Rheumatoid Arthritis
Conditions
Keywords
arthritis, joint pain, Methotrexate
Brief summary
This study will determine the efficacy, safety, and tolerability of denosumab (AMG 162) in the treatment of Rheumatoid Arthritis (RA).
Interventions
DRUGplacebo
placebo subcutaneous injection
DRUGdenosumab
For subcutaneous injection
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of RA. * All subjects will be required to have been taking a stable dose of methotrexate. * Active RA at screening defined as greater than or equal to 6 swollen joints. * The presence of erosive disease
Exclusion criteria
* Received any biologic agent (e.g., Enbrel®, Remicade®, Humira®, Kineret®) or Arava® within 8 weeks before randomization; past use of these agents is allowed. * Steroid use greater than 15 mg/day. * Scheduled for surgery or joint replacement in the hands, wrists or feet.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Rheumatoid Arthritis Erosion Score Measured From MRI Assessments (RA-MRI ES) at Month 6 | Baseline, Month 6 | Fifteen sites in each wrist and 10 sites in each hand were assessed by a blinded and independent reader. Each site was scored from 0 to 10 (in accordance with the European League Against Rheumatism \[EULAR\]-Outcome Measures in Rheumatology Clinical Trials convention), with each unit increment representing 10% incremental loss of the peripheral 1 cm of articular bone. The Erosion Score is a sum of erosion scores from 50 joint sites in both hands/wrists and ranges from 0 (normal, no erosion) to 500 (worst possible erosion). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Eosinophils at Month 1 | Baseline, month 1 | Laboratory hematology eosinophils |
| Change From Baseline in Eosinophils at Month 3 | Baseline, month 3 | Laboratory hematology eosinophils |
| Change From Baseline in Eosinophils at Month 6 | Baseline, month 6 | Laboratory hematology eosinophils |
| Change From Baseline in Eosinophils at Month 12 | Baseline, month 12 | Laboratory hematology eosinophils |
| Change From Baseline in Hematocrit at Month 1 | Baseline, month 1 | Laboratory hematology hematocrit |
| Change From Baseline in Hematocrit at Month 3 | Baseline, month 3 | Laboratory hematology hematocrit |
| Change From Baseline in Hematocrit at Month 6 | Baseline, month 6 | Laboratory hematology hematocrit |
| Change From Baseline in Alkaline Phosphatase at Month 1 | Baseline, month 1 | Laboratory chemistry alkaline phoshatatse |
| Change From Baseline in Alkaline Phosphatase at Month 3 | baseline, month 3 | Laboratory chemisrty alkaline phosphatase |
| Change From Baseline in Hematocrit at Month 12 | Baseline, month 12 | Laboratory hematology hematocrit |
| Change From Baseline in Alkaline Phosphatase at Month 6 | baseline, month 6 | Laboratory chemistry alkaline phosphatase |
| Change From Baseline in Alkaline Phosphatase at Month 12 | baseine, month 12 | Laboratory chemistry alkaline phosphatase |
| Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 12 | Baseline, Month 12 | TSS is the sum of erosion and joint space narrowing scores obtained from radiographs of the hands and feet, assessed by 2 independent readers. The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280. Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. The TSS ranged from 0 (normal) to 448 (worst). |
| Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 6 | Baseline, Month 6 | TSS is the sum of erosion and joint space narrowing scores obtained from radiographs of the hands and feet, assessed by 2 independent readers. The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280. Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. The TSS ranged from 0 (normal) to 448 (worst). |
| Change From Baseline in Radiographic Erosion Score at Month 12 | Baseline, Month 12 | The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet, obtained from radiographs of the hands and feet and assessed by 2 independent readers. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280. |
| Change From Baseline in Radiographic Erosion Score at Month 6 | Baseline, Month 6 | The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet, obtained from radiographs of the hands and feet and assessed by 2 independent readers. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280. |
| Change From Baseline in Radiographic Joint Space Narrowing Score at Month 12 | Baseline, Month 12 | Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet obtained from radiographs of the hands and feet and assessed by 2 independent readers. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score (indicating worst joint space narrowing) of 168. |
| Change From Baseline in Albumin at Month 1 | Baseline, month 1 | Laboratory Chemistry Albumin |
| Change From Baseline in Radiographic Joint Space Narrowing Score at Month 6 | Baseline, Month 6 | Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet obtained from radiographs of the hands and feet and assessed by 2 independent readers. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score (indicating worst joint space narrowing) of 168. |
| Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 1 | Baseline, Month 1 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((month 1 value - baseline value) / baseline value ) x 100. Least squares means are based on a repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic). |
| Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 6 | Baseline, month 6 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to month 6 calculated using ((month 6 value - baseline value) / baseline value ) x 100. Least squares means are based on a repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic). |
| Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 | Baseline, Month 12 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 12 calculated using ((Month 12 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic). |
| Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 1 | Baseline, Month 1 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((Month 1 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic). |
| Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 6 | Baseline, Month 6 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 6 calculated using ((Month 6 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic). |
| Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 12 | Baseline, Month 12 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 12 calculated using ((Month 12 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic). |
| Percent Change From Baseline in Total Hip Bone Mineral Density at Month 1 | Baseline, Month 1 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((Month 1 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic). |
| Change From Baseline in Albumin at Month 3 | Baseline, month 3 | Laboratory chemistry albumin |
| Change From Baseline in Albumin at Month 6 | Baseline, month 6 | Laboratory chemistry albumin |
| Change From Baseline in Albumin at Month 12 | Baseline, month 12 | Laboratory chemistry albumin |
| Percent Change From Baseline in Total Hip Bone Mineral Density at Month 6 | Baseline, Month 6 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 6 calculated using ((Month 6 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic). |
| Percent Change From Baseline in Total Hip Bone Mineral Density at Month 12 | Baseline, Month 12 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 12 calculated using ((Month 12 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic). |
| Percent Change From Baseline in Serum Collagen C-Telopeptide (CTX) at Month 3 | Baseline, Month 3 | Percent change from baseline to Month 3 in serum Collagen C-Telopeptide (CTX) Type I calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100. |
| Percent Change From Baseline in Serum CTX at Month 6 | Baseline, Month 6 | Percent change from baseline to Month 6 in serum Collagen C-Telopeptide (CTX) Type I calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100. |
| Percent Change From Baseline in Serum CTX at Month 12 | Baseline, Month 12 | Percent change from Baseline to Month 12 in serum C-Telopeptide (CTX) Type I calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100. |
| Percent Change From Baseline in Procollagen 1 N-terminal Peptide (P1NP) at Month 3 | Baseline, Month 3 | Percent change from baseline to Month 3 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100. |
| Percent Change From Baseline in P1NP at Month 6 | Baseline, Month 6 | Percent change from baseline to Month 6 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100. |
| Percent Change From Baseline in P1NP at Month 12 | Baseline, Month 12 | Percent change from baseline to Month 12 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100. |
| Percent Change From Baseline in Urine Type II Collagen C-telopeptide (C-Tx) /Creatinine at Month 3 | Baseline, Month 3 | Percent change from baseline to Month 3 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100. |
| Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 6 | Baseline, Month 6 | Percent change from baseline to Month 6 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100. |
| Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 12 | Baseline, Month 12 | Percent change from baseline to Month 12 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100. |
| Number of Participants With Anti-Denosumab Binding Antibodies | Assessed at Baseline and at Months 1, 3, 6 and 12. | Serum from participants was tested for antibodies to denosumab by immuoassay at months 1, 3, 6 and 12. The number of participants with anti-denosumab antibodies at any assessment is reported. |
| Number of Participants With Anti-Denosumab Binding Antibody and Neutralizing Antibody | Baseline to Month 12 | Serum from participants testing positive for anti-denosumab binding antibodies was tested in a cell-based bioassay for neutralizing activity against denosumab. |
| Change From Baseline in Bicarbonate at Month 3 | baseline, month 3 | Laboratory chemistry bicarbonate |
| Change From Baseline in Bicarbonate at Month 6 | Baseline, month 6 | Laboratory chemistry bicarbonate |
| Change From Baseline in Bicarbonate at Month 12 | Baseline, Month 12 | Laboratory chemistry bicarbonate |
| Change From Baseline in Total Bilirubin at Month 1 | baseline, month 1 | Laboratory chemistry total bilirubin |
| Change From Baseline in Total Bilirubin at Month 3 | Baseline, month 3 | Laboratory chemistry total bilirubin |
| Change From Baseline in Total Bilirubin at Month 6 | Baseline, month 6 | Laboratory chemistry total bilirubin |
| Change From Baseline in Total Bilirubin at Month 12 | Baseline, month 12 | Laboratory chemistry total bilirubin |
| Change From Baseline in Blood Urea Nitrogen at Month 1 | Baseline, month 1 | Laboratory chemistry blood urea nitrogen |
| Change From Baseline in Blood Urea Nitrogen at Month 3 | Baseline, month 3 | Laboratory chemistry blood urea nitrogen |
| Change From Baseline in Blood Urea Nitrogen at Month 6 | Baseline, month 6 | Laboratory chemistry blood urea nitrogen |
| Change From Baseline in Blood Urea Nitrogen at Month 12 | baseline, month 12 | Laboratory chemistry blood urea nitrogen |
| Change From Baseline in Calcium at Month 1 | baseline. month 1 | Laboratory chemistry calcium |
| Change From Baseline in Calcium at Month 3 | Baseline, month 3 | Laboratory chemistry calcium |
| Change From Baseline in Calcium at Month 6 | baseline, month 6 | Laboratory chemistry calcium |
| Change From Baseline in Calcium at Month 12 | Baseline, month 12 | Laboratory chemistry calcium |
| Change From Baseline in Calcium (Corrected) at Month 1 | Baseline, month 1 | Laboratory chemistry albumin-adjusted calcium |
| Change From Baseline in Calcium (Corrected) at Month 3 | baseline, month 3 | Laboratory chemistry albumin-adjusted calcium |
| Change From Baseline in Calcium (Corrected) at Month 6 | Baseline, Month 6 | Laboratory chemistry albumin-adjusted calcium |
| Change From Baseline in Calcium (Corrected) at Month 12 | Baselien, Month 12 | Laboratory chemistry albumin-adjusted calcium |
| Change From Baseline in Hemoglobin at Month 1 | Baseline, month 1 | Laboratory hematology hemoglobin |
| Change From Baseline in Chloride at Month 1 | baseline, month 1 | Laboratory chemistry chloride |
| Change From Baseline in Chloride at Month 3 | Baseline, month 3 | Laboratory chemistry chloride |
| Change From Baseline in Chloride at Month 6 | Baseline, month 6 | Laboratory chemistry chloride |
| Change From Baseline in Chloride at Month 12 | Baseline, month 12 | Laboratory chemistry chloride |
| Change From Baseline in Creatinine at Month 1 | Baseline, month 1 | Laboratory chemistry creatinine |
| Change From Baseline in Creatinine at Month 3 | Baseline, month 3 | Laboratory chemistry creatinine |
| Change From Baseline in Creatinine at Month 6 | Baseline, month 6 | Laboratory chemistry creatinine |
| Change From Baseline in Creatinine at Month 12 | Baseline, month 12 | Laboratory chemistry creatinine |
| Change From Baseline in Gamma-Glutamyl Transferase at Month 1 | Baseline, month 1 | Laboratory chemistry gamma-glutamyl transferase |
| Change From Baseline in Gamma-Glutamyl Transferase at Month 3 | Baseline, month 3 | Laboratory chemistry gamma-glutamyl transferase |
| Change From Baseline in Gamma-Glutamyl Transferase at Month 6 | Baseline, month 6 | Laboratory chemistry gamma-glutamyl transferase |
| Change From Baseline in Gamma-Glutamyl Transferase at Month 12 | Baseline, month 12 | Laboratory chemistry gamma-glutamyl transferase |
| Change From Baseline in Glucose at Month 1 | Baseline, month 1 | Laboratory chemistry glucose |
| Change From Baseline in Glucose at Month 3 | Baseline, month 3 | Laboratory chemistry glucose |
| Change From Baseline in Glucose at Month 6 | Baseline, month 6 | Laboratory chemistry glucose |
| Change From Baseline in Glucose at Month 12 | baseline, month 12 | Laboratory chemistry glucose |
| Change From Baseline in Potassium at Month 1 | Baseline, month 1 | Laboratory chemistry potassium |
| Change From Baseline in Potassium at Month 3 | Baseline, month 3 | Laboratory chemistry potassium |
| Change From Baseline in Potassium at Month 6 | Baseline, month 6 | Laboratory chemistry potassium |
| Change From Baseline in Potassium at Month 12 | Baseline, month 12 | Laboratory chemistry potassium |
| Change From Baseline in Magnesium at Month 1 | Baseline, month 1 | Laboratory chemistry magnesium |
| Change From Baseline in Magnesium at Month 3 | Baseline, month 3 | Laboratory chemistry magnesium |
| Change From Baseline in Magnesium at Month 6 | Baseline, month 6 | Laboratory chemistry magnesium |
| Change From Baseline in Magnesium at Month 12 | Baseline, month 12 | Laboratory chemistry magnesium |
| Change From Baseline in Sodium at Month 1 | Baseline, month 1 | Laboratory chemistry sodium |
| Change From Baseline in Sodium at Month 3 | Baseline, Month 3 | Change From Baseline in Sodium at Month 3 |
| Change From Baseline in Sodium at Month 6 | Baseline, month 6 | Laboratory chemistry sodium |
| Change From Baseline in Sodium at Month 12 | Baseline, month 12 | Laboratory chemistry sodium |
| Change From Baseline in Phosphorus at Month 1 | Baseline, month 1 | Laboratory chemistry phosphorus |
| Change From Baseline in Phosphorus at Month 3 | Baseline, month 3 | Laboratory chemistry phosphorus |
| Change From Baseline in Phosphorus at Month 6 | Baseline, month 6 | Laboratory chemistry phosphorus |
| Change From Baseline in Phosphorus at Month 12 | Baseline, month 12 | Change From Baseline in Phosphorus at Month 12 |
| Change From Baseline in Total Protein at Month 1 | Baseline, month 1 | Laboratory chemistry total protein |
| Change From Baseline in Total Protein at Month 3 | Baseline, month 3 | Laboratory chemistry total protein |
| Change From Baseline in Total Protein at Month 6 | Baseline, month 6 | Laboratory chemistry total protein |
| Change From Baseline in Total Protein at Month 12 | Baseline, month 12 | Laboratory chemistry total protein |
| Change From Baseline in Aspartate Amino Transferase at Month 1 | Baseline, month 1 | Laboratory chemistry aspartate amino transferase |
| Change From Baseline in Aspartate Amino Transferase at Month 3 | Baseline, month 3 | Laboratory chemistry aspartate amino transferase |
| Change From Baseline in Aspartate Amino Transferase | Baseline, month 6 | Laboratory chemistry aspartate amino transferase |
| Change From Baseline in Aspartate Amino Transferase at Month 12 | Baseline, month 12 | Laboratory chemistry aspartate amino transferase |
| Change From Baseline in Hemoglobin at Month 3 | Baseline, month 3 | Laboratory hematology hemoglobin |
| Change From Baseline in Alanine Amino Transferase at Month 1 | Baseline, month 1 | Laboratory chemistry alanine amino transferase |
| Change From Baseline in Alanine Amino Transferase at Month 3 | Baseline, month 3 | Laboratory Chemistry alanine amino transferase |
| Change From Baseline in Alanine Amino Transferase at Month 6 | Baseline, month 6 | Laboratory chemistry alanine amino transferase |
| Change From Baseline in Alanine Amino Transferase at Month 12 | Baseline, month 12 | Laboratory chemistry alanine amino transferase |
| Change From Baseline in Basophils at Month 1 | baseline, month 1 | Laboratory hematology basophils |
| Change From Baseline in Basophils at Month 3 | Baseline, month 3 | Laboratory hematology basophils |
| Change From Baseline in Basophils at Month 6 | Baseline, month 6 | Laboratory hematology basophils |
| Change From Baseline in Basophils at Month 12 | Baseline, month 12 | Laboratory hematology basophils |
| Change From Baseline in Hemoglobin at Month 6 | Baseline, month 6 | Laboratory hematology hemoglobin |
| Change From Baseline in Hemoglobin at Month 12 | Baseline, month 12 | Laboratory hematology hemoglobin |
| Change From Baseline in Lymphocytes at Month 1 | Baseline, month 1 | Laboratory hematology lymphocytes |
| Change From Baseline in Lymphocytes at Month 3 | Baseline, month 3 | Laboratory hematology lymphocytes |
| Change From Baseline in Lymphocytes at Month 6 | Baseline, month 6 | Laboratory hematology lymphocytes |
| Change From Baseline in Lymphocytes at Month 12 | Baseline, month 12 | Laboratory hematology lymphocytes |
| Change From Baseline in Monocytes at Month 1 | Baseline, month 1 | Laboratory hematology monocytes |
| Change From Baseline in Monocytes at Month 3 | Baseline, month 3 | Laboratory hematology monocytes |
| Change From Baseline in Monocytes at Month 6 | Baseline, month 6 | Laboratory hematology monocytes |
| Change From Baseline in Monocytes at Month 12 | Baseline, month 12 | Laboratory hematology monocytes |
| Change From Baseline in Bicarbonate at Month 1 | baseline, month 1 | Laboratory chemistry bicarbonate |
| Change From Baseline in Total Neutrophils at Month 3 | Baseline, month 3 | Laboratory hematology total neutrophils |
| Change From Baseline in Total Neutrophils at Month 6 | Baseline, month 6 | Laboratory hematology total neutrophils |
| Change From Baseline in Total Neutrophils at Month 12 | Baseline, month 12 | Laboratory hematology total neutrophils |
| Change From Baseline in Platelets at Month 1 | Baseline, month 1 | Laboratory hematology platelets |
| Change From Baseline in Platelets at Month 3 | Baseline, month 3 | Laboratory hematology platelets |
| Change From Baseline in Platelets at Month 6 | Baseline, month 6 | Laboratory hematology platelets |
| Change From Baseline in Platelets at Month 12 | Baseline, month 12 | Laboratory hematology platelets |
| Change From Baseline in Red Blood Cells at Month 1 | Baseline, month 1 | Laboratory hematology red blood cells |
| Change From Baseline in Red Blood Cells at Month 3 | Baseline, month 3 | Laboratory hematology red blood cells |
| Change From Baseline in Red Blood Cells at Month 6 | Baseline, month 6 | Laboratory hematology red blood cells |
| Change From Baseline in Red Blood Cells at Month 12 | Baseline, month 12 | Laboratory hematology red blood cells |
| Change From Baseline in White Blood Cells at Month 1 | Baseline, month 1 | Laboratory hematology white blood cells |
| Change From Baseline in White Blood Cells at Month 3 | Baseline, month 3 | Laboratpry hematology white blood cells |
| Change From Baseline in White Blood Cells at Month 6 | Baseline, month 6 | Laboratory hematology white blood cells |
| Change From Baseline in White Blood Cells at Month 12 | Baseline, month 12 | Laboratory hematology white blood cells |
| Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | Month 1, month 3, month 6, month 12 | Participants with laboratory toxicity of grade 3 or 4, graded according to the Common Terminology Criteria for Adverse Events, version 3.0, on the following general guideline: Grade 1 - Mild AE; Grade 2 - Moderate AE; Grade 3 - Severe AE; Grade 4 - Life-threatening or disabling AE; Grade 5 - Death related to AE. |
| Change From Baseline in Total Neutrophils at Month 1 | Baseline, month 1 | Laboratory hematology total neutrophils |
Participant flow
Recruitment details
First Subject Enrolled: 11-Aug-2004 Last Subject Enrolled: 07-Apr-2005
Participants by arm
| Arm | Count |
|---|---|
| Denosumab 180 mg Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6. | 76 |
| Denosumab 60 mg Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6. | 73 |
| Placebo Participants received placebo subcutaneous injections on Day 1 and at Month 6. | 78 |
| Total | 227 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 |
| Overall Study | Disease progression | 0 | 1 | 1 |
| Overall Study | Ineligibility determined | 3 | 0 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 | 2 |
| Overall Study | Noncompliance | 1 | 0 | 1 |
| Overall Study | Other | 6 | 7 | 6 |
| Overall Study | Physician Decision | 9 | 10 | 8 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Requirement for alternative therapy | 1 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 15 | 16 | 15 |
Baseline characteristics
| Characteristic | Denosumab 180 mg | Denosumab 60 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 58 Years STANDARD_DEVIATION 11 | 57.3 Years STANDARD_DEVIATION 11.4 | 57 Years STANDARD_DEVIATION 11.1 | 57.4 Years STANDARD_DEVIATION 11.2 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 3 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 6 Participants | 6 Participants | 9 Participants | 21 Participants |
| Race/Ethnicity, Customized Japanese | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White or Caucasian | 66 Participants | 59 Participants | 62 Participants | 187 Participants |
| Sex: Female, Male Female | 53 Participants | 51 Participants | 62 Participants | 166 Participants |
| Sex: Female, Male Male | 23 Participants | 22 Participants | 16 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 47 / 75 | 44 / 71 | 44 / 72 |
| serious Total, serious adverse events | 5 / 75 | 3 / 71 | 6 / 72 |
Outcome results
Primary
Change From Baseline in Rheumatoid Arthritis Erosion Score Measured From MRI Assessments (RA-MRI ES) at Month 6
Fifteen sites in each wrist and 10 sites in each hand were assessed by a blinded and independent reader. Each site was scored from 0 to 10 (in accordance with the European League Against Rheumatism \[EULAR\]-Outcome Measures in Rheumatology Clinical Trials convention), with each unit increment representing 10% incremental loss of the peripheral 1 cm of articular bone. The Erosion Score is a sum of erosion scores from 50 joint sites in both hands/wrists and ranges from 0 (normal, no erosion) to 500 (worst possible erosion).
Time frame: Baseline, Month 6
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Rheumatoid Arthritis Erosion Score Measured From MRI Assessments (RA-MRI ES) at Month 6 | 0.00 units on a scale | Full Range 3.49 |
| Denosumab 60 mg | Change From Baseline in Rheumatoid Arthritis Erosion Score Measured From MRI Assessments (RA-MRI ES) at Month 6 | 0.00 units on a scale | Full Range 3.43 |
| Placebo | Change From Baseline in Rheumatoid Arthritis Erosion Score Measured From MRI Assessments (RA-MRI ES) at Month 6 | 0.49 units on a scale | Full Range 5.08 |
p-value: 0.264van Elteren stratified rank test
p-value: 0.018van Elteren stratified rank test
Secondary
Change From Baseline in Alanine Amino Transferase at Month 1
Laboratory chemistry alanine amino transferase
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Alanine Amino Transferase at Month 1 | -1.84 U/L | Standard Deviation 8.61 |
| Denosumab 60 mg | Change From Baseline in Alanine Amino Transferase at Month 1 | -1.03 U/L | Standard Deviation 12.37 |
| Placebo | Change From Baseline in Alanine Amino Transferase at Month 1 | 1.20 U/L | Standard Deviation 15.44 |
Secondary
Change From Baseline in Alanine Amino Transferase at Month 12
Laboratory chemistry alanine amino transferase
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Alanine Amino Transferase at Month 12 | 4.86 U/L | Standard Deviation 24.46 |
| Denosumab 60 mg | Change From Baseline in Alanine Amino Transferase at Month 12 | 1.66 U/L | Standard Deviation 14.3 |
| Placebo | Change From Baseline in Alanine Amino Transferase at Month 12 | 1.82 U/L | Standard Deviation 14.41 |
Secondary
Change From Baseline in Alanine Amino Transferase at Month 3
Laboratory Chemistry alanine amino transferase
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Alanine Amino Transferase at Month 3 | 0.04 U/L | Standard Deviation 8.85 |
| Denosumab 60 mg | Change From Baseline in Alanine Amino Transferase at Month 3 | -2.10 U/L | Standard Deviation 14.34 |
| Placebo | Change From Baseline in Alanine Amino Transferase at Month 3 | 1.54 U/L | Standard Deviation 13 |
Secondary
Change From Baseline in Alanine Amino Transferase at Month 6
Laboratory chemistry alanine amino transferase
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Alanine Amino Transferase at Month 6 | 1.20 U/L | Standard Deviation 15.83 |
| Denosumab 60 mg | Change From Baseline in Alanine Amino Transferase at Month 6 | -1.76 U/L | Standard Deviation 14.12 |
| Placebo | Change From Baseline in Alanine Amino Transferase at Month 6 | 5.44 U/L | Standard Deviation 51.19 |
Secondary
Change From Baseline in Albumin at Month 1
Laboratory Chemistry Albumin
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Albumin at Month 1 | -0.36 g/L | Standard Deviation 2.29 |
| Denosumab 60 mg | Change From Baseline in Albumin at Month 1 | -0.24 g/L | Standard Deviation 2.25 |
| Placebo | Change From Baseline in Albumin at Month 1 | -0.30 g/L | Standard Deviation 2.21 |
Secondary
Change From Baseline in Albumin at Month 12
Laboratory chemistry albumin
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Albumin at Month 12 | -0.13 g/L | Standard Deviation 2.41 |
| Denosumab 60 mg | Change From Baseline in Albumin at Month 12 | -0.06 g/L | Standard Deviation 2.26 |
| Placebo | Change From Baseline in Albumin at Month 12 | -0.59 g/L | Standard Deviation 2.49 |
Secondary
Change From Baseline in Albumin at Month 3
Laboratory chemistry albumin
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Albumin at Month 3 | -0.30 g/L | Standard Deviation 2.18 |
| Denosumab 60 mg | Change From Baseline in Albumin at Month 3 | -0.12 g/L | Standard Deviation 2.28 |
| Placebo | Change From Baseline in Albumin at Month 3 | -0.18 g/L | Standard Deviation 2.07 |
Secondary
Change From Baseline in Albumin at Month 6
Laboratory chemistry albumin
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Albumin at Month 6 | -0.30 g/L | Standard Deviation 2.49 |
| Denosumab 60 mg | Change From Baseline in Albumin at Month 6 | -0.90 g/L | Standard Deviation 2.56 |
| Placebo | Change From Baseline in Albumin at Month 6 | -0.77 g/L | Standard Deviation 2.4 |
Secondary
Change From Baseline in Alkaline Phosphatase at Month 1
Laboratory chemistry alkaline phoshatatse
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Alkaline Phosphatase at Month 1 | -5.87 U/L | Standard Deviation 10.52 |
| Denosumab 60 mg | Change From Baseline in Alkaline Phosphatase at Month 1 | -3.66 U/L | Standard Deviation 11.97 |
| Placebo | Change From Baseline in Alkaline Phosphatase at Month 1 | 1.18 U/L | Standard Deviation 15.62 |
Secondary
Change From Baseline in Alkaline Phosphatase at Month 12
Laboratory chemistry alkaline phosphatase
Time frame: baseine, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Alkaline Phosphatase at Month 12 | -11.92 U/L | Standard Deviation 16.74 |
| Denosumab 60 mg | Change From Baseline in Alkaline Phosphatase at Month 12 | -11.34 U/L | Standard Deviation 18.18 |
| Placebo | Change From Baseline in Alkaline Phosphatase at Month 12 | -4.63 U/L | Standard Deviation 16.7 |
Secondary
Change From Baseline in Alkaline Phosphatase at Month 3
Laboratory chemisrty alkaline phosphatase
Time frame: baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Alkaline Phosphatase at Month 3 | -13.27 U/L | Standard Deviation 15.91 |
| Denosumab 60 mg | Change From Baseline in Alkaline Phosphatase at Month 3 | -12.38 U/L | Standard Deviation 13.09 |
| Placebo | Change From Baseline in Alkaline Phosphatase at Month 3 | -2.03 U/L | Standard Deviation 8.37 |
Secondary
Change From Baseline in Alkaline Phosphatase at Month 6
Laboratory chemistry alkaline phosphatase
Time frame: baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Alkaline Phosphatase at Month 6 | -7.84 U/L | Standard Deviation 31.94 |
| Denosumab 60 mg | Change From Baseline in Alkaline Phosphatase at Month 6 | -12.49 U/L | Standard Deviation 12.61 |
| Placebo | Change From Baseline in Alkaline Phosphatase at Month 6 | -0.54 U/L | Standard Deviation 18.46 |
Secondary
Change From Baseline in Aspartate Amino Transferase
Laboratory chemistry aspartate amino transferase
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Aspartate Amino Transferase | 3.85 U/L | Standard Deviation 15.66 |
| Denosumab 60 mg | Change From Baseline in Aspartate Amino Transferase | 0.87 U/L | Standard Deviation 7.58 |
| Placebo | Change From Baseline in Aspartate Amino Transferase | 3.24 U/L | Standard Deviation 15.9 |
Secondary
Change From Baseline in Aspartate Amino Transferase at Month 1
Laboratory chemistry aspartate amino transferase
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Aspartate Amino Transferase at Month 1 | -0.79 U/L | Standard Deviation 5.84 |
| Denosumab 60 mg | Change From Baseline in Aspartate Amino Transferase at Month 1 | -0.26 U/L | Standard Deviation 8.14 |
| Placebo | Change From Baseline in Aspartate Amino Transferase at Month 1 | 0.90 U/L | Standard Deviation 8.35 |
Secondary
Change From Baseline in Aspartate Amino Transferase at Month 12
Laboratory chemistry aspartate amino transferase
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Aspartate Amino Transferase at Month 12 | 3.86 U/L | Standard Deviation 18.62 |
| Denosumab 60 mg | Change From Baseline in Aspartate Amino Transferase at Month 12 | 3.75 U/L | Standard Deviation 18.11 |
| Placebo | Change From Baseline in Aspartate Amino Transferase at Month 12 | 2.24 U/L | Standard Deviation 7.32 |
Secondary
Change From Baseline in Aspartate Amino Transferase at Month 3
Laboratory chemistry aspartate amino transferase
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Aspartate Amino Transferase at Month 3 | 1.99 U/L | Standard Deviation 5.77 |
| Denosumab 60 mg | Change From Baseline in Aspartate Amino Transferase at Month 3 | 0.40 U/L | Standard Deviation 8.78 |
| Placebo | Change From Baseline in Aspartate Amino Transferase at Month 3 | 2.69 U/L | Standard Deviation 9.37 |
Secondary
Change From Baseline in Basophils at Month 1
Laboratory hematology basophils
Time frame: baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Basophils at Month 1 | 0 *10^9/L | Standard Deviation 0.07 |
| Denosumab 60 mg | Change From Baseline in Basophils at Month 1 | 0 *10^9/L | Standard Deviation 0.07 |
| Placebo | Change From Baseline in Basophils at Month 1 | -0.01 *10^9/L | Standard Deviation 0.07 |
Secondary
Change From Baseline in Basophils at Month 12
Laboratory hematology basophils
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Basophils at Month 12 | 0.02 * 10^9/L | Standard Deviation 0.09 |
| Denosumab 60 mg | Change From Baseline in Basophils at Month 12 | 0 * 10^9/L | Standard Deviation 0.09 |
| Placebo | Change From Baseline in Basophils at Month 12 | 0.03 * 10^9/L | Standard Deviation 0.07 |
Secondary
Change From Baseline in Basophils at Month 3
Laboratory hematology basophils
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Basophils at Month 3 | -0.01 * 10^9/L | Standard Deviation 0.06 |
| Denosumab 60 mg | Change From Baseline in Basophils at Month 3 | -0.01 * 10^9/L | Standard Deviation 0.07 |
| Placebo | Change From Baseline in Basophils at Month 3 | -0.01 * 10^9/L | Standard Deviation 0.07 |
Secondary
Change From Baseline in Basophils at Month 6
Laboratory hematology basophils
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Basophils at Month 6 | 0 * 10^9/L | Standard Deviation 0.06 |
| Denosumab 60 mg | Change From Baseline in Basophils at Month 6 | 0 * 10^9/L | Standard Deviation 0.07 |
| Placebo | Change From Baseline in Basophils at Month 6 | 0 * 10^9/L | Standard Deviation 0.06 |
Secondary
Change From Baseline in Bicarbonate at Month 1
Laboratory chemistry bicarbonate
Time frame: baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Bicarbonate at Month 1 | 0.78 mmol/L | Standard Deviation 2.31 |
| Denosumab 60 mg | Change From Baseline in Bicarbonate at Month 1 | 0.06 mmol/L | Standard Deviation 3.06 |
| Placebo | Change From Baseline in Bicarbonate at Month 1 | 0.54 mmol/L | Standard Deviation 2.94 |
Secondary
Change From Baseline in Bicarbonate at Month 12
Laboratory chemistry bicarbonate
Time frame: Baseline, Month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Bicarbonate at Month 12 | 0.81 mmol/L | Standard Deviation 2.12 |
| Denosumab 60 mg | Change From Baseline in Bicarbonate at Month 12 | 0.58 mmol/L | Standard Deviation 2.68 |
| Placebo | Change From Baseline in Bicarbonate at Month 12 | 0.23 mmol/L | Standard Deviation 2.5 |
Secondary
Change From Baseline in Bicarbonate at Month 3
Laboratory chemistry bicarbonate
Time frame: baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Bicarbonate at Month 3 | 0.12 mmol/L | Standard Deviation 2.4 |
| Denosumab 60 mg | Change From Baseline in Bicarbonate at Month 3 | 0.39 mmol/L | Standard Deviation 2.84 |
| Placebo | Change From Baseline in Bicarbonate at Month 3 | -0.67 mmol/L | Standard Deviation 3.17 |
Secondary
Change From Baseline in Bicarbonate at Month 6
Laboratory chemistry bicarbonate
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Bicarbonate at Month 6 | 0.45 mmol/L | Standard Deviation 2.29 |
| Denosumab 60 mg | Change From Baseline in Bicarbonate at Month 6 | -0.12 mmol/L | Standard Deviation 2.61 |
| Placebo | Change From Baseline in Bicarbonate at Month 6 | -0.18 mmol/L | Standard Deviation 2.67 |
Secondary
Change From Baseline in Blood Urea Nitrogen at Month 1
Laboratory chemistry blood urea nitrogen
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Blood Urea Nitrogen at Month 1 | 0 mmol/L | Standard Deviation 1.35 |
| Denosumab 60 mg | Change From Baseline in Blood Urea Nitrogen at Month 1 | 0.15 mmol/L | Standard Deviation 1.4 |
| Placebo | Change From Baseline in Blood Urea Nitrogen at Month 1 | -0.01 mmol/L | Standard Deviation 1.55 |
Secondary
Change From Baseline in Blood Urea Nitrogen at Month 12
Laboratory chemistry blood urea nitrogen
Time frame: baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Blood Urea Nitrogen at Month 12 | 0.32 mmol/L | Standard Deviation 1.37 |
| Denosumab 60 mg | Change From Baseline in Blood Urea Nitrogen at Month 12 | 0.24 mmol/L | Standard Deviation 1.46 |
| Placebo | Change From Baseline in Blood Urea Nitrogen at Month 12 | -0.09 mmol/L | Standard Deviation 1.56 |
Secondary
Change From Baseline in Blood Urea Nitrogen at Month 3
Laboratory chemistry blood urea nitrogen
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Blood Urea Nitrogen at Month 3 | 0.04 mmol/L | Standard Deviation 1.35 |
| Denosumab 60 mg | Change From Baseline in Blood Urea Nitrogen at Month 3 | 0.41 mmol/L | Standard Deviation 1.59 |
| Placebo | Change From Baseline in Blood Urea Nitrogen at Month 3 | 0.06 mmol/L | Standard Deviation 1.43 |
Secondary
Change From Baseline in Blood Urea Nitrogen at Month 6
Laboratory chemistry blood urea nitrogen
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Blood Urea Nitrogen at Month 6 | -0.21 mmol/L | Standard Deviation 1.44 |
| Denosumab 60 mg | Change From Baseline in Blood Urea Nitrogen at Month 6 | -0.08 mmol/L | Standard Deviation 1.41 |
| Placebo | Change From Baseline in Blood Urea Nitrogen at Month 6 | -0.04 mmol/L | Standard Deviation 2.29 |
Secondary
Change From Baseline in Calcium at Month 1
Laboratory chemistry calcium
Time frame: baseline. month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Calcium at Month 1 | -0.05 mmol/L | Standard Deviation 0.11 |
| Denosumab 60 mg | Change From Baseline in Calcium at Month 1 | -0.05 mmol/L | Standard Deviation 0.09 |
| Placebo | Change From Baseline in Calcium at Month 1 | 0.01 mmol/L | Standard Deviation 0.09 |
Secondary
Change From Baseline in Calcium at Month 12
Laboratory chemistry calcium
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Calcium at Month 12 | -0.01 mmol/L | Standard Deviation 0.11 |
| Denosumab 60 mg | Change From Baseline in Calcium at Month 12 | 0.01 mmol/L | Standard Deviation 0.09 |
| Placebo | Change From Baseline in Calcium at Month 12 | 0.01 mmol/L | Standard Deviation 0.08 |
Secondary
Change From Baseline in Calcium at Month 3
Laboratory chemistry calcium
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Calcium at Month 3 | -0.01 mmol/L | Standard Deviation 0.11 |
| Denosumab 60 mg | Change From Baseline in Calcium at Month 3 | -0.02 mmol/L | Standard Deviation 0.1 |
| Placebo | Change From Baseline in Calcium at Month 3 | 0 mmol/L | Standard Deviation 0.1 |
Secondary
Change From Baseline in Calcium at Month 6
Laboratory chemistry calcium
Time frame: baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Calcium at Month 6 | -0.01 mmol/L | Standard Deviation 0.1 |
| Denosumab 60 mg | Change From Baseline in Calcium at Month 6 | -0.03 mmol/L | Standard Deviation 0.11 |
| Placebo | Change From Baseline in Calcium at Month 6 | -0.01 mmol/L | Standard Deviation 0.1 |
Secondary
Change From Baseline in Calcium (Corrected) at Month 1
Laboratory chemistry albumin-adjusted calcium
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Calcium (Corrected) at Month 1 | -0.05 mmol/L | Standard Deviation 0.11 |
| Denosumab 60 mg | Change From Baseline in Calcium (Corrected) at Month 1 | -0.05 mmol/L | Standard Deviation 0.09 |
| Placebo | Change From Baseline in Calcium (Corrected) at Month 1 | 0.01 mmol/L | Standard Deviation 0.09 |
Secondary
Change From Baseline in Calcium (Corrected) at Month 12
Laboratory chemistry albumin-adjusted calcium
Time frame: Baselien, Month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Calcium (Corrected) at Month 12 | -0.01 mmol/L | Standard Deviation 0.11 |
| Denosumab 60 mg | Change From Baseline in Calcium (Corrected) at Month 12 | 0.01 mmol/L | Standard Deviation 0.09 |
| Placebo | Change From Baseline in Calcium (Corrected) at Month 12 | 0 mmol/L | Standard Deviation 0.08 |
Secondary
Change From Baseline in Calcium (Corrected) at Month 3
Laboratory chemistry albumin-adjusted calcium
Time frame: baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Calcium (Corrected) at Month 3 | -0.01 mmol/L | Standard Deviation 0.11 |
| Denosumab 60 mg | Change From Baseline in Calcium (Corrected) at Month 3 | -0.02 mmol/L | Standard Deviation 0.09 |
| Placebo | Change From Baseline in Calcium (Corrected) at Month 3 | 0 mmol/L | Standard Deviation 0.1 |
Secondary
Change From Baseline in Calcium (Corrected) at Month 6
Laboratory chemistry albumin-adjusted calcium
Time frame: Baseline, Month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Calcium (Corrected) at Month 6 | -0.01 mmol/L | Standard Deviation 0.1 |
| Denosumab 60 mg | Change From Baseline in Calcium (Corrected) at Month 6 | -0.02 mmol/L | Standard Deviation 0.1 |
| Placebo | Change From Baseline in Calcium (Corrected) at Month 6 | -0.01 mmol/L | Standard Deviation 0.09 |
Secondary
Change From Baseline in Chloride at Month 1
Laboratory chemistry chloride
Time frame: baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Chloride at Month 1 | 0.24 mmol/L | Standard Deviation 2.36 |
| Denosumab 60 mg | Change From Baseline in Chloride at Month 1 | 0.58 mmol/L | Standard Deviation 2.66 |
| Placebo | Change From Baseline in Chloride at Month 1 | 0.01 mmol/L | Standard Deviation 2.09 |
Secondary
Change From Baseline in Chloride at Month 12
Laboratory chemistry chloride
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Chloride at Month 12 | -0.62 mmol/L | Standard Deviation 2.45 |
| Denosumab 60 mg | Change From Baseline in Chloride at Month 12 | -0.21 mmol/L | Standard Deviation 2.58 |
| Placebo | Change From Baseline in Chloride at Month 12 | -0.08 mmol/L | Standard Deviation 2.39 |
Secondary
Change From Baseline in Chloride at Month 3
Laboratory chemistry chloride
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Chloride at Month 3 | -0.01 mmol/L | Standard Deviation 2.67 |
| Denosumab 60 mg | Change From Baseline in Chloride at Month 3 | 0.38 mmol/L | Standard Deviation 2.35 |
| Placebo | Change From Baseline in Chloride at Month 3 | 0.78 mmol/L | Standard Deviation 2.2 |
Secondary
Change From Baseline in Chloride at Month 6
Laboratory chemistry chloride
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Chloride at Month 6 | -0.57 mmol/L | Standard Deviation 2.85 |
| Denosumab 60 mg | Change From Baseline in Chloride at Month 6 | 0.48 mmol/L | Standard Deviation 2.19 |
| Placebo | Change From Baseline in Chloride at Month 6 | 0 mmol/L | Standard Deviation 2.79 |
Secondary
Change From Baseline in Creatinine at Month 1
Laboratory chemistry creatinine
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Creatinine at Month 1 | -0.88 µmol/L | Standard Deviation 9.89 |
| Denosumab 60 mg | Change From Baseline in Creatinine at Month 1 | 0.38 µmol/L | Standard Deviation 8.63 |
| Placebo | Change From Baseline in Creatinine at Month 1 | 1.47 µmol/L | Standard Deviation 8.78 |
Secondary
Change From Baseline in Creatinine at Month 12
Laboratory chemistry creatinine
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Creatinine at Month 12 | 5.44 µmol/L | Standard Deviation 10.09 |
| Denosumab 60 mg | Change From Baseline in Creatinine at Month 12 | 4.42 µmol/L | Standard Deviation 9.59 |
| Placebo | Change From Baseline in Creatinine at Month 12 | 3.73 µmol/L | Standard Deviation 7.84 |
Secondary
Change From Baseline in Creatinine at Month 3
Laboratory chemistry creatinine
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Creatinine at Month 3 | 0.62 µmol/L | Standard Deviation 11.11 |
| Denosumab 60 mg | Change From Baseline in Creatinine at Month 3 | 3.20 µmol/L | Standard Deviation 8.3 |
| Placebo | Change From Baseline in Creatinine at Month 3 | 3.81 µmol/L | Standard Deviation 9.24 |
Secondary
Change From Baseline in Creatinine at Month 6
Laboratory chemistry creatinine
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Creatinine at Month 6 | 3.30 µmol/L | Standard Deviation 10.97 |
| Denosumab 60 mg | Change From Baseline in Creatinine at Month 6 | 3.84 µmol/L | Standard Deviation 9.88 |
| Placebo | Change From Baseline in Creatinine at Month 6 | 3.54 µmol/L | Standard Deviation 11.6 |
Secondary
Change From Baseline in Eosinophils at Month 1
Laboratory hematology eosinophils
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Eosinophils at Month 1 | -0.02 * 10^9/L | Standard Deviation 0.09 |
| Denosumab 60 mg | Change From Baseline in Eosinophils at Month 1 | -0.01 * 10^9/L | Standard Deviation 0.09 |
| Placebo | Change From Baseline in Eosinophils at Month 1 | 0.01 * 10^9/L | Standard Deviation 0.08 |
Secondary
Change From Baseline in Eosinophils at Month 12
Laboratory hematology eosinophils
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Eosinophils at Month 12 | 0.03 * 10^9/L | Standard Deviation 0.16 |
| Denosumab 60 mg | Change From Baseline in Eosinophils at Month 12 | 0.02 * 10^9/L | Standard Deviation 0.12 |
| Placebo | Change From Baseline in Eosinophils at Month 12 | 0.01 * 10^9/L | Standard Deviation 0.12 |
Secondary
Change From Baseline in Eosinophils at Month 3
Laboratory hematology eosinophils
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Eosinophils at Month 3 | 0 * 10^9/L | Standard Deviation 0.1 |
| Denosumab 60 mg | Change From Baseline in Eosinophils at Month 3 | 0 * 10^9/L | Standard Deviation 0.1 |
| Placebo | Change From Baseline in Eosinophils at Month 3 | -0.01 * 10^9/L | Standard Deviation 0.09 |
Secondary
Change From Baseline in Eosinophils at Month 6
Laboratory hematology eosinophils
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Eosinophils at Month 6 | -0.03 * 10^9/L | Standard Deviation 0.09 |
| Denosumab 60 mg | Change From Baseline in Eosinophils at Month 6 | 0 * 10^9/L | Standard Deviation 0.13 |
| Placebo | Change From Baseline in Eosinophils at Month 6 | 0 * 10^9/L | Standard Deviation 0.13 |
Secondary
Change From Baseline in Gamma-Glutamyl Transferase at Month 1
Laboratory chemistry gamma-glutamyl transferase
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Gamma-Glutamyl Transferase at Month 1 | 1.04 U/L | Standard Deviation 8.13 |
| Denosumab 60 mg | Change From Baseline in Gamma-Glutamyl Transferase at Month 1 | -1.25 U/L | Standard Deviation 9.67 |
| Placebo | Change From Baseline in Gamma-Glutamyl Transferase at Month 1 | 0.26 U/L | Standard Deviation 10.63 |
Secondary
Change From Baseline in Gamma-Glutamyl Transferase at Month 12
Laboratory chemistry gamma-glutamyl transferase
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Gamma-Glutamyl Transferase at Month 12 | 2.98 U/L | Standard Deviation 10.94 |
| Denosumab 60 mg | Change From Baseline in Gamma-Glutamyl Transferase at Month 12 | 1.08 U/L | Standard Deviation 16.09 |
| Placebo | Change From Baseline in Gamma-Glutamyl Transferase at Month 12 | -1.38 U/L | Standard Deviation 14.7 |
Secondary
Change From Baseline in Gamma-Glutamyl Transferase at Month 3
Laboratory chemistry gamma-glutamyl transferase
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Gamma-Glutamyl Transferase at Month 3 | 2.32 U/L | Standard Deviation 10.94 |
| Denosumab 60 mg | Change From Baseline in Gamma-Glutamyl Transferase at Month 3 | 0.04 U/L | Standard Deviation 9.9 |
| Placebo | Change From Baseline in Gamma-Glutamyl Transferase at Month 3 | 1.51 U/L | Standard Deviation 15.87 |
Secondary
Change From Baseline in Gamma-Glutamyl Transferase at Month 6
Laboratory chemistry gamma-glutamyl transferase
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Gamma-Glutamyl Transferase at Month 6 | 7.37 U/L | Standard Deviation 36.42 |
| Denosumab 60 mg | Change From Baseline in Gamma-Glutamyl Transferase at Month 6 | 0.28 U/L | Standard Deviation 12.7 |
| Placebo | Change From Baseline in Gamma-Glutamyl Transferase at Month 6 | 5.67 U/L | Standard Deviation 37.98 |
Secondary
Change From Baseline in Glucose at Month 1
Laboratory chemistry glucose
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Glucose at Month 1 | 0.06 mmol/L | Standard Deviation 0.76 |
| Denosumab 60 mg | Change From Baseline in Glucose at Month 1 | 0.20 mmol/L | Standard Deviation 0.65 |
| Placebo | Change From Baseline in Glucose at Month 1 | 0.05 mmol/L | Standard Deviation 1.28 |
Secondary
Change From Baseline in Glucose at Month 12
Laboratory chemistry glucose
Time frame: baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Glucose at Month 12 | -0.04 mmol/L | Standard Deviation 0.66 |
| Denosumab 60 mg | Change From Baseline in Glucose at Month 12 | 0.22 mmol/L | Standard Deviation 0.96 |
| Placebo | Change From Baseline in Glucose at Month 12 | 0.19 mmol/L | Standard Deviation 1.27 |
Secondary
Change From Baseline in Glucose at Month 3
Laboratory chemistry glucose
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Glucose at Month 3 | 0.08 mmol/L | Standard Deviation 0.87 |
| Denosumab 60 mg | Change From Baseline in Glucose at Month 3 | 0.20 mmol/L | Standard Deviation 0.63 |
| Placebo | Change From Baseline in Glucose at Month 3 | 0.04 mmol/L | Standard Deviation 1.26 |
Secondary
Change From Baseline in Glucose at Month 6
Laboratory chemistry glucose
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Glucose at Month 6 | 0.12 mmol/L | Standard Deviation 0.85 |
| Denosumab 60 mg | Change From Baseline in Glucose at Month 6 | 0.20 mmol/L | Standard Deviation 0.65 |
| Placebo | Change From Baseline in Glucose at Month 6 | -0.05 mmol/L | Standard Deviation 1.26 |
Secondary
Change From Baseline in Hematocrit at Month 1
Laboratory hematology hematocrit
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Hematocrit at Month 1 | 0 Proportion of red blood cells in blood | Standard Deviation 0.02 |
| Denosumab 60 mg | Change From Baseline in Hematocrit at Month 1 | 0 Proportion of red blood cells in blood | Standard Deviation 0.02 |
| Placebo | Change From Baseline in Hematocrit at Month 1 | 0 Proportion of red blood cells in blood | Standard Deviation 0.02 |
Secondary
Change From Baseline in Hematocrit at Month 12
Laboratory hematology hematocrit
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Hematocrit at Month 12 | 0 Proportion of red blood cells in blood | Standard Deviation 0.02 |
| Denosumab 60 mg | Change From Baseline in Hematocrit at Month 12 | 0 Proportion of red blood cells in blood | Standard Deviation 0.03 |
| Placebo | Change From Baseline in Hematocrit at Month 12 | -0.01 Proportion of red blood cells in blood | Standard Deviation 0.03 |
Secondary
Change From Baseline in Hematocrit at Month 3
Laboratory hematology hematocrit
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Hematocrit at Month 3 | 0.01 Proportion of red blood cells in blood | Standard Deviation 0.02 |
| Denosumab 60 mg | Change From Baseline in Hematocrit at Month 3 | 0 Proportion of red blood cells in blood | Standard Deviation 0.03 |
| Placebo | Change From Baseline in Hematocrit at Month 3 | 0 Proportion of red blood cells in blood | Standard Deviation 0.03 |
Secondary
Change From Baseline in Hematocrit at Month 6
Laboratory hematology hematocrit
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Hematocrit at Month 6 | 0.01 Proportion of red blood cells in blood | Standard Deviation 0.02 |
| Denosumab 60 mg | Change From Baseline in Hematocrit at Month 6 | 0 Proportion of red blood cells in blood | Standard Deviation 0.03 |
| Placebo | Change From Baseline in Hematocrit at Month 6 | 0 Proportion of red blood cells in blood | Standard Deviation 0.03 |
Secondary
Change From Baseline in Hemoglobin at Month 1
Laboratory hematology hemoglobin
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Hemoglobin at Month 1 | -0.33 g/L | Standard Deviation 6.73 |
| Denosumab 60 mg | Change From Baseline in Hemoglobin at Month 1 | -1.48 g/L | Standard Deviation 6.39 |
| Placebo | Change From Baseline in Hemoglobin at Month 1 | -0.69 g/L | Standard Deviation 6.34 |
Secondary
Change From Baseline in Hemoglobin at Month 12
Laboratory hematology hemoglobin
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Hemoglobin at Month 12 | 1.21 g/L | Standard Deviation 9.26 |
| Denosumab 60 mg | Change From Baseline in Hemoglobin at Month 12 | 0.02 g/L | Standard Deviation 11.66 |
| Placebo | Change From Baseline in Hemoglobin at Month 12 | -0.46 g/L | Standard Deviation 10.08 |
Secondary
Change From Baseline in Hemoglobin at Month 3
Laboratory hematology hemoglobin
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Hemoglobin at Month 3 | 0.69 g/L | Standard Deviation 7.02 |
| Denosumab 60 mg | Change From Baseline in Hemoglobin at Month 3 | -1.02 g/L | Standard Deviation 8.36 |
| Placebo | Change From Baseline in Hemoglobin at Month 3 | -1.10 g/L | Standard Deviation 6.3 |
Secondary
Change From Baseline in Hemoglobin at Month 6
Laboratory hematology hemoglobin
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Hemoglobin at Month 6 | -0.36 g/L | Standard Deviation 7.8 |
| Denosumab 60 mg | Change From Baseline in Hemoglobin at Month 6 | -1.69 g/L | Standard Deviation 8.82 |
| Placebo | Change From Baseline in Hemoglobin at Month 6 | -0.69 g/L | Standard Deviation 8.21 |
Secondary
Change From Baseline in Lymphocytes at Month 1
Laboratory hematology lymphocytes
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Lymphocytes at Month 1 | -0.02 * 10^9/L | Standard Deviation 0.41 |
| Denosumab 60 mg | Change From Baseline in Lymphocytes at Month 1 | 0.10 * 10^9/L | Standard Deviation 0.4 |
| Placebo | Change From Baseline in Lymphocytes at Month 1 | 0 * 10^9/L | Standard Deviation 0.45 |
Secondary
Change From Baseline in Lymphocytes at Month 12
Laboratory hematology lymphocytes
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Lymphocytes at Month 12 | -0.02 * 10^9/L | Standard Deviation 0.49 |
| Denosumab 60 mg | Change From Baseline in Lymphocytes at Month 12 | 0.04 * 10^9/L | Standard Deviation 0.5 |
| Placebo | Change From Baseline in Lymphocytes at Month 12 | -0.02 * 10^9/L | Standard Deviation 0.49 |
Secondary
Change From Baseline in Lymphocytes at Month 3
Laboratory hematology lymphocytes
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Lymphocytes at Month 3 | 0.07 * 10^9/L | Standard Deviation 0.38 |
| Denosumab 60 mg | Change From Baseline in Lymphocytes at Month 3 | 0.14 * 10^9/L | Standard Deviation 0.48 |
| Placebo | Change From Baseline in Lymphocytes at Month 3 | 0.08 * 10^9/L | Standard Deviation 0.46 |
Secondary
Change From Baseline in Lymphocytes at Month 6
Laboratory hematology lymphocytes
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Lymphocytes at Month 6 | 0.12 * 10^9/L | Standard Deviation 0.41 |
| Denosumab 60 mg | Change From Baseline in Lymphocytes at Month 6 | 0.05 * 10^9/L | Standard Deviation 0.35 |
| Placebo | Change From Baseline in Lymphocytes at Month 6 | 0.03 * 10^9/L | Standard Deviation 0.68 |
Secondary
Change From Baseline in Magnesium at Month 1
Laboratory chemistry magnesium
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Magnesium at Month 1 | 0.01 mmol/L | Standard Deviation 0.06 |
| Denosumab 60 mg | Change From Baseline in Magnesium at Month 1 | 0.02 mmol/L | Standard Deviation 0.06 |
| Placebo | Change From Baseline in Magnesium at Month 1 | 0.01 mmol/L | Standard Deviation 0.05 |
Secondary
Change From Baseline in Magnesium at Month 12
Laboratory chemistry magnesium
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Magnesium at Month 12 | -0.01 mmol/L | Standard Deviation 0.06 |
| Denosumab 60 mg | Change From Baseline in Magnesium at Month 12 | -0.01 mmol/L | Standard Deviation 0.07 |
| Placebo | Change From Baseline in Magnesium at Month 12 | -0.01 mmol/L | Standard Deviation 0.08 |
Secondary
Change From Baseline in Magnesium at Month 3
Laboratory chemistry magnesium
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Magnesium at Month 3 | -0.01 mmol/L | Standard Deviation 0.06 |
| Denosumab 60 mg | Change From Baseline in Magnesium at Month 3 | 0.02 mmol/L | Standard Deviation 0.06 |
| Placebo | Change From Baseline in Magnesium at Month 3 | 0 mmol/L | Standard Deviation 0.06 |
Secondary
Change From Baseline in Magnesium at Month 6
Laboratory chemistry magnesium
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Magnesium at Month 6 | 0 mmol/L | Standard Deviation 0.06 |
| Denosumab 60 mg | Change From Baseline in Magnesium at Month 6 | 0.01 mmol/L | Standard Deviation 0.06 |
| Placebo | Change From Baseline in Magnesium at Month 6 | 0.01 mmol/L | Standard Deviation 0.07 |
Secondary
Change From Baseline in Monocytes at Month 1
Laboratory hematology monocytes
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Monocytes at Month 1 | 0.01 * 10^9/L | Standard Deviation 0.13 |
| Denosumab 60 mg | Change From Baseline in Monocytes at Month 1 | -0.01 * 10^9/L | Standard Deviation 0.1 |
| Placebo | Change From Baseline in Monocytes at Month 1 | 0.01 * 10^9/L | Standard Deviation 0.12 |
Secondary
Change From Baseline in Monocytes at Month 12
Laboratory hematology monocytes
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Monocytes at Month 12 | 0.03 * 10^9/L | Standard Deviation 0.15 |
| Denosumab 60 mg | Change From Baseline in Monocytes at Month 12 | 0 * 10^9/L | Standard Deviation 0.11 |
| Placebo | Change From Baseline in Monocytes at Month 12 | 0.02 * 10^9/L | Standard Deviation 0.13 |
Secondary
Change From Baseline in Monocytes at Month 3
Laboratory hematology monocytes
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Monocytes at Month 3 | 0.02 * 10^9/L | Standard Deviation 0.11 |
| Denosumab 60 mg | Change From Baseline in Monocytes at Month 3 | 0.01 * 10^9/L | Standard Deviation 0.11 |
| Placebo | Change From Baseline in Monocytes at Month 3 | 0.02 * 10^9/L | Standard Deviation 0.11 |
Secondary
Change From Baseline in Monocytes at Month 6
Laboratory hematology monocytes
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Monocytes at Month 6 | 0.05 * 10^9/L | Standard Deviation 0.17 |
| Denosumab 60 mg | Change From Baseline in Monocytes at Month 6 | 0.04 * 10^9/L | Standard Deviation 0.12 |
| Placebo | Change From Baseline in Monocytes at Month 6 | 0.04 * 10^9/L | Standard Deviation 0.13 |
Secondary
Change From Baseline in Phosphorus at Month 1
Laboratory chemistry phosphorus
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Phosphorus at Month 1 | -0.09 mmol/L | Standard Deviation 0.16 |
| Denosumab 60 mg | Change From Baseline in Phosphorus at Month 1 | -0.06 mmol/L | Standard Deviation 0.19 |
| Placebo | Change From Baseline in Phosphorus at Month 1 | 0.02 mmol/L | Standard Deviation 0.14 |
Secondary
Change From Baseline in Phosphorus at Month 12
Change From Baseline in Phosphorus at Month 12
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Phosphorus at Month 12 | -0.05 mmol/L | Standard Deviation 0.17 |
| Denosumab 60 mg | Change From Baseline in Phosphorus at Month 12 | 0 mmol/L | Standard Deviation 0.17 |
| Placebo | Change From Baseline in Phosphorus at Month 12 | 0 mmol/L | Standard Deviation 0.16 |
Secondary
Change From Baseline in Phosphorus at Month 3
Laboratory chemistry phosphorus
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Phosphorus at Month 3 | -0.03 mmol/L | Standard Deviation 0.16 |
| Denosumab 60 mg | Change From Baseline in Phosphorus at Month 3 | -0.03 mmol/L | Standard Deviation 0.18 |
| Placebo | Change From Baseline in Phosphorus at Month 3 | 0.01 mmol/L | Standard Deviation 0.2 |
Secondary
Change From Baseline in Phosphorus at Month 6
Laboratory chemistry phosphorus
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Phosphorus at Month 6 | -0.05 mmol/L | Standard Deviation 0.17 |
| Denosumab 60 mg | Change From Baseline in Phosphorus at Month 6 | -0.01 mmol/L | Standard Deviation 0.18 |
| Placebo | Change From Baseline in Phosphorus at Month 6 | 0.03 mmol/L | Standard Deviation 0.19 |
Secondary
Change From Baseline in Platelets at Month 1
Laboratory hematology platelets
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Platelets at Month 1 | 1.78 * 10^9/L | Standard Deviation 44.53 |
| Denosumab 60 mg | Change From Baseline in Platelets at Month 1 | 10.36 * 10^9/L | Standard Deviation 49.34 |
| Placebo | Change From Baseline in Platelets at Month 1 | 2.96 * 10^9/L | Standard Deviation 44.15 |
Secondary
Change From Baseline in Platelets at Month 12
Laboratory hematology platelets
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Platelets at Month 12 | 3.32 * 10^9/L | Standard Deviation 51.66 |
| Denosumab 60 mg | Change From Baseline in Platelets at Month 12 | -4.26 * 10^9/L | Standard Deviation 51.12 |
| Placebo | Change From Baseline in Platelets at Month 12 | 1.07 * 10^9/L | Standard Deviation 58.16 |
Secondary
Change From Baseline in Platelets at Month 3
Laboratory hematology platelets
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Platelets at Month 3 | -2.82 * 10^9/L | Standard Deviation 48.86 |
| Denosumab 60 mg | Change From Baseline in Platelets at Month 3 | 6.86 * 10^9/L | Standard Deviation 50.18 |
| Placebo | Change From Baseline in Platelets at Month 3 | -1.97 * 10^9/L | Standard Deviation 45.94 |
Secondary
Change From Baseline in Platelets at Month 6
Laboratory hematology platelets
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Platelets at Month 6 | 1.95 * 10^9/L | Standard Deviation 54.95 |
| Denosumab 60 mg | Change From Baseline in Platelets at Month 6 | 1.00 * 10^9/L | Standard Deviation 45.64 |
| Placebo | Change From Baseline in Platelets at Month 6 | 1.57 * 10^9/L | Standard Deviation 53.39 |
Secondary
Change From Baseline in Potassium at Month 1
Laboratory chemistry potassium
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Potassium at Month 1 | 0.06 mmol/L | Standard Deviation 0.38 |
| Denosumab 60 mg | Change From Baseline in Potassium at Month 1 | 0.06 mmol/L | Standard Deviation 0.36 |
| Placebo | Change From Baseline in Potassium at Month 1 | 0.04 mmol/L | Standard Deviation 0.36 |
Secondary
Change From Baseline in Potassium at Month 12
Laboratory chemistry potassium
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Potassium at Month 12 | -0.07 mmol/L | Standard Deviation 0.44 |
| Denosumab 60 mg | Change From Baseline in Potassium at Month 12 | -0.08 mmol/L | Standard Deviation 0.35 |
| Placebo | Change From Baseline in Potassium at Month 12 | -0.04 mmol/L | Standard Deviation 0.43 |
Secondary
Change From Baseline in Potassium at Month 3
Laboratory chemistry potassium
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Potassium at Month 3 | -0.01 mmol/L | Standard Deviation 0.39 |
| Denosumab 60 mg | Change From Baseline in Potassium at Month 3 | 0.06 mmol/L | Standard Deviation 0.4 |
| Placebo | Change From Baseline in Potassium at Month 3 | 0.04 mmol/L | Standard Deviation 0.38 |
Secondary
Change From Baseline in Potassium at Month 6
Laboratory chemistry potassium
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Potassium at Month 6 | 0.01 mmol/L | Standard Deviation 0.44 |
| Denosumab 60 mg | Change From Baseline in Potassium at Month 6 | -0.01 mmol/L | Standard Deviation 0.36 |
| Placebo | Change From Baseline in Potassium at Month 6 | 0 mmol/L | Standard Deviation 0.42 |
Secondary
Change From Baseline in Radiographic Erosion Score at Month 12
The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet, obtained from radiographs of the hands and feet and assessed by 2 independent readers. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280.
Time frame: Baseline, Month 12
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 12 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab 180 mg | Change From Baseline in Radiographic Erosion Score at Month 12 | 0 units on a scale |
| Denosumab 60 mg | Change From Baseline in Radiographic Erosion Score at Month 12 | 0 units on a scale |
| Placebo | Change From Baseline in Radiographic Erosion Score at Month 12 | 0 units on a scale |
p-value: 0.012van Elteren Stratified Rank Test
p-value: 0.007van Elteren Stratified Rank Test
Secondary
Change From Baseline in Radiographic Erosion Score at Month 6
The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet, obtained from radiographs of the hands and feet and assessed by 2 independent readers. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280.
Time frame: Baseline, Month 6
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab 180 mg | Change From Baseline in Radiographic Erosion Score at Month 6 | 0 units on a scale |
| Denosumab 60 mg | Change From Baseline in Radiographic Erosion Score at Month 6 | 0 units on a scale |
| Placebo | Change From Baseline in Radiographic Erosion Score at Month 6 | 0 units on a scale |
p-value: 0.277van Elteren Stratified Rank Test
p-value: 0.019van Elteren Stratified Rank Test
Secondary
Change From Baseline in Radiographic Joint Space Narrowing Score at Month 12
Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet obtained from radiographs of the hands and feet and assessed by 2 independent readers. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score (indicating worst joint space narrowing) of 168.
Time frame: Baseline, Month 12
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 12 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab 180 mg | Change From Baseline in Radiographic Joint Space Narrowing Score at Month 12 | 0 units on a scale |
| Denosumab 60 mg | Change From Baseline in Radiographic Joint Space Narrowing Score at Month 12 | 0 units on a scale |
| Placebo | Change From Baseline in Radiographic Joint Space Narrowing Score at Month 12 | 0 units on a scale |
p-value: 0.382van Elteren Stratified Rank Test
p-value: 0.488van Elteren Stratified Rank Test
Secondary
Change From Baseline in Radiographic Joint Space Narrowing Score at Month 6
Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet obtained from radiographs of the hands and feet and assessed by 2 independent readers. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score (indicating worst joint space narrowing) of 168.
Time frame: Baseline, Month 6
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab 180 mg | Change From Baseline in Radiographic Joint Space Narrowing Score at Month 6 | 0 units on a scale |
| Denosumab 60 mg | Change From Baseline in Radiographic Joint Space Narrowing Score at Month 6 | 0 units on a scale |
| Placebo | Change From Baseline in Radiographic Joint Space Narrowing Score at Month 6 | 0 units on a scale |
p-value: 0.236van Elteren Stratified Rank Test
p-value: 0.712van Elteren Stratified Rank Test
Secondary
Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 12
TSS is the sum of erosion and joint space narrowing scores obtained from radiographs of the hands and feet, assessed by 2 independent readers. The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280. Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. The TSS ranged from 0 (normal) to 448 (worst).
Time frame: Baseline, Month 12
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 12 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab 180 mg | Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 12 | 0 units on a scale |
| Denosumab 60 mg | Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 12 | 0 units on a scale |
| Placebo | Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 12 | 0.5 units on a scale |
p-value: 0.032van Elteren Stratified Rank Test
p-value: 0.18van Elteren Stratified Rank Test
Secondary
Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 6
TSS is the sum of erosion and joint space narrowing scores obtained from radiographs of the hands and feet, assessed by 2 independent readers. The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280. Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. The TSS ranged from 0 (normal) to 448 (worst).
Time frame: Baseline, Month 6
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab 180 mg | Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 6 | 0 units on a scale |
| Denosumab 60 mg | Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 6 | 0 units on a scale |
| Placebo | Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 6 | 0 units on a scale |
p-value: 0.602van Elteren Stratified Rank Test
p-value: 0.181van Elteren Stratified Rank Test
Secondary
Change From Baseline in Red Blood Cells at Month 1
Laboratory hematology red blood cells
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Red Blood Cells at Month 1 | -0.01 * 10^9/L | Standard Deviation 0.21 |
| Denosumab 60 mg | Change From Baseline in Red Blood Cells at Month 1 | -0.01 * 10^9/L | Standard Deviation 0.2 |
| Placebo | Change From Baseline in Red Blood Cells at Month 1 | -0.01 * 10^9/L | Standard Deviation 0.19 |
Secondary
Change From Baseline in Red Blood Cells at Month 12
Laboratory hematology red blood cells
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Red Blood Cells at Month 12 | 0.01 * 10^9/L | Standard Deviation 0.27 |
| Denosumab 60 mg | Change From Baseline in Red Blood Cells at Month 12 | -0.06 * 10^9/L | Standard Deviation 0.3 |
| Placebo | Change From Baseline in Red Blood Cells at Month 12 | -0.03 * 10^9/L | Standard Deviation 0.29 |
Secondary
Change From Baseline in Red Blood Cells at Month 3
Laboratory hematology red blood cells
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Red Blood Cells at Month 3 | 0.05 * 10^9/L | Standard Deviation 0.23 |
| Denosumab 60 mg | Change From Baseline in Red Blood Cells at Month 3 | 0.02 * 10^9/L | Standard Deviation 0.28 |
| Placebo | Change From Baseline in Red Blood Cells at Month 3 | 0 * 10^9/L | Standard Deviation 0.23 |
Secondary
Change From Baseline in Red Blood Cells at Month 6
Laboratory hematology red blood cells
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Red Blood Cells at Month 6 | 0.01 * 10^9/L | Standard Deviation 0.24 |
| Denosumab 60 mg | Change From Baseline in Red Blood Cells at Month 6 | -0.04 * 10^9/L | Standard Deviation 0.26 |
| Placebo | Change From Baseline in Red Blood Cells at Month 6 | 0.01 * 10^9/L | Standard Deviation 0.26 |
Secondary
Change From Baseline in Sodium at Month 1
Laboratory chemistry sodium
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Sodium at Month 1 | -0.03 mmol/L | Standard Deviation 1.93 |
| Denosumab 60 mg | Change From Baseline in Sodium at Month 1 | -0.06 mmol/L | Standard Deviation 2.62 |
| Placebo | Change From Baseline in Sodium at Month 1 | 0.33 mmol/L | Standard Deviation 2.03 |
Secondary
Change From Baseline in Sodium at Month 12
Laboratory chemistry sodium
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Sodium at Month 12 | -0.25 mmol/L | Standard Deviation 2.02 |
| Denosumab 60 mg | Change From Baseline in Sodium at Month 12 | -0.27 mmol/L | Standard Deviation 2.75 |
| Placebo | Change From Baseline in Sodium at Month 12 | 0.33 mmol/L | Standard Deviation 2.38 |
Secondary
Change From Baseline in Sodium at Month 3
Change From Baseline in Sodium at Month 3
Time frame: Baseline, Month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Sodium at Month 3 | -0.14 mmol/L | Standard Deviation 2.13 |
| Denosumab 60 mg | Change From Baseline in Sodium at Month 3 | -0.16 mmol/L | Standard Deviation 2.29 |
| Placebo | Change From Baseline in Sodium at Month 3 | 0.39 mmol/L | Standard Deviation 2.38 |
Secondary
Change From Baseline in Sodium at Month 6
Laboratory chemistry sodium
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Sodium at Month 6 | -0.12 mmol/L | Standard Deviation 1.98 |
| Denosumab 60 mg | Change From Baseline in Sodium at Month 6 | -0.06 mmol/L | Standard Deviation 1.75 |
| Placebo | Change From Baseline in Sodium at Month 6 | 0.03 mmol/L | Standard Deviation 2.27 |
Secondary
Change From Baseline in Total Bilirubin at Month 1
Laboratory chemistry total bilirubin
Time frame: baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Total Bilirubin at Month 1 | 0.26 umol/L | Standard Deviation 2.39 |
| Denosumab 60 mg | Change From Baseline in Total Bilirubin at Month 1 | -0.23 umol/L | Standard Deviation 2.45 |
| Placebo | Change From Baseline in Total Bilirubin at Month 1 | 0.42 umol/L | Standard Deviation 2.83 |
Secondary
Change From Baseline in Total Bilirubin at Month 12
Laboratory chemistry total bilirubin
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Total Bilirubin at Month 12 | 0.41 umol/L | Standard Deviation 2.58 |
| Denosumab 60 mg | Change From Baseline in Total Bilirubin at Month 12 | -0.35 umol/L | Standard Deviation 2.28 |
| Placebo | Change From Baseline in Total Bilirubin at Month 12 | 0.03 umol/L | Standard Deviation 2.8 |
Secondary
Change From Baseline in Total Bilirubin at Month 3
Laboratory chemistry total bilirubin
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Total Bilirubin at Month 3 | 0.92 umol/L | Standard Deviation 2.17 |
| Denosumab 60 mg | Change From Baseline in Total Bilirubin at Month 3 | -0.23 umol/L | Standard Deviation 2.36 |
| Placebo | Change From Baseline in Total Bilirubin at Month 3 | 0.44 umol/L | Standard Deviation 2.74 |
Secondary
Change From Baseline in Total Bilirubin at Month 6
Laboratory chemistry total bilirubin
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Total Bilirubin at Month 6 | 1.08 umol/L | Standard Deviation 2.58 |
| Denosumab 60 mg | Change From Baseline in Total Bilirubin at Month 6 | -0.61 umol/L | Standard Deviation 2.49 |
| Placebo | Change From Baseline in Total Bilirubin at Month 6 | 0.34 umol/L | Standard Deviation 3.3 |
Secondary
Change From Baseline in Total Neutrophils at Month 1
Laboratory hematology total neutrophils
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Total Neutrophils at Month 1 | 0 * 10^9/L | Standard Deviation 1.97 |
| Denosumab 60 mg | Change From Baseline in Total Neutrophils at Month 1 | 0.18 * 10^9/L | Standard Deviation 1.99 |
| Placebo | Change From Baseline in Total Neutrophils at Month 1 | -0.13 * 10^9/L | Standard Deviation 1.68 |
Secondary
Change From Baseline in Total Neutrophils at Month 12
Laboratory hematology total neutrophils
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Total Neutrophils at Month 12 | 0.65 * 10^9/L | Standard Deviation 2.37 |
| Denosumab 60 mg | Change From Baseline in Total Neutrophils at Month 12 | 0.04 * 10^9/L | Standard Deviation 1.79 |
| Placebo | Change From Baseline in Total Neutrophils at Month 12 | 0.10 * 10^9/L | Standard Deviation 2.31 |
Secondary
Change From Baseline in Total Neutrophils at Month 3
Laboratory hematology total neutrophils
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Total Neutrophils at Month 3 | 0.11 * 10^9/L | Standard Deviation 1.92 |
| Denosumab 60 mg | Change From Baseline in Total Neutrophils at Month 3 | 0.26 * 10^9/L | Standard Deviation 1.64 |
| Placebo | Change From Baseline in Total Neutrophils at Month 3 | -0.11 * 10^9/L | Standard Deviation 1.55 |
Secondary
Change From Baseline in Total Neutrophils at Month 6
Laboratory hematology total neutrophils
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Total Neutrophils at Month 6 | 0.18 * 10^9/L | Standard Deviation 1.67 |
| Denosumab 60 mg | Change From Baseline in Total Neutrophils at Month 6 | -0.05 * 10^9/L | Standard Deviation 1.66 |
| Placebo | Change From Baseline in Total Neutrophils at Month 6 | 0.27 * 10^9/L | Standard Deviation 2.36 |
Secondary
Change From Baseline in Total Protein at Month 1
Laboratory chemistry total protein
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Total Protein at Month 1 | -0.46 g/L | Standard Deviation 3.56 |
| Denosumab 60 mg | Change From Baseline in Total Protein at Month 1 | -0.40 g/L | Standard Deviation 3.22 |
| Placebo | Change From Baseline in Total Protein at Month 1 | 0.21 g/L | Standard Deviation 3 |
Secondary
Change From Baseline in Total Protein at Month 12
Laboratory chemistry total protein
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Total Protein at Month 12 | -0.97 g/L | Standard Deviation 3.76 |
| Denosumab 60 mg | Change From Baseline in Total Protein at Month 12 | -0.91 g/L | Standard Deviation 3.55 |
| Placebo | Change From Baseline in Total Protein at Month 12 | -0.98 g/L | Standard Deviation 3.1 |
Secondary
Change From Baseline in Total Protein at Month 3
Laboratory chemistry total protein
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Total Protein at Month 3 | -0.29 g/L | Standard Deviation 3.35 |
| Denosumab 60 mg | Change From Baseline in Total Protein at Month 3 | 0.07 g/L | Standard Deviation 3.42 |
| Placebo | Change From Baseline in Total Protein at Month 3 | -0.20 g/L | Standard Deviation 3.54 |
Secondary
Change From Baseline in Total Protein at Month 6
Laboratory chemistry total protein
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in Total Protein at Month 6 | -0.09 g/L | Standard Deviation 4.13 |
| Denosumab 60 mg | Change From Baseline in Total Protein at Month 6 | -0.62 g/L | Standard Deviation 3.4 |
| Placebo | Change From Baseline in Total Protein at Month 6 | -0.57 g/L | Standard Deviation 3.19 |
Secondary
Change From Baseline in White Blood Cells at Month 1
Laboratory hematology white blood cells
Time frame: Baseline, month 1
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in White Blood Cells at Month 1 | -0.03 * 10^9/L | Standard Deviation 2.07 |
| Denosumab 60 mg | Change From Baseline in White Blood Cells at Month 1 | 0.26 * 10^9/L | Standard Deviation 2.04 |
| Placebo | Change From Baseline in White Blood Cells at Month 1 | -0.10 * 10^9/L | Standard Deviation 1.88 |
Secondary
Change From Baseline in White Blood Cells at Month 12
Laboratory hematology white blood cells
Time frame: Baseline, month 12
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in White Blood Cells at Month 12 | 0.70 * 10^9/L | Standard Deviation 2.4 |
| Denosumab 60 mg | Change From Baseline in White Blood Cells at Month 12 | 0.11 * 10^9/L | Standard Deviation 1.86 |
| Placebo | Change From Baseline in White Blood Cells at Month 12 | 0.13 * 10^9/L | Standard Deviation 2.22 |
Secondary
Change From Baseline in White Blood Cells at Month 3
Laboratpry hematology white blood cells
Time frame: Baseline, month 3
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in White Blood Cells at Month 3 | 0.18 * 10^9/L | Standard Deviation 1.93 |
| Denosumab 60 mg | Change From Baseline in White Blood Cells at Month 3 | 0.40 * 10^9/L | Standard Deviation 1.71 |
| Placebo | Change From Baseline in White Blood Cells at Month 3 | -0.05 * 10^9/L | Standard Deviation 1.64 |
Secondary
Change From Baseline in White Blood Cells at Month 6
Laboratory hematology white blood cells
Time frame: Baseline, month 6
Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Change From Baseline in White Blood Cells at Month 6 | 0.30 * 10^9/L | Standard Deviation 1.78 |
| Denosumab 60 mg | Change From Baseline in White Blood Cells at Month 6 | 0.04 * 10^9/L | Standard Deviation 1.85 |
| Placebo | Change From Baseline in White Blood Cells at Month 6 | 0.35 * 10^9/L | Standard Deviation 2.34 |
Secondary
Number of Participants With Anti-Denosumab Binding Antibodies
Serum from participants was tested for antibodies to denosumab by immuoassay at months 1, 3, 6 and 12. The number of participants with anti-denosumab antibodies at any assessment is reported.
Time frame: Assessed at Baseline and at Months 1, 3, 6 and 12.
Population: Patients who received at least 1 dose of investigational product and with at least one postbaseline sample taken.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Denosumab 180 mg | Number of Participants With Anti-Denosumab Binding Antibodies | 4 Participants |
| Denosumab 60 mg | Number of Participants With Anti-Denosumab Binding Antibodies | 0 Participants |
| Placebo | Number of Participants With Anti-Denosumab Binding Antibodies | 2 Participants |
Secondary
Number of Participants With Anti-Denosumab Binding Antibody and Neutralizing Antibody
Serum from participants testing positive for anti-denosumab binding antibodies was tested in a cell-based bioassay for neutralizing activity against denosumab.
Time frame: Baseline to Month 12
Population: Patients who were positive for anti-denosumab antibodies
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Denosumab 180 mg | Number of Participants With Anti-Denosumab Binding Antibody and Neutralizing Antibody | 0 Participants |
| Placebo | Number of Participants With Anti-Denosumab Binding Antibody and Neutralizing Antibody | 0 Participants |
Secondary
Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3
Participants with laboratory toxicity of grade 3 or 4, graded according to the Common Terminology Criteria for Adverse Events, version 3.0, on the following general guideline: Grade 1 - Mild AE; Grade 2 - Moderate AE; Grade 3 - Severe AE; Grade 4 - Life-threatening or disabling AE; Grade 5 - Death related to AE.
Time frame: Month 1, month 3, month 6, month 12
Population: Patients who received at least 1 dose of investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Denosumab 180 mg | Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | Alanine Amino Transferase-above normal (grade 3) | 0 Participants |
| Denosumab 180 mg | Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | Aspartate Amino Transferase-above normal (grade 3) | 0 Participants |
| Denosumab 180 mg | Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | Glucose-above normal (grade 3) | 1 Participants |
| Denosumab 180 mg | Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | Lymphocytes-below normal (grade 3) | 1 Participants |
| Denosumab 180 mg | Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | Sodium-below normal (grade 3) | 1 Participants |
| Denosumab 180 mg | Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | White Blood Cells-below normal (grade 3) | 0 Participants |
| Denosumab 60 mg | Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | White Blood Cells-below normal (grade 3) | 1 Participants |
| Denosumab 60 mg | Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | Alanine Amino Transferase-above normal (grade 3) | 0 Participants |
| Denosumab 60 mg | Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | Lymphocytes-below normal (grade 3) | 3 Participants |
| Denosumab 60 mg | Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | Sodium-below normal (grade 3) | 2 Participants |
| Denosumab 60 mg | Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | Aspartate Amino Transferase-above normal (grade 3) | 1 Participants |
| Denosumab 60 mg | Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | Glucose-above normal (grade 3) | 0 Participants |
| Placebo | Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | Aspartate Amino Transferase-above normal (grade 3) | 0 Participants |
| Placebo | Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | Glucose-above normal (grade 3) | 0 Participants |
| Placebo | Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | White Blood Cells-below normal (grade 3) | 1 Participants |
| Placebo | Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | Lymphocytes-below normal (grade 3) | 2 Participants |
| Placebo | Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | Alanine Amino Transferase-above normal (grade 3) | 1 Participants |
| Placebo | Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | Sodium-below normal (grade 3) | 0 Participants |
Secondary
Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 1
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((Month 1 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
Time frame: Baseline, Month 1
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 1 month.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 1 | 0.64 Percent change from baseline | Standard Error 0.38 |
| Denosumab 60 mg | Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 1 | -0.15 Percent change from baseline | Standard Error 0.38 |
| Placebo | Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 1 | -0.16 Percent change from baseline | Standard Error 0.38 |
p-value: 0.98695% CI: [-1.06, 1.08]Repeated Measures Model
p-value: 0.14195% CI: [-0.27, 1.86]Repeated Measures Model
Secondary
Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 12
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 12 calculated using ((Month 12 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
Time frame: Baseline, Month 12
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 12 months.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 12 | 1.51 Percent change from baseline | Standard Error 0.47 |
| Denosumab 60 mg | Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 12 | 1.34 Percent change from baseline | Standard Error 0.47 |
| Placebo | Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 12 | -0.47 Percent change from baseline | Standard Error 0.47 |
p-value: 0.00795% CI: [0.51, 3.12]Repeated Measures Model
p-value: 0.00395% CI: [0.67, 3.29]Repeated Measures Model
Secondary
Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 6
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 6 calculated using ((Month 6 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
Time frame: Baseline, Month 6
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 6 | 0.84 Percent change from baseline | Standard Error 0.37 |
| Denosumab 60 mg | Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 6 | 0.89 Percent change from baseline | Standard Error 0.37 |
| Placebo | Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 6 | -0.06 Percent change from baseline | Standard Error 0.37 |
p-value: 0.07395% CI: [-0.09, 1.99]Repeated Measures Model
p-value: 0.0995% CI: [-0.14, 1.93]Repeated Measures Model
Secondary
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 1
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((month 1 value - baseline value) / baseline value ) x 100. Least squares means are based on a repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
Time frame: Baseline, Month 1
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 1 month.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 1 | 0.25 Percent change from baseline | Standard Error 0.29 |
| Denosumab 60 mg | Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 1 | 0.59 Percent change from baseline | Standard Error 0.29 |
| Placebo | Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 1 | -0.34 Percent change from baseline | Standard Error 0.29 |
p-value: 0.02695% CI: [0.11, 1.74]Repeated Measures Model
p-value: 0.15595% CI: [-0.23, 1.41]Repeated measures model
Secondary
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 12 calculated using ((Month 12 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
Time frame: Baseline, Month 12
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 12 months.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 | 4.09 Percent change from baseline | Standard Error 0.4 |
| Denosumab 60 mg | Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 | 3.00 Percent change from baseline | Standard Error 0.39 |
| Placebo | Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 | 0.80 Percent change from baseline | Standard Error 0.4 |
p-value: <0.00195% CI: [1.1, 3.29]Repeated Measures Model
p-value: <0.00195% CI: [2.18, 4.39]Repeated Measures Model
Secondary
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 6
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to month 6 calculated using ((month 6 value - baseline value) / baseline value ) x 100. Least squares means are based on a repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
Time frame: Baseline, month 6
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 6 | 2.61 Percent change from baseline | Standard Error 0.38 |
| Denosumab 60 mg | Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 6 | 2.40 Percent change from baseline | Standard Error 0.37 |
| Placebo | Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 6 | 0.73 Percent change from baseline | Standard Error 0.38 |
p-value: 0.00295% CI: [0.62, 2.72]Repeated Measures Model
p-value: <0.00195% CI: [0.84, 2.94]Repeated Measures Model
Secondary
Percent Change From Baseline in P1NP at Month 12
Percent change from baseline to Month 12 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
Time frame: Baseline, Month 12
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 12 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab 180 mg | Percent Change From Baseline in P1NP at Month 12 | -45.84 Percent change from baseline |
| Denosumab 60 mg | Percent Change From Baseline in P1NP at Month 12 | -41.8 Percent change from baseline |
| Placebo | Percent Change From Baseline in P1NP at Month 12 | -17.53 Percent change from baseline |
p-value: 0.016van Elteren Stratified Rank Test
p-value: <0.001van Elteren Stratified Rank Test
Secondary
Percent Change From Baseline in P1NP at Month 6
Percent change from baseline to Month 6 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100.
Time frame: Baseline, Month 6
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab 180 mg | Percent Change From Baseline in P1NP at Month 6 | -57.06 Percent change from baseline |
| Denosumab 60 mg | Percent Change From Baseline in P1NP at Month 6 | -51.57 Percent change from baseline |
| Placebo | Percent Change From Baseline in P1NP at Month 6 | -22.17 Percent change from baseline |
p-value: <0.001van Elteren Stratified Rank Test
p-value: <0.001van Elteren Stratified Rank Test
Secondary
Percent Change From Baseline in Procollagen 1 N-terminal Peptide (P1NP) at Month 3
Percent change from baseline to Month 3 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100.
Time frame: Baseline, Month 3
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 3 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab 180 mg | Percent Change From Baseline in Procollagen 1 N-terminal Peptide (P1NP) at Month 3 | -55.08 Percent change from baseline |
| Denosumab 60 mg | Percent Change From Baseline in Procollagen 1 N-terminal Peptide (P1NP) at Month 3 | -57.57 Percent change from baseline |
| Placebo | Percent Change From Baseline in Procollagen 1 N-terminal Peptide (P1NP) at Month 3 | -12.23 Percent change from baseline |
p-value: <0.001van Elteren Stratified Rank Test
p-value: <0.001van Elteren Stratified Rank Test
Secondary
Percent Change From Baseline in Serum Collagen C-Telopeptide (CTX) at Month 3
Percent change from baseline to Month 3 in serum Collagen C-Telopeptide (CTX) Type I calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100.
Time frame: Baseline, Month 3
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 3 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab 180 mg | Percent Change From Baseline in Serum Collagen C-Telopeptide (CTX) at Month 3 | -78.67 Percent change from baseline |
| Denosumab 60 mg | Percent Change From Baseline in Serum Collagen C-Telopeptide (CTX) at Month 3 | -80.46 Percent change from baseline |
| Placebo | Percent Change From Baseline in Serum Collagen C-Telopeptide (CTX) at Month 3 | -11.48 Percent change from baseline |
p-value: <0.001van Elteren Stratified Rank Test
p-value: <0.001van Elteren Stratified Rank Test
Secondary
Percent Change From Baseline in Serum CTX at Month 12
Percent change from Baseline to Month 12 in serum C-Telopeptide (CTX) Type I calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
Time frame: Baseline, Month 12
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 12 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab 180 mg | Percent Change From Baseline in Serum CTX at Month 12 | -65.65 Percent change from baseline |
| Denosumab 60 mg | Percent Change From Baseline in Serum CTX at Month 12 | -47.24 Percent change from baseline |
| Placebo | Percent Change From Baseline in Serum CTX at Month 12 | -23.36 Percent change from baseline |
p-value: <0.001van Elteren Stratified Rank Test
p-value: <0.001van Elteren Stratified Rank Test
Secondary
Percent Change From Baseline in Serum CTX at Month 6
Percent change from baseline to Month 6 in serum Collagen C-Telopeptide (CTX) Type I calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100.
Time frame: Baseline, Month 6
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab 180 mg | Percent Change From Baseline in Serum CTX at Month 6 | -62.69 Percent change from baseline |
| Denosumab 60 mg | Percent Change From Baseline in Serum CTX at Month 6 | -50.64 Percent change from baseline |
| Placebo | Percent Change From Baseline in Serum CTX at Month 6 | -12.94 Percent change from baseline |
p-value: <0.001van Elteren Stratified Rank Test
p-value: <0.001van Elteren Stratified Rank Test
Secondary
Percent Change From Baseline in Total Hip Bone Mineral Density at Month 1
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((Month 1 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
Time frame: Baseline, Month 1
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 1 month.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Percent Change From Baseline in Total Hip Bone Mineral Density at Month 1 | 0.06 Percent change from baseline | Standard Error 0.22 |
| Denosumab 60 mg | Percent Change From Baseline in Total Hip Bone Mineral Density at Month 1 | 0.00 Percent change from baseline | Standard Error 0.22 |
| Placebo | Percent Change From Baseline in Total Hip Bone Mineral Density at Month 1 | -0.02 Percent change from baseline | Standard Error 0.22 |
p-value: 0.93895% CI: [-0.58, 0.63]Repeated Measures Model
p-value: 0.78795% CI: [-0.53, 0.69]Repeated Measures Model
Secondary
Percent Change From Baseline in Total Hip Bone Mineral Density at Month 12
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 12 calculated using ((Month 12 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
Time frame: Baseline, Month 12
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 12 months.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Percent Change From Baseline in Total Hip Bone Mineral Density at Month 12 | 1.67 Percent change from baseline | Standard Error 0.33 |
| Denosumab 60 mg | Percent Change From Baseline in Total Hip Bone Mineral Density at Month 12 | 1.56 Percent change from baseline | Standard Error 0.33 |
| Placebo | Percent Change From Baseline in Total Hip Bone Mineral Density at Month 12 | -0.38 Percent change from baseline | Standard Error 0.33 |
p-value: <0.00195% CI: [1.02, 2.85]Repeated Measures Model
p-value: <0.00195% CI: [1.13, 2.96]Repeated Measures Model
Secondary
Percent Change From Baseline in Total Hip Bone Mineral Density at Month 6
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 6 calculated using ((Month 6 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).
Time frame: Baseline, Month 6
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 180 mg | Percent Change From Baseline in Total Hip Bone Mineral Density at Month 6 | 1.12 Percent change from baseline | Standard Error 0.24 |
| Denosumab 60 mg | Percent Change From Baseline in Total Hip Bone Mineral Density at Month 6 | 0.95 Percent change from baseline | Standard Error 0.24 |
| Placebo | Percent Change From Baseline in Total Hip Bone Mineral Density at Month 6 | -0.06 Percent change from baseline | Standard Error 0.24 |
p-value: 0.00495% CI: [0.33, 1.67]Repeated Measures Model
p-value: <0.00195% CI: [0.51, 1.85]Repeated Measures Model
Secondary
Percent Change From Baseline in Urine Type II Collagen C-telopeptide (C-Tx) /Creatinine at Month 3
Percent change from baseline to Month 3 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100.
Time frame: Baseline, Month 3
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 3 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab 180 mg | Percent Change From Baseline in Urine Type II Collagen C-telopeptide (C-Tx) /Creatinine at Month 3 | -46.59 Percent change from baseline |
| Denosumab 60 mg | Percent Change From Baseline in Urine Type II Collagen C-telopeptide (C-Tx) /Creatinine at Month 3 | -35.8 Percent change from baseline |
| Placebo | Percent Change From Baseline in Urine Type II Collagen C-telopeptide (C-Tx) /Creatinine at Month 3 | 2.71 Percent change from baseline |
p-value: <0.001van Elteren Stratified Rank Test
p-value: <0.001van Elteren Stratified Rank Test
Secondary
Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 12
Percent change from baseline to Month 12 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
Time frame: Baseline, Month 12
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 12 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab 180 mg | Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 12 | 36.92 Percent change from baseline |
| Denosumab 60 mg | Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 12 | 61.92 Percent change from baseline |
| Placebo | Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 12 | -3.93 Percent change from baseline |
p-value: 0.175van Elteren Stratified Rank Test
p-value: 0.133van Elteren Stratified Rank Test
Secondary
Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 6
Percent change from baseline to Month 6 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100.
Time frame: Baseline, Month 6
Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab 180 mg | Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 6 | 7.17 Percent change from baseline |
| Denosumab 60 mg | Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 6 | 9.65 Percent change from baseline |
| Placebo | Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 6 | 4.54 Percent change from baseline |
p-value: 0.673van Elteren Stratified Rank Test
p-value: 0.589van Elteren Stratified Rank Test