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

Official Title: “Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children”

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.

Intervention(s) in this Clinical Trial

• Drug: risedronate sodium (Actonel)
  • risedronate tablet once a day for one year followed by risedronate once a day for two years
• Drug: Placebo
  • placebo tablet once a day for one year followed by risedronate once a day for two years

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: Placebo Daily
  • placebo tablet, once a day for one year then for two years open label risedronate
• Experimental: Risedronate Daily
  • risedronate tablet, once a day for one year then for two years open label risedronate once a day

Primary Measures

• Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 12, ITT Population
  • Time Frame: Baseline and Month 12
    Safety Issue?: No

Secondary Measures

• Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 24, ITT Population
  • Time Frame: Baseline and Month 24
    Safety Issue?: No
• Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 36, ITT Population
  • Time Frame: Baseline and Month 36
    Safety Issue?: No
• Percent Change From Baseline in Total Body BMD at Month 12, ITT Population
  • Time Frame: Baseline and Month 12
    Safety Issue?: No
• Percent Change From Baseline in Total Body BMD at Month 24, ITT Population
  • Time Frame: Baseline and Month 24
    Safety Issue?: No
• Percent Change From Baseline in Total Body BMD at Month 36, ITT Population
  • Time Frame: Baseline and Month 36
    Safety Issue?: No
• Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 12, ITT Population
  • Time Frame: Baseline and Month 12
    Safety Issue?: No
• Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 24, ITT Population
  • Time Frame: Baseline and Month 24
    Safety Issue?: No
• Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 36, ITT Population
  • Time Frame: Baseline and Month 36
    Safety Issue?: No
• Percent Change From Baseline in Total Body BMC at Month 12, ITT Population
  • Time Frame: Baseline and Month 12
    Safety Issue?: No
• Percent Change From Baseline in Total Body BMC at Month 24, ITT Population
  • Time Frame: Baseline and Month 24
    Safety Issue?: No
• Percent Change From Baseline in Total Body BMC at Month 36, ITT Population
  • Time Frame: Baseline and Month 36
    Safety Issue?: No
• Lumbar Spine Z-score - Percent Change From Baseline to Month 12, ITT Population
  • Time Frame: Baseline and Month 12
    Safety Issue?: No
• Lumbar Spine Z-score - Percent Change From Baseline to Month 24, ITT Population
  • Time Frame: Baseline and Month 24
    Safety Issue?: No
• Lumbar Spine Z-score - Percent Change From Baseline to Month 36, ITT Population
  • Time Frame: Baseline and Month 36
    Safety Issue?: No
• Total Body Z-score- Percent Change From Baseline to Month 12, ITT Population
  • Time Frame: Baseline and Month 12
    Safety Issue?: No
• Total Body Z-score- Percent Change From Baseline to Month 24, ITT Population
  • Time Frame: Baseline and Month 24
    Safety Issue?: No
• Total Body Z-score- Percent Change From Baseline to Month 36, ITT Population
  • Time Frame: Baseline and Month 36
    Safety Issue?: No
• Percent Change From Baseline in Lumbar Spine Bone Area at Month 12, ITT Population
  • Time Frame: Baseline and Month 12
    Safety Issue?: No
• Percent Change From Baseline in Lumbar Spine Bone Area at Month 24, ITT Population
  • Time Frame: Baseline and Month 24
    Safety Issue?: No
• Percent Change From Baseline in Lumbar Spine Bone Area at Month 36, ITT Population
  • Time Frame: Baseline and Month 36
    Safety Issue?: No
• Percent Change From Baseline in Total Body Bone Area Month 12, ITT Population
  • Time Frame: Baseline and Month 12
    Safety Issue?: No
• Percent Change From Baseline in Total Body Bone Area Month 24, ITT Population
  • Time Frame: Baseline and Month 24
    Safety Issue?: No
• Percent Change From Baseline in Total Body Bone Area Month 36, ITT Population
  • Time Frame: Baseline and Month 36
    Safety Issue?: No
• New Morphometric Vertebral Fracture at Month 12, ITT Population
  • Time Frame: Baseline and Month 12
    Safety Issue?: No
• New Morphometric Vertebral Fracture at Month 36, ITT Population
  • Time Frame: Baseline and Month 36
    Safety Issue?: No
• Categorization by Number of New Morphometric Vertebral Fracture at Month 12, ITT
  • Time Frame: Baseline and Month 12
    Safety Issue?: No
• Categorization by Number of New Morphometric Vertebral Fracture at Month 36, ITT
  • Time Frame: Baseline and Month 36
    Safety Issue?: No
• Incidence New Vertebral Fractures by SQ (Semi-Quantitative) Score, Patients Aged 4-9 Years, Month 12, ITT Population
  • Time Frame: Month 12
    Safety Issue?: No
• Incidence New Vertebral Fractures by SQ Score, Patients Aged 10-15 Years, Month 12, ITT Population
  • Time Frame: Month 12
    Safety Issue?: No
• Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population
  • Time Frame: Time to First Event (days) up to 12 Months
    Safety Issue?: No
• Number of Clinical Fractures, Month 12, ITT Population
  • Time Frame: 12 Months
    Safety Issue?: No
• Serum BAP - Percent Change From Baseline to Month 12, ITT Population
  • Time Frame: Baseline and 12 Months
    Safety Issue?: No
• Serum BAP - Percent Change From Baseline to Month 24, ITT Population
  • Time Frame: Baseline and 24 Months
    Safety Issue?: No
• Serum BAP - Percent Change From Baseline to Month 36, ITT Population
  • Time Frame: Baseline and 36 Months
    Safety Issue?: No
• Urine NTX/Cr - Percent Change From Baseline at Month 12, ITT Population
  • Time Frame: Baseline and Endpoint / Month 12
    Safety Issue?: No
• Urine NTX/Cr - Percent Change From Baseline at Month 24, ITT Population
  • Time Frame: Baseline and Month 24
    Safety Issue?: No
• Urine NTX/Cr - Percent Change From Baseline at Month 36, ITT Population
  • Time Frame: Baseline and Month 36
    Safety Issue?: No
• Wong-Baker FACES Pain Rating Scale - Change From Baseline to Month 12, ITT Population
  • Time Frame: Baseline and Month 12
    Safety Issue?: No
• Bone Age (Years), Change From Baseline to Month 12, ITT Population
  • Time Frame: Baseline and Month 12
    Safety Issue?: Yes
• Bone Age (Years), Change From Baseline to Month 24, ITT Population
  • Time Frame: Baseline and Month 24
    Safety Issue?: Yes
• Bone Age (Years), Change From Baseline to Month 36, ITT Population
  • Time Frame: Baseline and Month 36
    Safety Issue?: Yes
• Annualized Growth Velocity - Change From Baseline to Month 12, ITT Population
  • Time Frame: Baseline and Month 12
    Safety Issue?: Yes
• Annualized Growth Velocity - Change From Baseline to Month 36, ITT Population
  • Time Frame: Baseline and Month 36
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 4 Years

Maximum Age for this Clinical Trial: 15 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Warner Chilcott Industry

Overall Clinical Trial Officials and Contacts

Dietrich H Wenderoth, MD Study Director Procter and Gamble  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00106028

Study ID Number: 2003100

ClinicalTrials.gov Identifier: NCT00106028

Health Authority: United States: Food and Drug Administration