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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: Placebo
* Drug: Acetaminophen
* Drug: Fluvastatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetaminophen<br>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). | Drug: Acetaminophen<br> <br> |
| Experimental: Fluvastatin<br>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). | Drug: Fluvastatin<br> <br> |
| Placebo Comparator: Placebo<br>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). | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 0 - 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 0 - 3 days | 
| 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. | 0 - 3 days | 
| 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. | 0 - 3 days | 
| 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. | 0 - 3 days | 
| 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). | 0 - 3 days | 
| 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. | 0 - 3 days | 
| 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. | 0 - 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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zoledronic acid, post dose symptoms, transient, acetaminophen, fluvastatin