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Continued Efficacy and Safety of Zoledronic Acid (q 4 Wks vs. q 12 Wks) in the 2nd Year of Treatment in Patients With Bone Metastases From Breast Cancer

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT00320710
Collaborator
(none)
416
Enrollment
92
Locations
3
Arms
88.9
Duration (Months)
4.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Clinical trial in breast cancer patients with bone metastases pretreated for approximately 1 year with a standard zoledronic acid regimen. Looking at the continued effectiveness and safety of giving zoledronic acid every 4 weeks versus every 12 weeks given over 1 year. This study is prospective, double-blind, stratified, multi-center, and two-arm.

Condition or Disease Intervention/Treatment Phase
  • Drug: Zoledronic acid
  • Drug: Placebo
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
416 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Prospective, Randomized, Double-blind, Stratified, Multi-center, 2-arm Trial of the Continued Efficacy and Safety of Zoledronic Acid (Every 4 Weeks vs. Every 12 Weeks) in in the 2nd Year of Treatment in Patients With Documented Bone Metastases From Breast Cancer
Study Start Date :
Feb 1, 2006
Actual Primary Completion Date :
Jul 1, 2013
Actual Study Completion Date :
Jul 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Zoledronic acid every (q) 4 weeks

Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.

Drug: Zoledronic acid
4mg IV
Other Names:
  • Zoledronate
  • ZOL446
  • Zometa

    		•
    Experimental: Zoledronic acid q 12 weeks

    Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind.

    Drug: Zoledronic acid
    4mg IV
    Other Names:
  • Zoledronate
  • ZOL446
  • Zometa

    • Drug: Placebo
    Placebo to zoledronic acid
    Experimental: Placebo / zoledronic acid

    Participants randomized to this arm received placebo but the arm was later dropped and participants in this arm were swithced to the zoledronic acid q 4 weeks according to a study amendment.

    Drug: Zoledronic acid
    4mg IV
    Other Names:
  • Zoledronate
  • ZOL446
  • Zometa

    • Drug: Placebo
    Placebo to zoledronic acid

    Outcome Measures

    Primary Outcome Measures

    1. Proportion of Patients Who Experienced at Least One Skeletal Related Event (SRE) [52 weeks]

      An SRE was defined as a pathologic fracture (vertebral and non-vertebral), spinal cord compression, radiation to bone or surgery to bone.

    Secondary Outcome Measures

    1. Time to First SRE [52 weeks]

      An SRE was defined as a pathologic bone fracture (vertebral and non-vertebral), spinal cord compression, radiation to bone, or surgery to bone. The time to first individual SRE was defined as the date of randomization to the date of first occurrence of any SRE.

    2. Time to First Individual Type of SRE [52 weeks]

      Types of SREs analyzed were pathologic fractures (vertebral and non-vertebral), spinal cord compression, radiation to bone and surgery to bone. The time to first indvidual SRE was defined as the date of randomization to the date of the first occurrence of any individual SRE.

    3. Change From Baseline in Mean Composite Brief Pain Inventory (BPI) Score [baseline, 52 weeks]

      Participants completed a BPI short form which is a 9 item self-administered questionnaire used to evaluate the severity of a participant's pain and the impact of this pain on the participant's daily functioning. The participant rates his or her worst, least, average, and current pain intensity, lists current treatments and perceived effectiveness, and rates the degree that pain interferes with general activity, mood, walking ability, normal work, relations with other persons, sleep, and enjoyment of life on a 10 point scale. The BPI composite score, which was calculated as the average of items 3, 4, 5 and 6 (worst pain, least pain, average pain and pain right now), ranged from 0 (best possible outcome, no pain) to 10 (worst possible outcome, pain as bad as you can imagine). A positive change from baseline indicates worsening.

    4. Change From Baseline in Mean Analgesic Score [baseline, 52 weeks]

      The analgesic score indicates the types of pain medication used. The scores range as follows: 0 = none medication; 1 = minor analgesics (aspirin, NSAID, acetaminophen, propoxyphene, etc.); 2 = Tranquilizers, antidepressants, muscle relaxants, and steroids; 3 = Mild narcotics (oxycodone, meperidine, codeine, etc.); and 4 = Strong narcotics (morphine, hydromorphone, etc.). A positive change from baseline indicates worsening.

    5. Change From Baseline in Urinary N-telopeptide / Creatinine Ratio [baseline, 48 weeks]

      Urine samples were collected to obtain n-telopeptide and creatinine values.

    6. Change From Baseline in Serum Bone Specific Alkaline Phosphatase [baseline, 48 weeks]

      Serum samples were collected to obtain bone specific alkaline phosphatase values.

    7. Skeletal Morbidity Rate [52 weeks]

      An SMR for a patient was defined as the "number of occurrences" of any (or a particular) SRE allowing for only 1 event in any 3-week interval, divided by the "time at risk" in years. The "number of occurrences" and the "time at risk" were counts of SRE and the time from the randomization date. Counting began from randomization in the way that every counted event was followed by a 20-day period during which no SRE was counted, nor was the time counted as "at risk". For example, if a patient had 1 SRE during the study, the "time at risk" was calculated as the total number of days in the study minus the 20-day follow-up period for that SRE. If a patient had no SRE events, the entire study period was counted as "time at risk". This SMR calculation method had the advantage of avoiding multiple counts of possibly interdependent SREs (e.g. having 1 fracture increases the probability of having a subsequent SRE).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    Female patients ≥ 18 years of age. Confirmed breast cancer with bone metastasis. Pretreated with Zometa®, or Aredia (pamidronate) or all sequential regimens of both, for a minimum of 9 doses;

    Exclusion Criteria:

    Abnormal kidney function determined by serum creatinine levels. Current active dental problems including: ongoing infection of the teeth or jawbone; current exposed bone in the mouth; and current or prior diagnosis of osteonecrosis of the jaw.

    Recent (within 8 weeks) or planned dental or jaw surgery (e.g., extraction, implants).

    Diagnosis of metabolic bone disease other than osteoporosis (e.g., Paget's disease of bone).

    Known hypersensitivity to Zometa. Treatment with other investigational drugs within 30 days prior to randomization.

    Other protocol-defined exclusion criteria may have applied.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Providence Alaska Medical Center Cancer Research Anchorage Alaska United States 99508
    2 Heritage Physicians Group Oncology Hot Springs Arkansas United States 71913
    3 The Center for Chest Care Springdale Arkansas United States 72764
    4 Pacific Cancer Medical Center, Inc. Anaheim California United States 92801
    5 South Bay Oncology Hematology Partners Campbell California United States 95008
    6 Bay Area Cancer Research Concord California United States 94520
    7 Pacific Coast Hem/Onc Fountain Valley California United States 92708
    8 Wilshire Oncology Medical Group La Verne California United States 91750
    9 Kenmar Research Institute Los Angeles California United States 90057
    10 North Valley Hematology/Oncology Providence Holy Cross Medical Northridge California United States 91328
    11 Medical Oncology Care Associates Orange California United States 92868
    12 Ventura County Hematology and Oncology Oxnard California United States 93030
    13 The Office of Dr. Swarna Chanduri, MD Pomona California United States 91767
    14 Access Clinical Research Rancho Mirage California United States 92270
    15 Cancer and Blood of the Desert Rancho Mirage California United States 92270
    16 University of California Davis Cancer Center Sacramento California United States 95817
    17 University of California at Los Angeles Sylmar California United States 91342
    18 Denver Health Medical Center CACZ885M2301 Denver Colorado United States 80204-4507
    19 Eastern Connecticut Hematology & Oncology Associates Norwich Connecticut United States 06360
    20 Georgetown University/Lombardi Cancer Center Washington District of Columbia United States 20007-2197
    21 Washington Hospital Center Washington District of Columbia United States 20010
    22 Baptist Cancer Center Jacksonville Florida United States 32209
    23 Pasco Hernando Oncology New Port Richey Florida United States 34652
    24 The Office of Dr. Elizabeth Tan-Chiu, MD PA Planatation Florida United States 33324
    25 Suburban Hematology-Oncology Lawrenceville Georgia United States 30045
    26 NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr Chicago Illinois United States 60611
    27 Evanston Northwestern Healthcare Medical Group Evanston Illinois United States 60201
    28 Edward Cancer Center Naperville Illinois United States 60540
    29 Midwest Cancer Research Group Skokie Illinois United States 60077
    30 Investigative Clinical Research Indianapolis Indiana United States 46254
    31 Cancer Care Center New Albany Indiana United States 47150
    32 Associated Physicians & Surgeons Clinic Terre Haute Indiana United States 47804
    33 Medical Associates Clinic, PC Dubuque Iowa United States 52001
    34 University of Iowa Health Care Iowa City Iowa United States 52242-1091
    35 Siouxland Hematology-Oncology Associates LLP Sioux City Iowa United States 51101
    36 Cotton O'Neil Oncology Clinic Topeka Kansas United States 66606
    37 Cancer Center of Kansas Witchita Kansas United States 67214-3728
    38 Kentucky Lung Clinic & Kentucky Sleep Clinic Hazard Kentucky United States 41701
    39 Lexington Oncology Associates Lexington Kentucky United States 40503
    40 Cabrini Center for Cancer Care Alexandria Louisiana United States 71301
    41 Southwest Oncology Associates Ltd. Lafayette Louisiana United States 70503
    42 Greenbaum Cancer Center Baltimore Maryland United States 21201-1595
    43 St. Agnes Hospital Baltimore Maryland United States 21229
    44 The Harry and Jeanette Weinberg Cancer Institute at Franklin Baltimore Maryland United States 21237
    45 Center for Cancer & Blood Disorders Bethesda Maryland United States 20817
    46 Frederick Memorial Hospital Frederick Maryland United States 21701
    47 Caritas Holy Family Hospital Methuen Massachusetts United States 01844
    48 University of Michigan Clinical Trials Office Ann Arbor Michigan United States 48109
    49 Wayne State University Detroit Michigan United States 48201
    50 Henry Ford Hospital Oncology Detroit Michigan United States 48202
    51 Oncology Care Associates, PLLC St. Joseph Michigan United States 49085
    52 St. Luke's Hospital and Health Network Duluth Minnesota United States 55805
    53 Fairview Clinical Trial Services Minneapolis Minnesota United States 55414
    54 Univ. of Minnesota Cancer Center 420 Delaware St. Minneapolis Minnesota United States 55455
    55 Hubert H. Humphrey Cancer Center Robbinsdale Minnesota United States 55422
    56 Jackson Oncology Associates Jackson Mississippi United States 39202
    57 Capitol Comprehensive Cancer Care Clinic Jefferson City Missouri United States 65109
    58 The Center for Cancer Care and Research St. Louis Missouri United States 63141
    59 Nebraska Hematology-Oncology PC Lincoln Nebraska United States 68506
    60 Nevada Cancer Centers 2851 North Tenaya Way Las Vegas Nevada United States 89109
    61 Center for Cancer and Hematologic Disease Cherry Hill New Jersey United States 08003
    62 Saint Barnabas Medical Center Livingston New Jersey United States 07039
    63 Somerset Hematology Oncology Associates Somerset New Jersey United States 08873
    64 Advanced Oncology Associates Armonk New York United States 10504
    65 Arena Oncology Associates, PC Great Neck New York United States 11021
    66 Benedictine Hospital Kingston New York United States 12401
    67 Beth Israel Medical Center New York New York United States 10003
    68 Columbia Presbyterian Medical Center New York New York United States 10032
    69 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    70 Jmaes P. Wilmot Cancer Center Rochester New York United States 14642
    71 Alamance Regional Medical Cancer Center Burlington North Carolina United States 27215
    72 Northeast Oncology Associates Suite 250 Concord North Carolina United States 28025
    73 Barberton Citizens Hospital Barberton Ohio United States 44203
    74 Gabrail Cancer Center Canton Ohio United States 44718
    75 Ohio Cancer Specialists Mansfield Ohio United States 44907
    76 Hematology/Oncology Consultants Inc. West Worthington Ohio United States 43235
    77 Trilogy Cancer Care Wooster Ohio United States 44691
    78 Bay Area Hospital - Pharmacy Coos Bay Oregon United States 97420
    79 The Corvallis Clinic, P.C. Corvallis Oregon United States 97330
    80 Milton S Hershey Medical Center Hershey Pennsylvania United States 17033
    81 Lancaster Cancer Center Lancaster Pennsylvania United States 17601
    82 U of Pittsburgh Cancer Institute Magee-Womens Hospital Pittsburgh Pennsylvania United States 15213
    83 Guthrie Cancer Center Sayre Pennsylvania United States 18840
    84 Mainline Oncology Hematology Assoc. Wynnewood Pennsylvania United States 19096
    85 M. Francisco Gonzalez, MD., FACP Columbia South Carolina United States 29203
    86 Santee Hematology/Oncology Sumter South Carolina United States 29150
    87 MD Anderson Cancer Center/University of Texas 1155 Herman Pressler Street Houston Texas United States 77031
    88 Cancer Centers of South Texas San Antonio Texas United States 78229
    89 Providence Everett Medical Clinic Everett Washington United States 98201
    90 Seattle Cancer Care Alliance Seattle Cancer Care Alliance Seattle Washington United States 98109
    91 Rockwood Clinic Rockwood Clinic, PS Spokane Washington United States 99202
    92 Medical College of Wisconsin Milwaukee Wisconsin United States 53226

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00320710
    Other Study ID Numbers:
    • CZOL446E2352
    First Posted:
    May 3, 2006
    Last Update Posted:
    Aug 22, 2014
    Last Verified:
    Aug 1, 2014
    Keywords provided by Novartis Pharmaceuticals
    Breast cancer
    zoledronic acid
    bone metastases
    Additional relevant MeSH terms:
    Breast Neoplasms
    Neoplasm Metastasis
    Zoledronic Acid

    Study Results

    Participant Flow

    Recruitment Details The initial study design contained 3 arms: zoledronic acid q4 weeks, zoledronic acid q12 weeks and placebo q4 weeks. Due to a study amendment, the placebo arm was discontinued and participants in this treatment group were switched to the zoledronic acid q4 week group. These participants were not included in the efficacy analysis.
    Pre-assignment Detail
    Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks Placebo / Zoledronic Acid
    Arm/Group Description Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks. Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind. Participants randomized to this arm received placebo but the arm was later dropped and participants in this arm were later switched to the zoledronic acid q 4 weeks according to a study amendment.
    Period Title: Overall Study
    STARTED 200 203 13
    Treated (Safety Set) 198 202 13
    COMPLETED 106 127 8
    NOT COMPLETED 94 76 5

    Baseline Characteristics

    Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks Placebo / Zoledronic Acid Total
    Arm/Group Description Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks. Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind. Participants randomized to this arm received placebo but the arm was later dropped and participants in this arm were later switched to the zoledronic acid q 4 weeks according to a study amendment. Total of all reporting groups
    Overall Participants 200 203 13 416
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    59.2
    (11.10)
    58.6
    (11.15)
    60.8
    (12.19)
    58.9
    (11.14)
    Sex/Gender, Customized (participants) [Number]
    Number [participants]
    200
    100%
    203
    100%
    13
    100%
    416
    100%

    Outcome Measures

    1. Primary Outcome
    Title Proportion of Patients Who Experienced at Least One Skeletal Related Event (SRE)
    Description An SRE was defined as a pathologic fracture (vertebral and non-vertebral), spinal cord compression, radiation to bone or surgery to bone.
    Time Frame 52 weeks

    Outcome Measure Data

    Analysis Population Description
    The population included participants who were in the zoledronic acid q4 weeks and zoledronic acid q12 weeks treatment groups.
    Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks
    Arm/Group Description Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks. Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind.
    Measure Participants 200 203
    Number [Percentage of participants]
    22
    11%
    23.2
    11.4%
    2. Secondary Outcome
    Title Time to First SRE
    Description An SRE was defined as a pathologic bone fracture (vertebral and non-vertebral), spinal cord compression, radiation to bone, or surgery to bone. The time to first individual SRE was defined as the date of randomization to the date of first occurrence of any SRE.
    Time Frame 52 weeks

    Outcome Measure Data

    Analysis Population Description
    The population included participants who were in the zoledronic acid q4 weeks and zoledronic acid q12 weeks treatment groups.
    Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks
    Arm/Group Description Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks. Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind.
    Measure Participants 200 203
    Median (95% Confidence Interval) [Days]
    NA
    NA
    3. Secondary Outcome
    Title Time to First Individual Type of SRE
    Description Types of SREs analyzed were pathologic fractures (vertebral and non-vertebral), spinal cord compression, radiation to bone and surgery to bone. The time to first indvidual SRE was defined as the date of randomization to the date of the first occurrence of any individual SRE.
    Time Frame 52 weeks

    Outcome Measure Data

    Analysis Population Description
    The population included participants who were in the zoledronic acid q4 weeks and zoledronic acid q12 weeks treatment groups.
    Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks
    Arm/Group Description Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks. Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind.
    Measure Participants 200 203
    Vertebral pathologic fractures
    NA
    NA
    Non-vertebral pathologic fractures
    NA
    NA
    Spinal cord compression
    NA
    NA
    Radiation to bone
    NA
    NA
    Surgery to bone
    NA
    NA
    4. Secondary Outcome
    Title Change From Baseline in Mean Composite Brief Pain Inventory (BPI) Score
    Description Participants completed a BPI short form which is a 9 item self-administered questionnaire used to evaluate the severity of a participant's pain and the impact of this pain on the participant's daily functioning. The participant rates his or her worst, least, average, and current pain intensity, lists current treatments and perceived effectiveness, and rates the degree that pain interferes with general activity, mood, walking ability, normal work, relations with other persons, sleep, and enjoyment of life on a 10 point scale. The BPI composite score, which was calculated as the average of items 3, 4, 5 and 6 (worst pain, least pain, average pain and pain right now), ranged from 0 (best possible outcome, no pain) to 10 (worst possible outcome, pain as bad as you can imagine). A positive change from baseline indicates worsening.
    Time Frame baseline, 52 weeks

    Outcome Measure Data

    Analysis Population Description
    The population included participants who were in the zoledronic acid q4 weeks and zoledronic acid q12 weeks treatment groups and had both baseline and week 52 values.
    Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks
    Arm/Group Description Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks. Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind.
    Measure Participants 89 100
    Mean (Standard Deviation) [scores on a scale]
    0.24
    (1.976)
    0.31
    (2.099)
    5. Secondary Outcome
    Title Change From Baseline in Mean Analgesic Score
    Description The analgesic score indicates the types of pain medication used. The scores range as follows: 0 = none medication; 1 = minor analgesics (aspirin, NSAID, acetaminophen, propoxyphene, etc.); 2 = Tranquilizers, antidepressants, muscle relaxants, and steroids; 3 = Mild narcotics (oxycodone, meperidine, codeine, etc.); and 4 = Strong narcotics (morphine, hydromorphone, etc.). A positive change from baseline indicates worsening.
    Time Frame baseline, 52 weeks

    Outcome Measure Data

    Analysis Population Description
    The population included participants who were in the zoledronic acid q4 weeks and zoledronic acid q12 weeks treatment groups and had both baseline and week 52 values.
    Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks
    Arm/Group Description Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks. Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind.
    Measure Participants 94 104
    Mean (Standard Deviation) [score]
    0.5
    (1.28)
    0.5
    (1.13)
    6. Secondary Outcome
    Title Change From Baseline in Urinary N-telopeptide / Creatinine Ratio
    Description Urine samples were collected to obtain n-telopeptide and creatinine values.
    Time Frame baseline, 48 weeks

    Outcome Measure Data

    Analysis Population Description
    The population included participants who were in the zoledronic acid q4 weeks and zoledronic acid q12 weeks treatment groups and had both baseline and week 48 values.
    Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks
    Arm/Group Description Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks. Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind.
    Measure Participants 106 119
    Mean (Standard Deviation) [ratio]
    10.612
    (40.4073)
    14.697
    (57.7315)
    7. Secondary Outcome
    Title Change From Baseline in Serum Bone Specific Alkaline Phosphatase
    Description Serum samples were collected to obtain bone specific alkaline phosphatase values.
    Time Frame baseline, 48 weeks

    Outcome Measure Data

    Analysis Population Description
    The population included participants who were in the zoledronic acid q4 weeks and zoledronic acid q12 weeks treatment groups and had both baseline and week 48 values.
    Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks
    Arm/Group Description Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks. Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind.
    Measure Participants 93 105
    Mean (Standard Deviation) [mcg/L]
    0.797
    (27.8800)
    4.514
    (12.4509)
    8. Secondary Outcome
    Title Skeletal Morbidity Rate
    Description An SMR for a patient was defined as the "number of occurrences" of any (or a particular) SRE allowing for only 1 event in any 3-week interval, divided by the "time at risk" in years. The "number of occurrences" and the "time at risk" were counts of SRE and the time from the randomization date. Counting began from randomization in the way that every counted event was followed by a 20-day period during which no SRE was counted, nor was the time counted as "at risk". For example, if a patient had 1 SRE during the study, the "time at risk" was calculated as the total number of days in the study minus the 20-day follow-up period for that SRE. If a patient had no SRE events, the entire study period was counted as "time at risk". This SMR calculation method had the advantage of avoiding multiple counts of possibly interdependent SREs (e.g. having 1 fracture increases the probability of having a subsequent SRE).
    Time Frame 52 weeks

    Outcome Measure Data

    Analysis Population Description
    This population included all participants who were in the zoledronic acid q 4 weeks and zoledronic acid q 12 weeks treatment groups.
    Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks
    Arm/Group Description Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks. Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind.
    Measure Participants 200 203
    Mean (Standard Deviation) [Number of events per year]
    0.46
    (1.063)
    0.50
    (1.500)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks Placebo / Zoledronic Acid
    Arm/Group Description Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks. Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind. Participants randomized to this arm received placebo but the arm was later dropped and participants in this arm were later switched to the zoledronic acid q 4 weeks according to a study amendment.
    All Cause Mortality
    Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks Placebo / Zoledronic Acid
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks Placebo / Zoledronic Acid
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 50/198 (25.3%) 51/202 (25.2%) 3/13 (23.1%)
    Blood and lymphatic system disorders
    Anaemia 1/198 (0.5%) 3/202 (1.5%) 0/13 (0%)
    Febrile neutropenia 1/198 (0.5%) 2/202 (1%) 0/13 (0%)
    Leukocytosis 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Leukopenia 2/198 (1%) 0/202 (0%) 0/13 (0%)
    Neutropenia 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Pancytopenia 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Cardiac disorders
    Atrial fibrillation 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Cardiac failure congestive 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Palpitations 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Pericardial effusion 1/198 (0.5%) 1/202 (0.5%) 0/13 (0%)
    Supraventricular tachycardia 1/198 (0.5%) 1/202 (0.5%) 0/13 (0%)
    Tachycardia 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Congenital, familial and genetic disorders
    Arteriovenous malformation 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Endocrine disorders
    Hypercalcaemia of malignancy 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Eye disorders
    Eye swelling 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Gastrointestinal disorders
    Abdominal pain 2/198 (1%) 5/202 (2.5%) 0/13 (0%)
    Ascites 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Diarrhoea 3/198 (1.5%) 3/202 (1.5%) 0/13 (0%)
    Dysphagia 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Gastrointestinal haemorrhage 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Haematemesis 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Megacolon 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Mesenteric vein thrombosis 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Nausea 2/198 (1%) 2/202 (1%) 0/13 (0%)
    Oesophageal stenosis 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Oesophagitis 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Oral disorder 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Varices oesophageal 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Vomiting 3/198 (1.5%) 2/202 (1%) 0/13 (0%)
    General disorders
    Asthenia 1/198 (0.5%) 1/202 (0.5%) 0/13 (0%)
    Disease progression 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Drug withdrawal syndrome 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Fibrosis 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    General physical health deterioration 2/198 (1%) 2/202 (1%) 0/13 (0%)
    Generalised oedema 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Mucosal inflammation 0/198 (0%) 1/202 (0.5%) 1/13 (7.7%)
    Oedema peripheral 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Pain 2/198 (1%) 0/202 (0%) 0/13 (0%)
    Perforated ulcer 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Pyrexia 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Hepatobiliary disorders
    Biliary dilatation 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Cholangitis 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Hepatic failure 1/198 (0.5%) 1/202 (0.5%) 0/13 (0%)
    Infections and infestations
    Bronchitis 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Cellulitis 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Clostridium difficile colitis 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Escherichia sepsis 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Gastroenteritis 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Pneumonia 4/198 (2%) 1/202 (0.5%) 0/13 (0%)
    Sepsis 2/198 (1%) 0/202 (0%) 0/13 (0%)
    Septic shock 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Urinary tract infection 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Injury, poisoning and procedural complications
    Clavicle fracture 2/198 (1%) 0/202 (0%) 0/13 (0%)
    Comminuted fracture 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Femur fracture 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Procedural pain 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Spinal compression fracture 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Subdural haematoma 0/198 (0%) 3/202 (1.5%) 0/13 (0%)
    Investigations
    Hepatic enzyme increased 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Troponin increased 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Metabolism and nutrition disorders
    Dehydration 4/198 (2%) 4/202 (2%) 0/13 (0%)
    Failure to thrive 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Hypercalcaemia 1/198 (0.5%) 2/202 (1%) 0/13 (0%)
    Hypocalcaemia 1/198 (0.5%) 0/202 (0%) 1/13 (7.7%)
    Hypokalaemia 1/198 (0.5%) 1/202 (0.5%) 0/13 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 1/198 (0.5%) 1/202 (0.5%) 0/13 (0%)
    Bone pain 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Muscular weakness 2/198 (1%) 1/202 (0.5%) 0/13 (0%)
    Musculoskeletal chest pain 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Musculoskeletal pain 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Musculoskeletal stiffness 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Osteoarthritis 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Osteonecrosis of jaw 2/198 (1%) 2/202 (1%) 0/13 (0%)
    Pain in extremity 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Pathological fracture 1/198 (0.5%) 0/202 (0%) 1/13 (7.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 1/198 (0.5%) 1/202 (0.5%) 0/13 (0%)
    Breast cancer metastatic 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Metastases to bone 3/198 (1.5%) 0/202 (0%) 0/13 (0%)
    Metastases to central nervous system 0/198 (0%) 2/202 (1%) 0/13 (0%)
    Metastases to liver 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Metastases to lung 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Metastases to meninges 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Non-small cell lung cancer 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Nervous system disorders
    Brain mass 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Cerebral haemorrhage 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Coma 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Convulsion 1/198 (0.5%) 1/202 (0.5%) 0/13 (0%)
    Depressed level of consciousness 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Encephalopathy 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Hemiparesis 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Hepatic encephalopathy 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Hydrocephalus 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Migraine 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Somnolence 1/198 (0.5%) 1/202 (0.5%) 0/13 (0%)
    Spinal cord compression 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Vasogenic cerebral oedema 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Psychiatric disorders
    Acute psychosis 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Confusional state 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Delirium 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Mental status changes 0/198 (0%) 2/202 (1%) 0/13 (0%)
    Renal and urinary disorders
    Haematuria 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Hydronephrosis 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Renal failure 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Renal failure acute 1/198 (0.5%) 1/202 (0.5%) 0/13 (0%)
    Urinary tract obstruction 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Reproductive system and breast disorders
    Pelvic pain 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Dyspnoea 3/198 (1.5%) 5/202 (2.5%) 0/13 (0%)
    Haemoptysis 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Hypoxia 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Pleural effusion 1/198 (0.5%) 4/202 (2%) 1/13 (7.7%)
    Pulmonary embolism 2/198 (1%) 1/202 (0.5%) 0/13 (0%)
    Respiratory distress 1/198 (0.5%) 1/202 (0.5%) 0/13 (0%)
    Respiratory failure 1/198 (0.5%) 1/202 (0.5%) 0/13 (0%)
    Tachypnoea 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Skin and subcutaneous tissue disorders
    Decubitus ulcer 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Swelling face 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Vascular disorders
    Deep vein thrombosis 1/198 (0.5%) 2/202 (1%) 0/13 (0%)
    Hypertension 0/198 (0%) 1/202 (0.5%) 0/13 (0%)
    Hypotension 2/198 (1%) 1/202 (0.5%) 0/13 (0%)
    Orthostatic hypotension 1/198 (0.5%) 0/202 (0%) 0/13 (0%)
    Other (Not Including Serious) Adverse Events
    Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks Placebo / Zoledronic Acid
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 182/198 (91.9%) 185/202 (91.6%) 12/13 (92.3%)
    Blood and lymphatic system disorders
    Anaemia 25/198 (12.6%) 32/202 (15.8%) 1/13 (7.7%)
    Leukopenia 9/198 (4.5%) 11/202 (5.4%) 0/13 (0%)
    Neutropenia 12/198 (6.1%) 21/202 (10.4%) 0/13 (0%)
    Thrombocytopenia 6/198 (3%) 6/202 (3%) 1/13 (7.7%)
    Cardiac disorders
    Palpitations 2/198 (1%) 1/202 (0.5%) 1/13 (7.7%)
    Pericardial effusion 2/198 (1%) 1/202 (0.5%) 1/13 (7.7%)
    Ventricular tachycardia 0/198 (0%) 0/202 (0%) 1/13 (7.7%)
    Eye disorders
    Vision blurred 4/198 (2%) 4/202 (2%) 1/13 (7.7%)
    Gastrointestinal disorders
    Abdominal pain 20/198 (10.1%) 15/202 (7.4%) 2/13 (15.4%)
    Abdominal pain upper 12/198 (6.1%) 4/202 (2%) 0/13 (0%)
    Constipation 43/198 (21.7%) 35/202 (17.3%) 1/13 (7.7%)
    Diarrhoea 39/198 (19.7%) 35/202 (17.3%) 2/13 (15.4%)
    Dry mouth 11/198 (5.6%) 5/202 (2.5%) 0/13 (0%)
    Dyspepsia 8/198 (4%) 16/202 (7.9%) 1/13 (7.7%)
    Dysphagia 8/198 (4%) 7/202 (3.5%) 1/13 (7.7%)
    Gastrooesophageal reflux disease 8/198 (4%) 11/202 (5.4%) 1/13 (7.7%)
    Nausea 57/198 (28.8%) 51/202 (25.2%) 3/13 (23.1%)
    Oesophagitis 1/198 (0.5%) 4/202 (2%) 1/13 (7.7%)
    Oral disorder 2/198 (1%) 1/202 (0.5%) 1/13 (7.7%)
    Stomatitis 20/198 (10.1%) 8/202 (4%) 2/13 (15.4%)
    Swollen tongue 0/198 (0%) 0/202 (0%) 1/13 (7.7%)
    Vomiting 30/198 (15.2%) 33/202 (16.3%) 4/13 (30.8%)
    General disorders
    Asthenia 12/198 (6.1%) 15/202 (7.4%) 1/13 (7.7%)
    Chills 10/198 (5.1%) 9/202 (4.5%) 0/13 (0%)
    Fatigue 60/198 (30.3%) 68/202 (33.7%) 3/13 (23.1%)
    Oedema 3/198 (1.5%) 3/202 (1.5%) 1/13 (7.7%)
    Oedema peripheral 26/198 (13.1%) 26/202 (12.9%) 3/13 (23.1%)
    Pain 15/198 (7.6%) 11/202 (5.4%) 0/13 (0%)
    Pyrexia 18/198 (9.1%) 21/202 (10.4%) 1/13 (7.7%)
    Infections and infestations
    Nasopharyngitis 14/198 (7.1%) 13/202 (6.4%) 0/13 (0%)
    Oral herpes 3/198 (1.5%) 1/202 (0.5%) 2/13 (15.4%)
    Sinusitis 11/198 (5.6%) 18/202 (8.9%) 2/13 (15.4%)
    Tooth infection 3/198 (1.5%) 1/202 (0.5%) 1/13 (7.7%)
    Upper respiratory tract infection 18/198 (9.1%) 23/202 (11.4%) 1/13 (7.7%)
    Urinary tract infection 15/198 (7.6%) 23/202 (11.4%) 2/13 (15.4%)
    Injury, poisoning and procedural complications
    Arthropod bite 1/198 (0.5%) 3/202 (1.5%) 1/13 (7.7%)
    Foot fracture 0/198 (0%) 0/202 (0%) 1/13 (7.7%)
    Laceration 1/198 (0.5%) 2/202 (1%) 1/13 (7.7%)
    Ligament sprain 2/198 (1%) 0/202 (0%) 1/13 (7.7%)
    Rib fracture 2/198 (1%) 4/202 (2%) 1/13 (7.7%)
    Investigations
    Alanine aminotransferase increased 8/198 (4%) 9/202 (4.5%) 1/13 (7.7%)
    Aspartate aminotransferase increased 13/198 (6.6%) 9/202 (4.5%) 2/13 (15.4%)
    Blood albumin decreased 2/198 (1%) 0/202 (0%) 1/13 (7.7%)
    Blood alkaline phosphatase increased 15/198 (7.6%) 9/202 (4.5%) 2/13 (15.4%)
    Blood bilirubin increased 3/198 (1.5%) 2/202 (1%) 1/13 (7.7%)
    Blood cholesterol increased 0/198 (0%) 0/202 (0%) 1/13 (7.7%)
    Blood creatinine increased 10/198 (5.1%) 4/202 (2%) 2/13 (15.4%)
    Blood glucose increased 3/198 (1.5%) 2/202 (1%) 1/13 (7.7%)
    Blood lactate dehydrogenase increased 7/198 (3.5%) 7/202 (3.5%) 1/13 (7.7%)
    Blood potassium decreased 3/198 (1.5%) 3/202 (1.5%) 2/13 (15.4%)
    Blood urea increased 3/198 (1.5%) 1/202 (0.5%) 1/13 (7.7%)
    Liver function test abnormal 3/198 (1.5%) 2/202 (1%) 1/13 (7.7%)
    Red blood cell count decreased 1/198 (0.5%) 1/202 (0.5%) 1/13 (7.7%)
    Serum ferritin decreased 0/198 (0%) 0/202 (0%) 1/13 (7.7%)
    Weight decreased 15/198 (7.6%) 18/202 (8.9%) 1/13 (7.7%)
    Weight increased 4/198 (2%) 4/202 (2%) 1/13 (7.7%)
    Metabolism and nutrition disorders
    Decreased appetite 31/198 (15.7%) 27/202 (13.4%) 0/13 (0%)
    Dehydration 8/198 (4%) 9/202 (4.5%) 1/13 (7.7%)
    Diabetes mellitus 1/198 (0.5%) 1/202 (0.5%) 1/13 (7.7%)
    Hypocalcaemia 3/198 (1.5%) 3/202 (1.5%) 1/13 (7.7%)
    Hypoglycaemia 0/198 (0%) 2/202 (1%) 1/13 (7.7%)
    Hypokalaemia 19/198 (9.6%) 20/202 (9.9%) 1/13 (7.7%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 65/198 (32.8%) 56/202 (27.7%) 6/13 (46.2%)
    Back pain 52/198 (26.3%) 38/202 (18.8%) 2/13 (15.4%)
    Bone pain 18/198 (9.1%) 20/202 (9.9%) 1/13 (7.7%)
    Muscle spasms 15/198 (7.6%) 18/202 (8.9%) 1/13 (7.7%)
    Muscular weakness 4/198 (2%) 6/202 (3%) 1/13 (7.7%)
    Musculoskeletal chest pain 29/198 (14.6%) 25/202 (12.4%) 2/13 (15.4%)
    Musculoskeletal pain 32/198 (16.2%) 30/202 (14.9%) 2/13 (15.4%)
    Myalgia 14/198 (7.1%) 15/202 (7.4%) 1/13 (7.7%)
    Neck pain 8/198 (4%) 12/202 (5.9%) 0/13 (0%)
    Pain in extremity 49/198 (24.7%) 48/202 (23.8%) 3/13 (23.1%)
    Nervous system disorders
    Balance disorder 6/198 (3%) 5/202 (2.5%) 1/13 (7.7%)
    Dizziness 24/198 (12.1%) 18/202 (8.9%) 1/13 (7.7%)
    Headache 33/198 (16.7%) 34/202 (16.8%) 1/13 (7.7%)
    Hypersomnia 0/198 (0%) 0/202 (0%) 1/13 (7.7%)
    Hypoaesthesia 11/198 (5.6%) 12/202 (5.9%) 1/13 (7.7%)
    Migraine 0/198 (0%) 1/202 (0.5%) 1/13 (7.7%)
    Neuralgia 1/198 (0.5%) 4/202 (2%) 1/13 (7.7%)
    Neuropathy peripheral 20/198 (10.1%) 21/202 (10.4%) 3/13 (23.1%)
    Paraesthesia 13/198 (6.6%) 12/202 (5.9%) 0/13 (0%)
    Peripheral sensory neuropathy 9/198 (4.5%) 7/202 (3.5%) 1/13 (7.7%)
    Restless legs syndrome 1/198 (0.5%) 0/202 (0%) 1/13 (7.7%)
    Somnolence 2/198 (1%) 3/202 (1.5%) 1/13 (7.7%)
    Psychiatric disorders
    Anxiety 15/198 (7.6%) 11/202 (5.4%) 2/13 (15.4%)
    Depression 13/198 (6.6%) 8/202 (4%) 0/13 (0%)
    Insomnia 18/198 (9.1%) 19/202 (9.4%) 2/13 (15.4%)
    Renal and urinary disorders
    Pollakiuria 1/198 (0.5%) 4/202 (2%) 1/13 (7.7%)
    Reproductive system and breast disorders
    Vaginal discharge 0/198 (0%) 2/202 (1%) 2/13 (15.4%)
    Respiratory, thoracic and mediastinal disorders
    Cough 22/198 (11.1%) 27/202 (13.4%) 1/13 (7.7%)
    Dyspnoea 32/198 (16.2%) 26/202 (12.9%) 2/13 (15.4%)
    Epistaxis 12/198 (6.1%) 11/202 (5.4%) 0/13 (0%)
    Oropharyngeal pain 10/198 (5.1%) 8/202 (4%) 1/13 (7.7%)
    Pleural effusion 9/198 (4.5%) 13/202 (6.4%) 1/13 (7.7%)
    Sleep apnoea syndrome 2/198 (1%) 2/202 (1%) 1/13 (7.7%)
    Skin and subcutaneous tissue disorders
    Alopecia 11/198 (5.6%) 10/202 (5%) 1/13 (7.7%)
    Night sweats 6/198 (3%) 6/202 (3%) 1/13 (7.7%)
    Palmar-plantar erythrodysaesthesia syndrome 6/198 (3%) 14/202 (6.9%) 0/13 (0%)
    Pruritus 7/198 (3.5%) 11/202 (5.4%) 0/13 (0%)
    Pruritus generalised 0/198 (0%) 1/202 (0.5%) 1/13 (7.7%)
    Rash 18/198 (9.1%) 14/202 (6.9%) 1/13 (7.7%)
    Vascular disorders
    Aortic aneurysm 0/198 (0%) 0/202 (0%) 1/13 (7.7%)
    Deep vein thrombosis 3/198 (1.5%) 1/202 (0.5%) 1/13 (7.7%)
    Hot flush 13/198 (6.6%) 11/202 (5.4%) 1/13 (7.7%)
    Hypertension 11/198 (5.6%) 12/202 (5.9%) 2/13 (15.4%)
    Lymphoedema 6/198 (3%) 8/202 (4%) 2/13 (15.4%)

    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 or disclosure of trial results in their entirety.

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis
    Phone 862-778-8300
    Email
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00320710
    Other Study ID Numbers:
    • CZOL446E2352
    First Posted:
    May 3, 2006
    Last Update Posted:
    Aug 22, 2014
    Last Verified:
    Aug 1, 2014