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Z-MARK: Zoledronic Acid Treatment (Every 4 or 12 Weeks) to Prevent Skeletal Complications in Advanced Multiple Myeloma Participants

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT00622505
Collaborator
(none)
121
Enrollment
42
Locations
1
Arm
52.9
Actual Duration (Months)
2.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study evaluated the effectiveness and safety of a dosing method for zoledronic acid in preventing skeletal complications in multiple myeloma participants who have been on an intravenous (IV) bisphosphonate for about one to two years.

Condition or Disease Intervention/Treatment Phase
  • Drug: zoledronic acid
 Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
121 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Bone Marker-directed Dosing of ZOMETA® (Zoledronic Acid) for the Prevention of Skeletal Complications in Patients With Advanced Multiple Myeloma.
Actual Study Start Date :
Nov 7, 2007
Actual Primary Completion Date :
Apr 3, 2012
Actual Study Completion Date :
Apr 3, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: Zoledronic acid

Participants received 4 milligrams (mg) or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes, every 4 weeks or every 12 weeks for up to 96 weeks based on the participants most recent urine N-telopeptide of type 1 collagen (NTx) measurement (greater than or equal to [≥] 50 nanomoles per millimoles [nmol/mmol] creatinine or <50 nmol/mmol creatinine, respectively).

Drug: zoledronic acid
Zoledronic acid concentrate (4 mg/5 milliliters [ml]) was diluted in 100 mL sterile 0.9% calcium-free sodium chloride or 5% dextrose injection, administered IV, either 4 or 12 weeks for 96 weeks.
Other Names:
  • Zometa

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With ≥1 SRE at the End of 1 Year on Study [1 year]

      SRE was defined as pathological bone fracture, initiation of radiotherapy or surgery on bone, spinal cord compression, or hypercalcemia of malignancy (HCM). SRE was assessed by centrally read radiographic bone surveys.

    Secondary Outcome Measures

    1. Time to First SRE on Study [Up to 2 years]

      The time to first SRE is defined as the date of enrollment to the date of the first occurrence of any SRE on the study. SRE includes pathological fracture, initiation of radiotherapy or surgery on bone, spinal cord compression, or HCM. Participants who drop-out was treated as censored observations. Time to first SRE on the study was assessed by the Kaplan-Meier method.

    2. Percentage of Participants Who Experienced Pathologic Bone Fracture [Years 1 and 2]

      Pathologic bone fractures are defined as bone fractures that occur spontaneously or as a result of trivial trauma.

    3. Percentage of Participants Who Experienced Spinal Cord Compression [Years 1 and 2]

      Spinal cord compression is caused by the impingement of a tumor on the spinal cord and is associated with neurologic impairment and/or back pain.

    4. Percentage of Participants Who Experienced Radiation to Bone [Years 1 and 2]

      Radiation therapy to bone events includes irradiation of bone to palliate painful lesions, to treat or prevent pathologic fractures, or to treat or prevent spinal cord compression.

    5. Percentage of Participants Who Experienced Surgery to Bone [Years 1 and 2]

      Surgery to bone events includes surgical procedures that are performed to set or stabilize pathologic fractures or areas of spinal cord compression and surgical procedures that are performed to prevent an imminent pathologic fracture or spinal cord compression.

    6. Percentage of Participants Who Experienced HCM [Years 1 and 2]

      HCM is defined as corrected serum calcium ≥ 12.0 milligrams per deciliter (mg/dL) (3.00 millimoles per liter [mmol/L]), or a lower level of hypercalcemia that was symptomatic and required active treatment other than rehydration.

    7. Skeletal Related Event (SRE) Rate [Years 1 and 2]

      The SRE rate for each participant was calculated as the number of SREs/total follow-up time. SRE included pathological bone fracture, initiation of radiotherapy or surgery on bone, spinal cord compression, or HCM.

    8. Change From Baseline in Urinary N-telopeptide of Type 1 Collagen (uNTx) [Baseline and Weeks 12, 24, 36, 48, 60, 72, 84 and 100/End of Study (EOS)]

      uNTx is a biomarker used to measure the rate of bone turnover found in urine.

    9. Time to Death [Up to 2 years]

      Time to death was defined as the time from the date of enrollment to the date of death. Participants who dropped out or completed the study were considered censored observations. Time to death was assessed by Kaplan-Meier method.

    Eligibility Criteria

    Criteria

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

    • Confirmed diagnosis of multiple myeloma

    • Have been on zoledronic acid or pamidronate for 1-2 years and therapy must have been initiated for osteolytic lesion, bone fracture, spinal compression, or osteopenia due to multiple myeloma

    • Stable renal function

    Exclusion Criteria:

    • Known sensitivity to bisphosphonates

    • Receiving investigational drugs considered not safe for co-administration or have a significant effect on bone turnover

    • Current active dental problems

    • Had bone marrow transplant or blood stem cell transplant within 2 months before study entry or planned transplant within 2 months following enrollment

    Other protocol-defined inclusion/exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 TriValley Cancer Research and Treatment Center Casa Grande Arizona United States 85222
    2 Wilshire Oncology Medical Group La Verne California United States 91750
    3 Cedars Sinai Medical Center Outpatient Cancer Ctr. (4) Los Angeles California United States 90048
    4 Palo Alto Medical Foundation Hematology/Oncology Mountain View California United States 94040
    5 Oncology Care Medical Associates San Gabriel California United States 91776
    6 Santa Clara Valley Health & Hospital System San Jose California United States 95128
    7 University of Colorado U of Colorado Cancer Center Aurora Colorado United States 80045
    8 Hematology Oncology PC Stamford Connecticut United States 06902
    9 Washington Hospital Center Washington District of Columbia United States 20010
    10 Palm Beach Institute of Hematology Oncology Boynton Beach Florida United States 33435
    11 Innovative Medical Research of South Florida Innovative Med Research Miami Shores Florida United States 33138
    12 Cancer Centers of Florida PA Cancer Centers of Central FL Ocoee Florida United States *see dep*
    13 Integrated Community Oncology Network Florida Oncology Associates Orange Park Florida United States 32073
    14 Cleveland Clinic Florida Weston Florida United States 33331
    15 Loyola University Medical Center /Cardinal Bernardin Cancer Loyola Univ Med Ctr Maywood Illinois United States 60153
    16 University of Maryland Greenebaum Cancer Center Baltimore Maryland United States 21201
    17 Center for Cancer & Blood Disorders Bethesda Maryland United States 20817
    18 Oncology - Hematology Associates, PA Oncology Hematology Assoc Clinton Maryland United States 20735
    19 Dana Farber Cancer Institute Clinical Research Coordinator Boston Massachusetts United States 02115
    20 Boston VA Healthcare Boston VA Boston Massachusetts United States 02131
    21 Berkshire Hematology Oncology Pittsfield Massachusetts United States 01201-8298
    22 N MS Hematology & Oncology Tupelo Mississippi United States 38801
    23 Hematology & Oncology Consultants, PC Hematology & Oncology Omaha Nebraska United States 68122-1799
    24 Somerset Hematology Oncology Associates Somerset Hema Oncol Assoc (2) Somerset New Jersey United States 08873
    25 Cooper Cancer Center Voorhees New Jersey United States 08043
    26 Rochester General Hospital / Lipson Cancer Center Lipson Cancer Center Rochester New York United States 14621
    27 University of Rochester MC / James P. Wilmot Cancer Center James P. Wilmot Cancer Center Rochester New York United States 14642
    28 SUNY - Upstate Medical University Div. of Hematology-Oncology Syracuse New York United States 13210
    29 Carolina Oncology Specialists, PC Hickory North Carolina United States 28602
    30 Regional Hematology-Oncology Associates PC Langhorne Pennsylvania United States 19047
    31 Temple University Temple University Philadelphia Pennsylvania United States 19140
    32 Medical Associates, PA Charleston South Carolina United States 29403
    33 Low Country Hematology Oncology Dept of Lowcountry Hem/Onc Mount Pleasant South Carolina United States 29464
    34 Lexington Oncology Associates West Columbia South Carolina United States 29169
    35 Avera Research Institute Sioux Falls South Dakota United States 57105
    36 Blood and Cancer Center of East Texas Tyler Texas United States 75701
    37 East Texas Medical Center Cancer Institute Tyler Texas United States 75701
    38 Northern Utah Cancer Associates Dept.ofNorthernUtahAssoc. Ogden Utah United States 84403-3105
    39 Central Utah Clinic Central Utah Clinic (8) Provo Utah United States 84604
    40 Peninsula Cancer Institute Newport News Virginia United States 23601
    41 Swedish Cancer Institute Seattle Washington United States 98104
    42 West Virginia University Health Research Center Clinical Trial Research Unit Morgantown West Virginia United States 26506

    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:
    NCT00622505
    Other Study ID Numbers:
    • CZOL446EUS129
    First Posted:
    Feb 25, 2008
    Last Update Posted:
    May 26, 2021
    Last Verified:
    May 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    Multiple myeloma
    zoledronic acid
    skeletal complications
    bone
    Additional relevant MeSH terms:
    Multiple Myeloma
    Neoplasms, Plasma Cell
    Zoledronic Acid

    Study Results

    Participant Flow

    Recruitment Details This study was conducted at 67 centers in the United States (US) from 07 November 2007 to 03 April 2012.
    Pre-assignment Detail A total of 121 participants with Advanced Multiple Myeloma were enrolled in this study. By study design, any participants who had a Skeletal-related Event (SRE) in Zoledronic Acid Every 12 Weeks group was switched to Zoledronic Acid Every 4 Weeks or 12 Weeks group and reported as Zoledronic Acid Every 4 Weeks or 12 Weeks group, respectively.
    Arm/Group Title Zoledronic Acid Every 12 Weeks Zoledronic Acid Every 4 Weeks or 12 Weeks
    Arm/Group Description Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement ( <50 nmol/mmol creatinine). Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 4 weeks or every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement (≥ 50 nmol/mmol creatinine or <50 nmol/mmol creatinine, respectively).
    Period Title: Overall Study
    STARTED 79 42
    COMPLETED 50 19
    NOT COMPLETED 29 23

    Baseline Characteristics

    Arm/Group Title Zoledronic Acid Every 12 Weeks Zoledronic Acid Every 4 Weeks or 12 Weeks Total
    Arm/Group Description Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement ( <50 nmol/mmol creatinine). Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 4 weeks or every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement (≥ 50 nmol/mmol creatinine or <50 nmol/mmol creatinine, respectively). Total of all reporting groups
    Overall Participants 79 42 121
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    62.8
    (9.91)
    65.8
    (12.66)
    63.8
    (10.99)
    Sex: Female, Male (Count of Participants)
    Female
    36
    45.6%
    21
    50%
    57
    47.1%
    Male
    43
    54.4%
    21
    50%
    64
    52.9%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With ≥1 SRE at the End of 1 Year on Study
    Description SRE was defined as pathological bone fracture, initiation of radiotherapy or surgery on bone, spinal cord compression, or hypercalcemia of malignancy (HCM). SRE was assessed by centrally read radiographic bone surveys.
    Time Frame 1 year

    Outcome Measure Data

    Analysis Population Description
    ITT analysis set included all participants who were enrolled in this study.
    Arm/Group Title Zoledronic Acid Every 12 Weeks Zoledronic Acid Every 4 Weeks or 12 Weeks
    Arm/Group Description Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement ( <50 nmol/mmol creatinine). Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 4 weeks or every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement (≥ 50 nmol/mmol creatinine or <50 nmol/mmol creatinine, respectively).
    Measure Participants 79 42
    Number (95% Confidence Interval) [percentage of participants]
    0
    0%
    0.17
    0.4%
    2. Secondary Outcome
    Title Time to First SRE on Study
    Description The time to first SRE is defined as the date of enrollment to the date of the first occurrence of any SRE on the study. SRE includes pathological fracture, initiation of radiotherapy or surgery on bone, spinal cord compression, or HCM. Participants who drop-out was treated as censored observations. Time to first SRE on the study was assessed by the Kaplan-Meier method.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    ITT analysis set included all participants who were enrolled in this study.
    Arm/Group Title Zoledronic Acid Every 12 Weeks Zoledronic Acid Every 4 Weeks or 12 Weeks
    Arm/Group Description Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement ( <50 nmol/mmol creatinine). Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 4 weeks or every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement (≥ 50 nmol/mmol creatinine or <50 nmol/mmol creatinine, respectively).
    Measure Participants 79 42
    Median (95% Confidence Interval) [years]
    NA
    NA
    3. Secondary Outcome
    Title Percentage of Participants Who Experienced Pathologic Bone Fracture
    Description Pathologic bone fractures are defined as bone fractures that occur spontaneously or as a result of trivial trauma.
    Time Frame Years 1 and 2

    Outcome Measure Data

    Analysis Population Description
    ITT analysis set included all participants who were enrolled in the study. Number analyzed signifies the number of participants with data available for analysis at given time point.
    Arm/Group Title Zoledronic Acid Every 12 Weeks Zoledronic Acid Every 4 Weeks or 12 Weeks
    Arm/Group Description Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement ( <50 nmol/mmol creatinine). Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 4 weeks or every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement (≥ 50 nmol/mmol creatinine or <50 nmol/mmol creatinine, respectively).
    Measure Participants 79 42
    Year 1
    0.00
    0%
    0.07
    0.2%
    Year 2
    0.00
    0%
    0.03
    0.1%
    4. Secondary Outcome
    Title Percentage of Participants Who Experienced Spinal Cord Compression
    Description Spinal cord compression is caused by the impingement of a tumor on the spinal cord and is associated with neurologic impairment and/or back pain.
    Time Frame Years 1 and 2

    Outcome Measure Data

    Analysis Population Description
    ITT analysis set included all participants who were enrolled in the study. Number analyzed signifies the number of participants with data available for analysis at given time point.
    Arm/Group Title Zoledronic Acid Every 12 Weeks Zoledronic Acid Every 4 Weeks or 12 Weeks
    Arm/Group Description Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement ( <50 nmol/mmol creatinine). Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 4 weeks or every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement (≥ 50 nmol/mmol creatinine or <50 nmol/mmol creatinine, respectively).
    Measure Participants 79 42
    Year 1
    0.00
    0%
    0.07
    0.2%
    Year 2
    0.00
    0%
    0.00
    0%
    5. Secondary Outcome
    Title Percentage of Participants Who Experienced Radiation to Bone
    Description Radiation therapy to bone events includes irradiation of bone to palliate painful lesions, to treat or prevent pathologic fractures, or to treat or prevent spinal cord compression.
    Time Frame Years 1 and 2

    Outcome Measure Data

    Analysis Population Description
    ITT analysis set included all participants who were enrolled in the study. Number analyzed signifies the number of participants with data available for analysis at given time point.
    Arm/Group Title Zoledronic Acid Every 12 Weeks Zoledronic Acid Every 4 Weeks or 12 Weeks
    Arm/Group Description Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement ( <50 nmol/mmol creatinine). Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 4 weeks or every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement (≥ 50 nmol/mmol creatinine or <50 nmol/mmol creatinine, respectively).
    Measure Participants 79 42
    Year 1
    0.00
    0%
    0.10
    0.2%
    Year 2
    0.00
    0%
    0.11
    0.3%
    6. Secondary Outcome
    Title Percentage of Participants Who Experienced Surgery to Bone
    Description Surgery to bone events includes surgical procedures that are performed to set or stabilize pathologic fractures or areas of spinal cord compression and surgical procedures that are performed to prevent an imminent pathologic fracture or spinal cord compression.
    Time Frame Years 1 and 2

    Outcome Measure Data

    Analysis Population Description
    ITT analysis set includes all participants who were enrolled in this study. Number analyzed signifies the number of participants with data available for analysis at given time point.
    Arm/Group Title Zoledronic Acid Every 12 Weeks Zoledronic Acid Every 4 Weeks or 12 Weeks
    Arm/Group Description Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement ( <50 nmol/mmol creatinine). Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 4 weeks or every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement (≥ 50 nmol/mmol creatinine or <50 nmol/mmol creatinine, respectively).
    Measure Participants 79 42
    Year 1
    0.00
    0%
    0.02
    0%
    Year 2
    0.00
    0%
    0.00
    0%
    7. Secondary Outcome
    Title Percentage of Participants Who Experienced HCM
    Description HCM is defined as corrected serum calcium ≥ 12.0 milligrams per deciliter (mg/dL) (3.00 millimoles per liter [mmol/L]), or a lower level of hypercalcemia that was symptomatic and required active treatment other than rehydration.
    Time Frame Years 1 and 2

    Outcome Measure Data

    Analysis Population Description
    ITT analysis set includes all participants who were enrolled in this study. Number analyzed signifies the number of participants with data available for analysis at given time point.
    Arm/Group Title Zoledronic Acid Every 12 Weeks Zoledronic Acid Every 4 Weeks or 12 Weeks
    Arm/Group Description Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement ( <50 nmol/mmol creatinine). Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 4 weeks or every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement (≥ 50 nmol/mmol creatinine or <50 nmol/mmol creatinine, respectively).
    Measure Participants 79 42
    Year 1
    0.00
    0%
    0.02
    0%
    Year 2
    0.00
    0%
    0.00
    0%
    8. Secondary Outcome
    Title Skeletal Related Event (SRE) Rate
    Description The SRE rate for each participant was calculated as the number of SREs/total follow-up time. SRE included pathological bone fracture, initiation of radiotherapy or surgery on bone, spinal cord compression, or HCM.
    Time Frame Years 1 and 2

    Outcome Measure Data

    Analysis Population Description
    ITT analysis set includes all participants who were enrolled in this study. Number analyzed signifies the number of participants with data available for analysis at given time point.
    Arm/Group Title Zoledronic Acid Every 12 Weeks Zoledronic Acid Every 4 Weeks or 12 Weeks
    Arm/Group Description Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement ( <50 nmol/mmol creatinine). Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 4 weeks or every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement (≥ 50 nmol/mmol creatinine or <50 nmol/mmol creatinine, respectively).
    Measure Participants 79 42
    Year 1
    0.00
    (0.00)
    0.03
    (0.080)
    Year 2
    0.00
    (0.00)
    0.02
    (0.049)
    9. Secondary Outcome
    Title Change From Baseline in Urinary N-telopeptide of Type 1 Collagen (uNTx)
    Description uNTx is a biomarker used to measure the rate of bone turnover found in urine.
    Time Frame Baseline and Weeks 12, 24, 36, 48, 60, 72, 84 and 100/End of Study (EOS)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all enrolled participants who received at least 1 dose of zoledronic acid. Number analyzed signifies the number of participants with data available for analysis at given time point.
    Arm/Group Title Zoledronic Acid Every 12 Weeks Zoledronic Acid Every 4 Weeks or 12 Weeks
    Arm/Group Description Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement ( <50 nmol/mmol creatinine). Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 4 weeks or every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement (≥ 50 nmol/mmol creatinine or <50 nmol/mmol creatinine, respectively).
    Measure Participants 79 42
    Baseline
    19.8
    (8.82)
    24.1
    (15.63)
    Change from Baseline to Week 12
    0.2
    (11.50)
    4.3
    (19.47)
    Change from Baseline to Week 24
    -1.4
    (8.72)
    -0.5
    (15.66)
    Change from Baseline to Week 36
    -2.0
    (9.77)
    -0.9
    (13.92)
    Change from Baseline to Week 48
    -2.3
    (9.24)
    1.7
    (18.39)
    Change from Baseline to Week 60
    -2.5
    (12.30)
    -0.8
    (17.54)
    Change from Baseline to Week 72
    -3.5
    (10.99)
    -6.7
    (15.50)
    Change from Baseline to Week 84
    -3.0
    (10.73)
    -7.6
    (18.51)
    Change from Baseline to Week 100
    -5.2
    (9.25)
    -7.4
    (17.68)
    10. Secondary Outcome
    Title Time to Death
    Description Time to death was defined as the time from the date of enrollment to the date of death. Participants who dropped out or completed the study were considered censored observations. Time to death was assessed by Kaplan-Meier method.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    ITT analysis set included all participants who were enrolled in this study.
    Arm/Group Title Zoledronic Acid Every 12 Weeks Zoledronic Acid Every 4 Weeks or 12 Weeks
    Arm/Group Description Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement ( <50 nmol/mmol creatinine). Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 4 weeks or every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement (≥ 50 nmol/mmol creatinine or <50 nmol/mmol creatinine, respectively).
    Measure Participants 79 42
    Median (95% Confidence Interval) [years]
    NA
    NA

    Adverse Events

    Time Frame Up to 2 Years
    Adverse Event Reporting Description Safety analysis set included all enrolled participants who received at least 1 dose of zoledronic acid. Number analyzed signifies the number of participants with data available for analysis at given time point.
    Arm/Group Title Zoledronic Acid Every 12 Weeks Zoledronic Acid Every 4 Weeks or 12 Weeks
    Arm/Group Description Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement ( <50 nmol/mmol creatinine). Participants received 4 mg or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes every 4 weeks or every 12 weeks for up to 96 weeks based on the participants most recent urine NTx measurement (≥ 50 nmol/mmol creatinine or <50 nmol/mmol creatinine, respectively).
    All Cause Mortality
    Zoledronic Acid Every 12 Weeks Zoledronic Acid Every 4 Weeks or 12 Weeks
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/79 (2.5%) 2/42 (4.8%)
    Serious Adverse Events
    Zoledronic Acid Every 12 Weeks Zoledronic Acid Every 4 Weeks or 12 Weeks
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 23/79 (29.1%) 25/42 (59.5%)
    Blood and lymphatic system disorders
    Anaemia 0/79 (0%) 4/42 (9.5%)
    Febrile neutropenia 1/79 (1.3%) 0/42 (0%)
    Pancytopenia 1/79 (1.3%) 1/42 (2.4%)
    Thrombocytopenia 1/79 (1.3%) 1/42 (2.4%)
    Cardiac disorders
    Acute myocardial infarction 0/79 (0%) 1/42 (2.4%)
    Atrial fibrillation 2/79 (2.5%) 0/42 (0%)
    Atrial flutter 0/79 (0%) 1/42 (2.4%)
    Atrioventricular block complete 0/79 (0%) 1/42 (2.4%)
    Cardiac failure congestive 1/79 (1.3%) 3/42 (7.1%)
    Cardiogenic shock 0/79 (0%) 1/42 (2.4%)
    Cardiomegaly 0/79 (0%) 1/42 (2.4%)
    Coronary artery disease 0/79 (0%) 1/42 (2.4%)
    Pericardial effusion 0/79 (0%) 1/42 (2.4%)
    Pericarditis 0/79 (0%) 1/42 (2.4%)
    Ventricular asystole 0/79 (0%) 1/42 (2.4%)
    Gastrointestinal disorders
    Colitis 1/79 (1.3%) 0/42 (0%)
    Diarrhoea 1/79 (1.3%) 2/42 (4.8%)
    Dysphagia 0/79 (0%) 1/42 (2.4%)
    Gastrointestinal haemorrhage 0/79 (0%) 2/42 (4.8%)
    Ileus 0/79 (0%) 1/42 (2.4%)
    Intestinal ischaemia 0/79 (0%) 1/42 (2.4%)
    Melaena 1/79 (1.3%) 0/42 (0%)
    Pancreatitis 0/79 (0%) 1/42 (2.4%)
    Rectal haemorrhage 0/79 (0%) 1/42 (2.4%)
    Small intestinal obstruction 0/79 (0%) 2/42 (4.8%)
    Vomiting 0/79 (0%) 1/42 (2.4%)
    General disorders
    Asthenia 0/79 (0%) 2/42 (4.8%)
    Chest pain 0/79 (0%) 2/42 (4.8%)
    Fatigue 0/79 (0%) 1/42 (2.4%)
    Generalised oedema 0/79 (0%) 1/42 (2.4%)
    Malaise 0/79 (0%) 1/42 (2.4%)
    Oedema peripheral 0/79 (0%) 2/42 (4.8%)
    Pyrexia 1/79 (1.3%) 3/42 (7.1%)
    Infections and infestations
    Acute sinusitis 1/79 (1.3%) 0/42 (0%)
    Bronchitis 0/79 (0%) 2/42 (4.8%)
    Catheter site infection 0/79 (0%) 1/42 (2.4%)
    Cellulitis 1/79 (1.3%) 1/42 (2.4%)
    Gastroenteritis viral 0/79 (0%) 1/42 (2.4%)
    Influenza 1/79 (1.3%) 0/42 (0%)
    Lobar pneumonia 0/79 (0%) 1/42 (2.4%)
    Parainfluenzae virus infection 0/79 (0%) 1/42 (2.4%)
    Pneumonia 6/79 (7.6%) 6/42 (14.3%)
    Pyelonephritis 0/79 (0%) 1/42 (2.4%)
    Viral infection 0/79 (0%) 1/42 (2.4%)
    Injury, poisoning and procedural complications
    Humerus fracture 0/79 (0%) 1/42 (2.4%)
    Pelvic fracture 0/79 (0%) 1/42 (2.4%)
    Rib fracture 1/79 (1.3%) 1/42 (2.4%)
    Spinal fracture 1/79 (1.3%) 0/42 (0%)
    Transfusion reaction 1/79 (1.3%) 0/42 (0%)
    Metabolism and nutrition disorders
    Dehydration 0/79 (0%) 3/42 (7.1%)
    Failure to thrive 0/79 (0%) 1/42 (2.4%)
    Gout 0/79 (0%) 1/42 (2.4%)
    Hypercalcaemia 0/79 (0%) 1/42 (2.4%)
    Hypocalcaemia 0/79 (0%) 1/42 (2.4%)
    Hyponatraemia 0/79 (0%) 1/42 (2.4%)
    Hypovolaemia 0/79 (0%) 1/42 (2.4%)
    Malnutrition 0/79 (0%) 1/42 (2.4%)
    Metabolic acidosis 0/79 (0%) 1/42 (2.4%)
    Tumour lysis syndrome 0/79 (0%) 1/42 (2.4%)
    Musculoskeletal and connective tissue disorders
    Back pain 1/79 (1.3%) 0/42 (0%)
    Musculoskeletal pain 1/79 (1.3%) 0/42 (0%)
    Osteonecrosis of jaw 4/79 (5.1%) 0/42 (0%)
    Pain in extremity 0/79 (0%) 1/42 (2.4%)
    Pathological fracture 0/79 (0%) 1/42 (2.4%)
    Synovial cyst 0/79 (0%) 1/42 (2.4%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Leukaemia plasmacytic 1/79 (1.3%) 0/42 (0%)
    Lung neoplasm malignant 1/79 (1.3%) 0/42 (0%)
    Multiple myeloma 1/79 (1.3%) 1/42 (2.4%)
    Rectal cancer 0/79 (0%) 1/42 (2.4%)
    Nervous system disorders
    Convulsion 1/79 (1.3%) 0/42 (0%)
    Metabolic encephalopathy 0/79 (0%) 1/42 (2.4%)
    Presyncope 0/79 (0%) 2/42 (4.8%)
    Spinal cord compression 0/79 (0%) 1/42 (2.4%)
    Syncope 0/79 (0%) 1/42 (2.4%)
    Psychiatric disorders
    Confusional state 1/79 (1.3%) 0/42 (0%)
    Delirium 0/79 (0%) 1/42 (2.4%)
    Depression 1/79 (1.3%) 0/42 (0%)
    Mental status changes 1/79 (1.3%) 0/42 (0%)
    Renal and urinary disorders
    Hydronephrosis 0/79 (0%) 1/42 (2.4%)
    Renal failure 0/79 (0%) 4/42 (9.5%)
    Renal failure acute 1/79 (1.3%) 4/42 (9.5%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome 0/79 (0%) 1/42 (2.4%)
    Chronic obstructive pulmonary disease 1/79 (1.3%) 0/42 (0%)
    Dysphonia 0/79 (0%) 1/42 (2.4%)
    Dyspnoea 1/79 (1.3%) 1/42 (2.4%)
    Dyspnoea exertional 0/79 (0%) 1/42 (2.4%)
    Pleural effusion 0/79 (0%) 2/42 (4.8%)
    Pneumothorax 0/79 (0%) 1/42 (2.4%)
    Productive cough 0/79 (0%) 1/42 (2.4%)
    Pulmonary oedema 0/79 (0%) 1/42 (2.4%)
    Respiratory distress 0/79 (0%) 1/42 (2.4%)
    Respiratory failure 2/79 (2.5%) 2/42 (4.8%)
    Sleep apnoea syndrome 0/79 (0%) 1/42 (2.4%)
    Skin and subcutaneous tissue disorders
    Telangiectasia 1/79 (1.3%) 0/42 (0%)
    Vascular disorders
    Hypotension 1/79 (1.3%) 1/42 (2.4%)
    Thrombosis 0/79 (0%) 1/42 (2.4%)
    Venous insufficiency 0/79 (0%) 1/42 (2.4%)
    Other (Not Including Serious) Adverse Events
    Zoledronic Acid Every 12 Weeks Zoledronic Acid Every 4 Weeks or 12 Weeks
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 70/79 (88.6%) 41/42 (97.6%)
    Blood and lymphatic system disorders
    Anaemia 6/79 (7.6%) 10/42 (23.8%)
    Leukopenia 3/79 (3.8%) 3/42 (7.1%)
    Neutropenia 4/79 (5.1%) 4/42 (9.5%)
    Thrombocytopenia 6/79 (7.6%) 9/42 (21.4%)
    Cardiac disorders
    Tachycardia 1/79 (1.3%) 5/42 (11.9%)
    Gastrointestinal disorders
    Abdominal discomfort 2/79 (2.5%) 3/42 (7.1%)
    Abdominal pain 3/79 (3.8%) 3/42 (7.1%)
    Constipation 9/79 (11.4%) 11/42 (26.2%)
    Diarrhoea 15/79 (19%) 11/42 (26.2%)
    Dyspepsia 4/79 (5.1%) 1/42 (2.4%)
    Gastrooesophageal reflux disease 0/79 (0%) 5/42 (11.9%)
    Nausea 9/79 (11.4%) 12/42 (28.6%)
    Toothache 4/79 (5.1%) 0/42 (0%)
    Vomiting 5/79 (6.3%) 3/42 (7.1%)
    General disorders
    Asthenia 8/79 (10.1%) 4/42 (9.5%)
    Chest discomfort 2/79 (2.5%) 4/42 (9.5%)
    Chest pain 3/79 (3.8%) 5/42 (11.9%)
    Fatigue 15/79 (19%) 16/42 (38.1%)
    Influenza like illness 4/79 (5.1%) 0/42 (0%)
    Oedema peripheral 6/79 (7.6%) 7/42 (16.7%)
    Pyrexia 10/79 (12.7%) 9/42 (21.4%)
    Infections and infestations
    Bronchitis 6/79 (7.6%) 7/42 (16.7%)
    Herpes zoster 8/79 (10.1%) 5/42 (11.9%)
    Nasopharyngitis 6/79 (7.6%) 5/42 (11.9%)
    Pneumonia 8/79 (10.1%) 7/42 (16.7%)
    Sinusitis 6/79 (7.6%) 6/42 (14.3%)
    Tooth infection 1/79 (1.3%) 3/42 (7.1%)
    Upper respiratory tract infection 18/79 (22.8%) 11/42 (26.2%)
    Urinary tract infection 8/79 (10.1%) 5/42 (11.9%)
    Investigations
    Blood creatinine increased 7/79 (8.9%) 4/42 (9.5%)
    Weight decreased 3/79 (3.8%) 4/42 (9.5%)
    Metabolism and nutrition disorders
    Decreased appetite 5/79 (6.3%) 2/42 (4.8%)
    Dehydration 4/79 (5.1%) 7/42 (16.7%)
    Hyperglycaemia 4/79 (5.1%) 3/42 (7.1%)
    Hyperkalaemia 2/79 (2.5%) 3/42 (7.1%)
    Hypocalcaemia 1/79 (1.3%) 4/42 (9.5%)
    Hypokalaemia 6/79 (7.6%) 5/42 (11.9%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 14/79 (17.7%) 7/42 (16.7%)
    Back pain 6/79 (7.6%) 10/42 (23.8%)
    Bone pain 7/79 (8.9%) 5/42 (11.9%)
    Muscle spasms 6/79 (7.6%) 10/42 (23.8%)
    Muscular weakness 2/79 (2.5%) 4/42 (9.5%)
    Musculoskeletal chest pain 1/79 (1.3%) 3/42 (7.1%)
    Musculoskeletal pain 9/79 (11.4%) 3/42 (7.1%)
    Myalgia 4/79 (5.1%) 1/42 (2.4%)
    Pain in extremity 7/79 (8.9%) 9/42 (21.4%)
    Pain in jaw 2/79 (2.5%) 3/42 (7.1%)
    Nervous system disorders
    Dizziness 5/79 (6.3%) 8/42 (19%)
    Headache 7/79 (8.9%) 3/42 (7.1%)
    Hypoaesthesia 5/79 (6.3%) 3/42 (7.1%)
    Neuropathy peripheral 4/79 (5.1%) 6/42 (14.3%)
    Psychiatric disorders
    Anxiety 6/79 (7.6%) 2/42 (4.8%)
    Depression 4/79 (5.1%) 4/42 (9.5%)
    Insomnia 5/79 (6.3%) 8/42 (19%)
    Respiratory, thoracic and mediastinal disorders
    Cough 16/79 (20.3%) 9/42 (21.4%)
    Dyspnoea 6/79 (7.6%) 3/42 (7.1%)
    Nasal congestion 4/79 (5.1%) 1/42 (2.4%)
    Oropharyngeal pain 6/79 (7.6%) 2/42 (4.8%)
    Respiratory tract congestion 2/79 (2.5%) 4/42 (9.5%)
    Skin and subcutaneous tissue disorders
    Rash 6/79 (7.6%) 5/42 (11.9%)
    Vascular disorders
    Hot flush 4/79 (5.1%) 0/42 (0%)
    Hypertension 6/79 (7.6%) 1/42 (2.4%)
    Hypotension 2/79 (2.5%) 5/42 (11.9%)

    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 (ie, data from all sites) in the clinical trial.

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862-778-8300
    Email Novartis.email@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00622505
    Other Study ID Numbers:
    • CZOL446EUS129
    First Posted:
    Feb 25, 2008
    Last Update Posted:
    May 26, 2021
    Last Verified:
    May 1, 2021