Trial Outcomes & Findings for 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 (NCT NCT00489424)

NCT ID: NCT00489424

Last Updated: 2011-02-18

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 793 participants
• Primary outcome timeframe: 0 - 3 days
• Results posted on: 2011-02-18

Participant Flow

Participant milestones

Measure	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).	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).	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).
Overall Study STARTED	267	264	262
Overall Study COMPLETED	263	259	257
Overall Study NOT COMPLETED	4	5	5

Reasons for withdrawal

Measure	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).	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).	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).
Overall Study Adverse Event	3	3	4
Overall Study Lack of Efficacy	1	0	0
Overall Study Administrative problems	0	2	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo n=267 Participants 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).	Acetaminophen n=264 Participants 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).	Fluvastatin n=262 Participants 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).	Total n=793 Participants Total of all reporting groups
Age, Customized Between 45 and 55 years	64 participants n=5 Participants	69 participants n=7 Participants	67 participants n=5 Participants	200 participants n=4 Participants
Age, Customized Between 56 and 64 years	102 participants n=5 Participants	98 participants n=7 Participants	92 participants n=5 Participants	292 participants n=4 Participants
Age, Customized >=65 years	101 participants n=5 Participants	97 participants n=7 Participants	103 participants n=5 Participants	301 participants n=4 Participants
Sex/Gender, Customized Female	267 participants n=5 Participants	264 participants n=7 Participants	262 participants n=5 Participants	793 participants n=4 Participants

PRIMARY outcome

Timeframe: 0 - 3 days

Population: Intent to Treat (ITT) population.

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.

Outcome measures

Measure	Placebo n=267 Participants 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).	Acetaminophen n=264 Participants 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).	Fluvastatin n=262 Participants 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).
Proportion of Patients With a Clinically Significant Increase in Oral Body Temperature or Use of Rescue Medication. Increase in oral body temperature:Yes	0.607 proportion of patients	0.398 proportion of patients	0.618 proportion of patients
Proportion of Patients With a Clinically Significant Increase in Oral Body Temperature or Use of Rescue Medication. Increase in oral body temperature:No	0.39 proportion of patients	0.602 proportion of patients	0.382 proportion of patients

SECONDARY outcome

Timeframe: 0 - 3 days

Population: Intent to Treat (ITT) population.

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.

Outcome measures

Measure	Placebo n=267 Participants 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).	Acetaminophen n=264 Participants 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).	Fluvastatin n=262 Participants 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).
Proportion of Patients With a Clinically Significant Increase in Oral Body Temperature. Increase in oral body temperature: Yes	0.105 proportion of patients	0.049 proportion of patients	0.115 proportion of patients
Proportion of Patients With a Clinically Significant Increase in Oral Body Temperature. Increase in oral body temperature: No	0.891 proportion of patients	0.951 proportion of patients	0.885 proportion of patients

SECONDARY outcome

Timeframe: 0 - 3 days

Population: 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.

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.

Outcome measures

Measure	Placebo n=267 Participants 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).	Acetaminophen n=264 Participants 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).	Fluvastatin n=262 Participants 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).
Proportion of Patients Who Used Rescue Medication. Took rescue medication >= 1 time: Yes	0.573 proportion of patients	0.386 proportion of patients	0.595 proportion of patients
Proportion of Patients Who Used Rescue Medication. Took rescue medication >= 1 time: No	0.423 proportion of patients	0.614 proportion of patients	0.405 proportion of patients

SECONDARY outcome

Timeframe: 0 - 3 days

Population: 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.

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.

Outcome measures

Measure	Placebo n=153 Participants 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).	Acetaminophen n=102 Participants 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).	Fluvastatin n=158 Participants 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).
Number of Rescue Medication Tablets Taken	6.3 tablets Standard Deviation 4.41	5.7 tablets Standard Deviation 4.73	6.5 tablets Standard Deviation 4.78

SECONDARY outcome

Timeframe: 0 - 3 days

Population: 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.

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.

Outcome measures

Measure	Placebo n=153 Participants 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).	Acetaminophen n=103 Participants 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).	Fluvastatin n=156 Participants 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).
Time to First Rescue Medication After Infusion of Zoledronic Acid 5 mg.	21.9 hours Standard Deviation 12.21	28.2 hours Standard Deviation 18.15	19.9 hours Standard Deviation 40.95

SECONDARY outcome

Timeframe: 0 - 3 days

Population: Intent to Treat (ITT) population.

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).

Outcome measures

Measure	Placebo n=267 Participants 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).	Acetaminophen n=264 Participants 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).	Fluvastatin n=262 Participants 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).
Proportion of Patients With a Major Increase (Worsening) in Severity of Questionnaire Symptoms. Feeling feverish	0.395 proportion of patients	0.235 proportion of patients	0.397 proportion of patients
Proportion of Patients With a Major Increase (Worsening) in Severity of Questionnaire Symptoms. Headache	0.391 proportion of patients	0.254 proportion of patients	0.439 proportion of patients
Proportion of Patients With a Major Increase (Worsening) in Severity of Questionnaire Symptoms. Aches and pains of muscles/joints	0.477 proportion of patients	0.337 proportion of patients	0.462 proportion of patients

SECONDARY outcome

Timeframe: 0 - 3 days

Population: Intent to Treat (ITT) population.

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.

Outcome measures

Measure	Placebo n=267 Participants 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).	Acetaminophen n=264 Participants 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).	Fluvastatin n=262 Participants 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).
Proportion of Patients Reporting Severe Questionnaire Symptoms. Feeling feverish	0.135 proportion of patients	0.076 proportion of patients	0.145 proportion of patients
Proportion of Patients Reporting Severe Questionnaire Symptoms. Aches and pains of muscles/joints	0.303 proportion of patients	0.212 proportion of patients	0.302 proportion of patients
Proportion of Patients Reporting Severe Questionnaire Symptoms. Headache	0.157 proportion of patients	0.068 proportion of patients	0.160 proportion of patients

SECONDARY outcome

Timeframe: 0 - 3 days

Population: 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.

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.

Outcome measures

Measure	Placebo n=267 Participants 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).	Acetaminophen n=264 Participants 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).	Fluvastatin n=262 Participants 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).
Change From Baseline in Visual Analog Scale (VAS) Measurement of Symptom Severity Change from baseline to Day 1 - late evening	7.6 units on a scale Standard Deviation 22.74	4.4 units on a scale Standard Deviation 18.00	6.0 units on a scale Standard Deviation 18.89
Change From Baseline in Visual Analog Scale (VAS) Measurement of Symptom Severity Change from baseline to Day 2 - late evening	18.9 units on a scale Standard Deviation 25.86	11.8 units on a scale Standard Deviation 23.22	20.8 units on a scale Standard Deviation 27.18
Change From Baseline in Visual Analog Scale (VAS) Measurement of Symptom Severity Change from baseline to Day 3 - late evening	6.2 units on a scale Standard Deviation 19.66	3.9 units on a scale Standard Deviation 17.59	6.6 units on a scale Standard Deviation 20.40

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 34 other events

Deaths: 0 deaths

Acetaminophen

Serious events: 2 serious events

Other events: 39 other events

Deaths: 0 deaths

Fluvastatin

Serious events: 2 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=267 participants at risk 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).	Acetaminophen n=264 participants at risk 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).	Fluvastatin n=262 participants at risk 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).
Eye disorders Uveitis	0.00% 0/267 • At the end of study Safety Population	0.00% 0/264 • At the end of study Safety Population	0.38% 1/262 • At the end of study Safety Population
General disorders Pyrexia	0.00% 0/267 • At the end of study Safety Population	0.00% 0/264 • At the end of study Safety Population	0.38% 1/262 • At the end of study Safety Population
Metabolism and nutrition disorders Hypokalaemia	0.37% 1/267 • At the end of study Safety Population	0.00% 0/264 • At the end of study Safety Population	0.00% 0/262 • At the end of study Safety Population
Nervous system disorders Convulsion	0.00% 0/267 • At the end of study Safety Population	0.00% 0/264 • At the end of study Safety Population	0.38% 1/262 • At the end of study Safety Population
Nervous system disorders Syncope	0.00% 0/267 • At the end of study Safety Population	0.38% 1/264 • At the end of study Safety Population	0.00% 0/262 • At the end of study Safety Population
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/267 • At the end of study Safety Population	0.38% 1/264 • At the end of study Safety Population	0.00% 0/262 • At the end of study Safety Population

Other adverse events

Measure	Placebo n=267 participants at risk 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).	Acetaminophen n=264 participants at risk 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).	Fluvastatin n=262 participants at risk 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).
Gastrointestinal disorders Nausea	2.6% 7/267 • At the end of study Safety Population	6.1% 16/264 • At the end of study Safety Population	3.1% 8/262 • At the end of study Safety Population
Musculoskeletal and connective tissue disorders Arthralgia	4.9% 13/267 • At the end of study Safety Population	3.4% 9/264 • At the end of study Safety Population	5.3% 14/262 • At the end of study Safety Population
Musculoskeletal and connective tissue disorders Myalgia	5.2% 14/267 • At the end of study Safety Population	4.2% 11/264 • At the end of study Safety Population	3.8% 10/262 • At the end of study Safety Population
Nervous system disorders Headache	3.0% 8/267 • At the end of study Safety Population	5.3% 14/264 • At the end of study Safety Population	5.7% 15/262 • At the end of study Safety Population

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER