A 2-year randomized, multicenter, double-blind, placebocontrolled study to determine the efficacy and safety of intravenous zoledronic acid 5 mg administered either annually at randomization and 12 months, or administered at randomization only in the prevention of bone loss in postmenopausal women with osteopenia - 2312

• Register: EUCTR
• Last refreshed on: 29 May 2012
• Main ID: EUCTR2004-000638-35-SE
• Date of registration: 29/07/2004
• Prospective Registration: Yes
• Primary sponsor: Novartis Sverige AB
• Public title: A 2-year randomized, multicenter, double-blind, placebocontrolled study to determine the efficacy and safety of intravenous zoledronic acid 5 mg administered either annually at randomization and 12 months, or administered at randomization only in the prevention of bone loss in postmenopausal women with osteopenia - 2312
• Scientific title: A 2-year randomized, multicenter, double-blind, placebocontrolled study to determine the efficacy and safety of intravenous zoledronic acid 5 mg administered either annually at randomization and 12 months, or administered at randomization only in the prevention of bone loss in postmenopausal women with osteopenia - 2312
• Date of first enrolment: 15/09/2004
• Target sample size: 582
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-000638-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: Single blind: Double blind: yes Parallel group: yes Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Spain, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
Women greater than or equal to 45 years of age inclusive at the time of randomization, considered postmenopausal according to one of the following guidelines:
• cessation of menses for 18 months in women < 50 years of age
• cessation of menses for 12 months in women age 50 years or over
• documented bilateral oophorectomy at least 1 year previously

Women with osteopenia defined as Bone Mineral Density T-score less than -1.0 and greater than - 2.5 at the lumbar spine

Bone Mineral Density T-score value greater than -2.5 at the femoral neck
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patiens with more than one Grade 1 vertebral fracture (as per Genant method; patients with one Grade 1 vertebral fracture are eligible to participate)

Patients with any Grade 2 or 3 vertebral fracture (as per Genant method)

Patients with 25-(OH) Vitamin D levels less than 15 ng/mL prior to randomization

Renal insufficiency (calculated creatinine clearance less than 30.0 mL/min) at Visit 1 or Visit 2

Hypercalcemia (serum calcium = 2.75 mmol/L (11.0 mg/dL) at Visit 1

Hypocalcemia (serum calcium = 2.0 mmol/L (8.0 mg/dL) at Visit 1

AST or ALT greater than 2.0 times the upper limit of normal

Serum alkaline phosphatase greater than 1.5 times the upper limit of normal


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Postmenopausal Osteoporosis

Intervention(s)

Product Name: zoledronic acid
Product Code: ZOL446
Pharmaceutical Form: Intravenous infusion
INN or Proposed INN: zoledronic acid
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.05-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: calcium + vitamin D, combined product. A registered product free of choice will be used.
Product Name: calcium + vitamin D, combined product. A registered product free of choice will be used.
Pharmaceutical Form:
INN or Proposed INN: calcium
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 500-
INN or Proposed INN: vitamin D
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 400-

Primary Outcome(s)

Primary end point(s): Change of BMD at the lumbar spine.

Main Objective: - To demonstrate that zoledronic acid 5 mg i.v. given annually at randomization and Month 12 is superior to placebo in percent change of BMD at the lumbar spine at Month 24 relative to baseline in Stratum I (women < 5 years from menopause) and in Stratum II (women = 5 years from menopause)

- To demonstrate that zoledronic acid 5 mg i.v. given at randomization only is superior to placebo in percent change of BMD at the lumbar spine at Month 24 relative to baseline in Stratum I and in Stratum II

Secondary Objective: To assess the percent change in BMD at the lumbar spine at Months 6, 12 and 18 relative to baseline in each strata comparing:
a) zoledronic acid 5 mg i.v. given at randomization and Month 12 to placebo
b) zoledronic acid 5 mg i.v. given at randomization only to placebo
c) zoledronic acid 5 mg i.v. given at randomization only to zoledronic acid 5 mg i.v. given at randomization and Month 12 (including Month 24 for this comparison)

To assess the percent change in BMD at the total hip, femoral neck, trochanter, and distal radius at Months 6, 12, 18, and 24 relative to baseline in each strata comparing: (a), (b) and (c) - see above.

To assess the change of biochemical markers of bone resorption and formation at Months 1, 3, 6, 9, 12, 15, 18, and 24 relative to baseline in each strata comparing: (a), (b) and (c) - see above.

To evaluate the overall safety and tolerability of zoledronic acid compared to placebo.

Secondary ID(s)

CZOL446N2312