Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children
- Conditions
- Osteogenesis Imperfecta
- Interventions
- Drug: risedronate sodium (Actonel)Drug: Placebo
- Registration Number
- NCT00106028
- Lead Sponsor
- Warner Chilcott
- 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 available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 143
- 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.
- Any bisphosphonate use within one year of enrollment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Risedronate Daily risedronate sodium (Actonel) risedronate tablet, once a day for one year then for two years open label risedronate once a day Placebo Daily Placebo placebo tablet, once a day for one year then for two years open label risedronate
- Primary Outcome Measures
Name Time Method Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 12, ITT Population 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
Name Time Method Serum BAP - Percent Change From Baseline to Month 12, ITT Population Baseline and 12 Months Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.
Percent Change From Baseline in Total Body BMD at Month 12, ITT Population 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 Baseline and Month 24 Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.
Total Body Z-score- Percent Change From Baseline to Month 24, ITT Population 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".
Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 12, ITT Population Baseline and Month 12 Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 24, ITT Population Baseline and Month 24 Lumbar Spine Z-score - Percent Change From Baseline to Month 12, ITT Population 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".
Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 24, ITT Population 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 in Lumbar Spine BMC (Bone Mineral Content) at Month 36, ITT Population Baseline and Month 36 Percent Change From Baseline in Total Body BMC at Month 12, ITT Population Baseline and Month 12 Percent Change From Baseline in Lumbar Spine Bone Area at Month 12, ITT Population Baseline and Month 12 Measured by DXA.
Percent Change From Baseline in Total Body Bone Area Month 12, ITT Population Baseline and Month 12 New Morphometric Vertebral Fracture at Month 12, ITT Population 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.
Categorization by Number of New Morphometric Vertebral Fracture at Month 36, ITT 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 Score, Patients Aged 10-15 Years, Month 12, ITT Population 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.
Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 36, ITT Population 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 36, ITT Population Baseline and Month 36 Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.
Percent Change From Baseline in Total Body BMC at Month 24, ITT Population Baseline and Month 24 Percent Change From Baseline in Total Body BMC at Month 36, ITT Population Baseline and Month 36 Lumbar Spine Z-score - Percent Change From Baseline to Month 24, ITT Population 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".
Percent Change From Baseline in Lumbar Spine Bone Area at Month 24, ITT Population Baseline and Month 24 Measured by DXA.
Total Body Z-score- Percent Change From Baseline to Month 36, ITT Population 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 Total Body Bone Area Month 24, ITT Population Baseline and Month 24 New Morphometric Vertebral Fracture at Month 36, ITT Population 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 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.
Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population Time to First Event (days) up to 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 36, ITT Population Baseline and 36 Months Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.
Bone Age (Years), Change From Baseline to Month 36, ITT Population Baseline and Month 36 Bone Age determined by visual assessment of hand / wrist radiographs.
Number of Clinical Fractures, Month 12, ITT Population 12 Months Long bones include radius, ulna, humerus, tibia, fibula, femur, upper limb and lower limb fracture.
Lumbar Spine Z-score - Percent Change From Baseline to Month 36, ITT Population 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 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".
Percent Change From Baseline in Lumbar Spine Bone Area at Month 36, ITT Population Baseline and Month 36 Measured by DXA.
Percent Change From Baseline in Total Body Bone Area Month 36, ITT Population Baseline and Month 36 Incidence New Vertebral Fractures by SQ (Semi-Quantitative) Score, Patients Aged 4-9 Years, Month 12, ITT Population 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.
Wong-Baker FACES Pain Rating Scale - Change From Baseline to Month 12, ITT Population 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.
Annualized Growth Velocity - Change From Baseline to Month 36, ITT Population Baseline and Month 36 Annualized Growth Velocity \[= bone age change from baseline x (365.25/time in days between baseline and the bone age measurement)\]
Serum BAP - Percent Change From Baseline to Month 24, ITT Population Baseline and 24 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 24, ITT Population 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 Baseline and Month 36 Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.
Annualized Growth Velocity - Change From Baseline to Month 12, ITT Population Baseline and Month 12 Annualized Growth Velocity \[= bone age change from baseline x (365.25/time in days between baseline and the bone age measurement)\]
Urine NTX/Cr - Percent Change From Baseline at Month 12, ITT Population Baseline and Endpoint / Month 12 Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.
Bone Age (Years), Change From Baseline to Month 12, ITT Population 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 Baseline and Month 24 Bone Age determined by visual assessment of hand / wrist radiographs.
Trial Locations
- Locations (20)
Klinikum und Poliklinik für Kinderheilkunde der Universität zu Köln
🇩🇪Koln, Germany
Cliniques Universitaires Saint Luc
🇧🇪Bruxelles, Belgium
The Children's Hospital at Westmead
🇦🇺Westmead, New South Wales, Australia
University of Nebraska Medical Center, Children's Hospital
🇺🇸Omaha, Nebraska, United States
Rheumatologic Rehabilitation Unit of the University of Verona
🇮🇹Valeggio sul Mincio, Italy
Hospital for Children and Adolescents
🇫🇮Helsinki, Finland
Bristol Royal Hospital for Children,
🇬🇧Bristol, United Kingdom
Little Company of Mary Hospital
🇿🇦Pretoria, Gauteng, South Africa
Royal Hospital for Sick Children
🇬🇧Glasgow, United Kingdom
Sheffield Children's Hospital
🇬🇧Sheffield, United Kingdom
Miami Children's Hospital
🇺🇸Miami, Florida, United States
Hospital for Special Surgery
🇺🇸New York, New York, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Australia
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Hospital Sant Joan de Deu
🇪🇸Barcelona, Spain
Osteocentrum, II. Interní klinika, Fakultní nemocnice Plzeň-Bory
🇨🇿Plzen, Czech Republic
Pontificia Universidad Catolica de Chile
🇨🇱Santiago, Chile
2nd Department of Pediatrics, Semmelwies University, Faculty of Medicine
🇭🇺Budapest, Hungary
Zaklad Biochemii i Medycyny Doswiadczalnej (Biochemisty Dept, Institute "Monument-Children Health Centre"
🇵🇱Warzawa-Międzylesie, Poland
Wright State University BioMedical Imaging Laboratory and Miami Valley Hospital
🇺🇸Dayton, Ohio, United States