Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
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
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01197300
Registration number
NCT01197300
Ethics application status
Date submitted
7/09/2010
Date registered
9/09/2010
Date last updated
20/09/2019
Titles & IDs
Public title
1 Year Open-label Extension to CZOL446H2337 Safety and Efficacy Trial of Zoledronic Acid Twice Yearly in Osteoporotic Children Treated With Glucocorticoids
Query!
Scientific title
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
Query!
Secondary ID [1]
0
0
2010-020399-41
Query!
Secondary ID [2]
0
0
CZOL446H2337E1
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Osteoporosis
0
0
Query!
Condition category
Condition code
Musculoskeletal
0
0
0
0
Query!
Osteoporosis
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - Zoledronic acid
Experimental: Zoledronic acid - Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
Treatment: Drugs: Zoledronic acid
intravenous infusion
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Long-term Safety of Zoledronic Acid for the Treatment of Osteoporotic Children Treated With Glucocorticoids.
Query!
Assessment method [1]
0
0
Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) 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 through the monitoring of relevant clinical and laboratory safety parameters.
Query!
Timepoint [1]
0
0
Baseline 1 (Visit 1 of the Core Study) through Month 24 (Visit 15/Final Extension Visit)
Query!
Secondary outcome [1]
0
0
Mean Change From Baseline 1 (Visit 1 of the Core Study) in Lumbar Spine Bone Mineral Density (BMD) Z-score at Month 18 and 24 by Core Treatment Group.
Query!
Assessment method [1]
0
0
Lumbar Spine Bone Mineral Density (BMD) Z-score was determined by the central imaging vendor at the final visit of Core study (Visit 8) or at 1st infusion visit (Visit 9), and thereafter at Visit 12 (Month 18) and Visit 15 (Month 24) (final Extension Study visit/EOS) of Extension study. The methods to be used to measure Lumbar Spine BMD Z-score were described in the respective DXA Manuals provided by central imaging vendor. Positive changes from Core baseline indicated an improvement in condition.
Query!
Timepoint [1]
0
0
Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)
Query!
Secondary outcome [2]
0
0
Mean Change From Baseline 1 (Visit 1 of the Core Study) in Lumbar Spine Bone Mineral Content (BMC) at Month 18 and 24 by Core Treatment Group.
Query!
Assessment method [2]
0
0
Lumbar Spine Bone Mineral Content (BMC) was determined by the central imaging vendor at the final visit of Core study (Visit 8) or at 1st infusion visit (Visit 9), and thereafter at Visit 12 (Month 18) and Visit 15 (Month 24) (final Extension Study visit/EOS) of Extension study. The methods to be used to measure BMC were described in the respective DXA Manuals. Positive changes from Core baseline indicated an improvement in condition.
Query!
Timepoint [2]
0
0
Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)
Query!
Secondary outcome [3]
0
0
Mean Change From Baseline 1 (Visit 1 of the Core Study) in Total Body BMC at Month 18 and 24 by Core Treatment Group.
Query!
Assessment method [3]
0
0
Total body BMC were determined by the central imaging vendor at the final visit of Core study (Visit 8) or at 1st infusion visit (Visit 9), and thereafter at Visit 12 (Month 18) and Visit 15 (Month 24) (final Extension Study visit/EOS) of Extension study. The methods to be used to measure BMC were described in the respective DXA Manuals. Positive changes from Core baseline indicated an improvement in condition.
Query!
Timepoint [3]
0
0
Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)
Query!
Secondary outcome [4]
0
0
Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum P1NP at Month 18 and 24 by Core Treatment Group.
Query!
Assessment method [4]
0
0
Serum Procollagen type 1 amino-terminal propeptide (P1NP) was collected at the final visit Core study at Visit 8, or at 1st infusion visit (Visit 9), and thereafter at Visit 12 (Month 18) and Visit 15 (Month 24) (final Extension study Visit/EOS) of Extension study according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory. Decrease or negative changes from Core baseline indicated a pharmacological response to therapy.
Query!
Timepoint [4]
0
0
Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)
Query!
Secondary outcome [5]
0
0
Mean Change From Baseline 1 (Visit 1 of the Core Study) in BSAP at Month 18 and 24 by Core Treatment Group.
Query!
Assessment method [5]
0
0
Bone specific alkaline phosphatase (BSAP) was collected at the final visit Core study at Visit 8, or at 1st infusion visit (Visit 9), and thereafter at Visit 12 (Month 18) and Visit 15 (Month 24) (final Extension study Visit/EOS) of Extension study according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory. Decrease or negative changes from Core baseline indicated a pharmacological response to therapy.
Query!
Timepoint [5]
0
0
Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)
Query!
Secondary outcome [6]
0
0
Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum NTX at Month 18 and 24 by Core Treatment Group.
Query!
Assessment method [6]
0
0
Serum Cross linked N-telopeptide (NTX) was collected at the final visit Core study at Visit 8, or at 1st infusion visit (Visit 9), and thereafter at Visit 12 (Month 18) and Visit 15 (Month 24) (final Extension study Visit/EOS) of Extension study according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory. Decrease or negative changes from Core baseline indicated a pharmacological response to therapy.
Query!
Timepoint [6]
0
0
Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)
Query!
Secondary outcome [7]
0
0
Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum TRAP-5b at Month 18 and 24 by Core Treatment Group.
Query!
Assessment method [7]
0
0
Serum Tartrate-resistant acid phosphatase isoform 5b (TRAP 5b) were collected at the final visit Core study at Visit 8, or at 1st infusion visit (Visit 9), and thereafter at Visit 12 (Month 18) and Visit 15 (Month 24) (final Extension study Visit/EOS) of Extension study according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory. Decrease or negative changes from Core baseline indicated a pharmacological response to therapy. Decrease or negative changes from Core baseline indicated a pharmacological response to therapy.
Query!
Timepoint [7]
0
0
Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)
Query!
Secondary outcome [8]
0
0
Number of Participants With New Vertebral Fractures During the 12 Month Extension Period by Core Treatment Group.
Query!
Assessment method [8]
0
0
New vertebral fractures are defined as fractures of Genant grade 1 or higher that occur at lumbar or thoracic spine from first extension dose infusion to the end of the study in a previously normal vertebra.
Query!
Timepoint [8]
0
0
Month 24 (Visit 15/Final Extension Visit)
Query!
Secondary outcome [9]
0
0
Number of Participants With New Morphometric Vertebral Fractures During the 12 Month Extension Period by Core Treatment Group.
Query!
Assessment method [9]
0
0
Vertebral morphometry (or concave index) was calculated using the average ratio between mid-height and posterior height from L1 to L4 and performed by a central reader. A new morphometric vertebral fractures during the 12 month Extension Period was defined as a morphometric vertebral fracture present at Month 24 X-ray which was not present at the Extension Baseline (Baseline 2).
Query!
Timepoint [9]
0
0
Month 24 (Visit 15/Final Extension Visit)
Query!
Secondary outcome [10]
0
0
Percentage of Patients With Reduction in Pain From Baseline 1 (Visit 1 of the Core Study) at Month 15, 18, 21 and 24 by Core Treatment Group.
Query!
Assessment method [10]
0
0
Pain was evaluated at each visit (at office and telephone visit) at the final visit of the Core study and first visit of the Extension study (Visit 9), Visits 11 (Month 15), 12 (Month 18), 14 (Month 21) and 15 (Month 24) using the Faces Pain Scale-Revised (FPS-R). Children were selecting the face that best fits their pain. The pain score ranged from 0 (No Pain) to 10 (Very Much Pain). The reduction in pain from Core baseline by visit was evaluated based on whether or not patients had a decrease in their FPS-R from baseline. If pain remained the same or worsened from baseline a patient was classified as '0' and if the pain scale decreased then the patient was classified as '1'.
Query!
Timepoint [10]
0
0
Month 15, Month 18, Month 21, Month 24
Query!
Secondary outcome [11]
0
0
Mean Change From Baseline (Core and Extension) in 2nd Metacarpal Cortical Width at Month 24 by Core Treatment Group.
Query!
Assessment method [11]
0
0
Left postero-anterior (PA) hand/wrist X-ray were taken at the final visit of Core study and at Visit 15/EOS (Month 24) to assess bone age. The change in 2nd metacarpal cortical width at Month 24 relative to the respective Baseline was calculated. If a fracture of the left upper extremity precluded radiographic imaging, (or precluded this X-ray in the Core study) then the right hand was evaluated for this purpose. In this case, an image of the right hand was carried out at both Visit 8 and at Visit 15/EOS (Month 24). The information was used in the assessment of bone density.
Query!
Timepoint [11]
0
0
Baseline 1 (Visit 1 of the Core Study) and Baseline 2 (Visit 9 of the Extension Study) through Month 24 (Visit 15/Final Extension Visit)
Query!
Eligibility
Key inclusion criteria
Key Inclusion criteria:
Written informed consent before any study-related procedure.
Group 1:
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.
Group 2:
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
Query!
Minimum age
5
Years
Query!
Query!
Maximum age
19
Years
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
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.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
N/A
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Single group
Query!
Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
25/10/2010
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
27/02/2019
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
25
Query!
Recruitment in Australia
Recruitment state(s)
NSW
Query!
Recruitment hospital [1]
0
0
Novartis Investigative Site - Westmead
Query!
Recruitment postcode(s) [1]
0
0
2145 - Westmead
Query!
Recruitment outside Australia
Country [1]
0
0
Canada
Query!
State/province [1]
0
0
British Columbia
Query!
Country [2]
0
0
Canada
Query!
State/province [2]
0
0
Ontario
Query!
Country [3]
0
0
Canada
Query!
State/province [3]
0
0
Quebec
Query!
Country [4]
0
0
Hungary
Query!
State/province [4]
0
0
Budapest
Query!
Country [5]
0
0
Russian Federation
Query!
State/province [5]
0
0
Moscow
Query!
Country [6]
0
0
Russian Federation
Query!
State/province [6]
0
0
Saint Petersburg
Query!
Country [7]
0
0
South Africa
Query!
State/province [7]
0
0
Gauteng
Query!
Country [8]
0
0
United Kingdom
Query!
State/province [8]
0
0
Birmingham
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Novartis Pharmaceuticals
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
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.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT01197300
Query!
Trial related presentations / publications
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. doi: 10.1056/NEJMoa067312.
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. doi: 10.1056/NEJM199810013391402.
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. doi: 10.1172/JCI6800.
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. doi: 10.1056/NEJMoa011807.
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;2007(4):CD005324. doi: 10.1002/14651858.CD005324.pub2.
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Novartis Pharmaceuticals
Query!
Address
0
0
Novartis Pharmaceuticals
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01197300
Download to PDF