Eldecalcitol for GLucocorticoid Induced OsteopoRosIs Versus Alfacalcidol

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of eldecalcitol monotherapy compared with alfacalcidol monotherapy in patients with glucocorticoid-induced osteoporosis, using a randomized, open-label, parallel-group, comparative design.

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: Eldecalcitol
* Drug: Alfacalcidol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (1) Patients who are currently taking or plan to take oral glucocorticoid medication for 3 months or longer and thus require treatment as per the 'Guidelines on the management and treatment of glucocorticoid-induced osteoporosis of the Japanese Society for Bone and mineral Research (2004),' and who meet at least one of the conditions below. No restriction is imposed on the underlying disease treated with the oral glucocorticoid medication. (i) Have any existing insufficiency fracture (ii) %YAM <80 (iii) Oral glucocorticoid daily dose >= 5 mg prednisolone equivalent (2) Aged between 20 and 85 years (both inclusive) at consent (3) Patients who are able to walk without assistance (4) Provided consent to participate in the study Exclusion Criteria: (1) BMD (L1-4 or T-Hip) T score < -3.5 (2) Have 3 or more vertebral fractures between L1 and L4. (3) Have 1 or more SQ grade 3 vertebral fractures, or 3 or more SQ grade 2 vertebral fractures. (4) Have received a bisphosphonate preparation for 2 weeks or longer within 6 months before the start of study treatment. (5) Have received a bisphosphonate preparation for 2 years or longer within 3 years before the start of study treatment. (6) Have received a parathyroid hormone preparation before the start of study treatment. (7) Have received one or more doses of an anti-RANKL (receptor activator of nuclear factor-kappa B ligand) antibody. (8) Have received one or more doses of an anti-sclerostin antibody or cathepsin K inhibitor. (9) Have received any other investigational product (including placebo) within 16 weeks before the start of study treatment in the present study. (10) Have received any of the following drugs that can affect bone metabolism within 8 weeks before the start of study treatment, with the exception of calcium preparations: (i) Bisphosphonates (ii) Active vitamin D preparations (including those for topical use) (iii) Selective estrogen receptor modulators (SERMs) (iv) Calcitonin preparations (v) Vitamin K2 preparations (vi) Ipriflavone preparations (vii) Reproductive hormone products (except those for vaginal use such as vaginal tablets and creams) (viii) Other drugs that can affect bone metabolism (11) Pregnant woman or woman who desires to become pregnant (12) Have corrected serum calcium >= 10.4 mg/dL or < 8.0 mg/dL at enrollment. (13) Have corrected urinary calcium > 0.4 mg/dL GF at enrollment. (14) Have a past or current history of urinary calculus. (15) Have eGFR < 30 mL/min/1.73 m2 at enrollment. (16) Have severe liver disease such as cirrhosis or severe heart disease such as severe cardiac failure. (17) Have active malignancy or received treatment for malignancy, including adjuvant therapy, within the past 3 years. (18) Have a history of hypersensitivity to eldecalcitol, alfacalcidol, or other vitamin D preparations. (19) Other persons judged by the investigator (or subinvestigator) to be inappropriate to participate in this study.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eldecalcitol group<br>Eldecalcitol 0.75 microgram once daily orally | Drug: Eldecalcitol<br>* Eldecalcitol 0.75 microgram once daily orally<br>|
| Active Comparator: Alfacalcidol group<br>Alfacalcidol 1 microgram once daily orally | Drug: Alfacalcidol<br>* Alfacalcidol 1 microgram once daily orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in lumbar spine (L1-4) bone mineral density |  | 12 months after the start of study drug administration | 
| Incidence of vertebral fractures | A vertebral fracture will be classified as a new fracture (i.e., change from grade 0 to grade 1, 2, or 3) or worsening of a prevalent fracture (i.e., change from grade 1 to grade 2 or 3, or change from grade 2 to grade 3) using a semi-quantitative [SQ] method according to the Vertebral Fracture Assessment Criteria, 2012 revised version. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of non-vertebral fractures (both traumatic and non-traumatic; All sites) |  | 36 months | 
| Incidence of non-vertebral fractures (both traumatic and non-traumatic; 3 Major sites) | The 3 Major sites are defined as the forearm, humerus, and femur. | 36 months | 
| Incidence of non-vertebral fractures (both traumatic and non-traumatic; 6 Major sites) | The 6 Major sites are defined as the femur, lower leg, humerus, forearm, clavicle, and pelvis. | 36 months | 
| Incidence of non-vertebral fractures (traumatic; All sites) |  | 36 months | 
| Incidence of non-vertebral fractures (traumatic; 3 Major sites) |  | 36 months | 
| Incidence of non-vertebral fractures (traumatic; 6 Major sites) |  | 36 months | 
| Incidence of non-vertebral fractures (non-traumatic; All sites) |  | 36 months | 
| Incidence of non-vertebral fractures (non-traumatic; 3 Major sites） |  | 36 months | 
| Incidence of non-vertebral fractures (non-traumatic; 6 Major sites） |  | 36 months | 
| Incidence of vertebral fractures (new vertebral fractures) |  | 36 months | 
| Incidence of vertebral fractures (worsening of prevalent vertebral fractures) |  | 36 months | 
| Incidence of vertebral fractures (clinical vertebral fractures) |  | 36 months | 
| Incidence of vertebral fracture (new or worsening of prevalent fractures) by glucocorticoid dose |  | 36 months | 
| Incidence of clinical vertebral fractures by glucocorticoid dose |  | 36 months | 
| Incidence of non-vertebral fractures (all sites) by glucocorticoid dose |  | 36 months | 
| Incidence of non-vertebral fractures (3 Major sites) by glucocorticoid dose |  | 36 months | 
| Incidence of non-vertebral fractures (6 Major sites) by glucocorticoid dose |  | 36 months | 
| Incidence of vertebral fractures (new or worsening) by bone mineral density |  | 36 months | 
| Incidence of clinical vertebral fractures by bone mineral density |  | 36 months | 
| Incidence of non-vertebral fractures (all sites) by bone mineral density |  | 36 months | 
| Incidence of non-vertebral fractures (3 Major sites) by bone mineral density |  | 36 months | 
| Incidence of non-vertebral fractures (6 Major sites) by bone mineral density |  | 36 months | 
| Incidence of vertebral fractures (new or worsening) by number of prevalent fractures |  | 36 months | 
| Incidence of clinical vertebral fractures by number of prevalent fractures |  | 36 months | 
| Incidence of non-vertebral fractures (all sites) by number of prevalent fractures |  | 36 months | 
| Incidence of non-vertebral fractures (3 Major sites) by number of prevalent fractures |  | 36 months | 
| Incidence of non-vertebral fractures (6 Major sites) by number of prevalent fractures |  | 36 months | 
| Incidence of new vertebral fractures by severity | Semiquantitative (SQ) method is used for grading of vertebral fractures. | 36 months | 
| Incidence of new clinical vertebral fractures by severity | SQ method is used for grading of vertebral fractures. | 36 months | 
| Incidence of new non-vertebral fractures (all sites) by severity | SQ method is used for grading of vertebral fractures. | 36 months | 
| Incidence of new non-vertebral fractures (3 Major sites) by severity | SQ method is used for grading of vertebral fractures. | 36 months | 
| Incidence of new non-vertebral fractures (6 Major sites) by severity |  | 36 months | 
| Incidence of osteoporotic fractures | An osteoporotic fracture is defined as a fracture of the following sites: vertebral body, ribs, pelvis, humerus, clavicle, scapula, sternum, proximal femur, other portions of the femur, tibia, fibula, and forearm. | 36 months | 
| Incidence of FRAX-defined major osteoporotic fractures | The 4 Major sites are defined as clinical fractures of the spine, forearm, hip, and shoulder. | 36 months | 
| Percent change in lumbar spine bone mineral density |  | 6 months after the start of study drug administration | 
| Percent change in lumbar spine bone mineral density |  | 24 months after the start of study drug administration | 
| Percent change in lumbar spine bone mineral density |  | 36 months after the start of study drug administration (or at the time of withdrawal from the study) | 
| Change in proximal femur (total-hip) bone mineral density |  | 6 months after the start of study drug administration | 
| Change in proximal femur (total-hip) bone mineral density |  | 12 months after the start of study drug administration | 
| Change in proximal femur (total-hip) bone mineral density |  | 24 months after the start of study drug administration | 
| Change in proximal femur (total-hip) bone mineral density |  | 36 months after the start of study drug administration (or at the time of withdrawal from the study) | 
| Percent change in TRACP-5b bone metabolism marker |  | 6 months after the start of study drug administration | 
| Percent change in TRACP-5b bone metabolism marker |  | 12 months after the start of study drug administration | 
| Percent change in PINP bone metabolism marker |  | 6 months after the start of study drug administration | 
| Percent change in PINP bone metabolism marker |  | 12 months after the start of study drug administration | 
| Frequency of falls |  | 36 months | 
| Change in muscle strength (back muscle strength) |  | 12 months after the start of study drug administration | 
| Change in muscle strength (back muscle strength) |  | 24 months after the start of study drug administration | 
| Change in muscle strength (back muscle strength) |  | 36 months after the start of study drug administration (or at the time of withdrawal from the study) | 
| Change in muscle strength (grip strength) |  | 12 months after the start of study drug administration | 
| Change in muscle strength (grip strength) |  | 24 months after the start of study drug administration | 
| Change in muscle strength (grip strength) |  | 36 months after the start of study drug administration (or at the time of withdrawal from the study) | 
| Change in height |  | 12 months after the start of study drug administration | 
| Change in height |  | 24 months after the start of study drug administration | 
| Change in height |  | 36 months after the start of study drug administration (or at the time of withdrawal from the study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glucocorticoid-induced osteoporosis