Osteoporosis Clinical Trial
A 1-year, Multicenter, Open-label Extension to CZOL446H2337 to Evaluate Safety and Efficacy of Zoledronic Acid Twice Yearly in Osteoporotic Children Treated With Glucocorticoids
|Other study ID #||CZOL446H2337E1|
|First received||September 7, 2010|
|Last updated||October 13, 2017|
|Start date||October 25, 2010|
|Est. completion date||April 15, 2019|
|Verified date||October 2017|
|Is FDA regulated||No|
This 1-year open-label extension to CZOL446H2337 is designed to evaluate the safety and efficacy of zoledronic acid twice yearly in osteoporotic children treated with glucocorticoids.
|Est. completion date||April 15, 2019|
|Est. primary completion date||April 15, 2019|
|Accepts healthy volunteers||No|
|Age group||5 Years to 19 Years|
Key Inclusion criteria:
Written informed consent before any study-related procedure.
1. Children and adolescents, male or female, 6-19 years old, who met the inclusion criteria for entry into the Core study and who took at least one dose of study drug and have completed Visit 8 of the CZOL446H2337 Core study.
2. Patient must be enrolled into the extension at Visit 9 up to 10 months after Visit 5 (month 6) of the Core study.
3. Patients who followed the regimen of calcium and vitamin D intake as required in the Core study through diet or supplementation.
1. Children and adolescents, male or female, 5 - 17 years old who met the inclusion criteria for entry into the Core study but were not enrolled because of clinically significant back pain from vertebral fracture and the preexisting clinical care at the Investigator site is to treat this type of patient with a bisphosphonate.
2. Confirmed diagnosis of non-malignant conditions (including but not limited to rheumatic conditions, inflammatory bowel disease, Duchenne muscular dystrophy, nephrotic syndrome), treated with systemic glucocorticoids (i.v. or oral) within the 12 months preceding enrollment in the study (any duration)
3. LS-BMD Z-score of -0.5 or worse confirmed by the central imaging vendor
4. Evidence of at least 1 vertebral compression fracture (at least Genant Grade 1 vertebral compression or radiographic signs of vertebral compression) confirmed by central reading OR At least one lower OR 2 upper extremity long-bone, low-trauma, fracture which occurred sometime within the 2 years or preceding enrollment in the study, confirmed by radiological report. (*Low trauma fracture is defined as falling from standing height or less).
Key Exclusion criteria:
1. Major protocol violation in the Core Study (Group 1 only).
2. Prior use of bisphosphonates (Group 2 only) or sodium fluoride (doses for osteoporosis not for dental hygiene).
3. Hypocalcemia and hypophosphatemia: any value (age-matched) below the normal range at Visit 8 or 8A.
4. Vitamin D deficiency (serum 25-hydroxy vitamin D concentrations of < 20 ng/mL or < 50 nmol/L) at Visit 8 (Group 1) or Visit 8A (Group 2).
5. Renal impairment defined as an estimated glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 at screening based on the Schwartz formula at Visit 8 or 8 A; a serum creatinine above the normal range at Visit 9 (Group 1) or an increase between Visit 8A and Visit 9 greater than 0.5 mg/dL (44.2 µmol/L) for Group 2.
6. Female patients of child bearing potential are eligible only if they are not pregnant/non-lactating. Females of child bearing potential must be practicing a medically acceptable form of birth control for greater than 2 months prior to screening visit and consent to pregnancy tests during the study.
|Australia||Novartis Investigative Site||Westmead||New South Wales|
|Canada||Novartis Investigative Site||Montreal||Quebec|
|Canada||Novartis Investigative Site||Ottawa||Ontario|
|Canada||Novartis Investigative Site||Vancouver||British Columbia|
|South Africa||Novartis Investigative Site||Soweto||Gauteng|
|Turkey||Novartis Investigative Site||Izmir|
|Turkey||Novartis Investigative Site||Pendik|
|United Kingdom||Novartis Investigative Site||Manchester|
|United Kingdom||Novartis Investigative Site||Sutton||Surrey|
|United Kingdom||Novartis Investigative Site||West Midlands||Birmingham|
Australia, Canada, South Africa, Turkey, United Kingdom,
Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR; HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007 May 3;356(18):1809-22. — View Citation
Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R. Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med. 1998 Oct 1;339(14):947-52. — View Citation
Plotkin LI, Weinstein RS, Parfitt AM, Roberson PK, Manolagas SC, Bellido T. Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest. 1999 Nov;104(10):1363-74. — View Citation
Reid IR, Brown JP, Burckhardt P, Horowitz Z, Richardson P, Trechsel U, Widmer A, Devogelaer JP, Kaufman JM, Jaeger P, Body JJ, Brandi ML, Broell J, Di Micco R, Genazzani AR, Felsenberg D, Happ J, Hooper MJ, Ittner J, Leb G, Mallmin H, Murray T, Ortolani S, Rubinacci A, Saaf M, Samsioe G, Verbruggen L, Meunier PJ. Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med. 2002 Feb 28;346(9):653-61. — View Citation
Ward L, Tricco AC, Phuong P, Cranney A, Barrowman N, Gaboury I, Rauch F, Tugwell P, Moher D. Bisphosphonate therapy for children and adolescents with secondary osteoporosis. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005324. Review. — View Citation
|Type||Measure||Description||Time frame||Safety issue|
|Other||Change from (Extension) baseline 2 (Visit 8A) in LS-BMD Z-score at Month 6 and 12.||Month 6 and 12|
|Other||Change from (Extension) baseline 2 (Visit 8A) in LS and total body BMC at Month 6 and 12.||Month 6 and 12|
|Other||Relative change from (Extension) Baseline 2 in serum N-terminal propeptide type I collagen (P1NP), cross linked N-telopeptide (NTX), bone specific alkaline phosphatase (BSAP) and tartrate-resistant acid phosphatase isoform 5b (TRAP-5b) at Month 6 and 12.||Month 6 and 12|
|Other||Proportion of patients with new clinical vertebral fractures during the 12 month period.||Month 12|
|Other||Proportion of patients with new morphometric vertebral fracture during the 12 month period.||Month 12|
|Other||Change from (Extension) baseline 2 in pain using the Faces Pain Scale-Revised (FPS-R) at Month 3, 6, 9 and 12.||Month 3, 6, 9 and 12|
|Other||Change from (Extension) baseline 2 in bone age and 2nd metacarpal cortical width at Month 12.||Month 12|
|Other||To demonstrate that zoledronic acid is safe for the treatment of osteoporotic children (with symptomatic vertebral fracture) treated with glucocorticoids, through the monitoring of relevant clinical and laboratory safety parameters.||Until 30 days after the patient has stopped study participation|
|Primary||Safety of zoledronic acid for the treatment of osteoporotic children treated with glucocorticoids.||To demonstrate that zoledronic acid given long-term, over an additional 12 months from the Core study (CZOL446H2337), is safe for the treatment of osteoporotic children treated with glucocorticoids (Group 1 only)||12 months|
|Secondary||Change from baseline (Visit 1 of the Core study) in LS BMD Z-score at Month 18 and 24 by core treatment group||Month 18 & 24|
|Secondary||Change from baseline 1 (Visit 1 of the Core study) in LS and total body BMC at Month 18 and 24 by core treatment group.||Month 18 & 24|
|Secondary||Change from baseline 1 in serum N-terminal propeptide type I collagen (P1NP), cross linked N-telopeptide (NTX), bone specific alkaline phosphatase (BSAP) and tartrate-resistant acid phosphatase isoform 5b (TRAP-5b) by core treatment group.||Month 18 & 24|
|Secondary||Proportion of patients with new clinical vertebral fractures during the 12 month extension period by core treatment group.||Month 12|
|Secondary||Proportion of patients with new morphometric vertebral fracture during the 12 month extension period by core treatment group.||Month 12|
|Secondary||Change from baseline 1 (Visit 1 of the Core study) in pain using the Faces Pain Scale-Revised (FPS-R) at Month 15, 18, 21 and 24 by core treatment group.||Month 15, 18, 21 and 24|
|Secondary||Change from baseline 1 (Visit 1 of the Core study) in 2nd metacarpal cortical width at month 24 by core treatment group.||Month 24|
|Secondary||Change from baseline 1(Visit 1 of the Core study) in bone age and 2nd metacarpal cortical width at month 24 by core treatment group.||Month 24|
|Not yet recruiting||
|Not yet recruiting||
|Active, not recruiting||