Trial Outcomes & Findings for 1 Year Open-label Extension to CZOL446H2337 Safety and Efficacy Trial of Zoledronic Acid Twice Yearly in Osteoporotic Children Treated With Glucocorticoids (NCT NCT01197300)
NCT ID: NCT01197300
Last Updated: 2019-09-20
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
25 participants
Primary outcome timeframe
Baseline 1 (Visit 1 of the Core Study) through Month 24 (Visit 15/Final Extension Visit)
Results posted on
2019-09-20
Participant Flow
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).
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.
Participant milestones
| Measure |
Core Treatment Zoledronic Acid
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
Core Treatment: Placebo
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
15
|
|
Overall Study
COMPLETED
|
10
|
13
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
Core Treatment Zoledronic Acid
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
Core Treatment: Placebo
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Protocol Violation
|
0
|
1
|
Baseline Characteristics
All patients with non-missing assessment
Baseline characteristics by cohort
| Measure |
Core Treatment Zoledronic Acid
n=10 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
Core Treatment: Placebo
n=15 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
Total
n=25 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
15.3 Years
STANDARD_DEVIATION 2.58 • n=10 Participants
|
13.2 Years
STANDARD_DEVIATION 3.38 • n=15 Participants
|
14.0 Years
STANDARD_DEVIATION 3.21 • n=25 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=10 Participants
|
5 Participants
n=15 Participants
|
8 Participants
n=25 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=10 Participants
|
10 Participants
n=15 Participants
|
17 Participants
n=25 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
8 Participants
n=10 Participants
|
13 Participants
n=15 Participants
|
21 Participants
n=25 Participants
|
|
Race/Ethnicity, Customized
Black
|
2 Participants
n=10 Participants
|
1 Participants
n=15 Participants
|
3 Participants
n=25 Participants
|
|
Race/Ethnicity, Customized
Native American
|
0 Participants
n=10 Participants
|
1 Participants
n=15 Participants
|
1 Participants
n=25 Participants
|
|
Lumbar Spine Bone Mineral Density (BMD) Z-score
|
-1.568 Z-score
STANDARD_DEVIATION 1.0196 • n=10 Participants
|
-2.291 Z-score
STANDARD_DEVIATION 1.0712 • n=15 Participants
|
-2.002 Z-score
STANDARD_DEVIATION 1.0909 • n=25 Participants
|
|
Lumbar Spine Bone Mineral Content (BMC)
|
42.106 gram (g)
STANDARD_DEVIATION 15.6967 • n=10 Participants
|
25.890 gram (g)
STANDARD_DEVIATION 7.3089 • n=15 Participants
|
32.376 gram (g)
STANDARD_DEVIATION 13.7584 • n=25 Participants
|
|
Total body Bone Mineral Content (BMC)
|
1976.698 gram (g)
STANDARD_DEVIATION 636.2144 • n=9 Participants • All patients with non-missing assessment
|
1144.613 gram (g)
STANDARD_DEVIATION 253.5405 • n=13 Participants • All patients with non-missing assessment
|
1485.011 gram (g)
STANDARD_DEVIATION 605.2026 • n=22 Participants • All patients with non-missing assessment
|
|
Serum Procollagen type 1 amino-terminal propeptide (P1NP)
|
141.300 nanogram per milliliter (ng/mL)
STANDARD_DEVIATION 100.8111 • n=10 Participants
|
523.933 nanogram per milliliter (ng/mL)
STANDARD_DEVIATION 475.5547 • n=15 Participants
|
370.880 nanogram per milliliter (ng/mL)
STANDARD_DEVIATION 415.1329 • n=25 Participants
|
|
Bone specific alkaline phosphatase (BSAP)
|
25.841 nanogram per milliliter (ng/mL)
STANDARD_DEVIATION 14.8595 • n=10 Participants
|
49.737 nanogram per milliliter (ng/mL)
STANDARD_DEVIATION 36.6580 • n=15 Participants
|
40.179 nanogram per milliliter (ng/mL)
STANDARD_DEVIATION 31.7718 • n=25 Participants
|
|
Serum Cross linked N-telopeptide (NTX)
|
19.092 nmol BCE/L
STANDARD_DEVIATION 8.3760 • n=10 Participants
|
42.217 nmol BCE/L
STANDARD_DEVIATION 25.2275 • n=15 Participants
|
35.967 nmol BCE/L
STANDARD_DEVIATION 24.3991 • n=25 Participants
|
|
Serum Tartrate-resistant acid phosphatase isoform 5b (TRAP-5b)
|
5.338 U/L
STANDARD_DEVIATION 2.5097 • n=10 Participants
|
8.636 U/L
STANDARD_DEVIATION 5.2925 • n=15 Participants
|
7.316 U/L
STANDARD_DEVIATION 4.6283 • n=25 Participants
|
|
Second metacarpal cortical width
|
0.45 millimeter (mm)
STANDARD_DEVIATION 0.207 • n=8 Participants • All patients with non-missing assessment
|
0.38 millimeter (mm)
STANDARD_DEVIATION 0.163 • n=13 Participants • All patients with non-missing assessment
|
0.41 millimeter (mm)
STANDARD_DEVIATION 0.179 • n=21 Participants • All patients with non-missing assessment
|
PRIMARY outcome
Timeframe: Baseline 1 (Visit 1 of the Core Study) through Month 24 (Visit 15/Final Extension Visit)Population: The Safety population, which consisted of all patients who had been exposed to at least one infusion of study drug, was considered.
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.
Outcome measures
| Measure |
Core Treatment Zoledronic Acid
n=10 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
Core Treatment: Placebo
n=15 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
|---|---|---|
|
Long-term Safety of Zoledronic Acid for the Treatment of Osteoporotic Children Treated With Glucocorticoids.
On-treatment Adverse Events (AEs)
|
7 Participants
|
12 Participants
|
|
Long-term Safety of Zoledronic Acid for the Treatment of Osteoporotic Children Treated With Glucocorticoids.
On-treatment Serious Adverse Events (SAEs)
|
3 Participants
|
0 Participants
|
|
Long-term Safety of Zoledronic Acid for the Treatment of Osteoporotic Children Treated With Glucocorticoids.
On-treatment Deaths
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)Population: 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.
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.
Outcome measures
| Measure |
Core Treatment Zoledronic Acid
n=10 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
Core Treatment: Placebo
n=15 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
|---|---|---|
|
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 BMD Z-score Change at Month 18
|
-40.648 Z-score
Standard Error 14.1205
|
-44.348 Z-score
Standard Error 14.0348
|
|
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 BMD Z-score Change at Month 24
|
-46.161 Z-score
Standard Error 12.4486
|
-67.913 Z-score
Standard Error 12.1722
|
SECONDARY outcome
Timeframe: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)Population: 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.
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.
Outcome measures
| Measure |
Core Treatment Zoledronic Acid
n=10 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
Core Treatment: Placebo
n=15 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
|---|---|---|
|
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 BMC Change at Month 18
|
12.293 gram
Standard Error 1.7749
|
9.933 gram
Standard Error 1.6717
|
|
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 BMC Change at Month 24
|
15.845 gram
Standard Error 2.2217
|
14.666 gram
Standard Error 2.0500
|
SECONDARY outcome
Timeframe: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)Population: 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.
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.
Outcome measures
| Measure |
Core Treatment Zoledronic Acid
n=10 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
Core Treatment: Placebo
n=15 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
|---|---|---|
|
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 Change at Month 18
|
387.721 gram
Standard Error 87396.2756
|
266.592 gram
Standard Error 87396.2698
|
|
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 Change at Month 24
|
496.997 gram
Standard Error 120.9281
|
431.323 gram
Standard Error 123.5462
|
SECONDARY outcome
Timeframe: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)Population: 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.
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.
Outcome measures
| Measure |
Core Treatment Zoledronic Acid
n=10 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
Core Treatment: Placebo
n=15 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
|---|---|---|
|
Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum P1NP at Month 18 and 24 by Core Treatment Group.
Serum P1NP Change at Month 18
|
-169.837 nanogram per milliliter (ng/mL)
Standard Error 86.8640
|
-22.157 nanogram per milliliter (ng/mL)
Standard Error 82.6761
|
|
Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum P1NP at Month 18 and 24 by Core Treatment Group.
Serum P1NP Change at Month 24
|
-228.068 nanogram per milliliter (ng/mL)
Standard Error 54.1402
|
-95.631 nanogram per milliliter (ng/mL)
Standard Error 53.0765
|
SECONDARY outcome
Timeframe: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)Population: 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.
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.
Outcome measures
| Measure |
Core Treatment Zoledronic Acid
n=10 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
Core Treatment: Placebo
n=15 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
|---|---|---|
|
Mean Change From Baseline 1 (Visit 1 of the Core Study) in BSAP at Month 18 and 24 by Core Treatment Group.
BSAP Change at Month 18
|
-13.716 nanogram per milliliter (ng/mL)
Standard Error 8.5909
|
3.975 nanogram per milliliter (ng/mL)
Standard Error 8.0523
|
|
Mean Change From Baseline 1 (Visit 1 of the Core Study) in BSAP at Month 18 and 24 by Core Treatment Group.
BSAP Change at Month 24
|
-9.675 nanogram per milliliter (ng/mL)
Standard Error 6.4159
|
-6.013 nanogram per milliliter (ng/mL)
Standard Error 5.9316
|
SECONDARY outcome
Timeframe: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)Population: 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.
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.
Outcome measures
| Measure |
Core Treatment Zoledronic Acid
n=10 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
Core Treatment: Placebo
n=15 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
|---|---|---|
|
Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum NTX at Month 18 and 24 by Core Treatment Group.
Serum NTX Change at Month 18
|
-17.577 nmol BCE/L
Standard Error 168.8975
|
-12.916 nmol BCE/L
Standard Error 168.8965
|
|
Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum NTX at Month 18 and 24 by Core Treatment Group.
Serum NTX Change at Month 24
|
-17.450 nmol BCE/L
Standard Error 2.3585
|
-14.891 nmol BCE/L
Standard Error 2.0590
|
SECONDARY outcome
Timeframe: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)Population: 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.
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.
Outcome measures
| Measure |
Core Treatment Zoledronic Acid
n=10 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
Core Treatment: Placebo
n=15 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
|---|---|---|
|
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 TRAP-5b Change at Month 18
|
-2.661 U/L
Standard Error 0.8126
|
-1.179 U/L
Standard Error 0.7725
|
|
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 TRAP-5b Change at Month 24
|
-2.670 U/L
Standard Error 0.7158
|
-2.260 U/L
Standard Error 0.6701
|
SECONDARY outcome
Timeframe: Month 24 (Visit 15/Final Extension Visit)Population: 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.
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.
Outcome measures
| Measure |
Core Treatment Zoledronic Acid
n=10 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
Core Treatment: Placebo
n=15 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
|---|---|---|
|
Number of Participants With New Vertebral Fractures During the 12 Month Extension Period by Core Treatment Group.
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Month 24 (Visit 15/Final Extension Visit)Population: 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.
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).
Outcome measures
| Measure |
Core Treatment Zoledronic Acid
n=10 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
Core Treatment: Placebo
n=15 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
|---|---|---|
|
Number of Participants With New Morphometric Vertebral Fractures During the 12 Month Extension Period by Core Treatment Group.
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Month 15, Month 18, Month 21, Month 24Population: 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.
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'.
Outcome measures
| Measure |
Core Treatment Zoledronic Acid
n=10 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
Core Treatment: Placebo
n=15 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
|---|---|---|
|
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.
Reduction in Pain at Month 15
|
55.6 Percentage of Patients
|
46.2 Percentage of Patients
|
|
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.
Reduction in Pain at Month 18
|
30.0 Percentage of Patients
|
50.0 Percentage of Patients
|
|
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.
Reduction in Pain at Month 21
|
30.0 Percentage of Patients
|
50.0 Percentage of Patients
|
|
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.
Reduction in Pain at Month 24
|
30.0 Percentage of Patients
|
38.5 Percentage of Patients
|
SECONDARY outcome
Timeframe: 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)Population: 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.
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.
Outcome measures
| Measure |
Core Treatment Zoledronic Acid
n=10 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
Core Treatment: Placebo
n=15 Participants
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
|---|---|---|
|
Mean Change From Baseline (Core and Extension) in 2nd Metacarpal Cortical Width at Month 24 by Core Treatment Group.
2nd metacarpal cortical width change from BL1
|
-0.04 millimeter (mm)
Standard Error 0.068
|
-0.03 millimeter (mm)
Standard Error 0.054
|
|
Mean Change From Baseline (Core and Extension) in 2nd Metacarpal Cortical Width at Month 24 by Core Treatment Group.
2nd metacarpal cortical width change from BL2
|
-0.09 millimeter (mm)
Standard Error 0.089
|
0.02 millimeter (mm)
Standard Error 0.063
|
Adverse Events
Core Treatment Zoledronic Acid
Serious events: 3 serious events
Other events: 7 other events
Deaths: 0 deaths
Core Treatment Placebo
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Core Treatment Zoledronic Acid
n=10 participants at risk
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
Core Treatment Placebo
n=15 participants at risk
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Gastrointestinal disorders
Nausea
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Nervous system disorders
Postictal state
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Nervous system disorders
Status epilepticus
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Psychiatric disorders
Depression
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Psychiatric disorders
Suicide attempt
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
Other adverse events
| Measure |
Core Treatment Zoledronic Acid
n=10 participants at risk
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
Core Treatment Placebo
n=15 participants at risk
Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid
|
|---|---|---|
|
Cardiac disorders
Tachycardia
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Ear and labyrinth disorders
Ear pain
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Endocrine disorders
Adrenal insufficiency
|
0.00%
0/10 • 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.
|
6.7%
1/15 • 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.
|
|
Eye disorders
Ocular hyperaemia
|
0.00%
0/10 • 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.
|
6.7%
1/15 • 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.
|
|
Gastrointestinal disorders
Abdominal pain
|
20.0%
2/10 • 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.
|
13.3%
2/15 • 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.
|
|
Gastrointestinal disorders
Abdominal pain lower
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Gastrointestinal disorders
Constipation
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Gastrointestinal disorders
Diarrhoea
|
10.0%
1/10 • 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.
|
6.7%
1/15 • 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.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/10 • 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.
|
6.7%
1/15 • 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.
|
|
Gastrointestinal disorders
Nausea
|
10.0%
1/10 • 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.
|
20.0%
3/15 • 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.
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
2/10 • 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.
|
6.7%
1/15 • 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.
|
|
General disorders
Chest pain
|
20.0%
2/10 • 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.
|
0.00%
0/15 • 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.
|
|
General disorders
Fatigue
|
0.00%
0/10 • 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.
|
20.0%
3/15 • 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.
|
|
General disorders
Infusion site pain
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
General disorders
Pain
|
0.00%
0/10 • 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.
|
6.7%
1/15 • 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.
|
|
General disorders
Pyrexia
|
20.0%
2/10 • 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.
|
20.0%
3/15 • 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.
|
|
Immune system disorders
Anaphylactic reaction
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Infections and infestations
Bronchitis
|
0.00%
0/10 • 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.
|
6.7%
1/15 • 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.
|
|
Infections and infestations
Candida infection
|
0.00%
0/10 • 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.
|
6.7%
1/15 • 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.
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/10 • 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.
|
13.3%
2/15 • 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.
|
|
Infections and infestations
Herpes virus infection
|
0.00%
0/10 • 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.
|
6.7%
1/15 • 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.
|
|
Infections and infestations
Influenza
|
10.0%
1/10 • 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.
|
20.0%
3/15 • 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.
|
|
Infections and infestations
Nasopharyngitis
|
10.0%
1/10 • 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.
|
13.3%
2/15 • 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.
|
|
Infections and infestations
Upper respiratory tract infection
|
10.0%
1/10 • 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.
|
6.7%
1/15 • 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.
|
|
Infections and infestations
Urinary tract infection
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/10 • 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.
|
13.3%
2/15 • 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.
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Investigations
Liver function test increased
|
0.00%
0/10 • 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.
|
6.7%
1/15 • 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.
|
|
Investigations
Therapeutic agent urine positive
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Investigations
Vitamin B12 decreased
|
0.00%
0/10 • 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.
|
6.7%
1/15 • 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.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/10 • 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.
|
6.7%
1/15 • 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.
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/10 • 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.
|
6.7%
1/15 • 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.
|
|
Metabolism and nutrition disorders
Insulin resistance
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/10 • 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.
|
33.3%
5/15 • 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.
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.0%
1/10 • 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.
|
20.0%
3/15 • 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.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/10 • 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.
|
6.7%
1/15 • 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.
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/10 • 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.
|
13.3%
2/15 • 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.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
10.0%
1/10 • 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.
|
6.7%
1/15 • 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.
|
|
Musculoskeletal and connective tissue disorders
Scoliosis
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Musculoskeletal and connective tissue disorders
Spinal pain
|
0.00%
0/10 • 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.
|
6.7%
1/15 • 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.
|
|
Musculoskeletal and connective tissue disorders
Trismus
|
0.00%
0/10 • 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.
|
6.7%
1/15 • 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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
|
10.0%
1/10 • 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.
|
6.7%
1/15 • 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.
|
|
Nervous system disorders
Epileptic aura
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Nervous system disorders
Headache
|
30.0%
3/10 • 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.
|
13.3%
2/15 • 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.
|
|
Nervous system disorders
Postictal state
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Nervous system disorders
Sciatica
|
0.00%
0/10 • 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.
|
6.7%
1/15 • 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.
|
|
Nervous system disorders
Tremor
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Psychiatric disorders
Depression
|
10.0%
1/10 • 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.
|
6.7%
1/15 • 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.
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/10 • 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.
|
6.7%
1/15 • 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.
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/10 • 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.
|
13.3%
2/15 • 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.
|
|
Psychiatric disorders
Suicide attempt
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/10 • 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.
|
13.3%
2/15 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Skin and subcutaneous tissue disorders
Butterfly rash
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Skin and subcutaneous tissue disorders
Ingrowing nail
|
0.00%
0/10 • 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.
|
6.7%
1/15 • 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.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/10 • 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.
|
6.7%
1/15 • 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.
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Surgical and medical procedures
Tooth extraction
|
0.00%
0/10 • 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.
|
6.7%
1/15 • 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.
|
|
Vascular disorders
Hypertension
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
|
Vascular disorders
Secondary hypertension
|
10.0%
1/10 • 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.
|
0.00%
0/15 • 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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER