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”

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.

Intervention(s) in this Clinical Trial

• Drug: Placebo
• Drug: Acetaminophen
• Drug: Fluvastatin

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Acetaminophen
  • 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).
• Experimental: Fluvastatin
  • 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).
• Placebo Comparator: Placebo
  • 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).

Primary Measures

• Proportion of Patients With a Clinically Significant Increase in Oral Body Temperature or Use of Rescue Medication.
  • Time Frame: 0 - 3 days
    Safety Issue?: No

Secondary Measures

• Proportion of Patients With a Clinically Significant Increase in Oral Body Temperature.
  • Time Frame: 0 - 3 days
    Safety Issue?: No
• Proportion of Patients Who Used Rescue Medication.
  • Time Frame: 0 - 3 days
    Safety Issue?: No
• Number of Rescue Medication Tablets Taken
  • Time Frame: 0 - 3 days
    Safety Issue?: No
• Time to First Rescue Medication After Infusion of Zoledronic Acid 5 mg.
  • Time Frame: 0 - 3 days
    Safety Issue?: No
• Proportion of Patients With a Major Increase (Worsening) in Severity of Questionnaire Symptoms.
  • Time Frame: 0 - 3 days
    Safety Issue?: No
• Proportion of Patients Reporting Severe Questionnaire Symptoms.
  • Time Frame: 0 - 3 days
    Safety Issue?: No
• Change From Baseline in Visual Analog Scale (VAS) Measurement of Symptom Severity
  • Time Frame: 0 - 3 days
    Safety Issue?: No

Inclusion Criteria:

• 1. Postmenopausal women greater than or equal to 45 and less than or equal to 79 years of age at randomization
• 2. 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:

• 1. Any prior treatment with intravenous Bisphosphonates
• 2. Oral treatment with Bisphosphonates for more than 8 weeks or within 6 months prior to the screening visit
• 3. Patients who are taking, and are unwilling or unable to stop taking, certain medications
• 4. Patients who require anticoagulant therapy
• 5. Patients with a known hypersensitivity to ibuprofen, ACET, bisphosphonates, statins or with allergies manifested by attacks of asthma, urticaria or acute rhinitis following
• 6. Proteinuria (protein detected on a urine dipstick) greater than or equal to 2+ at screening
• 7. Protocol specific laboratory values that fall out of range for this study
• 8. 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
• 9. Active dental infection, unhealed dental extraction or planned oral surgery within 3 months after randomization
• 10. History of iritis, uveitis or chronic conjunctivitis
• 11. History of hypoparathyroidism, hyperparathyroidism or Paget's Disease
• 12. Partial or total removal of parathyroid or thyroid gland
• 13. 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
• 14. Treatment with an investigational drug within the previous 30 days of screening
• 15. 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

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 45 Years

Maximum Age for this Clinical Trial: 79 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Novartis Pharmaceuticals Industry

Overall Clinical Trial Officials and Contacts

Novartis Pharmaceuticals Study Director Novartis Pharmaceuticals  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00489424

Study ID Number: CZOL446HUS136

ClinicalTrials.gov Identifier: NCT00489424

Health Authority: United States: Food and Drug Administration