Dettagli per singolo studio

DEC-NET Serial number GB389

Published online	11/04/2005 16.38.00
Last updated	10/04/2006 10.28.53

Other protocol ID number	2003100 N0220154466
This trial has been approved by an ethics committee
Current trial status	Open (actively recruiting new participants)
First subject enrolment Target N. of subjects	11/2004 30
Major Disease (ICD9 class)	OSTEOGENESIS IMPERFECTA
Experimental drug
Risedronate Treatment regimen (dosage and duration) 2.5mg or 5mg per day depending upon the weight of the patient
Gender	Both
Age (range)	4-16
Eligibility criteria
Inclusion criteria
Diagnosis of OI, Aged between 4 and 15 (both ages inclusive), Have increased risk of fractures defined by the following 2 risk factors = (1) History of at least 1 radiologically confirmed, non-traumatic or low impact fracture and low BMD (total body or lumbar spine), (2) Have low BMD (Z-score</=-1 at either total body or lumbar spine sites) with or without a history of fractures Female (post menarche) - agree to pregnancy test (must be negative) and use of contraceptives thoughout the study Parental/legal guardian consent plus patient assent Have at least 2 evaluable lumbar spine vertebral bodies (L1-L4) namely without fracture or degenerative disease The inclusion/exclusion criteria are set to define the patient population required to answer the research question
Exclusion criteria
Body weight less than 10kg History of cancer within the last 5 years Untreated rickets within 1 year prior to enrollment History of abnormal or allergic reaction to bisphosphonates History of use of bisphosphonates within 1 year of enrollment (except a single dose of an oral bisphosphonate) Osteoporosis, sescondary to diseases other than OI or drug therapies Current use of anticoagulants and anticonvulsants Abnormal laboratory results ie. - liver or kidney function impaired History of using the following medications for 1 month (3 months prior to the study) Anabolic agents, estrogen, progestogens calcitrol, calcitonin, fluoride, glucocorticoids, growth hormones, parathyroid hormone (PTH) and strontium
Trial design/methodology
Phase	3
Kind of study	Efficacy
Design	Controlled Randomised Blinded Double blind
Purpose of study
commercial product development and/or licensing
Primary outcomes
Efficacy of risedronate compared to placebo in children with OI, measured by the change in lumbar spine bone mineral density (BMD) between baseline value and after 12 months treatment with either risedronate or placebo
Secondary outcomes
Efficacy of risedronate - looking at a variety of percentage changes from baseline in BMD, BMC, Z-scores, fractures and bone markers The safety and tolerability of risedronate, shown by laboratory profiles, baseline bone age and annualised growth velocity from baseline
Summary of study design, objectives, and ongoing research findings
This will be a 1 year, randomised, double-blind, placebo-controlled, multicentre, parallel group study with 2 additional years of open-label treatment. At the end of 1 year of treatment, without the unblinding of individual patients, all patients will take open-label risedronate for the 2 additional years. Approximately 124 patients will be enrolled in this study at 15 - 20 study centres in North America, Australia and Europe Patients will be screened according to the Inclusion and Exclusion Criteria. Medical, surgical and medication histories will be recorded and a physical examination, including Tanner stage, vital signs, body weight and height will be performed. Dual-energy x-ray absorptiometry (DXA) scans of the lumbar spine and total body will be acquired at screening and months 6, 12, 24, and 36, and an x-ray of the hand/wrist will be acquired at months 12, 24, and 36. Clinical laboratory tests (serum chemistry, hematology, thyroid and parathyroid gunction tests, urinalysis and a serum pregnancy test [post menarchal females only]) Satisfactory results for these laboratory tests must be received prior to the patient receiving study drug. Bone biopsies will also be performed at Baseline and Month 12 on all patients who give consent. A whole body skeletal survey will be taken on all patients at Baseline and the Month 12 visit to assess the whole body skeletal status. However, in patients with mild OI the whole body skeletal survey may not be needed if the skeletal status is well known and documented. If the whole body skeletal survey is not obtained, regional radiography may be obtained at the discretion of the Investigator. In cases where x-rays are taken in other clinical settings or hospitals and used as source documentation in this study, the Investigator must obtain duplicate copies of the x-ray. Regardless of whole body skeletal survey, all patients will have lateral spine radiographs completed at screening and on a yearly basis. Peripheral quantitative computed tomography (pQCT) may be measured at Baseline, Months 6, 12, 24, and 36 at study centres that have the capability. This measurement will be exploratory in nature and not a study endpoint. Exploratory analyses may be performed on these data. Sites that perform pQCT will inform their patients and the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) of this additonal procedure and corresponding radiation exposure. A data safety monitoring board (DSMB) will assess all available safety and efficacy data at predefined time points. If the DSMB identifies a potential safety or efficacy concern, it will be discussed with the sponsor, and the sponsor will subsequently discuss with the regulatory agencies.