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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Warner Chilcott
ClinicalTrials.gov Identifier:
NCT00106028
First received: March 18, 2005
Last updated: April 15, 2013
Last verified: April 2013
History of Changes
  Purpose
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 Intervention Phase
Osteogenesis Imperfecta
 Drug: risedronate sodium (Actonel)
Drug: Placebo
 Phase 3

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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Warner Chilcott:

Primary Outcome Measures:
  • Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    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:
  • Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ] [ Designated as safety issue: No ]
    Lumbar Spine Bone Mineral Density (BMD) measured by dual-energy x-ray absorptiometry (DXA)and read by central reader.

  • Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ] [ Designated as safety issue: No ]
    Lumbar Spine Bone Mineral Density (BMD) measured by dual-energy x-ray absorptiometry (DXA)and read by central reader.

  • Percent Change From Baseline in Total Body BMD at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.

  • Percent Change From Baseline in Total Body BMD at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ] [ Designated as safety issue: No ]
    Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.

  • Percent Change From Baseline in Total Body BMD at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ] [ Designated as safety issue: No ]
    Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.

  • Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Total Body BMC at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Total Body BMC at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Total Body BMC at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ] [ Designated as safety issue: No ]
  • Lumbar Spine Z-score - Percent Change From Baseline to Month 12, ITT Population [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    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".

  • Lumbar Spine Z-score - Percent Change From Baseline to Month 24, ITT Population [ Time Frame: Baseline and Month 24 ] [ Designated as safety issue: No ]
    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".

  • Lumbar Spine Z-score - Percent Change From Baseline to Month 36, ITT Population [ Time Frame: Baseline and Month 36 ] [ Designated as safety issue: No ]
    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".

  • Total Body Z-score- Percent Change From Baseline to Month 12, ITT Population [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    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".

  • Total Body Z-score- Percent Change From Baseline to Month 24, ITT Population [ Time Frame: Baseline and Month 24 ] [ Designated as safety issue: No ]
    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".

  • Total Body Z-score- Percent Change From Baseline to Month 36, ITT Population [ Time Frame: Baseline and Month 36 ] [ Designated as safety issue: No ]
    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".

  • Percent Change From Baseline in Lumbar Spine Bone Area at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    Measured by DXA.

  • Percent Change From Baseline in Lumbar Spine Bone Area at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ] [ Designated as safety issue: No ]
    Measured by DXA.

  • Percent Change From Baseline in Lumbar Spine Bone Area at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ] [ Designated as safety issue: No ]
    Measured by DXA.

  • Percent Change From Baseline in Total Body Bone Area Month 12, ITT Population [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Total Body Bone Area Month 24, ITT Population [ Time Frame: Baseline and Month 24 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Total Body Bone Area Month 36, ITT Population [ Time Frame: Baseline and Month 36 ] [ Designated as safety issue: No ]
  • New Morphometric Vertebral Fracture at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    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.

  • New Morphometric Vertebral Fracture at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ] [ Designated as safety issue: No ]
    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.

  • Categorization by Number of New Morphometric Vertebral Fracture at Month 12, ITT [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    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.

  • Categorization by Number of New Morphometric Vertebral Fracture at Month 36, ITT [ Time Frame: Baseline and Month 36 ] [ Designated as safety issue: No ]
    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.

  • Incidence New Vertebral Fractures by SQ (Semi-Quantitative) Score, Patients Aged 4-9 Years, Month 12, ITT Population [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    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.

  • Incidence New Vertebral Fractures by SQ Score, Patients Aged 10-15 Years, Month 12, ITT Population [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    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.

  • Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population [ Time Frame: Time to First Event (days) up to 12 Months ] [ Designated as safety issue: No ]
    Long bones include radius, ulna, humerus, tibia, fibula, femur, upper limb and lower limb fracture.

  • Number of Clinical Fractures, Month 12, ITT Population [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    Long bones include radius, ulna, humerus, tibia, fibula, femur, upper limb and lower limb fracture.

  • Serum BAP - Percent Change From Baseline to Month 12, ITT Population [ Time Frame: Baseline and 12 Months ] [ Designated as safety issue: No ]
    Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.

  • Serum BAP - Percent Change From Baseline to Month 24, ITT Population [ Time Frame: Baseline and 24 Months ] [ Designated as safety issue: No ]
    Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.

  • Serum BAP - Percent Change From Baseline to Month 36, ITT Population [ Time Frame: Baseline and 36 Months ] [ Designated as safety issue: No ]
    Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.

  • Urine NTX/Cr - Percent Change From Baseline at Month 12, ITT Population [ Time Frame: Baseline and Endpoint / Month 12 ] [ Designated as safety issue: No ]
    Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.

  • Urine NTX/Cr - Percent Change From Baseline at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ] [ Designated as safety issue: No ]
    Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.

  • Urine NTX/Cr - Percent Change From Baseline at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ] [ Designated as safety issue: No ]
    Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.

  • Wong-Baker FACES Pain Rating Scale - Change From Baseline to Month 12, ITT Population [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    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.

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

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

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

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

  • Annualized Growth Velocity - Change From Baseline to Month 36, ITT Population [ Time Frame: Baseline and Month 36 ] [ Designated as safety issue: Yes ]
    Annualized Growth Velocity [= bone age change from baseline x (365.25/time in days between baseline and the bone age measurement)]
Enrollment: 143
Study Start Date: November 2004
Study Completion Date: March 2010
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility
Ages Eligible for Study:   4 Years to 15 Years   (Child)
Genders Eligible for Study:   Both
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
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: NCT00106028

  Show 20 Study Locations
Sponsors and Collaborators
Warner Chilcott
Investigators
Study Director: Dietrich H Wenderoth, MD Procter and Gamble
  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 
Study First Received: March 18, 2005
Results First Received: April 15, 2009
Last Updated: April 15, 2013
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 30, 2016