Safety and Efficacy Trial With Zoledronic Acid for the Tr... | NCT00103740

NCT00103740

ID	Type	Description	Link
ZOL446K2305	Other Identifier	Novartis Pharmaceuticals

Status Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Zoledronic acid and placebo to risedronate	Experimental	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.	Drug: zoledronic acid Drug: Placebo to risedronate Drug: Calcium and vitamin D supplements
Risedronate and placebo to zoledronic acid	Active Comparator	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.	Drug: placebo to zoledronic acid Drug: Risedronate Drug: Calcium and vitamin D supplements

Name	Type	Description	Arm Group Labels	Other Names
zoledronic acid	Drug	5 mg zoledronic acid in 5 mL of sterile water for infusion	Zoledronic acid and placebo to risedronate

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Patients Who Had Therapeutic Response at 6 Months	A therapeutic response was defined as a reduction of at least 75% from baseline (Visit 1) in serum alkaline phosphatase (SAP) excess (difference between measured level and midpoint to the normal range) or normalization of SAP at the end of six months.	Baseline, 6 months

Secondary Outcomes

Measure	Description	Time Frame
Relative Change in Serum Alkaline Phosphatase in U/L at Day 28	The percent change in serum alkaline phosphatase from baseline to Day 28 was measured.	Baseline and 28 days
Relative Change in Serum C-telopeptide (CTx) in ng/mL at Day 10

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative site		Tucson	Arizona	85732	United States
Novartis Investigative Site

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Zoledronic Acid and Placebo to Risedronate	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Zoledronic Acid and Placebo to Risedronate	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
BG001	Risedronate and Placebo to Zoledronic Acid	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG00084 OG00167

Secondary

Relative Change in Serum Alkaline Phosphatase in U/L at Day 28

The percent change in serum alkaline phosphatase from baseline to Day 28 was measured.

Intent-to-treat population: all randomized patients. Participants with observations at baseline and 28 days were included in this analysis.

Posted

Mean

Standard Deviation

percent change

Baseline and 28 days

ID	Title	Description
OG000	Zoledronic Acid and Placebo to Risedronate	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
OG001	Risedronate and Placebo to Zoledronic Acid	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.

Units	Counts
Participants

Secondary

Relative Change in Serum C-telopeptide (CTx) in ng/mL at Day 10

The percent change in serum C-telopeptide from baseline to Day 10 was measured.

Intent-to-treat population: all randomized patients. Participants with observations at baseline and day 10 were included in this analysis.

Posted

Mean

Standard Deviation

percent change

Baseline and day 10

ID	Title	Description
OG000	Zoledronic Acid and Placebo to Risedronate	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
OG001	Risedronate and Placebo to Zoledronic Acid	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.

Units	Counts
Participants

Secondary

Relative Change in Urine α-CTx in ug/mmol at Day 10

The percent change in urine α-CTx from baseline to Day 10 was measured.

Intent-to-treat population: all randomized patients. Participants with observations at baseline and day 10 were included in this analysis.

Posted

Mean

Standard Deviation

percent change

Baseline and day 10

ID	Title	Description
OG000	Zoledronic Acid and Placebo to Risedronate	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
OG001	Risedronate and Placebo to Zoledronic Acid	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.

Units	Counts
Participants

Secondary

Time to First Therapeutic Response

Therapeutic response was defined as a reduction of at least 75% from baseline in serum alkaline phosphatase excess (difference between measured level and midpoint to the normal range) or normalization of serum alkaline phosphatase.

Intent-to-treat population: all randomized patients.

Posted

Median

Inter-Quartile Range

days

182 days

ID	Title	Description
OG000	Zoledronic Acid and Placebo to Risedronate	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
OG001	Risedronate and Placebo to Zoledronic Acid	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.

Units	Counts
Participants

Secondary

Number of Patients Who Achieved Serum Alkaline Phosphatase Normalization at Day 28

Normalization of serum alkaline phosphatase occurred if the serum alkaline phosphatase measurement fell within the normal range. Central laboratory reference ranges for serum alkaline phosphatase: 31-110 U/L (female & male 20-58 years) and 35-115 U/L (female & male >58 years).

Intent-to-treat population: all randomized patients. Participants with observations at day 28 were included in this analysis.

Posted

Number

participants

Day 28

ID	Title	Description
OG000	Zoledronic Acid and Placebo to Risedronate	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
OG001	Risedronate and Placebo to Zoledronic Acid	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.

Secondary

Change in Pain Severity at Day 182

Change in pain severity score from Brief Pain Inventory-Short Form (BPI-SF). This scale values are 0 to 10, a lower score means little to no pain while a higher score means greater pain.

Intent-to-treat population: all randomized patients. Participants with observations at baseline and day 182 were included in this analysis.

Posted

Mean

Standard Deviation

units on a scale

Baseline and day 182

ID	Title	Description
OG000	Zoledronic Acid and Placebo to Risedronate	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
OG001	Risedronate and Placebo to Zoledronic Acid	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.

Units	Counts

Secondary

Change in Pain Interference at Day 182

Change in pain interference score from Brief Pain Inventory-Short Form (BPI-SF). This scale values are 0 to 10, a lower score means little to no pain while a higher score means greater pain.

Intent-to-treat population: all randomized patients. Participants with observations at baseline and day 182 were included in this analysis.

Posted

Mean

Standard Deviation

units on a scale

Baseline and day 182

ID	Title	Description
OG000	Zoledronic Acid and Placebo to Risedronate	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
OG001	Risedronate and Placebo to Zoledronic Acid	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.

Units	Counts

Secondary

Number of Participants With a Loss of Therapeutic Response During the Extended Observation Period

Extended observation period. A therapeutic response is defined as a reduction of at least 75% from baseline in serum alkaline phosphatase excess or normalization of serum alkaline phosphatase.

Extended modified Intent-to-treat population: patients who had at least one serum alkaline phosphatase measurement during the extension period.

Posted

Number

participants

8 years was the maximum

ID	Title	Description
OG000	Zoledronic Acid and Placebo to Risedronate	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
OG001	Risedronate and Placebo to Zoledronic Acid	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.

Units	Counts

Secondary

Number of Participants With a Partial Disease Relapse During the Extended Observation Period

Extended observation period. A partial disease relapse was defined as an increase in serum alkaline phosphatase >= 50% from the serum alkaline phosphatase measurement at Month 6 and at least 1.25 times the upper normal limit.

Extended modified Intent-to-treat population: patients who had at least one serum alkaline phosphatase measurement during the extension period.

Posted

Number

participants

8 years was the maximum

ID	Title	Description
OG000	Zoledronic Acid and Placebo to Risedronate	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
OG001	Risedronate and Placebo to Zoledronic Acid	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.

Secondary

Number of Participants With a Disease Relapse During the Extended Observation Period

Extended observation period. A disease relapse was defined as the occurrence of a serum alkaline phosphatase level that was >= 80% of baseline serum alkaline phosphatase value.

Extended modified Intent-to-treat population: patients who had at least one serum alkaline phosphatase measurement during the extension period.

Posted

Number

participants

8 years was maximum

ID	Title	Description
OG000	Zoledronic Acid and Placebo to Risedronate	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.
OG001	Risedronate and Placebo to Zoledronic Acid	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.

Units	Counts

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Zoledronic Acid	Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.			4	88	40	88
EG001	Risedronate	Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.			3	90	28	90

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Chest pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected88 at risk EG0011 affected90 at risk
Enterobacter sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected88 at risk EG0010 affected90 at risk
Escherichia infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected88 at risk EG0010 affected90 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected88 at risk EG0010 affected90 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected88 at risk EG0011 affected90 at risk
Spinal fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected88 at risk EG0010 affected90 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected88 at risk EG0010 affected90 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected88 at risk EG0010 affected90 at risk
Endometrial hyperplasia	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected88 at risk EG0011 affected90 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected88 at risk EG0010 affected90 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected88 at risk EG0010 affected90 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0005 affected88 at risk EG0012 affected90 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0006 affected88 at risk EG0017 affected90 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0006 affected88 at risk EG0013 affected90 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0006 affected88 at risk EG0012 affected90 at risk
Influenza like illness	General disorders	MedDRA	Systematic Assessment	EG00013 affected88 at risk EG0016 affected90 at risk
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG0005 affected88 at risk EG0012 affected90 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0005 affected88 at risk EG0014 affected90 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0006 affected88 at risk EG0012 affected90 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0005 affected88 at risk EG0014 affected90 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0009 affected88 at risk EG0016 affected90 at risk

Ancestor Terms

ID	Term
D004164	Diphosphonates
D063065	Organophosphonates
D009943	Organophosphorus Compounds
D009930	Organic Chemicals
D007093	Imidazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011725	Pyridines
D008673	Metals, Alkaline Earth
D004602	Elements
D007287	Inorganic Chemicals
D008670	Metals
D001779	Blood Coagulation Factors
D001685	Biological Factors

ID	Term
D001847	Bone Diseases
D009140	Musculoskeletal Diseases

ID	Term
D000077211	Zoledronic Acid
D000068296	Risedronic Acid
D002118	Calcium