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A Study to Evaluate the Safety and Efficacy of Denosumab and Ibandronate in Postmenopausal Women Sub-Optimally Treated With Daily or Weekly Bisphosphonates

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00936897
First received: July 9, 2009
Last updated: February 5, 2013
Last verified: February 2013
  Purpose

This is a multi-center, randomized, open-label, parallel group, study being conducted in the United States and in Europe in postmenopausal women. Approximately 800 subjects will be randomized across about 65 sites in a 1:1 ratio to either denosumab 60mg SC Q6M, or ibandronate 150mg PO QM.


Condition Intervention Phase
Postmenopausal Osteoporosis
Drug: Ibandronate
Drug: Denosumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Open-Label Study to Evaluate the Safety and Efficacy of Denosumab and Ibandronate in Postmenopausal Women Sub-Optimally Treated With Daily or Weekly Bisphosphonates

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Total Hip Bone Mineral Density Percent Change From Baseline at Month 12 [ Time Frame: Baseline to month 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Serum Type-1 C-Telopeptide Percent Change From Baseline at Month 1 [ Time Frame: Baseline to month 1 ] [ Designated as safety issue: No ]
  • Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 12 [ Time Frame: Baseline to Month 12 ] [ Designated as safety issue: No ]
  • Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 [ Time Frame: Baseline to month 12 ] [ Designated as safety issue: No ]

Enrollment: 833
Study Start Date: July 2009
Study Completion Date: January 2012
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ibandronate
Ibandronate 150mg PO QM (tablet)
Drug: Ibandronate
Ibandronate 150mg PO QM (tablet)
Experimental: Denosumab
denosumab 60mg Subcutaneous Q6M (pre-filled syringe)
Drug: Denosumab
denosumab 60mg SC Q6M (pre-filled syringe)

  Eligibility

Ages Eligible for Study:   55 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ambulatory, postmenopausal women (based on medical history) 55 years or older at screening
  • Postmenopause will be defined as no vaginal bleeding or spotting for at least 12 months
  • If the subject is 55 - 59 years old and there is uncertainty regarding menopausal status, confirmation of serum FSH (>= 50 mIU/mL) and serum estradiol (<= 20 pg/mL) must be obtained
  • If the subject is 60 years or older, evaluation of FSH and estradiol levels is not needed to confirm menopausal status
  • Have received their first prescription of daily or weekly bisphosphonate therapy at least 1 month prior to screening
  • May have received
  • raloxifene, calcitonin, prior to initiation of daily orweekly bisphosphonate therapy.
  • up to 3 doses of monthly bisphosphonate prior to initiation of daily or weekly bisphosphonate therapy
  • calcium, and vitamin D
  • Hormone replacement therapy (e.g. estrogen use for mitigation of menopausal symptoms)
  • Subject has:
  • Stopped daily or weekly bisphosphonate therapy (is denoted as non-persistent) at least one month before the screening visit, or
  • Demonstrated low adherence to therapy assessed by a score of less than 6 on the OS-MMAS
  • Screening BMD (g/cm2) values, at the lumbar spine OR total hip, that occur within the following ranges, based on the particular scanner that is used:

GE Lunar Lumbar spine 0.700 < or = BMD < and = 0.940 Total hip 0.504 < or = BMD < or = 0.756

Hologic Lumbar spine 0.607 < or = BMD < or = 0.827 Total hip 0.454 < or = BMD < or = 0.698 Both the initial and the repeat DXA scan of the lumbar spine OR the total hip must meet the above eligibility criteria.

  • At least 2 lumbar vertebrae must be evaluable by DXA.
  • At least one hip must be evaluable by DXA (eg, no history of either bilateral hip replacement or pins in both hips)
  • Provide signed informed consent before any study-specific procedures are conducted

Exclusion Criteria:

  • Any disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
  • Current or prior use of medications prescribed for osteoporosis treatment other than oral daily or weekly bisphosphonate
  • Contraindicated to receive oral ibandronate 150mg PO QM, including
  • Hypersensitivity to ibandronate 150mg PO QM or other constituents of ibandronate 150mg PO QM tablets
  • Abnormalities of the esophagus, which delay esophageal emptying such as stricture or achalasia
  • Inability to stand or sit upright for at least 60 minutes
  • Administration of any of the following treatments within 3 months of screening
  • Tibolone
  • Anabolic steroids or testosterone
  • Glucocorticosteroids (>= 5 mg prednisone equivalent per day for more than 10 days or a total cumulative dose of >= 50 mg)
  • Vitamin D deficiency [25(OH) vitamin D level < 20 ng/mL (<49.9 nmol/L)] - Repletion will be allowed and subjects may be re-screened
  • Evidence of any of the following per subject report, chart review or central laboratory result:
  • Significantly impaired renal function as determined by estimated Glomerular Filtration Rate less that 30mL/min/1.73 m2 determined by the central laboratory
  • Current hypo- or hypercalcemia based on the central laboratory reference ranges
  • Active gastric or duodenal ulcer; or any history of significant gastrointestinal bleed requiring hospitalization or transfusion
  • Known to have tested positive for human immunodeficiency virus, hepatitis C virus, or hepatitis B surface antigen
  • Malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5 years
  • Any metabolic bone disease or secondary cause of bone loss that is not controlled and may interfere with the interpretation of the findings
  • Previous participation in clinical trials with denosumab 60mg SC Q6M (regardless of treatment)
  • Received any solid organ or bone marrow transplant
  • Any laboratory abnormality which, in the opinion of the investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results
  • Known sensitivity to mammalian cell derived drug products
  • Known intolerance to calcium supplements
  • Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s)
  • Any physical or psychiatric disorder which, in the opinion of the investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results
  • Evidence of alcohol or substance-abuse within the last 12 months which the investigator believes would interfere with understanding or completing the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00936897

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided by Amgen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00936897     History of Changes
Other Study ID Numbers: 20080562
Study First Received: July 9, 2009
Results First Received: October 31, 2012
Last Updated: February 5, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Central EC, called Comite de Protection des Personnes
Italy: COMITATO ETICO DELL´ENTE OSPEDALIERO OSPEDALI GALLIERA DI GENOVA
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Comité ético del Hospital Vall d'Hebron
United States: Food and Drug Administration

Additional relevant MeSH terms:
Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases
Bone Diseases, Metabolic
Musculoskeletal Diseases
Diphosphonates
Ibandronic acid
Bone Density Conservation Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014