1 Year Open-label Extension to CZOL446H2337 Safety and Efficacy Trial of Zoledronic Acid Twice Yearly in Osteoporotic Children Treated With Glucocorticoids
- Registration Number
- NCT01197300
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 25
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Zoledronic acid Zoledronic acid Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
- Primary Outcome Measures
Name Time Method Long-term Safety of Zoledronic Acid for the Treatment of Osteoporotic Children Treated With Glucocorticoids. Baseline 1 (Visit 1 of the Core Study) through Month 24 (Visit 15/Final Extension Visit) 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.
- Secondary Outcome Measures
Name Time Method 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. Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) 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.
Mean Change From Baseline 1 (Visit 1 of the Core Study) in BSAP at Month 18 and 24 by Core Treatment Group. Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) 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.
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. Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) 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.
Mean Change From Baseline 1 (Visit 1 of the Core Study) in Total Body BMC at Month 18 and 24 by Core Treatment Group. Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) 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.
Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum NTX at Month 18 and 24 by Core Treatment Group. Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) 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.
Mean Change From Baseline (Core and Extension) in 2nd Metacarpal Cortical Width at Month 24 by Core Treatment Group. 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) 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.
Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum P1NP at Month 18 and 24 by Core Treatment Group. Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) 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.
Number of Participants With New Vertebral Fractures During the 12 Month Extension Period by Core Treatment Group. Month 24 (Visit 15/Final Extension Visit) 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.
Number of Participants With New Morphometric Vertebral Fractures During the 12 Month Extension Period by Core Treatment Group. Month 24 (Visit 15/Final Extension Visit) 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).
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. Month 15, Month 18, Month 21, Month 24 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'.
Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum TRAP-5b at Month 18 and 24 by Core Treatment Group. Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) 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.
Trial Locations
- Locations (1)
Novartis Investigative Site
🇬🇧West Midlands, Birmingham, United Kingdom