Acetaminophen or Fluvastatin Compared to Placebo on the T... | NCT00489424

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Acetaminophen	Experimental	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
Fluvastatin	Experimental	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	Placebo Comparator	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

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug		Placebo
Acetaminophen

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Eligibility Module

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

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Refer to the E-portal link for ZOL446HUS136		Http://www.osteoporosisclinicalresearch.com	New Jersey		United States

Label	URL
Click here for more information on this study	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	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).
BG001	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).
BG002	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).
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG000267 BG001264 BG002262 BG003793

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Intent to Treat (ITT) population.

Posted

Number

proportion of patients

0 - 3 days

ID	Title	Description
OG000	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).
OG001	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).
OG002	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).

Units	Counts
Participants	OG000267 OG001264 OG002262

Title

Denominators

Categories

Increase in oral body temperature:Yes

Title	Measurements
	OG0000.607 OG0010.398 OG0020.618

Increase in oral body temperature:No

Secondary

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.

Intent to Treat (ITT) population.

Posted

Number

proportion of patients

0 - 3 days

ID	Title	Description
OG000	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).
OG001	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).

Secondary

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.

Intent to Treat (ITT) population. One patient who used rescue medication in acetaminophen arm and two patients in fluvastatin arm were not included in analysis due to lack of documentation regarding use and exposure of rescue medication.

Posted

Number

proportion of patients

0 - 3 days

ID	Title	Description
OG000	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).
OG001	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).

Secondary

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.

Number of patients who took rescue medication at least once. One patient in acetaminophen arm was not included in analysis since the number of tablets taken was not recorded.

Posted

Mean

Standard Deviation

tablets

0 - 3 days

ID	Title	Description
OG000	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).
OG001	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).
OG002

Secondary

Time to First Rescue Medication After Infusion of Zoledronic Acid 5 mg.

Number of patients who took rescue medication at least once. Two patients who took rescue medication in fluvastatin arm were not included in analysis since the time rescue medication was taken was not recorded.

Posted

Mean

Standard Deviation

hours

0 - 3 days

ID	Title	Description
OG000	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).
OG001	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).

Secondary

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).

Intent to Treat (ITT) population.

Posted

Number

proportion of patients

0 - 3 days

ID	Title	Description
OG000	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).
OG001	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).
OG002

Secondary

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.

Intent to Treat (ITT) population.

Posted

Number

proportion of patients

0 - 3 days

ID	Title	Description
OG000	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).
OG001	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).
OG002	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).

Secondary

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.

Intent to Treat (ITT) population. Number of participants analyzed may vary from ITT population due to some patients not reporting baseline or post baseline VAS measurement. Calculating change requires both baseline and post baseline values to be present.

Posted

Mean

Standard Deviation

units on a scale

0 - 3 days

ID	Title	Description
OG000	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).
OG001	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).

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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).	1	267	34	267
EG001	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).	2	264	39	264
EG002	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).	2	262	36	262

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Uveitis	Eye disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected267 at risk EG0010 affected264 at risk EG0021 affected262 at risk
Pyrexia	General disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected267 at risk EG0010 affected264 at risk EG0021 affected262 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected267 at risk EG0010 affected264 at risk EG0020 affected262 at risk
Convulsion	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected267 at risk EG0010 affected264 at risk EG0021 affected262 at risk
Syncope	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected267 at risk EG0011 affected264 at risk EG0020 affected262 at risk
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected267 at risk EG0011 affected264 at risk EG0020 affected262 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 10.X	Systematic Assessment	EG0007 affected267 at risk EG00116 affected264 at risk EG0028 affected262 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG00013 affected267 at risk EG0019 affected264 at risk EG00214 affected262 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG00014 affected267 at risk EG00111 affected264 at risk EG00210 affected262 at risk
Headache	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0008 affected267 at risk EG00114 affected264 at risk EG00215 affected262 at risk

ID	Term
D001851	Bone Diseases, Metabolic
D001847	Bone Diseases
D009140	Musculoskeletal Diseases
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

ID	Term
D000083	Acetanilides
D000813	Anilides
D000577	Amides
D009930	Organic Chemicals
D000814	Aniline Compounds
D000588	Amines
D007211	Indoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D006538	Heptanoic Acids
D005227	Fatty Acids
D008055	Lipids