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

Osteogenesis Imperfecta Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00106028
• Other study ID #: 2003100
• Secondary ID: HMR4003I/3001
• Status: Completed
• Phase: Phase 3
• First received: March 18, 2005
• Last updated: April 15, 2013
• Start date: November 2004
• Est. completion date: March 2010

Study information

• Verified date: April 2013
• Source: Warner Chilcott
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 143
• Est. completion date: March 2010
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 4 Years to 15 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteogenesis Imperfecta

Intervention

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

Locations

Country	Name	City	State
Australia	Princess Margaret Hospital for Children	Perth
Australia	The Children's Hospital at Westmead	Westmead	New South Wales
Belgium	Cliniques Universitaires Saint Luc	Bruxelles
Chile	Pontificia Universidad Catolica de Chile	Santiago
Czech Republic	Osteocentrum, II. Interní klinika, Fakultní nemocnice Plzen-Bory	Plzen
Finland	Hospital for Children and Adolescents	Helsinki
Germany	Klinikum und Poliklinik für Kinderheilkunde der Universität zu Köln	Koln
Hungary	2nd Department of Pediatrics, Semmelwies University, Faculty of Medicine	Budapest
Italy	Rheumatologic Rehabilitation Unit of the University of Verona	Valeggio sul Mincio
Poland	Zaklad Biochemii i Medycyny Doswiadczalnej (Biochemisty Dept, Institute "Monument-Children Health Centre"	Warzawa-Miedzylesie
South Africa	Little Company of Mary Hospital	Pretoria	Gauteng
Spain	Hospital Sant Joan de Deu	Barcelona
United Kingdom	Bristol Royal Hospital for Children,	Bristol
United Kingdom	Royal Hospital for Sick Children	Glasgow
United Kingdom	Sheffield Children's Hospital	Sheffield
United States	Wright State University BioMedical Imaging Laboratory and Miami Valley Hospital	Dayton	Ohio
United States	Miami Children's Hospital	Miami	Florida
United States	Hospital for Special Surgery	New York	New York
United States	University of Nebraska Medical Center, Children's Hospital	Omaha	Nebraska
United States	Oregon Health & Science University	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Warner Chilcott

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Chile,  Czech Republic,  Finland,  Germany,  Hungary,  Italy,  Poland,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 12, ITT Population	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.	Baseline and Month 12	No
Secondary	Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 24, ITT Population	Lumbar Spine Bone Mineral Density (BMD) measured by dual-energy x-ray absorptiometry (DXA)and read by central reader.	Baseline and Month 24	No
Secondary	Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 36, ITT Population	Lumbar Spine Bone Mineral Density (BMD) measured by dual-energy x-ray absorptiometry (DXA)and read by central reader.	Baseline and Month 36	No
Secondary	Percent Change From Baseline in Total Body BMD at Month 12, ITT Population	Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.	Baseline and Month 12	No
Secondary	Percent Change From Baseline in Total Body BMD at Month 24, ITT Population	Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.	Baseline and Month 24	No
Secondary	Percent Change From Baseline in Total Body BMD at Month 36, ITT Population	Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.	Baseline and Month 36	No
Secondary	Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 12, ITT Population		Baseline and Month 12	No
Secondary	Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 24, ITT Population		Baseline and Month 24	No
Secondary	Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 36, ITT Population		Baseline and Month 36	No
Secondary	Percent Change From Baseline in Total Body BMC at Month 12, ITT Population		Baseline and Month 12	No
Secondary	Percent Change From Baseline in Total Body BMC at Month 24, ITT Population		Baseline and Month 24	No
Secondary	Percent Change From Baseline in Total Body BMC at Month 36, ITT Population		Baseline and Month 36	No
Secondary	Lumbar Spine Z-score - Percent Change From Baseline to Month 12, ITT Population	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".	Baseline and Month 12	No
Secondary	Lumbar Spine Z-score - Percent Change From Baseline to Month 24, ITT Population	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".	Baseline and Month 24	No
Secondary	Lumbar Spine Z-score - Percent Change From Baseline to Month 36, ITT Population	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".	Baseline and Month 36	No
Secondary	Total Body Z-score- Percent Change From Baseline to Month 12, ITT Population	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".	Baseline and Month 12	No
Secondary	Total Body Z-score- Percent Change From Baseline to Month 24, ITT Population	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".	Baseline and Month 24	No
Secondary	Total Body Z-score- Percent Change From Baseline to Month 36, ITT Population	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".	Baseline and Month 36	No
Secondary	Percent Change From Baseline in Lumbar Spine Bone Area at Month 12, ITT Population	Measured by DXA.	Baseline and Month 12	No
Secondary	Percent Change From Baseline in Lumbar Spine Bone Area at Month 24, ITT Population	Measured by DXA.	Baseline and Month 24	No
Secondary	Percent Change From Baseline in Lumbar Spine Bone Area at Month 36, ITT Population	Measured by DXA.	Baseline and Month 36	No
Secondary	Percent Change From Baseline in Total Body Bone Area Month 12, ITT Population		Baseline and Month 12	No
Secondary	Percent Change From Baseline in Total Body Bone Area Month 24, ITT Population		Baseline and Month 24	No
Secondary	Percent Change From Baseline in Total Body Bone Area Month 36, ITT Population		Baseline and Month 36	No
Secondary	New Morphometric Vertebral Fracture at Month 12, ITT Population	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.	Baseline and Month 12	No
Secondary	New Morphometric Vertebral Fracture at Month 36, ITT Population	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.	Baseline and Month 36	No
Secondary	Categorization by Number of New Morphometric Vertebral Fracture at Month 12, ITT	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.	Baseline and Month 12	No
Secondary	Categorization by Number of New Morphometric Vertebral Fracture at Month 36, ITT	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.	Baseline and Month 36	No
Secondary	Incidence New Vertebral Fractures by SQ (Semi-Quantitative) Score, Patients Aged 4-9 Years, Month 12, ITT Population	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.	Month 12	No
Secondary	Incidence New Vertebral Fractures by SQ Score, Patients Aged 10-15 Years, Month 12, ITT Population	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.	Month 12	No
Secondary	Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population	Long bones include radius, ulna, humerus, tibia, fibula, femur, upper limb and lower limb fracture.	Time to First Event (days) up to 12 Months	No
Secondary	Number of Clinical Fractures, Month 12, ITT Population	Long bones include radius, ulna, humerus, tibia, fibula, femur, upper limb and lower limb fracture.	12 Months	No
Secondary	Serum BAP - Percent Change From Baseline to Month 12, ITT Population	Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.	Baseline and 12 Months	No
Secondary	Serum BAP - Percent Change From Baseline to Month 24, ITT Population	Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.	Baseline and 24 Months	No
Secondary	Serum BAP - Percent Change From Baseline to Month 36, ITT Population	Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.	Baseline and 36 Months	No
Secondary	Urine NTX/Cr - Percent Change From Baseline at Month 12, ITT Population	Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.	Baseline and Endpoint / Month 12	No
Secondary	Urine NTX/Cr - Percent Change From Baseline at Month 24, ITT Population	Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.	Baseline and Month 24	No
Secondary	Urine NTX/Cr - Percent Change From Baseline at Month 36, ITT Population	Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.	Baseline and Month 36	No
Secondary	Wong-Baker FACES Pain Rating Scale - Change From Baseline to Month 12, ITT Population	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.	Baseline and Month 12	No
Secondary	Bone Age (Years), Change From Baseline to Month 12, ITT Population	Bone Age determined by visual assessment of hand / wrist radiographs.	Baseline and Month 12	Yes
Secondary	Bone Age (Years), Change From Baseline to Month 24, ITT Population	Bone Age determined by visual assessment of hand / wrist radiographs.	Baseline and Month 24	Yes
Secondary	Bone Age (Years), Change From Baseline to Month 36, ITT Population	Bone Age determined by visual assessment of hand / wrist radiographs.	Baseline and Month 36	Yes
Secondary	Annualized Growth Velocity - Change From Baseline to Month 12, ITT Population	Annualized Growth Velocity [= bone age change from baseline x (365.25/time in days between baseline and the bone age measurement)]	Baseline and Month 12	Yes
Secondary	Annualized Growth Velocity - Change From Baseline to Month 36, ITT Population	Annualized Growth Velocity [= bone age change from baseline x (365.25/time in days between baseline and the bone age measurement)]	Baseline and Month 36	Yes