Back to resultsAcetaminophen or Fluvastatin Compared to Placebo on the Transient Post-Dose Symptoms (PDS) Following an Intravenous (i.v.) Infusion of a Single Dose of Zoledronic Acid 5mg, in Post-menopausal Women With Low Bone Mass
Primary Purpose
Osteoporosis
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Placebo
Acetaminophen
Fluvastatin
Sponsored by
About this trial
This is an interventional treatment trial for Osteoporosis focused on measuring zoledronic acid, post dose symptoms, transient, acetaminophen, fluvastatin
Eligibility Criteria
Inclusion Criteria:
- Postmenopausal women greater than or equal to 45 and less than or equal to 79 years of age at randomization
- Women who are clinically indicated for treatment with Bisphosphonates for osteopenia or osteoporosis with a documented central (spine or hip) Bone Mineral Density T Score less than or equal to 1.5
Exclusion Criteria:
- Any prior treatment with intravenous Bisphosphonates
- Oral treatment with Bisphosphonates for more than 8 weeks or within 6 months prior to the screening visit
- Patients who are taking, and are unwilling or unable to stop taking, certain medications
- Patients who require anticoagulant therapy
- Patients with a known hypersensitivity to ibuprofen, ACET, bisphosphonates, statins or with allergies manifested by attacks of asthma, urticaria or acute rhinitis following
- Proteinuria (protein detected on a urine dipstick) greater than or equal to 2+ at screening
- Protocol specific laboratory values that fall out of range for this study
- Ongoing infection (oral body temperature greater than or equal to 37.5C (99.5°F),chronic febrile disease or fever of unknown origin at screening or randomization
- Active dental infection, unhealed dental extraction or planned oral surgery within 3 months after randomization
- History of iritis, uveitis or chronic conjunctivitis
- History of hypoparathyroidism, hyperparathyroidism or Paget's Disease
- Partial or total removal of parathyroid or thyroid gland
- History of malignancy of any organ system, treated or untreated, within the past 1 year whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin
- Treatment with an investigational drug within the previous 30 days of screening
- Patients with any medical or psychiatric condition which, in the opinion of the Principal Investigator, would preclude the participant from adhering to the protocol or completing the trial per protocol, or any patient who the Principal Investigator thinks should not participate in the study for any reason, including current drug or alcohol abuse
Other protocol-defined inclusion/exclusion criteria may apply
Sites / Locations
- Refer to the E-portal link for ZOL446HUS136
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Acetaminophen
Fluvastatin
Placebo
Arm Description
2 capsules of acetaminophen 325 mg and 2 capsules of placebo (matching fluvastatin) administered 45 +/- 15 minutes prior to i.v. infusion of zoledronic acid 5 mg, then 2 capsules of acetaminophen 325 mg 4 times per day (including medication taken at study site at visit 2/day 1) over the next 3 days (not exceeding 8 capsules in a 24-hour period).
2 capsules of fluvastatin 40 mg and 2 capsules of placebo (matching acetaminophen) administered 45 +/- 15 minutes prior to i.v. infusion of zoledronic acid 5 mg, then 2 capsules of placebo (matching acetaminophen) 4 times per day (including medication taken at study site at visit 2/day 1) over the next 3 days (not exceeding 8 capsules in a 24-hour period).
2 capsules of placebo (matching fluvastatin) and 2 capsules of placebo (matching acetaminophen) administered 45 +/- 15 minutes prior to intravenous (i.v.) infusion of zoledronic acid 5 mg, then 2 capsules of placebo (matching acetaminophen) 4 times per day (including medication taken at study site at visit 2/day 1) over the next 3 days (not exceeding 8 capsules in a 24-hour period).
Outcomes
Primary Outcome Measures
Proportion of Patients With a Clinically Significant Increase in Oral Body Temperature or Use of Rescue Medication.
Clinically significant increase in oral body temperature or used rescue medication ibuprofen >= 1 time during the 3-day period after i.v. infusion of zoledronic acid 5 mg. A clinically significant increase in body temperature was defined as an increase of at least 1 degree Celsius from baseline and a mean oral body temperature reading of at least 38.5 degrees Celsius occurring at least once during the 3-day treatment period.
Secondary Outcome Measures
Proportion of Patients With a Clinically Significant Increase in Oral Body Temperature.
Clinically significant increase in oral body temperature >= 1 time during the 3-day period after i.v. infusion of zoledronic acid 5 mg. A clinically significant increase in body temperature was defined as an increase of at least 1 degree Celsius from baseline and a mean oral body temperature reading of at least 38.5 degrees Celsius occurring at least once during the 3-day treatment period.
Proportion of Patients Who Used Rescue Medication.
Patients that took rescue medication >= 1 time during the 3-day period after i.v. infusion of zoledronic acid 5 mg. Patients who experienced severe discomfort after their first home measurements and self-administration of study medication were allowed to take ibuprofen (200 mg tablets every 4-6 hours as needed) as rescue medication while continuing to take their study medication.
Number of Rescue Medication Tablets Taken
Patients who experienced severe discomfort after their first home measurements and self-administration of study medication were allowed to take ibuprofen (200 mg tablets every 4-6 hours as needed) as rescue medication while continuing to take their study medication.
Time to First Rescue Medication After Infusion of Zoledronic Acid 5 mg.
Patients who experienced severe discomfort after their first home measurements and self-administration of study medication were allowed to take ibuprofen (200 mg tablets every 4-6 hours as needed) as rescue medication while continuing to take their study medication.
Proportion of Patients With a Major Increase (Worsening) in Severity of Questionnaire Symptoms.
A major increase (worsening) in severity was defined as an increase in severity of 2 units or more from baseline at least once during the 3 days immediately following i.v. infusion of zoledronic acid 5 mg. The severity of the symptom was evaluated using a 4-point categorical scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe).
Proportion of Patients Reporting Severe Questionnaire Symptoms.
A severe questionnaire symptom was defined as experiencing a severe specified symptom (feeling feverish, experiencing headaches, having aches and pains of muscles and joints) at least once post-baseline.
Change From Baseline in Visual Analog Scale (VAS) Measurement of Symptom Severity
Effect on severity of symptoms following i.v. infusion of zoledronic acid 5 mg. The VAS is a 100-mm linear visual analog scale (0 = no symptoms to 100 = severe symptoms). The baseline VAS measurement was defined as the VAS measurement recorded prior to the infusion.
Full Information
NCT ID
NCT00489424
First Posted
June 19, 2007
Last Updated
February 15, 2011
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00489424
Brief Title
Acetaminophen or Fluvastatin Compared to Placebo on the Transient Post-Dose Symptoms (PDS) Following an Intravenous (i.v.) Infusion of a Single Dose of Zoledronic Acid 5mg, in Post-menopausal Women With Low Bone Mass
Official Title
A Randomized, Multicenter, Double-blind, Double-dummy, Parallel-group Study of Acetaminophen or Fluvastatin Compared to Placebo on the Transient Post-Dose Symptoms (PDS) Following an i.v. Infusion of a Single Dose of Zoledronic Acid 5mg, in Post-menopausal Women With Low Bone Mass
Study Type
Interventional
2. Study Status
Record Verification Date
February 2011
Overall Recruitment Status
Completed
Study Start Date
June 2007 (undefined)
Primary Completion Date
December 2007 (Actual)
Study Completion Date
December 2007 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
5. Study Description
Brief Summary
This study will evaluate the efficacy of acetaminophen or fluvastatin in reducing the rate of occurrence and the severity of post dose symptoms that may occur during the 3 day period following a zoledronic acid infusion in post menopausal women with low bone mass.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoporosis
Keywords
zoledronic acid, post dose symptoms, transient, acetaminophen, fluvastatin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
793 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Acetaminophen
Arm Type
Experimental
Arm Description
2 capsules of acetaminophen 325 mg and 2 capsules of placebo (matching fluvastatin) administered 45 +/- 15 minutes prior to i.v. infusion of zoledronic acid 5 mg, then 2 capsules of acetaminophen 325 mg 4 times per day (including medication taken at study site at visit 2/day 1) over the next 3 days (not exceeding 8 capsules in a 24-hour period).
Arm Title
Fluvastatin
Arm Type
Experimental
Arm Description
2 capsules of fluvastatin 40 mg and 2 capsules of placebo (matching acetaminophen) administered 45 +/- 15 minutes prior to i.v. infusion of zoledronic acid 5 mg, then 2 capsules of placebo (matching acetaminophen) 4 times per day (including medication taken at study site at visit 2/day 1) over the next 3 days (not exceeding 8 capsules in a 24-hour period).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
2 capsules of placebo (matching fluvastatin) and 2 capsules of placebo (matching acetaminophen) administered 45 +/- 15 minutes prior to intravenous (i.v.) infusion of zoledronic acid 5 mg, then 2 capsules of placebo (matching acetaminophen) 4 times per day (including medication taken at study site at visit 2/day 1) over the next 3 days (not exceeding 8 capsules in a 24-hour period).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Type
Drug
Intervention Name(s)
Acetaminophen
Intervention Type
Drug
Intervention Name(s)
Fluvastatin
Primary Outcome Measure Information:
Title
Proportion of Patients With a Clinically Significant Increase in Oral Body Temperature or Use of Rescue Medication.
Description
Clinically significant increase in oral body temperature or used rescue medication ibuprofen >= 1 time during the 3-day period after i.v. infusion of zoledronic acid 5 mg. A clinically significant increase in body temperature was defined as an increase of at least 1 degree Celsius from baseline and a mean oral body temperature reading of at least 38.5 degrees Celsius occurring at least once during the 3-day treatment period.
Time Frame
0 - 3 days
Secondary Outcome Measure Information:
Title
Proportion of Patients With a Clinically Significant Increase in Oral Body Temperature.
Description
Clinically significant increase in oral body temperature >= 1 time during the 3-day period after i.v. infusion of zoledronic acid 5 mg. A clinically significant increase in body temperature was defined as an increase of at least 1 degree Celsius from baseline and a mean oral body temperature reading of at least 38.5 degrees Celsius occurring at least once during the 3-day treatment period.
Time Frame
0 - 3 days
Title
Proportion of Patients Who Used Rescue Medication.
Description
Patients that took rescue medication >= 1 time during the 3-day period after i.v. infusion of zoledronic acid 5 mg. Patients who experienced severe discomfort after their first home measurements and self-administration of study medication were allowed to take ibuprofen (200 mg tablets every 4-6 hours as needed) as rescue medication while continuing to take their study medication.
Time Frame
0 - 3 days
Title
Number of Rescue Medication Tablets Taken
Description
Patients who experienced severe discomfort after their first home measurements and self-administration of study medication were allowed to take ibuprofen (200 mg tablets every 4-6 hours as needed) as rescue medication while continuing to take their study medication.
Time Frame
0 - 3 days
Title
Time to First Rescue Medication After Infusion of Zoledronic Acid 5 mg.
Description
Patients who experienced severe discomfort after their first home measurements and self-administration of study medication were allowed to take ibuprofen (200 mg tablets every 4-6 hours as needed) as rescue medication while continuing to take their study medication.
Time Frame
0 - 3 days
Title
Proportion of Patients With a Major Increase (Worsening) in Severity of Questionnaire Symptoms.
Description
A major increase (worsening) in severity was defined as an increase in severity of 2 units or more from baseline at least once during the 3 days immediately following i.v. infusion of zoledronic acid 5 mg. The severity of the symptom was evaluated using a 4-point categorical scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe).
Time Frame
0 - 3 days
Title
Proportion of Patients Reporting Severe Questionnaire Symptoms.
Description
A severe questionnaire symptom was defined as experiencing a severe specified symptom (feeling feverish, experiencing headaches, having aches and pains of muscles and joints) at least once post-baseline.
Time Frame
0 - 3 days
Title
Change From Baseline in Visual Analog Scale (VAS) Measurement of Symptom Severity
Description
Effect on severity of symptoms following i.v. infusion of zoledronic acid 5 mg. The VAS is a 100-mm linear visual analog scale (0 = no symptoms to 100 = severe symptoms). The baseline VAS measurement was defined as the VAS measurement recorded prior to the infusion.
Time Frame
0 - 3 days
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Postmenopausal women greater than or equal to 45 and less than or equal to 79 years of age at randomization
Women who are clinically indicated for treatment with Bisphosphonates for osteopenia or osteoporosis with a documented central (spine or hip) Bone Mineral Density T Score less than or equal to 1.5
Exclusion Criteria:
Any prior treatment with intravenous Bisphosphonates
Oral treatment with Bisphosphonates for more than 8 weeks or within 6 months prior to the screening visit
Patients who are taking, and are unwilling or unable to stop taking, certain medications
Patients who require anticoagulant therapy
Patients with a known hypersensitivity to ibuprofen, ACET, bisphosphonates, statins or with allergies manifested by attacks of asthma, urticaria or acute rhinitis following
Proteinuria (protein detected on a urine dipstick) greater than or equal to 2+ at screening
Protocol specific laboratory values that fall out of range for this study
Ongoing infection (oral body temperature greater than or equal to 37.5C (99.5°F),chronic febrile disease or fever of unknown origin at screening or randomization
Active dental infection, unhealed dental extraction or planned oral surgery within 3 months after randomization
History of iritis, uveitis or chronic conjunctivitis
History of hypoparathyroidism, hyperparathyroidism or Paget's Disease
Partial or total removal of parathyroid or thyroid gland
History of malignancy of any organ system, treated or untreated, within the past 1 year whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin
Treatment with an investigational drug within the previous 30 days of screening
Patients with any medical or psychiatric condition which, in the opinion of the Principal Investigator, would preclude the participant from adhering to the protocol or completing the trial per protocol, or any patient who the Principal Investigator thinks should not participate in the study for any reason, including current drug or alcohol abuse
Other protocol-defined inclusion/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Refer to the E-portal link for ZOL446HUS136
City
Http://www.osteoporosisclinicalresearch.com
State/Province
New Jersey
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.osteoporosisclinicalresearch.com
Description
Click here for more information on this study
Learn more about this trial
Acetaminophen or Fluvastatin Compared to Placebo on the Transient Post-Dose Symptoms (PDS) Following an Intravenous (i.v.) Infusion of a Single Dose of Zoledronic Acid 5mg, in Post-menopausal Women With Low Bone Mass
We'll reach out to this number within 24 hrs