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 - Full Text View

Sponsor:	Novartis Pharmaceuticals
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00489424

Purpose

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.

Condition	Intervention	Phase
Osteoporosis	Drug: Placebo Drug: Acetaminophen Drug: Fluvastatin	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Bone Density Menopause Osteoporosis

Drug Information available for: Fluvastatin Acetaminophen Zoledronic acid CT 2584

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Proportion of Patients With a Clinically Significant Increase in Oral Body Temperature or Use of Rescue Medication. [ Time Frame: 0 - 3 days ] [ Designated as safety issue: No ]
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. [ Time Frame: 0 - 3 days ] [ Designated as safety issue: No ]
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. [ Time Frame: 0 - 3 days ] [ Designated as safety issue: No ]
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 [ Time Frame: 0 - 3 days ] [ Designated as safety issue: No ]
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. [ Time Frame: 0 - 3 days ] [ Designated as safety issue: No ]
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. [ Time Frame: 0 - 3 days ] [ Designated as safety issue: No ]
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. [ Time Frame: 0 - 3 days ] [ Designated as safety issue: No ]
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 [ Time Frame: 0 - 3 days ] [ Designated as safety issue: No ]
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.

Enrollment:	793
Study Start Date:	June 2007
Study Completion Date:	December 2007
Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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).	Drug: Acetaminophen
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).	Drug: Fluvastatin
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).	Drug: Placebo

Eligibility

Ages Eligible for Study:	45 Years to 79 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00489424

Locations

United States, New Jersey
Refer to the E-portal link for ZOL446HUS136
Http://www.osteoporosisclinicalresearch.com, New Jersey, United States

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00489424 History of Changes
Other Study ID Numbers:	CZOL446HUS136
Study First Received:	June 19, 2007
Results First Received:	August 6, 2009
Last Updated:	February 15, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Novartis:

zoledronic acid
post dose symptoms
transient
acetaminophen
fluvastatin

Additional relevant MeSH terms:

Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Acetaminophen
Fluvastatin
Zoledronic acid
Diphosphonates
Antipyretics
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics

Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Lipid Regulating Agents
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on February 09, 2012