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Osteogenesis ImperfectaPhase 3NCT00106028

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

A Phase 3 study testing risedronate sodium (Actonel) in people with Osteogenesis Imperfecta, run by Warner Chilcott at 20 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 4 to 15 years
Conditions the study is for
Osteogenesis Imperfecta
What is being tested?
risedronate sodium (Actonel)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
143 participants
Where
20 sitesin 13 countries
Study dates
Nov 2004to Mar 2010
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 4 to 15 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.

Who cannot join

  • Any bisphosphonate use within one year of enrollment

Trial locations and contacts

20 sites in 13 countries.

20 sites in 13 countries

United States5 sites
  • Wright State University BioMedical Imaging Laboratory and Miami Valley Hospital

    Dayton, Ohio, 45409

  • Miami Children's Hospital

    Miami, Florida, 33155

  • Hospital for Special Surgery

    New York, New York, 10021

  • University of Nebraska Medical Center, Children's Hospital

    Omaha, Nebraska, 68114

  • Oregon Health & Science University

    Portland, Oregon, 97239

Other trials in United States

United Kingdom3 sites
  • Bristol Royal Hospital for Children,

    Bristol

  • Royal Hospital for Sick Children

    Glasgow, Glasgow, G3 8SJ

  • Sheffield Children's Hospital

    Sheffield, Sheffield, S210 2TH

Other trials in United Kingdom

Australia2 sites
  • Princess Margaret Hospital for Children

    Perth

  • The Children's Hospital at Westmead

    Westmead, New South Wales

Other trials in Australia

Belgium1 site
  • Cliniques Universitaires Saint Luc

    Brussels

Other trials in Belgium

Chile1 site
  • Pontificia Universidad Catolica de Chile

    Santiago

Other trials in Chile

Czechia1 site
  • Osteocentrum, II. Interní klinika, Fakultní nemocnice Plzeň-Bory

    Pilsen

Other trials in Czechia

Finland1 site
  • Hospital for Children and Adolescents

    Helsinki

Other trials in Finland

Germany1 site
  • Klinikum und Poliklinik für Kinderheilkunde der Universität zu Köln

    Cologne

Other trials in Germany

Hungary1 site
  • 2nd Department of Pediatrics, Semmelwies University, Faculty of Medicine

    Budapest

Other trials in Hungary

Italy1 site
  • Rheumatologic Rehabilitation Unit of the University of Verona

    Valeggio sul Mincio

Other trials in Italy

Poland1 site
  • Zaklad Biochemii i Medycyny Doswiadczalnej (Biochemisty Dept, Institute "Monument-Children Health Centre"

    Warzawa-Międzylesie

Other trials in Poland

South Africa1 site
  • Little Company of Mary Hospital

    Pretoria, Gauteng

Other trials in South Africa

Spain1 site
  • Hospital Sant Joan de Deu

    Barcelona

Other trials in Spain

About this study

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.

Being tested
risedronate sodium (Actonel), Placebo
Keywords
Primary disease: Osteogenesis Imperfecta
Medical subject headings
Osteogenesis Imperfecta

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • risedronate sodium (Actonel)Drug

    risedronate tablet once a day for one year followed by risedronate once a day for two years

  • PlaceboDrug

    placebo tablet once a day for one year followed by risedronate once a day for two years

Study groups in NCT00106028
Study groupRoleWhat they receive
Placebo DailyPlacebo comparatorplacebo tablet, once a day for one year then for two years open label risedronate
Receives: Drug: Placebo
Risedronate DailyExperimentalrisedronate tablet, once a day for one year then for two years open label risedronate once a day
Receives: Drug: risedronate sodium (Actonel)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline and Month 12

Secondary outcomes (43)
  1. 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.

    Measured: Baseline and Month 24

  2. 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.

    Measured: Baseline and Month 36

  3. 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.

    Measured: Baseline and Month 12

  4. 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.

    Measured: Baseline and Month 24

  5. 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.

    Measured: Baseline and Month 36

  6. Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 12, ITT Population

    Measured: Baseline and Month 12

  7. Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 24, ITT Population

    Measured: Baseline and Month 24

  8. Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 36, ITT Population

    Measured: Baseline and Month 36

  9. Percent Change From Baseline in Total Body BMC at Month 12, ITT Population

    Measured: Baseline and Month 12

  10. Percent Change From Baseline in Total Body BMC at Month 24, ITT Population

    Measured: Baseline and Month 24

  11. Percent Change From Baseline in Total Body BMC at Month 36, ITT Population

    Measured: Baseline and Month 36

  12. 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".

    Measured: Baseline and Month 12

  13. 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".

    Measured: Baseline and Month 24

  14. 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".

    Measured: Baseline and Month 36

  15. 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".

    Measured: Baseline and Month 12

  16. 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".

    Measured: Baseline and Month 24

  17. 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".

    Measured: Baseline and Month 36

  18. Percent Change From Baseline in Lumbar Spine Bone Area at Month 12, ITT Population

    Measured by DXA.

    Measured: Baseline and Month 12

  19. Percent Change From Baseline in Lumbar Spine Bone Area at Month 24, ITT Population

    Measured by DXA.

    Measured: Baseline and Month 24

  20. Percent Change From Baseline in Lumbar Spine Bone Area at Month 36, ITT Population

    Measured by DXA.

    Measured: Baseline and Month 36

  21. Percent Change From Baseline in Total Body Bone Area Month 12, ITT Population

    Measured: Baseline and Month 12

  22. Percent Change From Baseline in Total Body Bone Area Month 24, ITT Population

    Measured: Baseline and Month 24

  23. Percent Change From Baseline in Total Body Bone Area Month 36, ITT Population

    Measured: Baseline and Month 36

  24. 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.

    Measured: Baseline and Month 12

  25. 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.

    Measured: Baseline and Month 36

  26. 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.

    Measured: Baseline and Month 12

  27. 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.

    Measured: Baseline and Month 36

  28. 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.

    Measured: Month 12

  29. 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.

    Measured: Month 12

  30. 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.

    Measured: Time to First Event (days) up to 12 Months

  31. Number of Clinical Fractures, Month 12, ITT Population

    Long bones include radius, ulna, humerus, tibia, fibula, femur, upper limb and lower limb fracture.

    Measured: 12 Months

  32. 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.

    Measured: Baseline and 12 Months

  33. 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.

    Measured: Baseline and 24 Months

  34. 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.

    Measured: Baseline and 36 Months

  35. 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.

    Measured: Baseline and Endpoint / Month 12

  36. 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.

    Measured: Baseline and Month 24

  37. 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.

    Measured: Baseline and Month 36

  38. 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.

    Measured: Baseline and Month 12

  39. Bone Age (Years), Change From Baseline to Month 12, ITT Population

    Bone Age determined by visual assessment of hand / wrist radiographs.

    Measured: Baseline and Month 12

  40. Bone Age (Years), Change From Baseline to Month 24, ITT Population

    Bone Age determined by visual assessment of hand / wrist radiographs.

    Measured: Baseline and Month 24

  41. Bone Age (Years), Change From Baseline to Month 36, ITT Population

    Bone Age determined by visual assessment of hand / wrist radiographs.

    Measured: Baseline and Month 36

  42. 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)]

    Measured: Baseline and Month 12

  43. 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)]

    Measured: Baseline and Month 36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Mar 2005 (estimated)
  2. Study startNov 2004
  3. Primary completionApr 2008
  4. Study completionMar 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
143 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00106028
Sponsor's protocol ID
2003100
Other IDs
HMR4003I/3001
Status last verified
Apr 2013
First submitted
18 Mar 2005
Last updated
22 Apr 2013
Data monitoring committee
No

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.

    PubMed 23927913

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing risedronate sodium (Actonel) in people with Osteogenesis Imperfecta, run by Warner Chilcott at 20 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United States, United Kingdom, Australia, Belgium, Chile and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jun 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 12, ITT Population (time frame: Baseline and Month 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00106028, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2013.

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