    80 Research Site Bialystok Poland 15-276
    81 Research Site Bytom Poland 41-902
    82 Research Site Krakow Poland 30-901
    83 Research Site Kraków Poland 31-826
    84 Research Site Lublin Poland 20-718
    85 Research Site Bucharest Romania 014461
    86 Research Site Bucuresti Romania 050098
    87 Research Site Timisoara Romania 300736
    88 Research Site Moscow Russian Federation 115280
    89 Research Site Moscow Russian Federation 117292
    90 Research Site Moscow Russian Federation 119049
    91 Research Site Moscow Russian Federation 127299
    92 Research Site Moscow Russian Federation 129327
    93 Research Site Saint Petersburg Russian Federation 196247
    94 Research Site Yaroslavl Russian Federation 150003
    95 Research Site Bratislava Slovakia 833 05
    96 Research Site Nitra Slovakia 950 01
    97 Research Site Piestany Slovakia 921 01
    98 Research Site Leeds United Kingdom LS1 3EX
    99 Research Site London United Kingdom E1 1BB
    100 Research Site Newcastle United Kingdom NE1 4LP
    101 Research Site Norwich United Kingdom NR4 7UY
    102 Research Site Oxford United Kingdom OX3 9DU
    103 Research Site Stanmore United Kingdom HA7 4LP

    Sponsors and Collaborators

    • Amgen
    • UCB Pharma

    Investigators

    • Study Director: MD, Amgen

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT00907296
    Other Study ID Numbers:
    • 20062017
    • 2008-008392-34
    First Posted:
    May 22, 2009
    Last Update Posted:
    May 1, 2019
    Last Verified:
    Mar 1, 2019
    Keywords provided by Amgen
    Fracture Healing
    Tibial Diaphyseal Fracture
    Additional relevant MeSH terms:
    Fractures, Bone

    Study Results

    Participant Flow

    Recruitment Details This study was conducted at 66 centers in Europe, India, North America, Australia, New Zealand, Hong Kong, and Mexico. Participants were enrolled from 02 September 2009 to 19 September 2011.
    Pre-assignment Detail Participants were randomized 1:1:1:1:1:1:1:1:1:3 to 1 of 9 romosozumab treatment groups or placebo. Randomization followed surgery and was stratified by type of fracture and definitive fracture fixation.
    Arm/Group Title Placebo Romosozumab 70 mg: 2 Doses Romosozumab 70 mg: 3 Doses Romosozumab 70 mg: 4 Doses Romosozumab 140 mg: 2 Doses Romosozumab 140 mg: 3 Doses Romosozumab 140 mg: 4 Doses Romosozumab 210 mg: 2 Doses Romosozumab 210 mg: 3 Doses Romosozumab 210 mg: 4 Doses
    Arm/Group Description Participants received subcutaneous injections of matching placebo on day 1 and at weeks 2, 6, and 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2, 6, and 12. Participants received subcutaneous injections of 140 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2, 6, and 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2, 6, and 12.
    Period Title: Overall Study
    STARTED 103 34 34 33 33 33 33 33 31 35
    Received Treatment 100 34 34 32 33 32 31 32 30 35
    COMPLETED 83 29 32 29 32 24 27 26 27 28
    NOT COMPLETED 20 5 2 4 1 9 6 7 4 7

    Baseline Characteristics

    Arm/Group Title Placebo Romosozumab 70 mg: 2 Doses Romosozumab 70 mg: 3 Doses Romosozumab 70 mg: 4 Doses Romosozumab 140 mg: 2 Doses Romosozumab 140 mg: 3 Doses Romosozumab 140 mg: 4 Doses Romosozumab 210 mg: 2 Doses Romosozumab 210 mg: 3 Doses Romosozumab 210 mg: 4 Doses Total
    Arm/Group Description Participants received subcutaneous injections of matching placebo on day 1 and at weeks 2, 6, and 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2, 6, and 12. Participants received subcutaneous injections of 140 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2, 6, and 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2, 6, and 12. Total of all reporting groups
    Overall Participants 103 34 34 33 33 33 33 33 31 35 402
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    40.3
    (13.8)
    38.6
    (13.8)
    43.2
    (17.7)
    45.9
    (15.6)
    41.3
    (13.7)
    41.0
    (14.9)
    38.7
    (12.7)
    42.8
    (13.7)
    36.8
    (13.8)
    41.7
    (14.4)
    40.9
    (14.4)
    Sex: Female, Male (Count of Participants)
    Female
    29
    28.2%
    7
    20.6%
    10
    29.4%
    8
    24.2%
    8
    24.2%
    11
    33.3%
    11
    33.3%
    5
    15.2%
    13
    41.9%
    12
    34.3%
    114
    28.4%
    Male
    74
    71.8%
    27
    79.4%
    24
    70.6%
    25
    75.8%
    25
    75.8%
    22
    66.7%
    22
    66.7%
    28
    84.8%
    18
    58.1%
    23
    65.7%
    288
    71.6%
    Race/Ethnicity, Customized (Count of Participants)
    White
    80
    77.7%
    20
    58.8%
    24
    70.6%
    29
    87.9%
    22
    66.7%
    23
    69.7%
    24
    72.7%
    25
    75.8%
    24
    77.4%
    28
    80%
    299
    74.4%
    Black or African American
    2
    1.9%
    2
    5.9%
    1
    2.9%
    0
    0%
    1
    3%
    1
    3%
    1
    3%
    0
    0%
    0
    0%
    0
    0%
    8
    2%
    Hispanic or Latino
    1
    1%
    1
    2.9%
    0
    0%
    1
    3%
    1
    3%
    1
    3%
    0
    0%
    1
    3%
    1
    3.2%
    1
    2.9%
    8
    2%
    Asian
    20
    19.4%
    11
    32.4%
    9
    26.5%
    3
    9.1%
    9
    27.3%
    8
    24.2%
    8
    24.2%
    7
    21.2%
    6
    19.4%
    5
    14.3%
    86
    21.4%
    Other
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    2.9%
    1
    0.2%
    Randomization Stratification (Count of Participants)
    Closed with reamed IM nail
    88
    85.4%
    30
    88.2%
    30
    88.2%
    29
    87.9%
    29
    87.9%
    29
    87.9%
    29
    87.9%
    29
    87.9%
    28
    90.3%
    29
    82.9%
    350
    87.1%
    Gustilo type I/II open with reamed IM nail
    10
    9.7%
    3
    8.8%
    4
    11.8%
    3
    9.1%
    3
    9.1%
    4
    12.1%
    4
    12.1%
    4
    12.1%
    3
    9.7%
    4
    11.4%
    42
    10.4%
    Gustilo type I/II open with unreamed IM nail
    5
    4.9%
    1
    2.9%
    0
    0%
    1
    3%
    1
    3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    5.7%
    10
    2.5%

    Outcome Measures

    1. Primary Outcome
    Title Time to Radiographic Healing
    Description Time to radiographic healing was defined as the time from intramedullary (IM) nailing to the first occurrence of bridging of 3 out of 4 cortices. Radiographic fracture healing was determined by a panel of independent reviewers (orthopedic/trauma surgeons and radiologists) blinded to treatment. The cumulative incidence function (CIF) method was used to estimate the median time to radiographic healing and the confidence intervals. Unplanned revision surgery to promote healing was considered a competing risk in CIF estimate.
    Time Frame 52 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study drug.
    Arm/Group Title Placebo Romosozumab 70 mg: 2 Doses Romosozumab 70 mg: 3 Doses Romosozumab 70 mg: 4 Doses Romosozumab 140 mg: 2 Doses Romosozumab 140 mg: 3 Doses Romosozumab 140 mg: 4 Doses Romosozumab 210 mg: 2 Doses Romosozumab 210 mg: 3 Doses Romosozumab 210 mg: 4 Doses
    Arm/Group Description Participants received subcutaneous injections of matching placebo on day 1 and at weeks 2, 6, and 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2, 6, and 12. Participants received subcutaneous injections of 140 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2, 6, and 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2, 6, and 12.
    Measure Participants 100 34 34 32 33 32 31 32 30 35
    Median (95% Confidence Interval) [weeks]
    16.4
    18.6
    18.3
    18.2
    17.8
    18.1
    17.0
    14.4
    15.4
    16.4
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 70 mg: 2 Doses
    Comments The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3598
    Comments
    Method Cox proportional hazard model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.82
    Confidence Interval (2-Sided) 95%
    0.53 to 1.26
    Parameter Dispersion Type:
    Value:
    Estimation Comments A hazard ratio > 1 favors romosozumab.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 70 mg: 3 Doses
    Comments The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6544
    Comments
    Method Cox proportional hazard model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.91
    Confidence Interval (2-Sided) 95%
    0.59 to 1.39
    Parameter Dispersion Type:
    Value:
    Estimation Comments A hazard ratio > 1 favors romosozumab.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 70 mg: 4 Doses
    Comments The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9958
    Comments
    Method Cox proportional hazard model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.00
    Confidence Interval (2-Sided) 95%
    0.64 to 1.58
    Parameter Dispersion Type:
    Value:
    Estimation Comments A hazard ratio > 1 favors romosozumab.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 140 mg: 2 Doses
    Comments The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6276
    Comments
    Method Cox proportional hazard model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.90
    Confidence Interval (2-Sided) 95%
    0.59 to 1.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments A hazard ratio > 1 favors romosozumab.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 140 mg: 3 Doses
    Comments The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8819
    Comments
    Method Cox proportional hazard model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.97
    Confidence Interval (2-Sided) 95%
    0.63 to 1.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments A hazard ratio > 1 favors romosozumab.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 140 mg: 4 Doses
    Comments The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7197
    Comments
    Method Cox proportional hazard model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.92
    Confidence Interval (2-Sided) 95%
    0.60 to 1.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments A hazard ratio > 1 favors romosozumab.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 210 mg: 2 Doses
    Comments The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6204
    Comments
    Method Cox proportional hazard model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.11
    Confidence Interval (2-Sided) 95%
    0.73 to 1.70
    Parameter Dispersion Type:
    Value:
    Estimation Comments A hazard ratio > 1 favors romosozumab.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 210 mg: 3 Doses
    Comments The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4779
    Comments
    Method Cox proportional hazard model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.18
    Confidence Interval (2-Sided) 95%
    0.75 to 1.84
    Parameter Dispersion Type:
    Value:
    Estimation Comments A hazard ratio > 1 favors romosozumab.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 210 mg: 4 Doses
    Comments The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9952
    Comments
    Method Cox proportional hazard model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.00
    Confidence Interval (2-Sided) 95%
    0.65 to 1.53
    Parameter Dispersion Type:
    Value:
    Estimation Comments A hazard ratio > 1 favors romosozumab.
    2. Secondary Outcome
    Title Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain
    Description The Medical Outcome Study Short Form 36-Item Health Survey (SF-36), Version 2, is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical functioning domain includes 10 questions that assess limitations in physical activities because of health problems. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. The range of SF-36 physical functioning is 14.94 - 57.03. Higher scores indicate a higher level of functioning. A positive change from baseline score indicates an improvement in physical functioning.
    Time Frame Week 8 and weeks 12, 16, 20, 24, 36, and 52

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study drug and with available data at each time point.
    Arm/Group Title Placebo Romosozumab 70 mg: 2 Doses Romosozumab 70 mg: 3 Doses Romosozumab 70 mg: 4 Doses Romosozumab 140 mg: 2 Doses Romosozumab 140 mg: 3 Doses Romosozumab 140 mg: 4 Doses Romosozumab 210 mg: 2 Doses Romosozumab 210 mg: 3 Doses Romosozumab 210 mg: 4 Doses
    Arm/Group Description Participants received subcutaneous injections of matching placebo on day 1 and at weeks 2, 6, and 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2, 6, and 12. Participants received subcutaneous injections of 140 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2, 6, and 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2, 6, and 12.
    Measure Participants 100 34 34 32 33 32 31 32 30 35
    Week 12
    5.77
    (9.90)
    6.31
    (6.84)
    5.67
    (8.60)
    5.04
    (9.01)
    4.28
    (8.22)
    7.08
    (8.06)
    3.63
    (9.30)
    3.65
    (9.06)
    7.33
    (7.99)
    5.64
    (6.67)
    Week 16
    9.64
    (10.36)
    9.83
    (7.24)
    9.19
    (11.30)
    9.28
    (11.14)
    8.89
    (10.71)
    11.18
    (9.23)
    8.78
    (11.34)
    9.23
    (9.59)
    9.50
    (9.01)
    9.01
    (10.41)
    Week 20
    13.20
    (12.25)
    14.53
    (9.69)
    10.45
    (11.66)
    13.50
    (12.02)
    12.13
    (10.88)
    14.77
    (13.52)
    12.44
    (11.97)
    12.61
    (10.88)
    12.50
    (10.76)
    11.05
    (11.56)
    Week 24
    15.87
    (11.55)
    15.07
    (9.31)
    10.34
    (13.31)
    15.90
    (11.26)
    14.57
    (10.34)
    16.84
    (12.70)
    11.79
    (17.64)
    13.05
    (10.99)
    13.05
    (10.25)
    12.38
    (14.04)
    Week 36
    19.57
    (11.60)
    20.96
    (11.68)
    11.48
    (17.84)
    17.23
    (10.15)
    17.61
    (11.03)
    19.43
    (12.83)
    15.70
    (19.03)
    15.01
    (11.23)
    17.47
    (14.34)
    15.22
    (15.20)
    Week 52
    20.74
    (11.96)
    23.47
    (11.55)
    13.63
    (19.04)
    19.02
    (10.80)
    19.63
    (12.17)
    24.80
    (11.24)
    17.19
    (15.51)
    15.50
    (13.17)
    18.29
    (14.94)
    15.44
    (17.15)
    3. Secondary Outcome
    Title Number of Participants With Unplanned Revision Surgeries
    Description
    Time Frame 52 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study drug
    Arm/Group Title Placebo Romosozumab 70 mg: 2 Doses Romosozumab 70 mg: 3 Doses Romosozumab 70 mg: 4 Doses Romosozumab 140 mg: 2 Doses Romosozumab 140 mg: 3 Doses Romosozumab 140 mg: 4 Doses Romosozumab 210 mg: 2 Doses Romosozumab 210 mg: 3 Doses Romosozumab 210 mg: 4 Doses
    Arm/Group Description Participants received subcutaneous injections of matching placebo on day 1 and at weeks 2, 6, and 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2, 6, and 12. Participants received subcutaneous injections of 140 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2, 6, and 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2, 6, and 12.
    Measure Participants 100 34 34 32 33 32 31 32 30 35
    Count of Participants [Participants]
    8
    7.8%
    1
    2.9%
    3
    8.8%
    3
    9.1%
    1
    3%
    0
    0%
    0
    0%
    0
    0%
    1
    3.2%
    1
    2.9%
    4. Secondary Outcome
    Title Time to Clinical Healing
    Description Time to clinical healing was defined as the time from the IM nailing surgery date to the first date that both the score for ability to bear weight on the fractured limb and the score for absence of pain at the fracture site were equal to 6. The score for the ability to bear weight on the fractured limb was based on the ability to stand on affected leg without assistive device and the ability to walk without assistive device. The score ranges from 0 (unable to bear full body weight on the fractured limb) to 6 (able to bear full body weight on the fractured limb). Absence of pain at the fracture site was based on the absence of pain at the fracture site when applying direct pressure to the fracture site and applying a stress to the fracture site. The score ranges from 0 (pain without palpation at fracture site) to 6 (total absence of pain at fracture site). Time to clinical healing was estimated using CIF; unplanned revision surgery was considered a competing risk in CIF estimate.
    Time Frame 52 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of study drug
    Arm/Group Title Placebo Romosozumab 70 mg: 2 Doses Romosozumab 70 mg: 3 Doses Romosozumab 70 mg: 4 Doses Romosozumab 140 mg: 2 Doses Romosozumab 140 mg: 3 Doses Romosozumab 140 mg: 4 Doses Romosozumab 210 mg: 2 Doses Romosozumab 210 mg: 3 Doses Romosozumab 210 mg: 4 Doses
    Arm/Group Description Participants received subcutaneous injections of matching placebo on day 1 and at weeks 2, 6, and 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2, 6, and 12. Participants received subcutaneous injections of 140 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2, 6, and 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2, 6, and 12.
    Measure Participants 100 34 34 32 33 32 31 32 30 35
    Median (95% Confidence Interval) [weeks]
    18.4
    21.4
    18.3
    17.1
    20.8
    22.3
    15.0
    16.3
    14.6
    17.6
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 70 mg: 2 Doses
    Comments The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1713
    Comments
    Method Cox proportional hazard model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.73
    Confidence Interval (2-Sided) 95%
    0.47 to 1.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments A hazard ratio > 1 favors romosozumab.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 70 mg: 3 Doses
    Comments The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9958
    Comments
    Method Cox proportional hazard model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.00
    Confidence Interval (2-Sided) 95%
    0.65 to 1.53
    Parameter Dispersion Type:
    Value:
    Estimation Comments A hazard ratio > 1 favors romosozumab.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 70 mg: 4 Doses
    Comments The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2950
    Comments
    Method Cox proportional hazard model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.27
    Confidence Interval (2-Sided) 95%
    0.81 to 1.97
    Parameter Dispersion Type:
    Value:
    Estimation Comments A hazard ratio > 1 favors romosozumab.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 140 mg: 2 Doses
    Comments The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0844
    Comments
    Method Cox proportional hazard model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.68
    Confidence Interval (2-Sided) 95%
    0.44 to 1.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments A hazard ratio > 1 favors romosozumab.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 140 mg: 3 Doses
    Comments The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3225
    Comments
    Method Cox proportional hazard model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.80
    Confidence Interval (2-Sided) 95%
    0.52 to 1.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments A hazard ratio > 1 favors romosozumab.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 140 mg: 4 Doses
    Comments The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4754
    Comments
    Method Cox proportional hazard model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.17
    Confidence Interval (2-Sided) 95%
    0.76 to 1.81
    Parameter Dispersion Type:
    Value:
    Estimation Comments A hazard ratio > 1 favors romosozumab.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 210 mg: 2 Doses
    Comments The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5578
    Comments
    Method Cox proportional hazard model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.14
    Confidence Interval (2-Sided) 95%
    0.74 to 1.75
    Parameter Dispersion Type:
    Value:
    Estimation Comments A hazard ratio > 1 favors romosozumab.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 210 mg: 3 Doses
    Comments The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1864
    Comments
    Method Cox proportional hazard model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.34
    Confidence Interval (2-Sided) 95%
    0.87 to 2.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments A hazard ratio > 1 favors romosozumab
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, Romosozumab 210 mg: 4 Doses
    Comments The cause-specific hazard was modeled using a Cox proportional hazards model with 10 treatment groups as the independent variable, stratified by type of fracture and definitive fracture fixation (closed with reamed IM nail, Gustilo type I/II open with reamed IM nail, Gustilo type I/II open with unreamed IM nail) and adjusting for quality of surgical fixation.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8488
    Comments
    Method Cox proportional hazard model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.04
    Confidence Interval (2-Sided) 95%
    0.68 to 1.59
    Parameter Dispersion Type:
    Value:
    Estimation Comments A hazard ratio > 1 favors romosozumab.

    Adverse Events

    Time Frame 52 weeks
    Adverse Event Reporting Description Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
    Arm/Group Title Placebo Romosozumab 70 mg: 2 Doses Romosozumab 70 mg: 3 Doses Romosozumab 70 mg: 4 Doses Romosozumab 140 mg: 2 Doses Romosozumab 140 mg: 3 Doses Romosozumab 140 mg: 4 Doses Romosozumab 210 mg: 2 Doses Romosozumab 210 mg: 3 Doses Romosozumab 210 mg: 4 Doses
    Arm/Group Description Participants received subcutaneous injections of matching placebo on day 1 and at weeks 2, 6, and 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2, 6, and 12. Participants received subcutaneous injections of 140 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12 Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12 Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2, 6, and 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2, 6, and 12.
    All Cause Mortality
    Placebo Romosozumab 70 mg: 2 Doses Romosozumab 70 mg: 3 Doses Romosozumab 70 mg: 4 Doses Romosozumab 140 mg: 2 Doses Romosozumab 140 mg: 3 Doses Romosozumab 140 mg: 4 Doses Romosozumab 210 mg: 2 Doses Romosozumab 210 mg: 3 Doses Romosozumab 210 mg: 4 Doses
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Placebo Romosozumab 70 mg: 2 Doses Romosozumab 70 mg: 3 Doses Romosozumab 70 mg: 4 Doses Romosozumab 140 mg: 2 Doses Romosozumab 140 mg: 3 Doses Romosozumab 140 mg: 4 Doses Romosozumab 210 mg: 2 Doses Romosozumab 210 mg: 3 Doses Romosozumab 210 mg: 4 Doses
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 10/100 (10%) 4/34 (11.8%) 2/34 (5.9%) 3/32 (9.4%) 3/33 (9.1%) 4/32 (12.5%) 2/31 (6.5%) 3/32 (9.4%) 3/30 (10%) 0/35 (0%)
    Gastrointestinal disorders
    Abdominal pain upper 0/100 (0%) 1/34 (2.9%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    General disorders
    Chest pain 0/100 (0%) 1/34 (2.9%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Chills 0/100 (0%) 1/34 (2.9%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Device breakage 0/100 (0%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 1/33 (3%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Inflammation 0/100 (0%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 1/33 (3%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Malaise 0/100 (0%) 1/34 (2.9%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Oedema peripheral 0/100 (0%) 1/34 (2.9%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Infections and infestations
    Cellulitis 1/100 (1%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Device related infection 1/100 (1%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 1/30 (3.3%) 0/35 (0%)
    Infection 0/100 (0%) 0/34 (0%) 1/34 (2.9%) 0/32 (0%) 0/33 (0%) 1/32 (3.1%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Localised infection 1/100 (1%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Malaria 0/100 (0%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 1/32 (3.1%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Pneumonia 1/100 (1%) 0/34 (0%) 1/34 (2.9%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Post procedural infection 0/100 (0%) 0/34 (0%) 1/34 (2.9%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Wound infection 0/100 (0%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 1/32 (3.1%) 1/31 (3.2%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Injury, poisoning and procedural complications
    Bone fissure 1/100 (1%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Femur fracture 1/100 (1%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 1/32 (3.1%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Fracture displacement 0/100 (0%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 1/32 (3.1%) 0/30 (0%) 0/35 (0%)
    Loss of anatomical alignment after fracture reduction 0/100 (0%) 1/34 (2.9%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Lower limb fracture 1/100 (1%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Ulna fracture 0/100 (0%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 1/33 (3%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Wound 2/100 (2%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Investigations
    Blood creatine phosphokinase increased 0/100 (0%) 1/34 (2.9%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Oxygen saturation decreased 1/100 (1%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/100 (0%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 1/33 (3%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Exostosis 0/100 (0%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 1/32 (3.1%) 0/30 (0%) 0/35 (0%)
    Pain in extremity 0/100 (0%) 1/34 (2.9%) 0/34 (0%) 1/32 (3.1%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Rotator cuff syndrome 0/100 (0%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 1/30 (3.3%) 0/35 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cholesteatoma 0/100 (0%) 1/34 (2.9%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Nervous system disorders
    Cerebral ischaemia 1/100 (1%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Paraplegia 0/100 (0%) 0/34 (0%) 0/34 (0%) 1/32 (3.1%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Transient ischaemic attack 0/100 (0%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 1/31 (3.2%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Psychiatric disorders
    Delirium 0/100 (0%) 1/34 (2.9%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Renal and urinary disorders
    Calculus ureteric 0/100 (0%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 1/30 (3.3%) 0/35 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism 0/100 (0%) 0/34 (0%) 0/34 (0%) 1/32 (3.1%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Skin and subcutaneous tissue disorders
    Erythema 0/100 (0%) 1/34 (2.9%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Surgical and medical procedures
    Medical device removal 0/100 (0%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 1/32 (3.1%) 0/30 (0%) 0/35 (0%)
    Vascular disorders
    Deep vein thrombosis 0/100 (0%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 1/32 (3.1%) 0/30 (0%) 0/35 (0%)
    Haematoma 1/100 (1%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Vascular insufficiency 1/100 (1%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo Romosozumab 70 mg: 2 Doses Romosozumab 70 mg: 3 Doses Romosozumab 70 mg: 4 Doses Romosozumab 140 mg: 2 Doses Romosozumab 140 mg: 3 Doses Romosozumab 140 mg: 4 Doses Romosozumab 210 mg: 2 Doses Romosozumab 210 mg: 3 Doses Romosozumab 210 mg: 4 Doses
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 38/100 (38%) 9/34 (26.5%) 17/34 (50%) 12/32 (37.5%) 16/33 (48.5%) 7/32 (21.9%) 9/31 (29%) 10/32 (31.3%) 9/30 (30%) 6/35 (17.1%)
    Gastrointestinal disorders
    Diarrhoea 2/100 (2%) 0/34 (0%) 2/34 (5.9%) 0/32 (0%) 2/33 (6.1%) 0/32 (0%) 0/31 (0%) 1/32 (3.1%) 3/30 (10%) 0/35 (0%)
    Vomiting 4/100 (4%) 0/34 (0%) 1/34 (2.9%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 2/30 (6.7%) 0/35 (0%)
    General disorders
    Asthenia 0/100 (0%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 2/33 (6.1%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Medical device discomfort 3/100 (3%) 2/34 (5.9%) 1/34 (2.9%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 1/32 (3.1%) 0/30 (0%) 0/35 (0%)
    Oedema peripheral 6/100 (6%) 0/34 (0%) 4/34 (11.8%) 4/32 (12.5%) 3/33 (9.1%) 2/32 (6.3%) 1/31 (3.2%) 3/32 (9.4%) 2/30 (6.7%) 1/35 (2.9%)
    Pain 7/100 (7%) 0/34 (0%) 2/34 (5.9%) 1/32 (3.1%) 1/33 (3%) 1/32 (3.1%) 1/31 (3.2%) 0/32 (0%) 0/30 (0%) 1/35 (2.9%)
    Pyrexia 5/100 (5%) 2/34 (5.9%) 1/34 (2.9%) 0/32 (0%) 0/33 (0%) 2/32 (6.3%) 1/31 (3.2%) 2/32 (6.3%) 1/30 (3.3%) 1/35 (2.9%)
    Infections and infestations
    Influenza 1/100 (1%) 2/34 (5.9%) 1/34 (2.9%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Nasopharyngitis 4/100 (4%) 2/34 (5.9%) 2/34 (5.9%) 0/32 (0%) 2/33 (6.1%) 0/32 (0%) 0/31 (0%) 1/32 (3.1%) 1/30 (3.3%) 0/35 (0%)
    Rhinitis 1/100 (1%) 2/34 (5.9%) 0/34 (0%) 1/32 (3.1%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 1/30 (3.3%) 0/35 (0%)
    Upper respiratory tract infection 3/100 (3%) 1/34 (2.9%) 4/34 (11.8%) 0/32 (0%) 0/33 (0%) 1/32 (3.1%) 0/31 (0%) 1/32 (3.1%) 0/30 (0%) 0/35 (0%)
    Injury, poisoning and procedural complications
    Fall 3/100 (3%) 0/34 (0%) 0/34 (0%) 1/32 (3.1%) 1/33 (3%) 1/32 (3.1%) 0/31 (0%) 0/32 (0%) 2/30 (6.7%) 0/35 (0%)
    Limb injury 0/100 (0%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 2/30 (6.7%) 0/35 (0%)
    Procedural pain 2/100 (2%) 0/34 (0%) 0/34 (0%) 2/32 (6.3%) 2/33 (6.1%) 0/32 (0%) 1/31 (3.2%) 1/32 (3.1%) 0/30 (0%) 0/35 (0%)
    Investigations
    Alanine aminotransferase increased 0/100 (0%) 0/34 (0%) 0/34 (0%) 1/32 (3.1%) 0/33 (0%) 0/32 (0%) 2/31 (6.5%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Metabolism and nutrition disorders
    Diabetes mellitus 1/100 (1%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 2/33 (6.1%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 1/35 (2.9%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 6/100 (6%) 1/34 (2.9%) 1/34 (2.9%) 5/32 (15.6%) 4/33 (12.1%) 3/32 (9.4%) 0/31 (0%) 4/32 (12.5%) 2/30 (6.7%) 2/35 (5.7%)
    Bone pain 3/100 (3%) 1/34 (2.9%) 0/34 (0%) 3/32 (9.4%) 1/33 (3%) 1/32 (3.1%) 0/31 (0%) 0/32 (0%) 2/30 (6.7%) 0/35 (0%)
    Pain in extremity 6/100 (6%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 1/33 (3%) 2/32 (6.3%) 3/31 (9.7%) 1/32 (3.1%) 1/30 (3.3%) 0/35 (0%)
    Nervous system disorders
    Headache 3/100 (3%) 0/34 (0%) 2/34 (5.9%) 0/32 (0%) 0/33 (0%) 1/32 (3.1%) 2/31 (6.5%) 0/32 (0%) 1/30 (3.3%) 0/35 (0%)
    Paraesthesia 3/100 (3%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 2/33 (6.1%) 0/32 (0%) 0/31 (0%) 1/32 (3.1%) 1/30 (3.3%) 0/35 (0%)
    Psychiatric disorders
    Depressed mood 0/100 (0%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 2/33 (6.1%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Insomnia 5/100 (5%) 1/34 (2.9%) 2/34 (5.9%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 1/31 (3.2%) 0/32 (0%) 0/30 (0%) 0/35 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 2/100 (2%) 1/34 (2.9%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 0/32 (0%) 2/30 (6.7%) 0/35 (0%)
    Oropharyngeal pain 1/100 (1%) 0/34 (0%) 0/34 (0%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 1/31 (3.2%) 0/32 (0%) 2/30 (6.7%) 1/35 (2.9%)
    Skin and subcutaneous tissue disorders
    Blister 0/100 (0%) 0/34 (0%) 2/34 (5.9%) 0/32 (0%) 0/33 (0%) 0/32 (0%) 0/31 (0%) 1/32 (3.1%) 0/30 (0%) 0/35 (0%)

    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 medinfo@amgen.com
    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT00907296
    Other Study ID Numbers:
    • 20062017
    • 2008-008392-34
    First Posted:
    May 22, 2009
    Last Update Posted:
    May 1, 2019
    Last Verified:
    Mar 1, 2019