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

Osteoporosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00431444
• Other study ID #: CZOL446HUS121
• Status: Completed
• Phase: Phase 4
• First received: February 1, 2007
• Last updated: March 25, 2011
• Start date: January 2007
• Est. completion date: July 2008

Study information

• Verified date: March 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 45 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteoporosis

Intervention

Drug:
• Raloxifene

• Zoledronic acid

• Placebo oral pills

• Placebo intravenous (i.v.) infusion

Locations

Country	Name	City	State
United States	Associated Pharma Research Center	Buena Park	California
United States	Kernodle Clinic, Inc.	Burlington	North Carolina
United States	Texas Institute for Clinical Research	Fort Worth	Texas
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Women's Physicians of Jacksonville	Jacksonville	Florida
United States	UMDNJ-Robert Wood Johnson Medical Center	New Brunswick	New Jersey
United States	Columbia University	New York	New York
United States	Alegent Health	Omaha	Nebraska
United States	Specialty Medical and Research Center	Pahrump	Nevada
United States	Women's Health Research	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon
United States	The Portland Clinic	Portland	Oregon
United States	Valley Women's Health Clinic	Renton	Washington
United States	Springfield Clinic	Springfield	Illinois
United States	Consultants in Women's Health Care	St Louis	Missouri
United States	Tampa Clinical Research	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Urine N-telopeptide of Type 1 Collagen (NTx.)	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.	Baseline and 6 months	No
Secondary	Change From Baseline in Urine NTx at 2 Months	The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine.	Baseline and 2 months	No
Secondary	Change From Baseline in Urine NTx at 4 Months	The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine.	Baseline and 4 months	No
Secondary	Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 2 Months		Baseline and 2 months	No
Secondary	Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 4 Months		Baseline and 4 months	No
Secondary	Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 6 Months		Baseline and 6 months	No
Secondary	Overall Principal Investigator Satisfaction Assessed by Satisfaction Questionnaire	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."	Immediately after infusion procedure	No
Secondary	Overall Nurse Satisfaction Assessed by Satisfaction Questionnaire	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."	Immediately after infusion procedure	No
Secondary	Overall Patient Satisfaction Assessed by Satisfaction Questionnaire	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."	Immediately after infusion procedure	No
Secondary	Patient Preference at 6 Months for Annual i.v Therapy or Daily Oral Regimens	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."	At 6 month visit	No