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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-001510-20 | EudraCT Number |
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| Name | Class |
|---|---|
| Aalborg University | OTHER |
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The only known cure for primary hyperparathyroidism is surgical removal of one or more parathyroid glands. Some patients however, do not fulfill criteria for surgery or do not want to undergo a procedure due to fear of the associated risks. Therefore a medical alternative is warranted.
This study aims to evaluate the effects of Denosumab alone, and in combination with Cinacalcet, as a medical treatment for patients suffering from primary hyperparathyroidism, with mild osteoporosis. To the best of our knowledge no previously reported randomized controlled trial has investigated the use of denosumab in primary hyperparathyroidism.
60 patients will be enrolled in three different treatment-groups: 20 receiving both Denosumab and Cinacalcet, 20 Denosumab and placebo and 20 placebo and placebo. Patients included do not meet the criteria for, or have no wish for a surgical procedure.
By combining the two drugs, this study could possibly contribute to the discovery of a realistic medical alternative to surgery. It is expected that the therapy will be able to both control s-calcium and s-intact parathyroid hormone (iPTH), and simultaneously enhance bone-structure. The therapy thus has the potential of preventing fractures and possibly other long-term effects of primary hyperparathyroidism such as formation of kidney stones, and coronary calcification. Another objective of this project is to investigate whether the combined therapy can facilitate an actual reset of the Calcium-sensing receptor, and thereby de facto cure the disease.
Background/Context:
This project deals with medical treatment of primary hyperparathyroidism. The only cure currently available is surgical removal of one or more parathyroid glands, but this option is neither feasible, nor desirable in all patients with the diagnosis.
Today a major group of patients are being diagnosed by coincidence with biochemical blood-screening, and are therefore in an asymptomatic state of the disease at the time of diagnosis. Long term studies show that these patients over time often have progression in their disease, and develop complications such as osteoporosis. Thus a medical alternative is warranted.
Previous studies have investigated the effects of well known antiresorptive drugs such as bisphosphonates, as well as estrogen-related compounds. These drugs have had effects on particularly bone mineral density (BMD) and biochemical bone-turnover markers, but have been able only transiently to lower blood-calcium levels. Combined with too many unwanted side-effects and a high prevalence of contraindications for a large proportion of the patients needing treatment, these drugs have not provided a realistic alternative to surgery.
Treatment today generally follows the international consensus for treatment of asymptomatic patients with primary hyperparathyroidism. Briefly this includes watchful waiting with biannual control-sessions for indication of surgery, screening for kidney stones/nephrolithiasis, osteoporosis and s-calcium - and s-iPTH levels.
This randomized controlled trial involves the drugs Cinacalcet og Denosumab. Denosumab has previously been shown to greatly improve BMD, lower s-calcium, lower the rate of bone-turnover and prevent osteoporotic fractures in several populations with different diseases, but has never been tested in a published randomized controlled trial in patients with primary hyperparathyroidism.
Cinacalcet has been proved able to lower s-iPTH, lower s-Calcium and thereby relieve symptoms of hypercalcaemia caused by primary hyperparathyroidism. It does not however, lower the rate of bone turnover, and it has not been show to improve BMD.
By combining the two drugs, this study could possibly contribute to the discovery of a realistic medical alternative to surgery. It is expected that the therapy will be able to both control s-calcium and s-iPTH, and simultaneously enhance bone-structure. The therapy thus has the potential of preventing fractures and possibly other long-term effects of primary hyperparathyroidism such as formation of kidney stones, and coronary calcification. Another objective of this project is to investigate whether the combined therapy can facilitate an actual reset of the Calcium-sensing receptor, and thereby de facto cure the disease.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Combined treatment. | Experimental | 20 subjects will be treated with combined 60mg denosumab bi-annually , 30 mg cinacalcet daily and 50 micrograms vitamin-D daily. |
|
| Monotherapy | Active Comparator | 20 subjects will receive 60mg denosumab bi-annually, placebo and 50 micrograms vitamin-D daily. |
|
| Placebo | Placebo Comparator | 20 subjects will receive a saline injection bi-annually (blinded), placebo-tablets and 50 micrograms vitamin-D daily. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cinacalcet 30 mg Tablet | Drug | Participants in one arm will receive 30 mg cinacalcet each day. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Lumbar Spine Bone Mineral Density | Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan. | Baseline,one year |
| Change in Total Hip Bone Mineral Density | Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan. | Baseline,one year |
| Change in Femoral Neck Bone Mineral Density | Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan. | Baseline,one year |
| Change in 1/3 Forearm Bone Mineral Density | Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan. | Baseline,one year |
| Percentage Change in Lumbar Spine Bone Mineral Density | Percentage change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan. | Baseline,one year |
| Percentage Change in Total Hip Bone Mineral Density | Percentage change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan. | Baseline,one year |
| Percentage Change in Femoral Neck Bone Mineral Density |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Volumetric BMD for the Lumbar Spine. | Measured at baseline and after one year by QCT. | Baseline, one year |
| Mean P-calcium During Treatment. | Blood samples were acquired once every 4 weeks for safety-purposes. |
| Measure | Description | Time Frame |
|---|---|---|
| Safety Measures | Biochemical measures of changes in liver, infection, kidney and electrolyte-status and urinary excretion of calcium. | Monthly up to one year. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Julius Simoni Leere, MD | Aalborg University and Aalborg University Hospital | Principal Investigator |
| Peter Vestergaard, DMSc | Aalborg University and Aalborg University Hospital | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aalborg University Hospital | Aalborg | 9000 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32333877 | Derived | Leere JS, Karmisholt J, Robaczyk M, Lykkeboe S, Handberg A, Steinkohl E, Brondum Frokjaer J, Vestergaard P. Denosumab and cinacalcet for primary hyperparathyroidism (DENOCINA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2020 May;8(5):407-417. doi: 10.1016/S2213-8587(20)30063-2. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Combined Treatment. | 15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily. |
| FG001 | Denosumab Monotherapy | 16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily. |
| FG002 | Placebo | 15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Combined Treatment. | 15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily. |
| BG001 | Denosumab Monotherapy |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Lumbar Spine Bone Mineral Density | Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. | Posted | Mean | Standard Error | g/cm^2 | Baseline,one year |
|
Adverse events were collected for each participant from baseline until two weeks after treatment-cessation, up to 1 year.
Adverse events were collected at each visit using a adverse event questionnaire as well as assessment by a study-physician.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Combined Treatment. | 15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angina, Unstable | Cardiac disorders | MedDRA (Unspecified) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leg edema | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
Important limitations are the relatively small number of study-participants, and the lack of a cinacalcet monotherapy-arm.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor Peter Vestergaard | Aalborg University Hospital | +45 97 66 36 00 | p.vestergaard@rn.dk |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 10, 2017 | Jan 31, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D049950 | Hyperparathyroidism, Primary |
| D010282 | Parathyroid Neoplasms |
| ID | Term |
|---|---|
| D006961 | Hyperparathyroidism |
| D010279 | Parathyroid Diseases |
| D004700 | Endocrine System Diseases |
| D004701 | Endocrine Gland Neoplasms |
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| ID | Term |
|---|---|
| D000069449 | Cinacalcet |
| D013607 | Tablets |
| D000069448 | Denosumab |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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| Denosumab Inj 60 mg/ml | Drug | Participants in two arms will receive 60 mg Denosumab biannually. |
|
|
| Placebo tablets | Other | Participants in two arms will receive one placebo-tablet each day. |
|
| Saline Injection (Placebo) | Other | Participants in one arm will receive saline injections as placebo for denosumab. |
|
|
Percentage change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan. |
| Baseline,one year |
| Percentage Change in 1/3 Forearm Bone Mineral Density | Percentage change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan. | Baseline,one year |
| Monthly up to one year. |
| Percent Change From Baseline in P-carboxy-terminal Collagen Crosslinks (CTX) | p-CTX, change from baseline at 48 weeks. | Change from baseline at 48 weeks reported. |
| Median Agatstons Score Final | Simultaneously with QCT-measurements coronary calcification was be assessed. Agatston score is a score based on the extent of coronary artery calcification calculated on the amount of plaque observed in a CT scan. A score of zero indicates absence of coronary calcium, 1-10: minimal calcification, 11-100 mild calcification, 101-400 moderate calcification, >400 severe calcification. Thus the score increases with increasing level of calcification in the coronary vessels. | Baseline, one year |
| Patients With Nephrolithiasis Final Scan. | Number of subjects w. renal stones at final scan. | Patients with nephrolithiasis at one year reported. |
| Patients With Pancreas-calcifications Final Scan. | By QCT. | Patients with pancreas-calcifications at one year reported. |
| Reset of the Calcium Sensing Receptor? | Measured from effect on s-calcium and PTH weeks after termination of IMP | 2 weeks after termination of medication. |
| Vertebral Fracture Assessment - Final Scan | Number of participants with vertebral fractures as assessed by VFA at final scan. | Patients with vertebral fractures at one year reported. |
| Change MDI-score | Major Depression Inventory (MDI)-score, Baseline, 6 months, one year (week 52)., change between baseline and 1 year reported. The Major Depression Inventory (MDI) is a mood questionnaire developed by the World Health Organization. To calculate the total score, a sum of ten individual items (each with an individual score between 0-5, with 0 indicating absence of a symptom and 5 indicating constant presence of a given symptom) is used. A higher score signifies deeper depression with 50 being the maximum score. | Baseline, 6 mths, one year. |
| Adverse Reactions. | All participants filled in questionnaires regarding symptoms related to the treatment. Results are reported in the Adverse Events section. | Monthly up to one year. |
| Bone Mineral Content | Measured at baseline and after one year at the lumbar spine and distal 1/3 of the non-dominant antebrachii. | Baseline, one year |
| Change in Cortical Width. | Measured at baseline and after one year at the distal non-dominant antebrachii. | Baseline, one year. |
| Change in Volumetric BMD for the Distal Forearm. | Measured at baseline and after one year by QCT. | Baseline, one year |
| Percentage Change in Volumetric BMD for the Lumbar Spine. | Measured at baseline and after one year by QCT. | Baseline, one year |
| Percentage Change in Volumetric BMD for the Distal Forearm. | Measured at baseline and after one year by QCT. | Baseline, one year |
| Mean p-PTH During Treatment. | Blood samples were acquired once every 4 weeks for safety-purposes. | Monthly up to one year. |
| Mean p-Phosphate During Treatment. | Blood samples were acquired once every 4 weeks for safety-purposes. | Monthly up to one year. |
| Percent Change From Baseline in p-N-terminal Propeptide of Type I Procollagen (p-P1NP). | p-P1NP, change from baseline at 48 weeks. | Change from baseline at 48 weeks reported. |
| Percent Change From Baseline in P-osteocalcin. | p-osteocalcin, change from baseline at 48 weeks. | Change from baseline at 48 weeks reported. |
| Percent Change From Baseline in S-bone-specific Alkaline Phosphatase (BAP). | S-Bone specific alkaline phosphatase, change from baseline at 48 weeks. | Change from baseline at 48 weeks reported. |
| Percent Change From Baseline in p-Tartrate-resistant Acid Phosphatase 5b (Trap5b). | P-Trap5b, change from baseline at 48 weeks. | Change from baseline at 48 weeks reported. |
| Percent Change From Baseline in p-Sclerostin. | P-Sclerostin, change from baseline at 48 weeks. | Change from baseline at 48 weeks reported. |
| Percent Change From Baseline in P-fibroblast Growth Factor 23 (FGF23). | P-FGF23 , change from baseline at 48 weeks. | Change from baseline at 48 weeks reported. |
| Changes in p-25-vitamin D | P-25-vitD , change from baseline at 48 weeks. | Change from baseline at 48 weeks reported. |
| Changes in s-1,25-vitamin D | S-1,25-vitD, change from baseline at 48 weeks. | Change from baseline at 48 weeks reported. |
| Patients With Nephrocalcinosis, Final Scan. | Number of subjects w. renal calcifications at final scan. | Baseline, one year |
16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.
| BG002 | Placebo | 15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| T-score Lumbar Spine (LS) by Dual X-ray Absorptiometry (DXA) | Baseline Bone mineral density (BMD) at lumbar spine (L2-L4) T-score. The T-score is the number of units that the bone density is above or below the average. -1 and above-bone density is considered normal; Between -1 and -2.5-is a sign of osteopenia, a condition in which bone density is below normal and may lead to osteoporosis. -2.5 and below-indicates osteoporosis | Mean | Standard Deviation | T-score |
|
| T-score TH (by DXA) | Baseline Bone mineral density (BMD) at Total Hip (TH) T-score. The T-score is the number of units that the bone density is above or below the average. -1 and above-bone density is considered normal; Between -1 and -2.5-is a sign of osteopenia, a condition in which bone density is below normal and may lead to osteoporosis. -2.5 and below-indicates osteoporosis. | Mean | Standard Deviation | T-score |
|
| T-score FN (by DXA) | Baseline Bone mineral density (BMD) at Femoral Neck (FN) T-score. The T-score is the number of units that the bone density is above or below the average. -1 and above-bone density is considered normal; Between -1 and -2.5-is a sign of osteopenia, a condition in which bone density is below normal and may lead to osteoporosis. -2.5 and below-indicates osteoporosis. | Mean | Standard Deviation | T-score |
|
| T-score 1/3 FA (by DXA) | Baseline Bone mineral density (BMD) at 1/3 distal forearm (1/3 FA)T-score. The T-score is the number of units that the bone density is above or below the average. -1 and above-bone density is considered normal; Between -1 and -2.5-is a sign of osteopenia, a condition in which bone density is below normal and may lead to osteoporosis. -2.5 and below-indicates osteoporosis. | Mean | Standard Deviation | T-score |
|
| Volumetric Bone Mineral Density (vBMD) LS | Baseline lumbar spine BMD by quantitative computed tomography (QCT) | Mean | Standard Deviation | mg/cm^3 |
|
| vBMD distal forearm | Bone Mineral Density at the distal forearm by QCT | Mean | Standard Deviation | mg/cm^3 |
|
| Cortical width | Baseline cortical Width of the distal forearm. | Mean | Standard Deviation | mm |
|
| Nephrolithiasis | Subjects with nephrolithiasis at baseline | Count of Participants | Participants |
|
| Nephrocalcinosis | Subjects with nephrocalcinosis at baseline | Count of Participants | Participants |
|
| Pancreas calcifications | Subjects with pancreatic calcifications at baseline | Count of Participants | Participants |
|
| Fracture by Vertebral Fracture Assessment (VFA) | Subjects with vertebral fractures by VFA at baseline | Count of Participants | Participants |
|
| Body Mass Index | Body Mass Index at baseline | Mean | Standard Deviation | kg/m^2 |
|
| Ionized Calcium | Baseline ionized calcium levels. | Mean | Standard Deviation | mmol/l |
|
| P-Parathyroid Hormone (PTH) | Baseline Parathyroid Hormone level. | Mean | Standard Deviation | pmol/l |
|
| Agatston Score | Agatston score is a score based on the extent of coronary artery calcification calculated on the amount of plaque observed in a CT scan. A score of zero indicates absence of coronary calcium, 1-10: minimal calcification, 11-100 mild calcification, 101-400 moderate calcification, >400 severe calcification. Thus the score increases with increasing level of calcification in the coronary vessels. | Median | Inter-Quartile Range | units on a scale |
|
| U-Calcium | Baseline urine calcium excretion per day. | Median | Inter-Quartile Range | mg/d |
|
| U-Phosphorous | Baseline daily excretion of phosphorous in urine. | Median | Inter-Quartile Range | mmol/d |
|
| P-Phosphorous | Baseline p-phosphorous. | Mean | Standard Deviation | mmol/l |
|
| Major Depression Inventory score | The Major Depression Inventory (MDI) is a mood questionnaire developed by the World Health Organization. To calculate the total score, a sum of ten individual items (each with an individual score between 0-5, with 0 indicating absence of a symptom and 5 indicating constant presence of a given symptom) is used. A higher score signifies deeper depression with 50 being the maximum score. | Median | Inter-Quartile Range | MDI-points |
|
| OG002 | Placebo | 15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily. |
|
|
|
| Primary | Change in Total Hip Bone Mineral Density | Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the placebo group did not provide results for this analysis as he/she had had a hip-replacement performed. | Posted | Mean | Standard Error | g/cm^2 | Baseline,one year |
|
|
|
|
| Primary | Change in Femoral Neck Bone Mineral Density | Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the placebo group did not provide results for this analysis as he/she had had a hip-replacement performed. | Posted | Mean | Standard Error | g/cm^2 | Baseline,one year |
|
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|
| Primary | Change in 1/3 Forearm Bone Mineral Density | Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the denosumab group did not provide results for this analysis as he/she experienced a wrist fracture prior to the final scan. | Posted | Mean | Standard Error | g/cm^2 | Baseline,one year |
|
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| Primary | Percentage Change in Lumbar Spine Bone Mineral Density | Percentage change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. | Posted | Mean | Standard Error | % change | Baseline,one year |
|
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|
| Primary | Percentage Change in Total Hip Bone Mineral Density | Percentage change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the placebo group did not provide results for this analysis as he/she had had a hip-replacement performed. | Posted | Mean | Standard Error | % change | Baseline,one year |
|
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|
| Primary | Percentage Change in Femoral Neck Bone Mineral Density | Percentage change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the placebo group did not provide results for this analysis as he/she had had a hip-replacement performed. | Posted | Mean | Standard Error | % change | Baseline,one year |
|
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|
| Primary | Percentage Change in 1/3 Forearm Bone Mineral Density | Percentage change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the denosumab group did not provide results for this analysis as he/she experienced a wrist fracture prior to the final scan. | Posted | Mean | Standard Error | % change | Baseline,one year |
|
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| Secondary | Change in Volumetric BMD for the Lumbar Spine. | Measured at baseline and after one year by QCT. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. Another scan could not be included due to a technical problems with the image analysis. | Posted | Mean | Standard Error | mg/cm^3 | Baseline, one year |
|
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| Secondary | Mean P-calcium During Treatment. | Blood samples were acquired once every 4 weeks for safety-purposes. | Posted | Mean | Standard Error | mmol/l | Monthly up to one year. | p-calcium measurements | p-calcium measurements |
|
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| Secondary | Percent Change From Baseline in P-carboxy-terminal Collagen Crosslinks (CTX) | p-CTX, change from baseline at 48 weeks. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling. | Posted | Median | Inter-Quartile Range | % change | Change from baseline at 48 weeks reported. |
|
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|
|
| Secondary | Median Agatstons Score Final | Simultaneously with QCT-measurements coronary calcification was be assessed. Agatston score is a score based on the extent of coronary artery calcification calculated on the amount of plaque observed in a CT scan. A score of zero indicates absence of coronary calcium, 1-10: minimal calcification, 11-100 mild calcification, 101-400 moderate calcification, >400 severe calcification. Thus the score increases with increasing level of calcification in the coronary vessels. | Some participant from the combined and placebo groups could not be included in the analysis because they had coronary stents. | Posted | Median | Inter-Quartile Range | score on a scale | Baseline, one year |
|
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| Secondary | Patients With Nephrolithiasis Final Scan. | Number of subjects w. renal stones at final scan. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling. | Posted | Count of Participants | Participants | Patients with nephrolithiasis at one year reported. |
|
|
|
| Secondary | Patients With Pancreas-calcifications Final Scan. | By QCT. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. | Posted | Count of Participants | Participants | Patients with pancreas-calcifications at one year reported. |
|
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| Secondary | Reset of the Calcium Sensing Receptor? | Measured from effect on s-calcium and PTH weeks after termination of IMP | Not Posted | 2 weeks after termination of medication. | Participants |
| Secondary | Vertebral Fracture Assessment - Final Scan | Number of participants with vertebral fractures as assessed by VFA at final scan. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. | Posted | Count of Participants | Participants | Patients with vertebral fractures at one year reported. |
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| Secondary | Change MDI-score | Major Depression Inventory (MDI)-score, Baseline, 6 months, one year (week 52)., change between baseline and 1 year reported. The Major Depression Inventory (MDI) is a mood questionnaire developed by the World Health Organization. To calculate the total score, a sum of ten individual items (each with an individual score between 0-5, with 0 indicating absence of a symptom and 5 indicating constant presence of a given symptom) is used. A higher score signifies deeper depression with 50 being the maximum score. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final collection of MDI-questionnaires. | Posted | Median | Inter-Quartile Range | MDI-score | Baseline, 6 mths, one year. |
|
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|
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| Secondary | Adverse Reactions. | All participants filled in questionnaires regarding symptoms related to the treatment. Results are reported in the Adverse Events section. | Not Posted | Monthly up to one year. | Participants |
| Secondary | Bone Mineral Content | Measured at baseline and after one year at the lumbar spine and distal 1/3 of the non-dominant antebrachii. | Data were not collected | Posted | Baseline, one year |
|
|
| Secondary | Change in Cortical Width. | Measured at baseline and after one year at the distal non-dominant antebrachii. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the denosumab group experienced a wrist fracture prior to the final scan and was excluded. 4 patients did not provide data for the analysis due to errors in the technique of the obtained images. | Posted | Mean | Standard Error | mm | Baseline, one year. |
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| Secondary | Change in Volumetric BMD for the Distal Forearm. | Measured at baseline and after one year by QCT. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the denosumab group experienced a wrist fracture prior to the final scan and was excluded. 5 patients did not provide data for the analysis due to errors in the technique of the obtained images. | Posted | Mean | Standard Error | mg/cm^3 | Baseline, one year |
|
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| Secondary | Percentage Change in Volumetric BMD for the Lumbar Spine. | Measured at baseline and after one year by QCT. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. Another scan could not be included due to a technical problems with the image analysis. | Posted | Mean | Standard Error | % change | Baseline, one year |
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| Secondary | Percentage Change in Volumetric BMD for the Distal Forearm. | Measured at baseline and after one year by QCT. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the denosumab group experienced a wrist fracture prior to the final scan and was excluded. 5 patients did not provide data for the analysis due to errors in the technique of the obtained images. | Posted | Mean | Standard Error | % change | Baseline, one year |
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| Secondary | Mean p-PTH During Treatment. | Blood samples were acquired once every 4 weeks for safety-purposes. | Posted | Median | 95% Confidence Interval | pmol/l | Monthly up to one year. | p-PTH measurements | p-PTH measurements |
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|
| Secondary | Mean p-Phosphate During Treatment. | Blood samples were acquired once every 4 weeks for safety-purposes. | Posted | Mean | Standard Error | pmol/l | Monthly up to one year. | p-phosphate measurements | p-phosphate measurements |
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| Secondary | Percent Change From Baseline in p-N-terminal Propeptide of Type I Procollagen (p-P1NP). | p-P1NP, change from baseline at 48 weeks. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling. | Posted | Median | Inter-Quartile Range | % change | Change from baseline at 48 weeks reported. |
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| Secondary | Percent Change From Baseline in P-osteocalcin. | p-osteocalcin, change from baseline at 48 weeks. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling. | Posted | Median | Inter-Quartile Range | % change | Change from baseline at 48 weeks reported. |
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| Secondary | Percent Change From Baseline in S-bone-specific Alkaline Phosphatase (BAP). | S-Bone specific alkaline phosphatase, change from baseline at 48 weeks. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling. | Posted | Median | Inter-Quartile Range | % change | Change from baseline at 48 weeks reported. |
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| Secondary | Percent Change From Baseline in p-Tartrate-resistant Acid Phosphatase 5b (Trap5b). | P-Trap5b, change from baseline at 48 weeks. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling. | Posted | Median | Inter-Quartile Range | % change | Change from baseline at 48 weeks reported. |
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| Secondary | Percent Change From Baseline in p-Sclerostin. | P-Sclerostin, change from baseline at 48 weeks. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling. | Posted | Median | Inter-Quartile Range | % change | Change from baseline at 48 weeks reported. |
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| Secondary | Percent Change From Baseline in P-fibroblast Growth Factor 23 (FGF23). | P-FGF23 , change from baseline at 48 weeks. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling. | Posted | Median | Inter-Quartile Range | % change | Change from baseline at 48 weeks reported. |
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| Secondary | Changes in p-25-vitamin D | P-25-vitD , change from baseline at 48 weeks. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling. | Posted | Median | Inter-Quartile Range | nmol/l | Change from baseline at 48 weeks reported. |
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| Secondary | Changes in s-1,25-vitamin D | S-1,25-vitD, change from baseline at 48 weeks. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling. | Posted | Median | Inter-Quartile Range | pmol/l | Change from baseline at 48 weeks reported. |
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| Secondary | Patients With Nephrocalcinosis, Final Scan. | Number of subjects w. renal calcifications at final scan. | One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling. | Posted | Count of Participants | Participants | Baseline, one year |
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| Other Pre-specified | Safety Measures | Biochemical measures of changes in liver, infection, kidney and electrolyte-status and urinary excretion of calcium. | Not Posted | Monthly up to one year. | Participants |
| 0 |
| 15 |
| 2 |
| 15 |
| 13 |
| 15 |
| EG001 | Denosumab Monotherapy | 16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily. | 0 | 16 | 1 | 16 | 15 | 16 |
| EG002 | Placebo | 15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily. | 0 | 15 | 3 | 15 | 15 | 15 |
| Polycythaemia Vera | Blood and lymphatic system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Epilepsy | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Inflammatory Bowel Disease | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Erysipelas | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Coughing | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Paraesthesia, hands | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Paraesthesia, feet | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Dizziness | Ear and labyrinth disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Gastroenteritis | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Cystitis | Renal and urinary disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Hypocalcaemia | Endocrine disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
| Male |
|