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

Sponsor:	Novartis
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00431444

Purpose

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.

Condition	Intervention	Phase
Osteoporosis	Drug: Raloxifene Drug: Zoledronic acid Drug: Placebo oral pills Drug: Placebo intravenous (i.v.) infusion	Phase 4

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

Resource links provided by NLM:

MedlinePlus related topics: Bone Density Minerals Osteoporosis Urine and Urination

Drug Information available for: Raloxifene hydrochloride Zoledronic acid

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Change From Baseline in Urine N-telopeptide of Type 1 Collagen (NTx.) [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
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:

Change From Baseline in Urine NTx at 2 Months [ Time Frame: Baseline and 2 months ] [ Designated as safety issue: No ]
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 Months [ Time Frame: Baseline and 4 months ] [ Designated as safety issue: No ]
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 Months [ Time Frame: Baseline and 2 months ] [ Designated as safety issue: No ]
Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 4 Months [ Time Frame: Baseline and 4 months ] [ Designated as safety issue: No ]
Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 6 Months [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
Overall Principal Investigator Satisfaction Assessed by Satisfaction Questionnaire [ Time Frame: Immediately after infusion procedure ] [ Designated as safety issue: No ]
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 Questionnaire [ Time Frame: Immediately after infusion procedure ] [ Designated as safety issue: No ]
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 Questionnaire [ Time Frame: Immediately after infusion procedure ] [ Designated as safety issue: No ]
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 Regimens [ Time Frame: At 6 month visit ] [ Designated as safety issue: No ]
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."

Enrollment:	110
Study Start Date:	January 2007
Study Completion Date:	July 2008
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Zoledronic Acid Zoledronic acid 5 mg (single i.v. infusion) + daily oral placebo for 6 months (zoledronic acid group)	Drug: Zoledronic acid Other Name: Reclast, Aclasta Drug: Placebo oral pills
Active Comparator: Raloxifene Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)	Drug: Raloxifene Drug: Placebo intravenous (i.v.) infusion

Eligibility

Ages Eligible for Study:	45 Years to 80 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00431444

Locations

United States, Arizona
Women's Health Research
Phoenix, Arizona, United States, 85015
United States, California
Associated Pharma Research Center
Buena Park, California, United States, 90620
United States, District of Columbia

Washington, District of Columbia, United States, 20036
United States, Florida
Women's Physicians of Jacksonville
Jacksonville, Florida, United States, 32256
Jacksonville Center for Clinical Research
Jacksonville, Florida, United States, 32216
Tampa Clinical Research
Tampa, Florida, United States, 33624
United States, Illinois
Springfield Clinic
Springfield, Illinois, United States, 62703
United States, Missouri
Consultants in Women's Health Care
St Louis, Missouri, United States, 63131
United States, Nebraska
Alegent Health
Omaha, Nebraska, United States, 68152
United States, Nevada
Specialty Medical and Research Center
Pahrump, Nevada, United States, 89048
United States, New Jersey
UMDNJ-Robert Wood Johnson Medical Center
New Brunswick, New Jersey, United States, 08901
United States, New York
Columbia University
New York, New York, United States, 10032
United States, North Carolina
Kernodle Clinic, Inc.
Burlington, North Carolina, United States, 27215
United States, Oregon
The Portland Clinic
Portland, Oregon, United States, 97205
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Texas
Texas Institute for Clinical Research
Fort Worth, Texas, United States, 76104
United States, Washington
Valley Women's Health Clinic
Renton, Washington, United States, 98055

Sponsors and Collaborators

Novartis

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bachmann G, Kriegman A, Gonçalves J, Kianifard F, Warren M, Simon JA. Effect of zoledronic acid compared with raloxifene on bone turnover markers in postmenopausal women with low bone density. Menopause. 2011 Aug;18(8):851-6.

Responsible Party:	External Affairs, Novartis
ClinicalTrials.gov Identifier:	NCT00431444 History of Changes
Other Study ID Numbers:	CZOL446HUS121
Study First Received:	February 1, 2007
Results First Received:	November 12, 2010
Last Updated:	March 25, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Novartis:

Osteoporosis
Post-menopausal
Bone mineral density

Additional relevant MeSH terms:

Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Raloxifene
Zoledronic acid
Diphosphonates
Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Estrogen Antagonists

ClinicalTrials.gov processed this record on May 22, 2012