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

Official Title: “A Multi-center, Randomized, Double-blind, Double-dummy Study in Postmenopausal Women With Low Bone Mineral Density to Compare the Effects of a Single Dose of i.v. Zoledronic Acid 5 mg, With Daily Oral Raloxifene 60 mg OD on Bone Turnover Markers”

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.

Intervention(s) in this Clinical Trial

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

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Zoledronic Acid
  • Zoledronic acid 5 mg (single i.v. infusion) + daily oral placebo for 6 months (zoledronic acid group)
• Active Comparator: Raloxifene
  • Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)

Primary Measures

• Change From Baseline in Urine N-telopeptide of Type 1 Collagen (NTx.)
  • Time Frame: Baseline and 6 months
    Safety Issue?: No

Secondary Measures

• Change From Baseline in Urine NTx at 2 Months
  • Time Frame: Baseline and 2 months
    Safety Issue?: No
• Change From Baseline in Urine NTx at 4 Months
  • Time Frame: Baseline and 4 months
    Safety Issue?: No
• Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 2 Months
  • Time Frame: Baseline and 2 months
    Safety Issue?: No
• Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 4 Months
  • Time Frame: Baseline and 4 months
    Safety Issue?: No
• Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 6 Months
  • Time Frame: Baseline and 6 months
    Safety Issue?: No
• Overall Principal Investigator Satisfaction Assessed by Satisfaction Questionnaire
  • Time Frame: Immediately after infusion procedure
    Safety Issue?: No
• Overall Nurse Satisfaction Assessed by Satisfaction Questionnaire
  • Time Frame: Immediately after infusion procedure
    Safety Issue?: No
• Overall Patient Satisfaction Assessed by Satisfaction Questionnaire
  • Time Frame: Immediately after infusion procedure
    Safety Issue?: No
• Patient Preference at 6 Months for Annual i.v Therapy or Daily Oral Regimens
  • Time Frame: At 6 month visit
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 45 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Novartis Industry

Overall Clinical Trial Officials and Contacts

Novartis Pharmaceuticals Study Director Novartis Pharmaceuticals  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00431444

Study ID Number: CZOL446HUS121

ClinicalTrials.gov Identifier: NCT00431444

Health Authority: United States: Food and Drug Administration