Please note that the ANZCTR website will be unavailable from 9am until 9.30am (AEST) on Monday 22nd July for website maintenance. Please be sure to log out of the system in order to avoid any loss of data. Thank you and apologies for any inconvenience caused.

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00106028




Registration number
NCT00106028
Ethics application status
Date submitted
18/03/2005
Date registered
21/03/2005
Date last updated
22/04/2013

Titles & IDs
Public title
Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children
Scientific title
Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children
Secondary ID [1] 0 0
HMR4003I/3001
Secondary ID [2] 0 0
2003100
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteogenesis Imperfecta 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Injuries and Accidents 0 0 0 0
Fractures

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - risedronate sodium (Actonel)
Treatment: Drugs - Placebo

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


Treatment: Drugs: risedronate sodium (Actonel)
risedronate tablet once a day for one year followed by risedronate once a day for two years

Treatment: Drugs: Placebo
placebo tablet once a day for one year followed by risedronate once a day for two years

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline and Month 12
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline and Month 24
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline and Month 36
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Baseline and Month 12
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Baseline and Month 24
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Baseline and Month 36
Secondary outcome [6] 0 0
Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 12, ITT Population
Timepoint [6] 0 0
Baseline and Month 12
Secondary outcome [7] 0 0
Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 24, ITT Population
Timepoint [7] 0 0
Baseline and Month 24
Secondary outcome [8] 0 0
Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 36, ITT Population
Timepoint [8] 0 0
Baseline and Month 36
Secondary outcome [9] 0 0
Percent Change From Baseline in Total Body BMC at Month 12, ITT Population
Timepoint [9] 0 0
Baseline and Month 12
Secondary outcome [10] 0 0
Percent Change From Baseline in Total Body BMC at Month 24, ITT Population
Timepoint [10] 0 0
Baseline and Month 24
Secondary outcome [11] 0 0
Percent Change From Baseline in Total Body BMC at Month 36, ITT Population
Timepoint [11] 0 0
Baseline and Month 36
Secondary outcome [12] 0 0
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".
Timepoint [12] 0 0
Baseline and Month 12
Secondary outcome [13] 0 0
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".
Timepoint [13] 0 0
Baseline and Month 24
Secondary outcome [14] 0 0
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".
Timepoint [14] 0 0
Baseline and Month 36
Secondary outcome [15] 0 0
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".
Timepoint [15] 0 0
Baseline and Month 12
Secondary outcome [16] 0 0
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".
Timepoint [16] 0 0
Baseline and Month 24
Secondary outcome [17] 0 0
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".
Timepoint [17] 0 0
Baseline and Month 36
Secondary outcome [18] 0 0
Percent Change From Baseline in Lumbar Spine Bone Area at Month 12, ITT Population - Measured by DXA.
Timepoint [18] 0 0
Baseline and Month 12
Secondary outcome [19] 0 0
Percent Change From Baseline in Lumbar Spine Bone Area at Month 24, ITT Population - Measured by DXA.
Timepoint [19] 0 0
Baseline and Month 24
Secondary outcome [20] 0 0
Percent Change From Baseline in Lumbar Spine Bone Area at Month 36, ITT Population - Measured by DXA.
Timepoint [20] 0 0
Baseline and Month 36
Secondary outcome [21] 0 0
Percent Change From Baseline in Total Body Bone Area Month 12, ITT Population
Timepoint [21] 0 0
Baseline and Month 12
Secondary outcome [22] 0 0
Percent Change From Baseline in Total Body Bone Area Month 24, ITT Population
Timepoint [22] 0 0
Baseline and Month 24
Secondary outcome [23] 0 0
Percent Change From Baseline in Total Body Bone Area Month 36, ITT Population
Timepoint [23] 0 0
Baseline and Month 36
Secondary outcome [24] 0 0
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.
Timepoint [24] 0 0
Baseline and Month 12
Secondary outcome [25] 0 0
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.
Timepoint [25] 0 0
Baseline and Month 36
Secondary outcome [26] 0 0
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.
Timepoint [26] 0 0
Baseline and Month 12
Secondary outcome [27] 0 0
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.
Timepoint [27] 0 0
Baseline and Month 36
Secondary outcome [28] 0 0
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.
Timepoint [28] 0 0
Month 12
Secondary outcome [29] 0 0
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.
Timepoint [29] 0 0
Month 12
Secondary outcome [30] 0 0
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.
Timepoint [30] 0 0
Time to First Event (days) up to 12 Months
Secondary outcome [31] 0 0
Number of Clinical Fractures, Month 12, ITT Population - Long bones include radius, ulna, humerus, tibia, fibula, femur, upper limb and lower limb fracture.
Timepoint [31] 0 0
12 Months
Secondary outcome [32] 0 0
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.
Timepoint [32] 0 0
Baseline and 12 Months
Secondary outcome [33] 0 0
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.
Timepoint [33] 0 0
Baseline and 24 Months
Secondary outcome [34] 0 0
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.
Timepoint [34] 0 0
Baseline and 36 Months
Secondary outcome [35] 0 0
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.
Timepoint [35] 0 0
Baseline and Endpoint / Month 12
Secondary outcome [36] 0 0
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.
Timepoint [36] 0 0
Baseline and Month 24
Secondary outcome [37] 0 0
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.
Timepoint [37] 0 0
Baseline and Month 36
Secondary outcome [38] 0 0
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.
Timepoint [38] 0 0
Baseline and Month 12
Secondary outcome [39] 0 0
Bone Age (Years), Change From Baseline to Month 12, ITT Population - Bone Age determined by visual assessment of hand / wrist radiographs.
Timepoint [39] 0 0
Baseline and Month 12
Secondary outcome [40] 0 0
Bone Age (Years), Change From Baseline to Month 24, ITT Population - Bone Age determined by visual assessment of hand / wrist radiographs.
Timepoint [40] 0 0
Baseline and Month 24
Secondary outcome [41] 0 0
Bone Age (Years), Change From Baseline to Month 36, ITT Population - Bone Age determined by visual assessment of hand / wrist radiographs.
Timepoint [41] 0 0
Baseline and Month 36
Secondary outcome [42] 0 0
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)]
Timepoint [42] 0 0
Baseline and Month 12
Secondary outcome [43] 0 0
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)]
Timepoint [43] 0 0
Baseline and Month 36

Eligibility
Key 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.
Minimum age
4 Years
Maximum age
15 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Any bisphosphonate use within one year of enrollment

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
- Westmead
Recruitment postcode(s) [2] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Nebraska
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Oregon
Country [6] 0 0
Belgium
State/province [6] 0 0
Bruxelles
Country [7] 0 0
Chile
State/province [7] 0 0
Santiago
Country [8] 0 0
Czech Republic
State/province [8] 0 0
Plzen
Country [9] 0 0
Finland
State/province [9] 0 0
Helsinki
Country [10] 0 0
Germany
State/province [10] 0 0
Koln
Country [11] 0 0
Hungary
State/province [11] 0 0
Budapest
Country [12] 0 0
Italy
State/province [12] 0 0
Valeggio sul Mincio
Country [13] 0 0
Poland
State/province [13] 0 0
Warzawa-Miedzylesie
Country [14] 0 0
South Africa
State/province [14] 0 0
Gauteng
Country [15] 0 0
Spain
State/province [15] 0 0
Barcelona
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Bristol
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Glasgow
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Warner Chilcott
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00106028
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Dietrich H Wenderoth, MD
Address 0 0
Procter and Gamble
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications