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

Phase 4
Completed
Conditions
Osteoporosis
Interventions
Drug: Placebo oral pills
Drug: Placebo intravenous (i.v.) infusion
Registration Number
NCT00431444
Lead Sponsor
Novartis
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
110
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
RaloxifeneRaloxifenePlacebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)
Zoledronic AcidZoledronic acidZoledronic acid 5 mg (single i.v. infusion) + daily oral placebo for 6 months (zoledronic acid group)
Zoledronic AcidPlacebo oral pillsZoledronic acid 5 mg (single i.v. infusion) + daily oral placebo for 6 months (zoledronic acid group)
RaloxifenePlacebo intravenous (i.v.) infusionPlacebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Urine N-telopeptide of Type 1 Collagen (NTx.)Baseline and 6 months

The primary efficacy variable was the change from baseline in urine NTx (corrected by creatinine). The primary analysis time point was at 6 months of treatment. The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Urine NTx at 2 MonthsBaseline and 2 months

The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine.

Change From Baseline in Urine NTx at 4 MonthsBaseline and 4 months

The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine.

Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 2 MonthsBaseline and 2 months
Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 4 MonthsBaseline and 4 months
Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 6 MonthsBaseline and 6 months
Overall Principal Investigator Satisfaction Assessed by Satisfaction QuestionnaireImmediately after infusion procedure

The investigator was asked to complete satisfaction questionnaires at baseline (Visit 2/Day 1) when each patient's i.v. drug administration occurred. The questionnaire assessed overall satisfaction with the i.v. infusion procedure. The possible answers to the question were: "not at all," "a little," "somewhat," "quite," or "completely."

Overall Nurse Satisfaction Assessed by Satisfaction QuestionnaireImmediately after infusion procedure

The study coordinator (nurse) was asked to complete satisfaction questionnaires at baseline (Visit 2/Day 1) when each patient's i.v. drug administration occurred. The questionnaire assessed overall satisfaction with the i.v. infusion procedure. The possible answers to the question were: "not at all," "a little," "somewhat," "quite," or "completely."

Overall Patient Satisfaction Assessed by Satisfaction QuestionnaireImmediately after infusion procedure

Patients were asked to complete the satisfaction questionnaire at baseline. The questionnaire assessed overall satisfaction with the i.v. infusion procedure. The possible answers to the question were: "not at all," "a little," "somewhat," "quite," or "completely."

Patient Preference at 6 Months for Annual i.v Therapy or Daily Oral RegimensAt 6 month visit

At the end-of-study visit, Month 6, patients were asked to complete a questionnaire to assess preference for the different treatment modalities (annual i.v. infusion vs. daily oral capsule). The possible answers to question were: "once a year i.v. infusion," "once daily pill," or "both are equal."

Trial Locations

Locations (16)

Women's Health Research

🇺🇸

Phoenix, Arizona, United States

Alegent Health

🇺🇸

Omaha, Nebraska, United States

UMDNJ-Robert Wood Johnson Medical Center

🇺🇸

New Brunswick, New Jersey, United States

Specialty Medical and Research Center

🇺🇸

Pahrump, Nevada, United States

Women's Physicians of Jacksonville

🇺🇸

Jacksonville, Florida, United States

The Portland Clinic

🇺🇸

Portland, Oregon, United States

Texas Institute for Clinical Research

🇺🇸

Fort Worth, Texas, United States

Kernodle Clinic, Inc.

🇺🇸

Burlington, North Carolina, United States

Consultants in Women's Health Care

🇺🇸

St Louis, Missouri, United States

Columbia University

🇺🇸

New York, New York, United States

Oregon Health and Science University

🇺🇸

Portland, Oregon, United States

Valley Women's Health Clinic

🇺🇸

Renton, Washington, United States

Tampa Clinical Research

🇺🇸

Tampa, Florida, United States

Associated Pharma Research Center

🇺🇸

Buena Park, California, United States

Jacksonville Center for Clinical Research

🇺🇸

Jacksonville, Florida, United States

Springfield Clinic

🇺🇸

Springfield, Illinois, United States

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