A Study of Bone Turnover Markers in Post-Menopausal Women With Osteoporosis Treated With Monthly Boniva (Ibandronate)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00303485
First received: March 16, 2006
Last updated: March 30, 2016
Last verified: March 2016
  Purpose
This study will determine the rapidity of suppression of the bone resorption marker sCTX in post-menopausal women with osteoporosis.Other bone turnover markers will also be evaluated. Patients will be randomised to either monthly Boniva 150mg or placebo, in combination with vitamin D and calcium supplementation. The anticipated time on study treatment is approximately 7 months, and the target sample size is <100 individuals.

Condition Intervention Phase
Post Menopausal Osteoporosis
Drug: Placebo
Drug: Vitamin D and calcium supplementation
Drug: ibandronate [Bonviva/Boniva]
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Study to Determine Time to Onset of Suppression of the Bone Resorption Marker sCTX With Once Monthly Ibandronate in the Treatment of Postmenopausal Osteoporosis

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Relative Percent Change in Serum C-terminal Telopeptide of Type 1 Collagen Concentration (sCTX) From Baseline to Day 3 [ Time Frame: Baseline (Visit 1) and Day 3 ] [ Designated as safety issue: No ]
    Serum C-terminal Telopeptide of Type 1 Collagen (sCTX) is a biochemical marker for bone turnover that has been shown to detect increased bone resorption, a process by which bone is broken down within the body. It is measured in units of nanograms (ng) per milliliter (mL). The relative change in sCTX was defined as the relative difference between the value at each time point and the value at Baseline, using the following formula: Relative change = (sCTX time point- sCTX Baseline) / (sCTX Baseline) * 100. The sCTX value used for Baseline was the average of the results from the 2 blood samples taken at screening. If 1 of these 2 samples was nonquantifiable or missing, then the Baseline sCTX was the result from the non-missing sample. Baseline visit was defined as Visit 1.


Secondary Outcome Measures:
  • Relative Percent Change in Serum C-terminal Telopeptide of Type 1 Collagen (sCTX) Concentration From Baseline Over Time [ Time Frame: Baseline (Visit 1), Day (D) 3, D7, D14, D21, D28 of Month (M)1, M2, M3, M4, M5, M6 ] [ Designated as safety issue: No ]
    sCTX is a biochemical marker for bone turnover that has been shown to detect increased bone resorption, a process by which bone is broken down within the body. The relative change in sCTX was defined as the relative difference between the value at each time point and the value at Baseline, using the following formula: Relative change = (sCTX Time point- sCTX Baseline) / (sCTX Baseline) * 100. The sCTX value used for Baseline was the average of the results from the 2 blood samples taken at screening. If 1 of these 2 samples was nonquantifiable or missing, then the Baseline sCTX was the result from the non-missing sample. Baseline visit was defined as Visit 1.

  • Relative Percent Change in Bone Specific Alkaline Phosphatase (BSAP) Concentration From Baseline Over Time [ Time Frame: Baseline (Visit 1), Day (D) 7 and D 28 of Month (M)1, M2, M3, M4, M5, M6 ] [ Designated as safety issue: No ]
    BSAP is a biochemical marker of bone formation and measured in units per litre (U/L). The relative percent change in BSAP was defined as the relative difference between the value at each time point and the value at Baseline, using the following formula: Relative change = (BSAP time point- BSAP Baseline) / (BSAP Baseline) * 100. The greater the percent decrease from Baseline, the greater the response to therapy. Baseline visit was defined as Visit 1.

  • Relative Percent Change in Parathyroid Hormone (PTH) From Baseline to Post Treatment Assessments [ Time Frame: Baseline (Visit 1), Month (M)1 Day (D)7, and M6D7 ] [ Designated as safety issue: No ]
    Parathyroid hormone (PTH) regulates calcium and phosphate metabolism in bone and kidney, and is measured in picogram/milliliter (pg/mL). The relative percent change in PTH was defined as the relative difference between the value at each time point and the value at Baseline, using the following formula: Relative change = (PTH time point- PTH Baseline) / (PTH Baseline) * 100. Post treatment assessments were done at Baseline, Month (M)1 Day (D)7, and M6D7

  • Percentage of Participants With a Serum C-terminal Telopeptide of Type1 Collagen (sCTX) Concentration Between 0.011 and 0.631 ng/mL and Who Have Achieved a Decrease in sCTX Concentration of at Least 8 Percent [ Time Frame: Baseline (Visit 1) and Day (D)3 of Month (M)1 and; D7, D14, D21, D28 of each M1, M2, M3, M4, M5, and M6 ] [ Designated as safety issue: No ]
    The Cochran-Mantel Haenszel test stratified by Baseline sCTX category was used to compare the 2 treatment groups for proportion of participants whose sCTX concentration was between 0.011 and 0.631 ng/mL (premenopausal normal range mean +/- 2 SD) who achieved a decrease in sCTX of at least 8% from Baseline. Mean and SD are based on the normal range for premenopausal women: Mean = 0.321 ng/mL, SD=0.155 ng/mL. Baseline visit was defined as Visit 1.

  • Percentage of Participants With a Serum C-terminal Telopeptide of Type 1 Collagen (sCTX) Concentration Between 0.011 and 0.476 ng/mL [ Time Frame: Baseline (Visit 1) and Day (D)3 of M1 and D7, D14, D21, D28 of each M1, M2, M3, M4, M5, M6 ] [ Designated as safety issue: No ]
    Percentage of participants whose sCTX concentration was between 0.011 and 0.476 ng/mL (Mean -2 to + 1 SD) were analyzed at particular time points. Mean and SD are based on the normal range for premenopausal women: Mean = 0.321 ng/mL, SD = 0.155 ng/mL. Baseline visit was defined as Visit 1.

  • Percentage of Participants With a Serum C-terminal Telopeptide of Type 1 Collagen (sCTX) Concentration Between 0.011 and 0.321 ng/mL [ Time Frame: Baseline (Visit 1), Day (D)3 of M1, and D7, D14, D21, D28 of each M1, M2, M3, M4, M5, M6 ] [ Designated as safety issue: No ]
    Percentage of participants whose sCTX concentration was between 0.011 and 0.321 ng/mL (Mean -2 to + 0 SD) were analyzed at particular time points. Mean and SD are based on the normal range for premenopausal women: Mean = 0.321 ng/mL, SD = 0.155 ng/mL.

  • Difference Between the Minimum and Maximum Relative Percent Change in Serum C-terminal Telopeptide of Type 1 Collagen (sCTX) Concentrations [ Time Frame: Day (D)7, D14, D21 and D28 of Month 6 ] [ Designated as safety issue: No ]
    Overall minimum and maximum relative percent change in sCTX concentrations from Baseline were calculated for all participants over D7, D14, D21 and D28 of Month 6 and the difference between it was analyzed.

  • Number of Participants With Any Marked Abnormality in Laboratory Parameters [ Time Frame: Up to 7 months ] [ Designated as safety issue: No ]
    Marked laboratory abnormalities are those which exceed the marked abnormality range (i.e., greater or less than the Roche defined marked abnormality range; i.e Low or High) and which also represents a clinically relevant change from Baseline of at least a designated amount. The indicated abnormal laboratory parameters (along with their marked reference range) are as follows : Hematocrit (0.31- 0.56 fraction), hemoglobin (110 - 200 g/L), platelets (100 - 550 *10^9/L), white blood cell (WBC) (3.0 - 18.0 *10^9/L), alanine aminotransferase (ALT) (0 - 110 U/L), creatinine (0 - 154 µmol/L), chloride (95 - 115 mmol/L), phosphate (0.75 - 1.60 mmol/L ). Creatinine clearance was calculated using the Cockroft-Gault formula.

  • Number of Participants With Any Adverse Event or Serious Adverse Event [ Time Frame: Up to 7 months ] [ Designated as safety issue: No ]
    An Adverse Event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. A Serious Adverse Event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect.


Enrollment: 67
Study Start Date: February 2006
Study Completion Date: June 2007
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ibandronate
Participants received Ibandronate 150 mg tablet once-monthly along with a combination dietary supplement containing vitamin D 200 international units (IU) and elemental calcium 500 mg twice daily with meals for 6 months.
Drug: Vitamin D and calcium supplementation
As prescribed
Drug: ibandronate [Bonviva/Boniva]
150mg po monthly for 6 months
Placebo Comparator: Placebo
Participants received a matching placebo tablet to Ibandronate once-monthly along with a combination dietary supplement containing vitamin D 200 IU and elemental calcium 500 mg twice daily with meals for 6 months.
Drug: Placebo
po monthly for 6 months
Drug: Vitamin D and calcium supplementation
As prescribed

  Eligibility

Ages Eligible for Study:   65 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • women who have been newly diagnosed with post-menopausal osteoporosis, requiring treatment;
  • naive to bisphosphonate treatment,or had bisphosphonate treatment for a maximum of 3 months, at least 5 years before screening.

Exclusion Criteria:

  • patients on hormone replacement therapy (HRT) within the last 3 months;
  • patients on other osteoporosis medication within the last 3 months;
  • sCTX below lower limit, or above 3 times the upper limit, of normal premenopausal level;
  • hypersensitivity to any component of ibandronate;
  • contraindication for calcium or vitamin D therapy;
  • history of major gastrointestinal upset;
  • malignant disease diagnosed within the previous 10 years (except resected basal cell cancer).
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00303485

Locations
United States, California
Beverly Hills, California, United States, 90211
La Jolla, California, United States, 92093
United States, Georgia
Augusta, Georgia, United States, 30904
United States, Minnesota
Woodbury, Minnesota, United States, 55125
United States, New York
Bronx, New York, United States, 10461
United States, Pennsylvania
Hopwood, Pennsylvania, United States, 15445
United States, Wisconsin
Madison, Wisconsin, United States, 53705
Puerto Rico
Ponce, Puerto Rico, 00717-1318
San Juan, Puerto Rico, 00927
San Juan, Puerto Rico, 00935
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00303485     History of Changes
Other Study ID Numbers: ML19334 
Study First Received: March 16, 2006
Results First Received: February 23, 2016
Last Updated: March 30, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Vitamins
Vitamin D
Ergocalciferols
Ibandronic acid
Calcium, Dietary
Diphosphonates
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on August 25, 2016