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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-020399-41 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Zoledronic acid | Experimental | Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zoledronic acid | Drug | intravenous infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Long-term Safety of Zoledronic Acid for the Treatment of Osteoporotic Children Treated With Glucocorticoids. | 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. | Baseline 1 (Visit 1 of the Core Study) through Month 24 (Visit 15/Final Extension Visit) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. |
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Key Inclusion criteria:
Written informed consent before any study-related procedure.
Group 1:
Group 2:
Key Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Westmead | New South Wales | 2145 | Australia | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17476007 | Background | 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. | |
| 9753709 |
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Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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This was an open label extension to the Core study CZOL446H2337 (NCT00799266), where all patients received zoledronic acid. However, the study groups from the Core study were used to compare the patient populations within this extension phase, who received the same treatment under each particular group.
This study was conducted in 10 centers in 6 countries: Australia (1), Canada (4), Hungary (1), United Kingdom (1), Russian Federation (2), and South Africa (1).
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| ID | Title | Description |
|---|---|---|
| FG000 | Core Treatment Zoledronic Acid | Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid |
| FG001 | Core Treatment: Placebo | Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 18, 2016 | Aug 19, 2019 |
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| Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) |
| 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. | 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. | Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) |
| Mean Change From Baseline 1 (Visit 1 of the Core Study) in Total Body BMC at Month 18 and 24 by Core Treatment Group. | 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. | Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) |
| Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum P1NP at Month 18 and 24 by Core Treatment Group. | 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. | Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) |
| Mean Change From Baseline 1 (Visit 1 of the Core Study) in BSAP at Month 18 and 24 by Core Treatment Group. | 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. | Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) |
| Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum NTX at Month 18 and 24 by Core Treatment Group. | 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. | Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) |
| Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum TRAP-5b at Month 18 and 24 by Core Treatment Group. | 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. | Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) |
| Number of Participants With New Vertebral Fractures During the 12 Month Extension Period by Core Treatment Group. | 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. | Month 24 (Visit 15/Final Extension Visit) |
| Number of Participants With New Morphometric Vertebral Fractures During the 12 Month Extension Period by Core Treatment Group. | 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). | Month 24 (Visit 15/Final Extension Visit) |
| 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. | 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'. | Month 15, Month 18, Month 21, Month 24 |
| Mean Change From Baseline (Core and Extension) in 2nd Metacarpal Cortical Width at Month 24 by Core Treatment Group. | 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. | 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) |
| Vancouver |
| British Columbia |
| V6H 3V4 |
| Canada |
| Novartis Investigative Site | Ottawa | Ontario | K1H 8L1 | Canada |
| Novartis Investigative Site | Montreal | Quebec | H3H 1P3 | Canada |
| Novartis Investigative Site | Montreal | Quebec | H3T 1C5 | Canada |
| Novartis Investigative Site | Budapest | 1085 | Hungary |
| Novartis Investigative Site | Moscow | 119991 | Russia |
| Novartis Investigative Site | Saint Petersburg | 195067 | Russia |
| Novartis Investigative Site | Soweto | Gauteng | 2013 | South Africa |
| Novartis Investigative Site | West Midlands | Birmingham | B4 6NH | United Kingdom |
| Background |
| 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. |
| 10562298 | Background | 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. |
| 11870242 | Background | 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. |
| 17943849 | Background | 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. |
|
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Core Treatment Zoledronic Acid | Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid |
| BG001 | Core Treatment: Placebo | Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age at extension informed consent | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Participants |
| ||||||||||||||||
| Lumbar Spine Bone Mineral Density (BMD) Z-score | Lumbar Spine Bone Mineral Density (BMD) Z-score in the Full Analysis (FAS) population. Extension baseline was defined as the last non-missing measurement on or prior to the date of first study drug infusion in the extension study. Bone mass, as measured by DXA, is reported as BMC (g) or areal BMD (g/cm2). These values are compared with reference values from healthy youth of similar age, sex, and race/ ethnicity to calculate a z score, the number of SDs from the expected mean. A BMC or BMD z score that is >2 SDs below expected (< -2.0) is referred to as "low for age". | Mean | Standard Deviation | Z-score |
| ||||||||||||||
| Lumbar Spine Bone Mineral Content (BMC) | Lumbar Spine Bone Mineral Content (BMC) in the Full Analysis (FAS) population. Extension baseline was defined as the last non-missing measurement on or prior to the date of first study drug infusion in the extension study. | Mean | Standard Deviation | gram (g) |
| ||||||||||||||
| Total body Bone Mineral Content (BMC) | Total body Bone Mineral Content (BMC) in the Full Analysis (FAS) population. Extension baseline was defined as the last non-missing measurement on or prior to the date of first study drug infusion in the extension study. | All patients with non-missing assessment | Mean | Standard Deviation | gram (g) |
| |||||||||||||
| Serum Procollagen type 1 amino-terminal propeptide (P1NP) | Serum Procollagen type 1 amino-terminal propeptide (P1NP) in the Full Analysis (FAS) population. Extension baseline was defined as the last non-missing measurement on or prior to the date of first study drug infusion in the extension study. | Mean | Standard Deviation | nanogram per milliliter (ng/mL) |
| ||||||||||||||
| Bone specific alkaline phosphatase (BSAP) | Serum Bone specific alkaline phosphatase (BSAP) in the Full Analysis (FAS) population. Extension baseline was defined as the last non-missing measurement on or prior to the date of first study drug infusion in the extension study. | Mean | Standard Deviation | nanogram per milliliter (ng/mL) |
| ||||||||||||||
| Serum Cross linked N-telopeptide (NTX) | Serum Cross linked N-telopeptide (NTX) in the Full Analysis (FAS) population. Extension baseline was defined as the last non-missing measurement on or prior to the date of first study drug infusion in the extension study. | Mean | Standard Deviation | nmol BCE/L |
| ||||||||||||||
| Serum Tartrate-resistant acid phosphatase isoform 5b (TRAP-5b) | Serum Tartrate-resistant acid phosphatase isoform 5b (TRAP-5b) in the Full Analysis (FAS) population. Extension baseline was defined as the last non-missing measurement on or prior to the date of first study drug infusion in the extension study. | Mean | Standard Deviation | U/L |
| ||||||||||||||
| Second metacarpal cortical width | Second metacarpal cortical width in the Full Analysis (FAS) population. Metacarpal cortical width of "0" was not included. An analysis of covariance model used with treatment, pooled centers, underlying condition treated with glucocorticoids at baseline value as explanatory variables and pooled centers as random effect. | All patients with non-missing assessment | Mean | Standard Deviation | millimeter (mm) |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Long-term Safety of Zoledronic Acid for the Treatment of Osteoporotic Children Treated With Glucocorticoids. | 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. | The Safety population, which consisted of all patients who had been exposed to at least one infusion of study drug, was considered. | Posted | Count of Participants | Participants | Baseline 1 (Visit 1 of the Core Study) through Month 24 (Visit 15/Final Extension Visit) |
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| Secondary | 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. | 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. | The Full Analysis population, which consisted of all randomized patients who had both Core Baseline and at least one post-baseline lumbar spine BMD Z-score in the Extension study, was considered. | Posted | Least Squares Mean | Standard Error | Z-score | Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) |
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| Secondary | 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. | 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. | The Full Analysis population, which consisted of all randomized patients who had both Core Baseline and at least one post-baseline lumbar spine BMD Z-score in the Extension study, was considered. | Posted | Least Squares Mean | Standard Error | gram | Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) |
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| Secondary | Mean Change From Baseline 1 (Visit 1 of the Core Study) in Total Body BMC at Month 18 and 24 by Core Treatment Group. | 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. | The Full Analysis population, which consisted of all randomized patients who had both Core Baseline and at least one post-baseline lumbar spine BMD Z-score in the Extension study, was considered. | Posted | Least Squares Mean | Standard Error | gram | Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) |
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| Secondary | Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum P1NP at Month 18 and 24 by Core Treatment Group. | 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. | The Full Analysis population, which consisted of all randomized patients who had both Core Baseline and at least one post-baseline lumbar spine BMD Z-score in the Extension study, was considered. | Posted | Least Squares Mean | Standard Error | nanogram per milliliter (ng/mL) | Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) |
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| Secondary | Mean Change From Baseline 1 (Visit 1 of the Core Study) in BSAP at Month 18 and 24 by Core Treatment Group. | 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. | The Full Analysis population, which consisted of all randomized patients who had both Core Baseline and at least one post-baseline lumbar spine BMD Z-score in the Extension study, was considered. | Posted | Least Squares Mean | Standard Error | nanogram per milliliter (ng/mL) | Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) |
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| Secondary | Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum NTX at Month 18 and 24 by Core Treatment Group. | 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. | The Full Analysis population, which consisted of all randomized patients who had both Core Baseline and at least one post-baseline lumbar spine BMD Z-score in the Extension study, was considered. | Posted | Least Squares Mean | Standard Error | nmol BCE/L | Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) |
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| Secondary | Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum TRAP-5b at Month 18 and 24 by Core Treatment Group. | 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. | The Full Analysis population, which consisted of all randomized patients who had both Core Baseline and at least one post-baseline lumbar spine BMD Z-score in the Extension study, was considered. | Posted | Least Squares Mean | Standard Error | U/L | Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit) |
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| Secondary | Number of Participants With New Vertebral Fractures During the 12 Month Extension Period by Core Treatment Group. | 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. | The Full Analysis population, which consisted of all randomized patients who had both Core Baseline and at least one post-baseline lumbar spine BMD Z-score in the Extension study, was considered. | Posted | Count of Participants | Participants | Month 24 (Visit 15/Final Extension Visit) |
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| Secondary | Number of Participants With New Morphometric Vertebral Fractures During the 12 Month Extension Period by Core Treatment Group. | 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). | The Full Analysis population, which consisted of all randomized patients who had both Core Baseline and at least one post-baseline lumbar spine BMD Z-score in the Extension study, was considered. | Posted | Count of Participants | Participants | Month 24 (Visit 15/Final Extension Visit) |
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| Secondary | 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. | 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'. | The Full Analysis population, which consisted of all randomized patients who had both Core Baseline and at least one post-baseline lumbar spine BMD Z-score in the Extension study, was considered. | Posted | Number | Percentage of Patients | Month 15, Month 18, Month 21, Month 24 |
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| Secondary | Mean Change From Baseline (Core and Extension) in 2nd Metacarpal Cortical Width at Month 24 by Core Treatment Group. | 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. | The Full Analysis population, which consisted of all randomized patients who had both Core Baseline and at least one post-baseline lumbar spine BMD Z-score in the Extension study, was considered. | Posted | Least Squares Mean | Standard Error | millimeter (mm) | 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) |
|
Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 13 months.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Core Treatment Zoledronic Acid | Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid | 0 | 10 | 3 | 10 | 7 | 10 |
| EG001 | Core Treatment Placebo | Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid | 0 | 15 | 0 | 15 | 12 | 15 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Postictal state | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Status epilepticus | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Suicide attempt | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tachycardia | Cardiac disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Adrenal insufficiency | Endocrine disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Ocular hyperaemia | Eye disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Infusion site pain | General disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
| |
| Candida infection | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
| |
| Herpes virus infection | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
| |
| Joint dislocation | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
| |
| Liver function test increased | Investigations | MedDRA (21.0) | Systematic Assessment |
| |
| Therapeutic agent urine positive | Investigations | MedDRA (21.0) | Systematic Assessment |
| |
| Vitamin B12 decreased | Investigations | MedDRA (21.0) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Insulin resistance | Metabolism and nutrition disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Scoliosis | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Trismus | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (21.0) | Systematic Assessment |
| |
| Epileptic aura | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Postictal state | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Sleep disorder | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Suicide attempt | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Butterfly rash | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Ingrowing nail | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Skin discolouration | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Tooth extraction | Surgical and medical procedures | MedDRA (21.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Secondary hypertension | Vascular disorders | MedDRA (21.0) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | Novartis.email@novartis.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 4, 2018 | Aug 19, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D010024 | Osteoporosis |
| D020388 | Muscular Dystrophy, Duchenne |
| ID | Term |
|---|---|
| D001851 | Bone Diseases, Metabolic |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D009136 | Muscular Dystrophies |
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077211 | Zoledronic Acid |
| ID | Term |
|---|---|
| D004164 | Diphosphonates |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
|
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