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Zoledronic Acid in the Prevention of Cancer Treatment Related Bone Loss in Postmenopausal Women Receiving Letrozole for Breast Cancer.

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT00171340
Collaborator
(none)
1,065
Enrollment
106
Locations
2
Arms
81.1
Duration (Months)
10
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Post-menopausal breast cancer patients will receive letrozole 2.5 mg daily for the treatment of breast cancer and will be randomized to a treatment group to receive either upfront zoledronic acid 4 mg IV 15-minute infusion every 6 months or delayed start zoledronic acid 4 mg IV 15-minute infusion every 6 months. Delayed start zoledronic acid will be initiated when either the Bone Mineral Density T-score is below -2 Standard Deviations at either the lumbar spine or hip or any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the month 36 scheduled visit. Letrozole 2.5 mg will be given daily for 5 years.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
1065 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label, Randomized, MultiCenter Study to Evaluate the Use of Zolendronic Acid in the Prevention of Cancer Treatment-Related Bone Loss in Postmenopausal Women With Estrogen Positive and/or Progesterone Positive Breast Cancer Receiving Letrozole as Adjuvant Therapy
Study Start Date :
May 1, 2003
Actual Primary Completion Date :
Feb 1, 2010
Actual Study Completion Date :
Feb 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Experimental: Upfront Zoledronic Acid

Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.

Drug: Zoledronic acid
Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months.
Other Names:
  • ZOL446
  • Zometa®

    • Drug: Letrozole
    Letrozole tablets 2.5 mg/day taken orally for 5 years.
    Other Names:
  • Femara®

    		•
    Experimental: Delayed Zoledronic Acid

    Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score <= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.

    Drug: Zoledronic acid
    Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months.
    Other Names:
  • ZOL446
  • Zometa®

    • Drug: Letrozole
    Letrozole tablets 2.5 mg/day taken orally for 5 years.
    Other Names:
  • Femara®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage Change in Bone Mineral Density (BMD) of the Lumbar Spine (L2-L4) at 12 Months of Therapy. [Baseline, 12 months]

      Bone Mineral Density (g/cm^2) of the Lumbar Spine (L2-L4) as measured by energy x-ray absorptiometry (DXA).

    Secondary Outcome Measures

    1. Percentage Change in Bone Mineral Density (BMD) of the Lumbar Spine (L2-L4) at 2, 3, 4 and 5 Years of Therapy. [Baseline, 2 years. Baseline, 3 years. Baseline, 4 years. Baseline, 5 years.]

      Bone Mineral Density (g/cm^2) of the Lumbar Spine (L2-L4) as measured by dual energy x-ray absorptiometry (DXA)

    2. Percentage Change in Bone Mineral Density (BMD)of the Lumbar Spine (L1-L4) Over 5 Years of Therapy. [Baseline, 5 years.]

      Bone Mineral Density (g/cm^2) of the Lumbar Spine (L1-L4)as measured by dual energy x-ray absorptiometry (DXA)

    3. Percentage Change in Bone Mineral Density (BMD) of the Total Hip at 12 Months, 2 Years, 3 Years, 4 Years and 5 Years After Therapy. [Baseline, 12 months. Baseline, 2 years. Baseline, 3 years. Baseline, 4 years. Baseline, 5 years.]

      Bone Mineral Density (g/cm^2) of the Lumbar Spine (L2-L4) as measured by dual energy x-ray absorptiometry (DXA)

    4. Percentage of Participants With Clinical Fractures at 3 Years of Therapy Which Were Not Present at Baseline [Baseline,3 years]

      At 3 years of therapy the percentage of participants with fractures as detected by X-ray and/ or bone scan.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Stage I-IIIa breast cancer

    • Postmenopausal or recently postmenopausal

    • Recent surgery for breast cancer

    • Estrogen Receptor positive and/or progesterone receptor positive hormone receptor status

    • No prior treatment with letrozole

    Other protocol-defined inclusion criteria may apply.

    Exclusion Criteria:

    • Metastatic disease

    • Invasive bilateral disease

    • Clinical or radiological evidence of existing fracture in spine or hip

    • Prior treatment with IV bisphosphonates in the past 12 months

    • Current treatment with oral bisphosphonates ( must be discontinued within 3 weeks of baseline evaluation)

    • Use of Tibolone within 6 months

    • Prior use of parathyroid hormone for more than 1 week

    • Previous or concomitant malignancy

    • Abnormal renal function

    • History of disease effecting bone metabolism

    Other protocol-defined exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Buenos Aires Argentina
    2 Novartis Investigative Site Rosario Santa Fe Argentina
    3 Novartis Investigative Site New South Wales Australia
    4 Novartis Investigative Site Perth Australia
    5 Novartis Investigative Site South Australia Australia
    6 Novartis Investigative Site Victoria Australia
    7 Novartis Investigative Site Bonheiden Belgium
    8 Novartis Investigative Site Brasschaat Belgium
    9 Novartis Investigative Site Brussels Belgium
    10 Novartis Investigative Site Leuven Belgium
    11 Novartis Investigative Site Wilrijk Belgium
    12 Novartis Investigative Site Porto Alegre Brazil
    13 Novartis Investigative Site Sao Paulo Brazil
    14 Novartis Investigative Site Santiago Chile
    15 Novartis Investigative Site Beijing China
    16 Novartis Investigative Site Shanghai China
    17 Novartis Investigative Site Medellin Colombia
    18 Novartis Investigative Site Nemocnice Czech Republic
    19 Novartis Investigative Site Cairo Egypt
    20 Novartis Investigative Site Pori Finland
    21 Novartis Investigative Site Turku Finland
    22 Novartis Investigative Site Bordeaux Cedex France
    23 Novartis Investigative Site Le Havre France
    24 Novartis Investigative Site Montpellier Cedex France
    25 Novartis Investigative Site Poitiers Cedex France
    26 Novartis Investigative Site St. Cloud France
    27 Novartis Investigative Site Augsberg Germany
    28 Novartis Investigative Site Berlin Germany
    29 Novartis Investigative Site Ebersberg Germany
    30 Novartis Investigative Site Frankfurt Germany
    31 Novartis Investigative Site Halberstadt Germany
    32 Novartis Investigative Site Hamburg Germany
    33 Novartis Investigative Site Hoyerswerda Germany
    34 Novartis Investigative Site Kassel Germany
    35 Novartis Investigative Site Kiel Germany
    36 Novartis Investigative Site Muenchen Germany
    37 Novartis Investigative Site Munich Germany
    38 Novartis Investigative Site Neunkirchen Germany
    39 Novartis Investigative Site Rostock Germany
    40 Novartis Investigative Site Stadthagen Germany
    41 Novartis Investigative Site Stendal Germany
    42 Novartis Investigative Site Trier Germany
    43 Novartis Investigative Site Tubingen Germany
    44 Novartis Investigative Site Wiesbaden Germany
    45 Novartis Investigative Site Guatemala City Guatemala
    46 Novartis Investigative Site Hong Kong Hong Kong
    47 Novartis Investigative Site Ancona Italy
    48 Novartis Investigative Site Aviano Italy 33081
    49 Novartis Investigative Site Bergamo Italy
    50 Novartis Investigative Site Catanzaro Italy 88100
    51 Novartis Investigative Site Firenze Italy 50139
    52 Novartis Investigative Site Genova Italy
    53 Novartis Investigative Site Meldola Italy
    54 Novartis Investigative Site Modena Italy
    55 Novartis Investigative Site Orbassano Torino Italy
    56 Novartis Investigative Site Perugia Italy
    57 Novartis Investigative Site Torino Italy
    58 Novartis Investigative Site Varese Italy
    59 Novartis Investigative Site Gyeonggi Korea, Republic of
    60 Novartis Investigative Site Seoul Korea, Republic of 110
    61 Novartis Investigative Site Seoul Korea, Republic of 137
    62 Novartis Investigative Site Seoul Korea, Republic of 138
    63 Novartis Investigative Site Seoul Korea, Republic of 139
    64 Novartis Investigative Site Distrito Federal Mexico
    65 Novartis Investigative Site Almere Netherlands
    66 Novartis Investigative Site Arnhem Netherlands
    67 Novartis Investigative Site Den Haag Netherlands
    68 Novartis Investigative Site Ede Netherlands
    69 Novartis Investigative Site Eindhoven Netherlands
    70 Novartis Investigative Site Hoogeveen Netherlands
    71 Novartis Investigative Site Leiden Netherlands
    72 Novartis Investigative Site Nijmegen Netherlands
    73 Novartis Investigative Site Utrecht Netherlands
    74 Novartis Investigative Site Hamilton New Zealand
    75 Novartis Investigative Site Wellington New Zealand
    76 Novartis Investigative Site Jesus Maria Peru
    77 Novartis Investigative Site La Victoria Peru
    78 Novartis Investigative Site Surquillo Peru
    79 Novartis Investigative Site Cebu City Philippines
    80 Novartis Investigative Site Quezon City Philippines
    81 Novartis Investigative Site Coimbra Portugal
    82 Novartis Investigative Site Barcelona Spain
    83 Novartis Investigative Site Cordoba Spain
    84 Novartis Investigative Site Gea Spain
    85 Novartis Investigative Site Ibanez Spain
    86 Novartis Investigative Site La Maso Spain
    87 Novartis Investigative Site Villaroel Spain
    88 Novartis Investigative Site Bern Switzerland
    89 Novartis Investigative Site Locarno Switzerland
    90 Novartis Investigative Site Lugano Switzerland
    91 Novartis Investigative Site Chang Hwa Taiwan 500
    92 Novartis Investigative Site Taipei Taiwan 100
    93 Novartis Investigative Site Taipei Taiwan 105
    94 Novartis Investigative Site Taipei Taiwan 112
    95 Novartis Investigative Site Bangkok Thailand 10400
    96 Novartis Investigative Site Bangkok Thailand
    97 Ratchathew Khonkaen Thailand 40002
    98 Novartis Investigative Site Birmingham United Kingdom
    99 Novartis Investigative Site Essex United Kingdom
    100 Novartis Investigative Site Manchester United Kingdom
    101 Novartis Investigative Site New Castle Upon Tyne United Kingdom
    102 Novartis Investigative Site Nottingham United Kingdom
    103 Novartis Investigative Site Plymouth United Kingdom
    104 Novartis Investigative Site Sheffield United Kingdom
    105 Novartis Investigative Site Swansea United Kingdom
    106 Novartis Investigative Site Caracas Venezuela

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00171340
    Other Study ID Numbers:
    • CFEM345D2405
    First Posted:
    Sep 15, 2005
    Last Update Posted:
    Apr 16, 2012
    Last Verified:
    Apr 1, 2012
    Keywords provided by Novartis Pharmaceuticals
    Bone Loss
    Osteopenia
    Breast cancer
    letrozole
    zoledronic acid
    postmenopausal
    Additional relevant MeSH terms:
    Breast Neoplasms
    Bone Diseases, Metabolic
    Zoledronic Acid
    Letrozole

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Zoledronic Acid 4 mg Upfront Zoledronic Acid 4 mg Delayed
    Arm/Group Description Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1. Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score <= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
    Period Title: Overall Study
    STARTED 532 533
    COMPLETED 408 398
    NOT COMPLETED 124 135

    Baseline Characteristics

    Arm/Group Title Zoledronic Acid 4 mg Upfront Zoledronic Acid 4 mg Delayed Total
    Arm/Group Description Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1. Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score <= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1. Total of all reporting groups
    Overall Participants 532 533 1065
    Age (Years) [Median (Full Range) ]
    Median (Full Range) [Years]
    57
    ((36-87))
    58
    ((37-81))
    57
    Sex: Female, Male (Count of Participants)
    Female
    532
    100%
    533
    100%
    1065
    100%
    Male
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Percentage Change in Bone Mineral Density (BMD) of the Lumbar Spine (L2-L4) at 12 Months of Therapy.
    Description Bone Mineral Density (g/cm^2) of the Lumbar Spine (L2-L4) as measured by energy x-ray absorptiometry (DXA).
    Time Frame Baseline, 12 months

    Outcome Measure Data

    Analysis Population Description
    The Safety Population consists of all Randomized Patients who received at least 1 dose of study medication.
    Arm/Group Title Zoledronic Acid 4 mg Upfront Zoledronic Acid 4 mg Delayed
    Arm/Group Description Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1. Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score <= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
    Measure Participants 423 418
    Mean (Standard Deviation) [Percentage change in BMD]
    2.208
    (3.4194)
    -3.617
    (4.2151)
    2. Secondary Outcome
    Title Percentage Change in Bone Mineral Density (BMD) of the Lumbar Spine (L2-L4) at 2, 3, 4 and 5 Years of Therapy.
    Description Bone Mineral Density (g/cm^2) of the Lumbar Spine (L2-L4) as measured by dual energy x-ray absorptiometry (DXA)
    Time Frame Baseline, 2 years. Baseline, 3 years. Baseline, 4 years. Baseline, 5 years.

    Outcome Measure Data

    Analysis Population Description
    The Safety Population consists of all Randomized Patients who received at least 1 dose of study medication. n in each of the categories is the number of participants who had safety data at baseline and the given time point.
    Arm/Group Title Zolendronic Acid 4 mg Upfront Zolendronic Acid 4 mg Delayed
    Arm/Group Description
    Measure Participants 525 535
    At 2 years (n=339,343)
    3.463
    (4.2691)
    -4.601
    (5.5273)
    At 3 years (n=313,311)
    3.730
    (4.884)
    -4.871
    (6.271)
    At 4 years (n=290,294)
    3.782
    (5.7300)
    -5.154
    (7.1079)
    At 5 years (n=264,264)
    4.308
    (6.0242)
    -5.414
    (7.6185)
    3. Secondary Outcome
    Title Percentage Change in Bone Mineral Density (BMD)of the Lumbar Spine (L1-L4) Over 5 Years of Therapy.
    Description Bone Mineral Density (g/cm^2) of the Lumbar Spine (L1-L4)as measured by dual energy x-ray absorptiometry (DXA)
    Time Frame Baseline, 5 years.

    Outcome Measure Data

    Analysis Population Description
    The Safety Population consists of all Randomized Patients who received at least 1 dose of study medication. n in each of the categories is the number of participants who had safety data at baseline and the given time point.
    Arm/Group Title Zolendronic Acid 4 mg Upfront Zolendronic Acid 4 mg Delayed
    Arm/Group Description
    Measure Participants 525 535
    At 12 months (n=360,369)
    2.128
    (3.2106)
    -3603
    (4.1808)
    At 2 years (n=339,343)
    3.300
    (4.0700)
    -4.521
    (5.2624)
    At 3 years (n=313,311)
    3.521
    (4.5936)
    -4.869
    (6.0310)
    At 4 years (n=290,294)
    3.529
    (5.5410)
    -5.148
    (6.8803)
    At 5 years (n=264,264)
    3.898
    (5.7995)
    -5.427
    (7.4818)
    4. Secondary Outcome
    Title Percentage Change in Bone Mineral Density (BMD) of the Total Hip at 12 Months, 2 Years, 3 Years, 4 Years and 5 Years After Therapy.
    Description Bone Mineral Density (g/cm^2) of the Lumbar Spine (L2-L4) as measured by dual energy x-ray absorptiometry (DXA)
    Time Frame Baseline, 12 months. Baseline, 2 years. Baseline, 3 years. Baseline, 4 years. Baseline, 5 years.

    Outcome Measure Data

    Analysis Population Description
    The Safety Population consists of all Randomized Patients who received at least 1 dose of study medication. n in each of the categories is the number of participants who had safety data at baseline and the given time point.
    Arm/Group Title Zolendronic Acid 4 mg Upfront Zolendronic Acid 4 mg Delayed
    Arm/Group Description
    Measure Participants 525 535
    At 12 months (n=419,434)
    1.222
    (2.3257)
    -2.239
    (3.3614)
    At 2 years (n=394,393)
    1.649
    (2.7333)
    -2.990
    (4.4318)
    At 3 years (n=376,365)
    1.754
    (3.1375)
    -3.302
    (4.8942)
    At 4 years (n=336,349)
    1.716
    (3.5228)
    -3.922
    (5.6505)
    At 5 years (n=306,314)
    1.615
    (3.7490)
    -4.162
    (6.0270)
    5. Secondary Outcome
    Title Percentage of Participants With Clinical Fractures at 3 Years of Therapy Which Were Not Present at Baseline
    Description At 3 years of therapy the percentage of participants with fractures as detected by X-ray and/ or bone scan.
    Time Frame Baseline,3 years

    Outcome Measure Data

    Analysis Population Description
    The Safety Population consists of all Randomized Patients who received at least 1 dose of study medication.
    Arm/Group Title Zoledronic Acid 4 mg Upfront Zoledronic Acid 4 mg Delayed
    Arm/Group Description Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1. Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score <= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
    Measure Participants 525 535
    Number [Percentage of Participants]
    0.6
    0.1%
    1.5
    0.3%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description Safety Population = Randomized participants who had received at least one dose of randomized treatment medication.
    Arm/Group Title Zoledronic Acid 4mg Upfront Zolendronic Acid 4mg Delayed
    Arm/Group Description Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1 and Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1. Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score <= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
    All Cause Mortality
    Zoledronic Acid 4mg Upfront Zolendronic Acid 4mg Delayed
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Zoledronic Acid 4mg Upfront Zolendronic Acid 4mg Delayed
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 133/525 (25.3%) 124/535 (23.2%)
    Blood and lymphatic system disorders
    Anaemia 1/525 (0.2%) 1/535 (0.2%)
    Febrile neutropenia 1/525 (0.2%) 0/535 (0%)
    Cardiac disorders
    Acute myocardial infarction 2/525 (0.4%) 0/535 (0%)
    Angina pectoris 3/525 (0.6%) 2/535 (0.4%)
    Angina unstable 1/525 (0.2%) 0/535 (0%)
    Aortic valve incompetence 1/525 (0.2%) 1/535 (0.2%)
    Arrhythmia 0/525 (0%) 1/535 (0.2%)
    Atrial fibrillation 1/525 (0.2%) 4/535 (0.7%)
    Atrioventricular block complete 0/525 (0%) 1/535 (0.2%)
    Cardiac arrest 0/525 (0%) 2/535 (0.4%)
    Cardiac failure 3/525 (0.6%) 0/535 (0%)
    Cardiac failure congestive 1/525 (0.2%) 0/535 (0%)
    Cardiomegaly 0/525 (0%) 1/535 (0.2%)
    Coronary artery stenosis 1/525 (0.2%) 0/535 (0%)
    Cytotoxic cardiomyopathy 1/525 (0.2%) 0/535 (0%)
    Myocardial infarction 3/525 (0.6%) 1/535 (0.2%)
    Myocardial ischaemia 0/525 (0%) 1/535 (0.2%)
    Supraventricular tachycardia 0/525 (0%) 1/535 (0.2%)
    Tachyarrhythmia 0/525 (0%) 1/535 (0.2%)
    Tachycardia 0/525 (0%) 2/535 (0.4%)
    Endocrine disorders
    Goitre 0/525 (0%) 3/535 (0.6%)
    Hyperparathyroidism 1/525 (0.2%) 0/535 (0%)
    Hyperthyroidism 0/525 (0%) 1/535 (0.2%)
    Eye disorders
    Cataract 1/525 (0.2%) 0/535 (0%)
    Conjunctival haemorrhage 1/525 (0.2%) 0/535 (0%)
    Diplopia 1/525 (0.2%) 0/535 (0%)
    Eye pain 1/525 (0.2%) 0/535 (0%)
    Glaucoma 1/525 (0.2%) 1/535 (0.2%)
    Iridocyclitis 2/525 (0.4%) 0/535 (0%)
    Iris cyst 1/525 (0.2%) 0/535 (0%)
    Macular degeneration 1/525 (0.2%) 0/535 (0%)
    Retinal disorder 0/525 (0%) 1/535 (0.2%)
    Vision blurred 1/525 (0.2%) 0/535 (0%)
    Visual acuity reduced 1/525 (0.2%) 0/535 (0%)
    Gastrointestinal disorders
    Abdominal discomfort 1/525 (0.2%) 0/535 (0%)
    Abdominal pain 0/525 (0%) 2/535 (0.4%)
    Abdominal strangulated hernia 1/525 (0.2%) 1/535 (0.2%)
    Alcoholic pancreatitis 1/525 (0.2%) 0/535 (0%)
    Ascites 2/525 (0.4%) 2/535 (0.4%)
    Colitis 0/525 (0%) 1/535 (0.2%)
    Colitis ischaemic 1/525 (0.2%) 0/535 (0%)
    Colitis ulcerative 1/525 (0.2%) 0/535 (0%)
    Constipation 1/525 (0.2%) 0/535 (0%)
    Dental caries 1/525 (0.2%) 0/535 (0%)
    Diarrhoea 0/525 (0%) 2/535 (0.4%)
    Diverticulum intestinal 0/525 (0%) 1/535 (0.2%)
    Femoral hernia 1/525 (0.2%) 0/535 (0%)
    Haematemesis 0/525 (0%) 2/535 (0.4%)
    Haemorrhoids 1/525 (0.2%) 1/535 (0.2%)
    Hernial eventration 0/525 (0%) 1/535 (0.2%)
    Hiatus hernia 0/525 (0%) 1/535 (0.2%)
    Inguinal hernia 1/525 (0.2%) 0/535 (0%)
    Intestinal obstruction 1/525 (0.2%) 0/535 (0%)
    Intestinal prolapse 1/525 (0.2%) 0/535 (0%)
    Melaena 0/525 (0%) 1/535 (0.2%)
    Nausea 2/525 (0.4%) 0/535 (0%)
    Pancreatitis 0/525 (0%) 1/535 (0.2%)
    Peptic ulcer 0/525 (0%) 1/535 (0.2%)
    Peritonitis 1/525 (0.2%) 0/535 (0%)
    Rectal haemorrhage 0/525 (0%) 2/535 (0.4%)
    Reflux oesophagitis 1/525 (0.2%) 0/535 (0%)
    Small intestinal stenosis 0/525 (0%) 1/535 (0.2%)
    Splenic artery aneurysm 1/525 (0.2%) 0/535 (0%)
    Umbilical hernia 0/525 (0%) 1/535 (0.2%)
    Umbilical hernia, obstructive 0/525 (0%) 1/535 (0.2%)
    Upper gastrointestinal haemorrhage 1/525 (0.2%) 0/535 (0%)
    Varices oesophageal 1/525 (0.2%) 0/535 (0%)
    Vomiting 1/525 (0.2%) 1/535 (0.2%)
    General disorders
    Asthenia 1/525 (0.2%) 0/535 (0%)
    Chest discomfort 0/525 (0%) 1/535 (0.2%)
    Chest pain 2/525 (0.4%) 4/535 (0.7%)
    Death 1/525 (0.2%) 2/535 (0.4%)
    General physical health deterioration 1/525 (0.2%) 0/535 (0%)
    Impaired healing 3/525 (0.6%) 0/535 (0%)
    Inflammation 0/525 (0%) 1/535 (0.2%)
    Pain 1/525 (0.2%) 1/535 (0.2%)
    Pyrexia 5/525 (1%) 3/535 (0.6%)
    Sudden death 0/525 (0%) 1/535 (0.2%)
    Hepatobiliary disorders
    Cholecystitis 0/525 (0%) 1/535 (0.2%)
    Cholecystitis acute 1/525 (0.2%) 2/535 (0.4%)
    Cholecystitis chronic 1/525 (0.2%) 0/535 (0%)
    Cholelithiasis 4/525 (0.8%) 10/535 (1.9%)
    Hepatic cirrhosis 0/525 (0%) 1/535 (0.2%)
    Liver disorder 1/525 (0.2%) 0/535 (0%)
    Immune system disorders
    Anaphylactic reaction 0/525 (0%) 1/535 (0.2%)
    Hypersensitivity 0/525 (0%) 1/535 (0.2%)
    Infections and infestations
    Actinomycosis 1/525 (0.2%) 0/535 (0%)
    Biliary tract infection bacterial 0/525 (0%) 1/535 (0.2%)
    Breast infection 1/525 (0.2%) 0/535 (0%)
    Bronchopneumonia 0/525 (0%) 1/535 (0.2%)
    Cellulitis 2/525 (0.4%) 2/535 (0.4%)
    Device related infection 0/525 (0%) 1/535 (0.2%)
    Diverticulitis 0/525 (0%) 1/535 (0.2%)
    Erysipelas 2/525 (0.4%) 1/535 (0.2%)
    Escherichia sepsis 1/525 (0.2%) 1/535 (0.2%)
    Gallbladder empyema 0/525 (0%) 1/535 (0.2%)
    Gastroenteritis 0/525 (0%) 1/535 (0.2%)
    Hepatic infection bacterial 0/525 (0%) 1/535 (0.2%)
    Herpes zoster 0/525 (0%) 1/535 (0.2%)
    Incision site cellulitis 0/525 (0%) 1/535 (0.2%)
    Intervertebral discitis 0/525 (0%) 1/535 (0.2%)
    Localised infection 0/525 (0%) 1/535 (0.2%)
    Lower respiratory tract infection 0/525 (0%) 2/535 (0.4%)
    Mastitis bacterial 0/525 (0%) 1/535 (0.2%)
    Pharyngitis 0/525 (0%) 1/535 (0.2%)
    Pneumonia 0/525 (0%) 4/535 (0.7%)
    Post procedural infection 0/525 (0%) 1/535 (0.2%)
    Postoperative wound infection 0/525 (0%) 1/535 (0.2%)
    Pyelonephritis acute 0/525 (0%) 1/535 (0.2%)
    Respiratory moniliasis 0/525 (0%) 1/535 (0.2%)
    Scrub typhus 1/525 (0.2%) 0/535 (0%)
    Sepsis 1/525 (0.2%) 1/535 (0.2%)
    Sinusitis 1/525 (0.2%) 0/535 (0%)
    Staphylococcal sepsis 0/525 (0%) 1/535 (0.2%)
    Urinary tract infection 4/525 (0.8%) 1/535 (0.2%)
    Urosepsis 1/525 (0.2%) 1/535 (0.2%)
    Wound infection 1/525 (0.2%) 1/535 (0.2%)
    Wound infection bacterial 1/525 (0.2%) 0/535 (0%)
    Injury, poisoning and procedural complications
    Accident 1/525 (0.2%) 0/535 (0%)
    Ankle fracture 1/525 (0.2%) 2/535 (0.4%)
    Back injury 0/525 (0%) 1/535 (0.2%)
    Cartilage injury 0/525 (0%) 1/535 (0.2%)
    Concussion 0/525 (0%) 1/535 (0.2%)
    Contusion 1/525 (0.2%) 1/535 (0.2%)
    Dislocation of joint prosthesis 0/525 (0%) 1/535 (0.2%)
    Fall 7/525 (1.3%) 7/535 (1.3%)
    Femur fracture 2/525 (0.4%) 0/535 (0%)
    Fibula fracture 1/525 (0.2%) 1/535 (0.2%)
    Hand fracture 2/525 (0.4%) 0/535 (0%)
    Humerus fracture 1/525 (0.2%) 1/535 (0.2%)
    Incisional hernia 1/525 (0.2%) 0/535 (0%)
    Intentional overdose 1/525 (0.2%) 0/535 (0%)
    Joint dislocation 2/525 (0.4%) 0/535 (0%)
    Joint sprain 1/525 (0.2%) 0/535 (0%)
    Meniscus lesion 1/525 (0.2%) 0/535 (0%)
    Muscle rupture 0/525 (0%) 1/535 (0.2%)
    Post procedural complication 1/525 (0.2%) 0/535 (0%)
    Post procedural fistula 1/525 (0.2%) 0/535 (0%)
    Procedural nausea 1/525 (0.2%) 0/535 (0%)
    Procedural site reaction 0/525 (0%) 1/535 (0.2%)
    Radius fracture 2/525 (0.4%) 1/535 (0.2%)
    Road traffic accident 1/525 (0.2%) 1/535 (0.2%)
    Skin laceration 1/525 (0.2%) 2/535 (0.4%)
    Skull fracture 0/525 (0%) 1/535 (0.2%)
    Subdural haematoma 0/525 (0%) 1/535 (0.2%)
    Tendon rupture 1/525 (0.2%) 0/535 (0%)
    Traumatic fracture 1/525 (0.2%) 0/535 (0%)
    Upper limb fracture 2/525 (0.4%) 0/535 (0%)
    Wrist fracture 3/525 (0.6%) 1/535 (0.2%)
    Investigations
    Bone density decreased 1/525 (0.2%) 0/535 (0%)
    Weight decreased 0/525 (0%) 1/535 (0.2%)
    Metabolism and nutrition disorders
    Decreased appetite 1/525 (0.2%) 2/535 (0.4%)
    Dehydration 1/525 (0.2%) 0/535 (0%)
    Diabetes mellitus 0/525 (0%) 1/535 (0.2%)
    Hypercalcaemia 1/525 (0.2%) 0/535 (0%)
    Hypokalaemia 1/525 (0.2%) 1/535 (0.2%)
    Hyponatraemia 1/525 (0.2%) 1/535 (0.2%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/525 (0.4%) 0/535 (0%)
    Arthritis 1/525 (0.2%) 1/535 (0.2%)
    Arthropathy 1/525 (0.2%) 0/535 (0%)
    Back pain 1/525 (0.2%) 3/535 (0.6%)
    Bone pain 0/525 (0%) 1/535 (0.2%)
    Bunion 1/525 (0.2%) 1/535 (0.2%)
    Dupuytren's contracture 1/525 (0.2%) 0/535 (0%)
    Foot deformity 1/525 (0.2%) 2/535 (0.4%)
    Intervertebral disc protrusion 1/525 (0.2%) 3/535 (0.6%)
    Ligament disorder 1/525 (0.2%) 1/535 (0.2%)
    Lumbar spinal stenosis 1/525 (0.2%) 0/535 (0%)
    Monarthritis 0/525 (0%) 1/535 (0.2%)
    Musculoskeletal pain 1/525 (0.2%) 1/535 (0.2%)
    Myalgia 1/525 (0.2%) 0/535 (0%)
    Neck pain 0/525 (0%) 1/535 (0.2%)
    Osteoarthritis 5/525 (1%) 7/535 (1.3%)
    Osteonecrosis 4/525 (0.8%) 1/535 (0.2%)
    Pain in extremity 1/525 (0.2%) 2/535 (0.4%)
    Pathological fracture 0/525 (0%) 1/535 (0.2%)
    Rotator cuff syndrome 2/525 (0.4%) 0/535 (0%)
    Spinal column stenosis 1/525 (0.2%) 1/535 (0.2%)
    Tenosynovitis stenosans 1/525 (0.2%) 0/535 (0%)
    Trigger finger 3/525 (0.6%) 0/535 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 0/525 (0%) 1/535 (0.2%)
    Benign breast neoplasm 2/525 (0.4%) 0/535 (0%)
    Benign gastrointestinal neoplasm 1/525 (0.2%) 0/535 (0%)
    Benign pancreatic neoplasm 1/525 (0.2%) 0/535 (0%)
    Bowen's disease 0/525 (0%) 1/535 (0.2%)
    Chronic lymphocytic leukaemia 1/525 (0.2%) 0/535 (0%)
    Colon cancer 1/525 (0.2%) 0/535 (0%)
    Fibroadenoma of breast 0/525 (0%) 1/535 (0.2%)
    Lung adenocarcinoma stage 0 1/525 (0.2%) 0/535 (0%)
    Lung neoplasm malignant 1/525 (0.2%) 0/535 (0%)
    Malignant melanoma 1/525 (0.2%) 2/535 (0.4%)
    Meningioma benign 0/525 (0%) 1/535 (0.2%)
    Metastases to pleura 1/525 (0.2%) 0/535 (0%)
    Myeloproliferative disorder 1/525 (0.2%) 0/535 (0%)
    Parathyroid tumour benign 1/525 (0.2%) 0/535 (0%)
    Rectal cancer 1/525 (0.2%) 1/535 (0.2%)
    Renal cell carcinoma 1/525 (0.2%) 1/535 (0.2%)
    Salivary gland adenoma 2/525 (0.4%) 0/535 (0%)
    Thyroid cancer 2/525 (0.4%) 0/535 (0%)
    Uterine leiomyoma 2/525 (0.4%) 1/535 (0.2%)
    Nervous system disorders
    Brain stem haemorrhage 1/525 (0.2%) 0/535 (0%)
    Carotid artery stenosis 0/525 (0%) 1/535 (0.2%)
    Carpal tunnel syndrome 2/525 (0.4%) 2/535 (0.4%)
    Cerebrovascular accident 0/525 (0%) 3/535 (0.6%)
    Depressed level of consciousness 0/525 (0%) 1/535 (0.2%)
    Facial paresis 1/525 (0.2%) 0/535 (0%)
    Haemorrhagic cerebral infarction 1/525 (0.2%) 0/535 (0%)
    Headache 2/525 (0.4%) 1/535 (0.2%)
    Hemiparesis 1/525 (0.2%) 0/535 (0%)
    Intracranial aneurysm 1/525 (0.2%) 0/535 (0%)
    Loss of consciousness 0/525 (0%) 1/535 (0.2%)
    Meningorrhagia 0/525 (0%) 1/535 (0.2%)
    Migraine 1/525 (0.2%) 0/535 (0%)
    Multiple sclerosis relapse 1/525 (0.2%) 0/535 (0%)
    Normal pressure hydrocephalus 1/525 (0.2%) 0/535 (0%)
    Paraesthesia 0/525 (0%) 1/535 (0.2%)
    Peripheral sensory neuropathy 1/525 (0.2%) 1/535 (0.2%)
    Sciatica 2/525 (0.4%) 0/535 (0%)
    Subarachnoid haemorrhage 0/525 (0%) 1/535 (0.2%)
    Syncope 1/525 (0.2%) 0/535 (0%)
    Transient ischaemic attack 0/525 (0%) 1/535 (0.2%)
    Psychiatric disorders
    Agitation 1/525 (0.2%) 0/535 (0%)
    Alcoholic psychosis 1/525 (0.2%) 0/535 (0%)
    Anxiety 1/525 (0.2%) 0/535 (0%)
    Confusional state 2/525 (0.4%) 0/535 (0%)
    Depression 2/525 (0.4%) 0/535 (0%)
    Depression suicidal 0/525 (0%) 1/535 (0.2%)
    Insomnia 1/525 (0.2%) 1/535 (0.2%)
    Mental disorder 0/525 (0%) 1/535 (0.2%)
    Panic attack 1/525 (0.2%) 0/535 (0%)
    Suicide attempt 0/525 (0%) 1/535 (0.2%)
    Renal and urinary disorders
    Calculus ureteric 2/525 (0.4%) 1/535 (0.2%)
    Hydronephrosis 0/525 (0%) 1/535 (0.2%)
    Nephrolithiasis 0/525 (0%) 2/535 (0.4%)
    Nephrotic syndrome 1/525 (0.2%) 0/535 (0%)
    Obstructive uropathy 0/525 (0%) 1/535 (0.2%)
    Renal colic 0/525 (0%) 2/535 (0.4%)
    Renal failure acute 0/525 (0%) 2/535 (0.4%)
    Renal impairment 0/525 (0%) 1/535 (0.2%)
    Stress urinary incontinence 0/525 (0%) 1/535 (0.2%)
    Reproductive system and breast disorders
    Breast atrophy 0/525 (0%) 1/535 (0.2%)
    Breast calcifications 0/525 (0%) 1/535 (0.2%)
    Breast fibrosis 0/525 (0%) 2/535 (0.4%)
    Ovarian cyst 1/525 (0.2%) 1/535 (0.2%)
    Perineal fistula 0/525 (0%) 1/535 (0.2%)
    Rectocele 1/525 (0.2%) 0/535 (0%)
    Uterine enlargement 0/525 (0%) 1/535 (0.2%)
    Uterine polyp 1/525 (0.2%) 0/535 (0%)
    Uterine prolapse 0/525 (0%) 1/535 (0.2%)
    Vaginal haemorrhage 1/525 (0.2%) 0/535 (0%)
    Vaginal prolapse 2/525 (0.4%) 1/535 (0.2%)
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema 1/525 (0.2%) 0/535 (0%)
    Asthma 0/525 (0%) 3/535 (0.6%)
    Dyspnoea 0/525 (0%) 1/535 (0.2%)
    Dyspnoea exertional 1/525 (0.2%) 0/535 (0%)
    Epistaxis 0/525 (0%) 1/535 (0.2%)
    Increased viscosity of bronchial secretion 1/525 (0.2%) 0/535 (0%)
    Lung disorder 0/525 (0%) 1/535 (0.2%)
    Pleural effusion 0/525 (0%) 1/535 (0.2%)
    Pulmonary congestion 0/525 (0%) 1/535 (0.2%)
    Pulmonary oedema 1/525 (0.2%) 0/535 (0%)
    Pulmonary vascular disorder 1/525 (0.2%) 0/535 (0%)
    Respiratory distress 1/525 (0.2%) 0/535 (0%)
    Skin and subcutaneous tissue disorders
    Pruritus 1/525 (0.2%) 0/535 (0%)
    Skin fibrosis 0/525 (0%) 1/535 (0.2%)
    Subcutaneous emphysema 0/525 (0%) 1/535 (0.2%)
    Social circumstances
    Physical assault 1/525 (0.2%) 0/535 (0%)
    Vascular disorders
    Femoral arterial stenosis 1/525 (0.2%) 0/535 (0%)
    Hypertension 0/525 (0%) 1/535 (0.2%)
    Hypertensive crisis 1/525 (0.2%) 0/535 (0%)
    Hypotension 0/525 (0%) 1/535 (0.2%)
    Lymphoedema 1/525 (0.2%) 0/535 (0%)
    Varicose vein 0/525 (0%) 1/535 (0.2%)
    Other (Not Including Serious) Adverse Events
    Zoledronic Acid 4mg Upfront Zolendronic Acid 4mg Delayed
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 477/525 (90.9%) 486/535 (90.8%)
    Gastrointestinal disorders
    Abdominal pain upper 18/525 (3.4%) 29/535 (5.4%)
    Constipation 27/525 (5.1%) 31/535 (5.8%)
    Diarrhoea 24/525 (4.6%) 31/535 (5.8%)
    Dyspepsia 23/525 (4.4%) 28/535 (5.2%)
    Nausea 52/525 (9.9%) 55/535 (10.3%)
    General disorders
    Asthenia 36/525 (6.9%) 50/535 (9.3%)
    Fatigue 93/525 (17.7%) 95/535 (17.8%)
    Influenza like illness 49/525 (9.3%) 16/535 (3%)
    Oedema peripheral 49/525 (9.3%) 47/535 (8.8%)
    Pyrexia 76/525 (14.5%) 17/535 (3.2%)
    Infections and infestations
    Nasopharyngitis 35/525 (6.7%) 29/535 (5.4%)
    Urinary tract infection 16/525 (3%) 36/535 (6.7%)
    Investigations
    Weight decreased 31/525 (5.9%) 23/535 (4.3%)
    Weight increased 57/525 (10.9%) 57/535 (10.7%)
    Metabolism and nutrition disorders
    Hypercholesterolaemia 58/525 (11%) 60/535 (11.2%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 256/525 (48.8%) 251/535 (46.9%)
    Back pain 78/525 (14.9%) 78/535 (14.6%)
    Bone pain 97/525 (18.5%) 64/535 (12%)
    Musculoskeletal pain 57/525 (10.9%) 45/535 (8.4%)
    Myalgia 68/525 (13%) 71/535 (13.3%)
    Neck pain 31/525 (5.9%) 19/535 (3.6%)
    Osteoarthritis 42/525 (8%) 28/535 (5.2%)
    Pain in extremity 69/525 (13.1%) 80/535 (15%)
    Nervous system disorders
    Dizziness 28/525 (5.3%) 38/535 (7.1%)
    Headache 75/525 (14.3%) 63/535 (11.8%)
    Psychiatric disorders
    Depression 30/525 (5.7%) 44/535 (8.2%)
    Insomnia 51/525 (9.7%) 38/535 (7.1%)
    Respiratory, thoracic and mediastinal disorders
    Cough 38/525 (7.2%) 52/535 (9.7%)
    Vascular disorders
    Hot flush 152/525 (29%) 163/535 (30.5%)
    Hypertension 55/525 (10.5%) 59/535 (11%)
    Lymphoedema 41/525 (7.8%) 36/535 (6.7%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862- 778 8300
    Email
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00171340
    Other Study ID Numbers:
    • CFEM345D2405
    First Posted:
    Sep 15, 2005
    Last Update Posted:
    Apr 16, 2012
    Last Verified:
    Apr 1, 2012