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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

Tracking Information
First Submitted Date  ICMJE March 18, 2005
First Posted Date  ICMJE March 21, 2005
Results First Submitted Date  ICMJE April 15, 2009
Results First Posted Date  ICMJE June 28, 2010
Last Update Posted Date April 22, 2013
Study Start Date  ICMJE November 2004
Actual Primary Completion Date April 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 27, 2011)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 23, 2005)
The primary objective of the study is to determine the efficacy of risedronate compared to placebo in children 4 to <16 years of age with osteogenesis imperfecta as assessed by percent change from Baseline in lumbar spine bone mineral density at Month 12
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 27, 2011)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]
  • Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]
  • Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]
  • Percent Change From Baseline in Total Body BMC at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]
  • Percent Change From Baseline in Total Body BMC at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]
  • Percent Change From Baseline in Total Body BMC at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]
  • 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".
  • 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".
  • 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".
  • 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".
  • 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".
  • 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".
  • Percent Change From Baseline in Lumbar Spine Bone Area at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]
    Measured by DXA.
  • Percent Change From Baseline in Lumbar Spine Bone Area at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]
    Measured by DXA.
  • Percent Change From Baseline in Lumbar Spine Bone Area at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]
    Measured by DXA.
  • Percent Change From Baseline in Total Body Bone Area Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]
  • Percent Change From Baseline in Total Body Bone Area Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]
  • Percent Change From Baseline in Total Body Bone Area Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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)]
  • 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)]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children
Official Title  ICMJE Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Osteogenesis Imperfecta
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Placebo Comparator: Placebo Daily
    placebo tablet, once a day for one year then for two years open label risedronate
    Intervention: Drug: Placebo
  • Experimental: Risedronate Daily
    risedronate tablet, once a day for one year then for two years open label risedronate once a day
    Intervention: Drug: risedronate sodium (Actonel)
Publications * Bishop N, Adami S, Ahmed SF, Anton J, Arundel P, Burren CP, Devogelaer JP, Hangartner T, Hosszu E, Lane JM, Lorenc R, Makitie O, Munns CF, Paredes A, Pavlov H, Plotkin H, Raggio CL, Reyes ML, Schoenau E, Semler O, Sillence DO, Steiner RD. Risedronate in children with osteogenesis imperfecta: a randomised, double-blind, placebo-controlled trial. Lancet. 2013 Oct 26;382(9902):1424-32. doi: 10.1016/S0140-6736(13)61091-0. Epub 2013 Aug 6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 19, 2010)
143
Original Enrollment  ICMJE
 (submitted: June 23, 2005)
124
Actual Study Completion Date  ICMJE March 2010
Actual Primary Completion Date April 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years to 15 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Chile,   Czech Republic,   Finland,   Germany,   Hungary,   Italy,   Poland,   South Africa,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00106028
Other Study ID Numbers  ICMJE 2003100
HMR4003I/3001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Warner Chilcott
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE Warner Chilcott
Original Study Sponsor  ICMJE Procter and Gamble
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Dietrich H Wenderoth, MD Procter and Gamble
PRS Account Warner Chilcott
Verification Date April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP