A Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel Group Study of One-year Duration Followed by 2 Years of Open-label Treatment to Determine the Safety and Efficacy of Orally Administered 2.5 mg or 5.0 mg Daily Risedronate, in Children = 4 to < 16 Years Old with Osteogenesis Imperfecta. - POISE

• Register: EUCTR
• Last refreshed on: 7 October 2014
• Main ID: EUCTR2004-000485-13-BE
• Date of registration: 30/05/2006
• Prospective Registration: Yes
• Primary sponsor: Procter & Gamble Ltd
• Public title: A Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel Group Study of One-year Duration Followed by 2 Years of Open-label Treatment to Determine the Safety and Efficacy of Orally Administered 2.5 mg or 5.0 mg Daily Risedronate, in Children = 4 to < 16 Years Old with Osteogenesis Imperfecta. - POISE
• Scientific title: A Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel Group Study of One-year Duration Followed by 2 Years of Open-label Treatment to Determine the Safety and Efficacy of Orally Administered 2.5 mg or 5.0 mg Daily Risedronate, in Children = 4 to < 16 Years Old with Osteogenesis Imperfecta. - POISE
• Date of first enrolment: 22/08/2006
• Target sample size: 124
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-000485-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: followed by open-label period If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Belgium, Czech Republic, Denmark, Finland, Hungary, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
To be enrolled in this study, a child must meet the following:
a) diagnosed with OI as based on a modified classification scale7,8 (Appendix 1)
b) aged 4 through 15 years (= 4 to < 16), inclusive
c) have an increased risk of fractures as defined by:
• a history of at least 1 radiographically confirmed, non-traumatic or low impact
fracture, plus low BMD (Z-score = -1 at either total body or lumbar spine sites);
or
• very low BMD (Z-score = -2.0 at either total body or lumbar spine sites) with or
without a history of fractures
d) have at least 2 evaluable lumbar spine vertebral bodies (L1-L4), namely without fracture or degenerative disease
e) if female, post-menarche and sexually active, must be willing to agree to use a reliable contraceptive measure for the duration of the study. Acceptable forms of contraception include oral, injected or implanted contraceptives, or intrauterine devices.
f) if female and post-menarche, must have a negative serum and urine pregnancy test at Screening
g) able and willing to participate in the study as evidenced by a parent/legal guardian signing a valid written informed consent and the patient signing an assent (if appropriate).
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
a) body weight < 10 kg
b) history of cancer within the past 5 years
c) untreated rickets within 1 year prior to enrollment
d) history of clinically significant organic or psychiatric disease or findings on physical
examination, which in the opinion of the Investigator, would prevent the patient from
completing the study
e) documented history of an abnormal or allergic reaction to bisphosphonates
f) abuse of alcohol
g) abuse of prescription or illicit drugs
h) history of using any of the following medications, regardless of dose, for at least
1 month, within 3 months of enrollment:
• anabolic agents
• estrogen (except contraceptives)
• progestogens (except contraceptives)
• calcitriol, calcidiol, or alfacalcidol
• calcitonin
• fluoride (except dental health products)
• glucocorticoids (does not include inhaled glucocorticoids)
• growth hormones
• parathyroid hormone (PTH)
• strontium
i) history of using any bisphosphonates within 1 year of enrollment, except for a single dose of oral bisphosphonate, such as risedronate or alendronate
j) osteoporosis, secondary to diseases other than OI or drug therapies
k) clinically significant abnormal laboratory finding at Screening, as follows:
• liver function test (LFT), either AST or ALT > 2 x ULN
• thyroid stimulating hormone (TSH) and PTH outside of the normal reference range
Note: An iPTH level below the lower limit of the normal range may be associated
with calcium supplementation. Therefore, the Investigator and the Medical Monitor
will review the patient's personal data and medical history to confirm or refute that
the low iPTH level is associated with high calcium supplementation
• serum 25(OH) vitamin D < 20 nmol/L (8 ng/mL)
• serum creatinine > 106 µmol/L (1.2 mg/dL)
l) current use of anticonvulsant medication
m) current use of anticoagulant medication
n) participation in another clinical trial within 3 months of enrollment.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Osteogenesis Imperfecta

Intervention(s)

Product Name: risedronate sodium 2.5mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: risedronic acid
CAS Number: 115436-72-1
Current Sponsor code: NE-58095
Concentration unit: mg milligram(s)
Concentration number: 2.5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Risedronate sodium 5mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: risedronic acid
CAS Number: 115436-72-1
Current Sponsor code: NE-58095
Concentration unit: mg milligram(s)
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of this study is to determine the efficacy of risedronate compared to placebo in children = 4 to < 16 years of age with osteogenesis imperfecta (OI) as assessed by % change from Baseline in lumbar spine BMD at Month 12.

Secondary Objective: a) to evaluate the efficacy of risedronate compared to placebo in children = 4 to < 16 year of age with OI as assessed by:
• % change from Baseline in lumbar spine BMD at Month 6
• % change from Baseline in total body BMD
• % change from Baseline in total body and lumbar spine BMC
• change and % change from Baseline in total body and lumbar spine BMD Z score
• % change from Baseline in lumbar spine and total body bone area
• incidence and rate of new vertebral fractures
• incidence and rate of clinical vertebral and non-vertebral fractures
• percent change from Baseline in bone turnover markers
• improvement from Baseline in musculoskeletal pain relief
• improvement from Baseline in Quality of Life (QOL

b) to evaluate the safety and tolerability of risedronate treatment in children = 4 to < 16 year of age with OI as assessed by:
• adverse events
• laboratory profiles including bone biopsy
• change from Baseline in bone age
• annualized growth velocity from Baseline

Primary end point(s): The primary efficacy endpoint is the percent change from Baseline in lumbar spine BMD at Month 12.

Secondary ID(s)

2003100 - HMR4003I/3001

2004-000485-13-FI