ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00106028
Recruitment Status : Completed
First Posted : March 21, 2005
Results First Posted : June 28, 2010
Last Update Posted : April 22, 2013
Sponsor:
Information provided by (Responsible Party):
Warner Chilcott

Study Description
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
Children with Osteogenesis Imperfecta (OI) have bone pain, low bone mass and fractures. There are no approved drugs for the treatment of OI in children, even though some intravenous (IV) bisphosphonates are used off-label in some countries. In a single dose, pharmacokinetic study, data showed that risedronate was well tolerated in 28 children with OI. This three year study will test the safety and efficacy of risedronate in the treatment of children with OI. For the first year, patients will be randomized to the risedronate and placebo groups in a 2:1 ratio. For the second and third years of the study, all patients will receive risedronate.

Condition or disease Intervention/treatment Phase
Osteogenesis Imperfecta Drug: risedronate sodium (Actonel) Drug: Placebo Phase 3

Study Design
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 143 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children
Study Start Date : November 2004
Actual Primary Completion Date : April 2008
Actual Study Completion Date : March 2010

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Placebo Comparator: Placebo Daily
placebo tablet, once a day for one year then for two years open label risedronate
 Drug: Placebo
placebo tablet once a day for one year followed by risedronate once a day for two years
Experimental: Risedronate Daily
risedronate tablet, once a day for one year then for two years open label risedronate once a day
 Drug: risedronate sodium (Actonel)
risedronate tablet once a day for one year followed by risedronate once a day for two years


Outcome Measures
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]
    Lumbar Spine Bone Mineral Density (BMD) measured by dual-energy x-ray absorptiometry (DXA)and read by central reader. Duplicate scans obtained at screening and Month 12.


Secondary Outcome Measures :
  1. Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]
    Lumbar Spine Bone Mineral Density (BMD) measured by dual-energy x-ray absorptiometry (DXA)and read by central reader.

  2. Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]
    Lumbar Spine Bone Mineral Density (BMD) measured by dual-energy x-ray absorptiometry (DXA)and read by central reader.

  3. Percent Change From Baseline in Total Body BMD at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]
    Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.

  4. Percent Change From Baseline in Total Body BMD at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]
    Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.

  5. Percent Change From Baseline in Total Body BMD at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]
    Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.

  6. Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]
  7. Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]
  8. Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]
  9. Percent Change From Baseline in Total Body BMC at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]
  10. Percent Change From Baseline in Total Body BMC at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]
  11. Percent Change From Baseline in Total Body BMC at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]
  12. Lumbar Spine Z-score - Percent Change From Baseline to Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]
    Lumbar Spine Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values".

  13. Lumbar Spine Z-score - Percent Change From Baseline to Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]
    Lumbar Spine Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values".

  14. Lumbar Spine Z-score - Percent Change From Baseline to Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]
    Lumbar Spine Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values".

  15. Total Body Z-score- Percent Change From Baseline to Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]
    Total Body Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values".

  16. Total Body Z-score- Percent Change From Baseline to Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]
    Total Body Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values".

  17. Total Body Z-score- Percent Change From Baseline to Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]
    Total Body Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values".

  18. Percent Change From Baseline in Lumbar Spine Bone Area at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]
    Measured by DXA.

  19. Percent Change From Baseline in Lumbar Spine Bone Area at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]
    Measured by DXA.

  20. Percent Change From Baseline in Lumbar Spine Bone Area at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]
    Measured by DXA.

  21. Percent Change From Baseline in Total Body Bone Area Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]
  22. Percent Change From Baseline in Total Body Bone Area Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]
  23. Percent Change From Baseline in Total Body Bone Area Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]
  24. New Morphometric Vertebral Fracture at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]
    Morphometric Vertebral Fracture measured by semi-quantitative (SQ) analysis of x-rays using the Genant scoring system at endpoint. (Ref: Genant 1993). SQ-Scores range from 0 (no fracture) to 3 (severe fracture). New fracture = SQ score is 0 at baseline and >0 at the specified end visit.

  25. New Morphometric Vertebral Fracture at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]
    Morphometric Vertebral Fracture measured by SQ analysis of x-rays using the Genant scoring system. (Ref: Genant 1993). SQ-Scores range from 0 (no fracture) to 3 (severe fracture). New fracture = SQ score is 0 at baseline and >0 at the specified end visit.

  26. Categorization by Number of New Morphometric Vertebral Fracture at Month 12, ITT [ Time Frame: Baseline and Month 12 ]
    Patients with 1 or more New Morphometric Vertebral Fracture as measured by SQ analysis of x-rays using the Genant scoring system (Ref: Genant 1993). SQ-Scores range from 0 (no fracture) to 3 (severe fracture). Incidence = SQ score is 0 at baseline and >0 at post-baseline.

  27. Categorization by Number of New Morphometric Vertebral Fracture at Month 36, ITT [ Time Frame: Baseline and Month 36 ]
    Patients with 1 or more New Morphometric Vertebral Fracture as measured by SQ analysis of x-rays using the Genant scoring system (Ref: Genant 1993). SQ-Scores range from 0 (no fracture) to 3 (severe fracture). Incidence = SQ score is 0 at baseline and >0 at post-baseline.

  28. Incidence New Vertebral Fractures by SQ (Semi-Quantitative) Score, Patients Aged 4-9 Years, Month 12, ITT Population [ Time Frame: Month 12 ]
    Patients aged 4-9 years with new morphometric vertebral fractures as measured by SQ analysis of x-rays using the Genant scoring system at Month 12 +/- 14 days. (Ref: Genant 1993). SQ Score mild - 0/no fracture to Grade 1, Moderate to Severe - change from 0/no fracture to Grade 2-3.

  29. Incidence New Vertebral Fractures by SQ Score, Patients Aged 10-15 Years, Month 12, ITT Population [ Time Frame: Month 12 ]
    Patients aged 10-15 years with new morphometric vertebral fractures as measured by SQ analysis of x-rays using the Genant scoring system at Month 12 +/- 14 days. (Ref: Genant 1993). SQ Score mild - 0/no fracture to Grade 1, Moderate to Severe - change from 0/no fracture to Grade 2-3.

  30. Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population [ Time Frame: Time to First Event (days) up to 12 Months ]
    Long bones include radius, ulna, humerus, tibia, fibula, femur, upper limb and lower limb fracture.

  31. Number of Clinical Fractures, Month 12, ITT Population [ Time Frame: 12 Months ]
    Long bones include radius, ulna, humerus, tibia, fibula, femur, upper limb and lower limb fracture.

  32. Serum BAP - Percent Change From Baseline to Month 12, ITT Population [ Time Frame: Baseline and 12 Months ]
    Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.

  33. Serum BAP - Percent Change From Baseline to Month 24, ITT Population [ Time Frame: Baseline and 24 Months ]
    Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.

  34. Serum BAP - Percent Change From Baseline to Month 36, ITT Population [ Time Frame: Baseline and 36 Months ]
    Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.

  35. Urine NTX/Cr - Percent Change From Baseline at Month 12, ITT Population [ Time Frame: Baseline and Endpoint / Month 12 ]
    Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.

  36. Urine NTX/Cr - Percent Change From Baseline at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]
    Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.

  37. Urine NTX/Cr - Percent Change From Baseline at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]
    Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.

  38. Wong-Baker FACES Pain Rating Scale - Change From Baseline to Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]
    Wong-Baker FACES Pain Rating Scale (pain assessment scale using facial expressions, translated into a range from 0= no pain [smiling face] to 10= worst pain possible [distorted face with tears]; negative values indicate decrease in pain). Reference: Wong DL et al.

  39. Bone Age (Years), Change From Baseline to Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]
    Bone Age determined by visual assessment of hand / wrist radiographs.

  40. Bone Age (Years), Change From Baseline to Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]
    Bone Age determined by visual assessment of hand / wrist radiographs.

  41. Bone Age (Years), Change From Baseline to Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]
    Bone Age determined by visual assessment of hand / wrist radiographs.

  42. Annualized Growth Velocity - Change From Baseline to Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]
    Annualized Growth Velocity [= bone age change from baseline x (365.25/time in days between baseline and the bone age measurement)]

  43. Annualized Growth Velocity - Change From Baseline to Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]
    Annualized Growth Velocity [= bone age change from baseline x (365.25/time in days between baseline and the bone age measurement)]


Eligibility Criteria
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   4 Years to 15 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • OI diagnosis
  • increased risk of fracture: either has a history of at least 1 radiographically confirmed, non-traumatic or low impact fracture plus low bone mineral density (BMD) or has very low BMD with or without a history of fractures.

Exclusion Criteria:

  • Any bisphosphonate use within one year of enrollment
Contacts and Locations
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00106028


  Show 20 Study Locations
Sponsors and Collaborators
Warner Chilcott
Investigators
Study Director: Dietrich H Wenderoth, MD Procter and Gamble
More Information
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Responsible Party: Warner Chilcott
ClinicalTrials.gov Identifier: NCT00106028     History of Changes
Other Study ID Numbers: 2003100
HMR4003I/3001
First Posted: March 21, 2005    Key Record Dates
Results First Posted: June 28, 2010
Last Update Posted: April 22, 2013
Last Verified: April 2013

Keywords provided by Warner Chilcott:
Primary disease: Osteogenesis Imperfecta

Additional relevant MeSH terms:
Osteogenesis Imperfecta
Osteochondrodysplasias
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Collagen Diseases
Connective Tissue Diseases
 Risedronate Sodium
Etidronic Acid
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Bone Density Conservation Agents
Physiological Effects of Drugs