Effects of Zoledronic Acid and Raloxifene on Bone Turnover Markers in Postmenopausal Women With Low Bone Mineral Density

Novartis

Status and phase: Completed; Phase 4

Conditions: Osteoporosis

Treatments: Drug: Raloxifene; Drug: Placebo oral pills; Drug: Placebo intravenous (i.v.) infusion; Drug: Zoledronic acid

Study type: Interventional

Funder types: Industry

Identifiers

NCT00431444

CZOL446HUS121

Details and patient eligibility

About

This study will compare the effects of Zoledronic acid and Raloxifene in reducing bone turnover markers in postmenopausal women with low bone mineral density over 6 months.

Enrollment: 110 patients

Sex: Female

Ages: 45 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Females, between 45 and 80 years (inclusive) of age, considered post-menopausal 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
• Documented T score of less than or equal to -1.5 on dual energy X-ray absorptiometry (DXA) scan at the lumbar spine, total hip or femoral neck within 24 months prior to screening, and clinically indicated for treatment with bisphosphonates (BPs) for osteopenia or osteoporosis
• Signed informed consent prior to initiation of any study procedure

Exclusion criteria

• Prior treatment with i.v. bisphosphonates within the last 2 years
• Previous use of oral bisphosphonates within the past 2 years (unless used for less than 8 weeks*).
• *NOTE: If used less than 8 weeks, the washout period is 6 months.
• Treatment with raloxifene, calcitonin, tibolone or hormone replacement therapy. The washout period for these medications is 6 months prior to randomization.
• Any treatment with strontium renalate, sodium fluoride or parathyroid hormone
• Use of systemic high dose corticosteroids at an average dose of ≥ 7.5 mg per day of oral prednisone or equivalent for a period of three months or more within the previous year
• Treatment with any investigational drug within 30 days prior to randomization
• Any woman of child bearing potential
• Patients with fractures occurring within three months prior to randomization
• History of hypersensitivity to bisphosphonates
• History of non-traumatic uveitis or iritis, within 2 years prior to study entry.
• A history of invasive malignancy of any organ system, treated or untreated, within the past 12 months prior to screening; excluding, basal cell or squamous cell carcinoma of the skin, colonic polyps with non-invasive malignancy which have been removed, Ductal Carcinoma in-situ (DCIS) that has been surgically removed, and Carcinoma in-situ (CIS) of the uterine cervix that has been surgically removed.
• Previous major solid organ transplant recipient or on a transplant waiting list
• History of hyperparathyroidism, hypoparathyroidism, Osteogenesis imperfecta, Paget's disease or any metabolic bone disease other than osteoporosis
• Any medical condition which would interfere with the action of the study drug or limit life expectancy to less than 6 months
• Any medical or psychiatric condition which, in the opinion of the investigator, would preclude the participant from adhering to the protocol or completing the trial
• Active dental infection, unhealed dental extraction or planned oral surgery within 3 month prior to randomization.
• Calculated creatinine clearance < 30 mL/min
• Greater than 2+ protein on urine dipstick without evidence of contamination or bacteriuria (may be repeated one time, at least a day apart).
• Serum calcium > 2.75 mmol/L (11.0 mg/dL) or < 2.08 mmol/L (8.3 mg/dL) at screening
• AST, ALT or serum alkaline phosphatase greater than twice the upper limit of normal

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

110 participants in 2 patient groups

Zoledronic Acid

Active Comparator group

Description:

Zoledronic acid 5 mg (single i.v. infusion) + daily oral placebo for 6 months (zoledronic acid group)

Treatment:

Drug: Zoledronic acid

Drug: Placebo oral pills

Raloxifene

Active Comparator group

Description:

Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)

Treatment:

Drug: Placebo intravenous (i.v.) infusion

Drug: Raloxifene