BAD: Alendronate in an Weekly Effervescent Tablet Formulation Following Denosumab Discontinuation

Sponsor

251 Hellenic Air Force & VA General Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04338529

Collaborator

Laikο General Hospital, Athens (Other), 424 General Military Hospital (Other)

100

Enrollment

Location

Anticipated Duration (Months)

2.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Discontinuation of denosumab results in a rebound response of bone turnover markers, which rise above baseline at 3 months and remain elevated until reaching again baseline levels approximately 30 months after the last dose. Bone mineral density (BMD) gains are also lost and BMD values reach original baseline values after 1-2 years off-treatment.For the above reasons, current literature recommends that patients who discontinue denosumab should continue to receive either intravenous (iv) or oral (peros) bisphosphonate therapy for some time. The study aims to investigate changes in the BMD of the lumbar spine 12 months after transitioning from denosumab to oral alendronate 70 mg in a weekly effervescent tablet formulation

Condition or Disease	Intervention/Treatment	Phase
Postmenopausal Osteoporosis	Drug: Binosto 70Mg Effervescent Tablet

Detailed Description

Denosumab, a monoclonal antibody against the receptor activator of nuclear factor κ-Β ligand (RANKL), is a potent antiresorptive agent commonly prescribed in patients with postmenopausal osteoporosis. Discontinuation of denosumab results in a rebound response of bone turnover markers, which rise above baseline at 3 months and remain elevated until reaching again baseline levels approximately 30 months after the last dose. Bone mineral density (BMD) gains are also lost and BMD values reach original baseline values after 1-2 years off-treatment, in contrast to bisphosphonates, which remain within the skeleton acting for several months or even years after discontinuation while preserving most of the BMD gains achieved despite the cessation of treatment.

For the above reasons, current literature recommends that patients who discontinue denosumab should continue to receive either intravenous (iv) or oral (peros) bisphosphonate therapy for some time. Due to lack of specifically designed studies, the period of treatment with bisphosphonates after denosumab discontinuation has been arbitrarily proposed to be 1 to 2 years. Preservation of BMD gains after denosumab discontinuation has so far been demonstrated: (a) with one year of alendronate treatment, in a study designed to investigate patients' compliance to treatment, and b) with a single dose of zolendronate 5mg iv in a recent study specifically designed to address this question in which BMD levels remained stable for the next two years.

Preventing bone loss, and the reported high risk of multiple vertebral fractures after discontinuation of denosumab treatment, is a clinical issue of critical importance raising serious concerns to the international scientific community and needs to be addressed. Clinical studies specifically designed to investigate both the efficacy of various bisphosphonates and the optimal duration of their administration in order to avoid the reported adverse effects of denosumab discontinuation are currently lacking.

This study aims to investigate changes in the BMD of the lumbar spine (LS) and femoral neck (FN) 12 months after transitioning from denosumab to oral alendronate 70 mg in a weekly effervescent tablet formulation. Alendronate will be given either for 6 or 12 months following Denosumab discontinuation

Study Design

Study Type:

Observational

Anticipated Enrollment :

100 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Alendronate in an Weekly Effervescent Tablet Formulation for Preservation of Bone Mass After Denosumab Discontinuation in Postmenopausal Women With Low Bone Mass. An Observational Study (Binosto After Denosumab - The BAD Study)

Actual Study Start Date :

Apr 1, 2020

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Group Alendronate 6m Postmenopausal Caucasian women who were treated with denosumab and became osteopenic (BMD T-score of > -2.5 at the LS and the non-dominant FN) and were assigned from their treating physician to receive treatment with alendronate in an effervescent tablet formulation for 6 months and then followed for another 6 months without medication.	Drug: Binosto 70Mg Effervescent Tablet As discussed in group descriptions Other Names: calcium carbonate 1000 mg/d and cholecalciferol 800 IU/d
Group Alendronate 12m Postmenopausal Caucasian women who were treated with denosumab and became osteopenic (BMD T-score of > -2.5 at the LS and the non-dominant FN) and were assigned from their treating physician to receive treatment with alendronate in an effervescent tablet formulation for 12 months.	Drug: Binosto 70Mg Effervescent Tablet As discussed in group descriptions Other Names: calcium carbonate 1000 mg/d and cholecalciferol 800 IU/d

Arm

Intervention/Treatment

Group Alendronate 6m

Postmenopausal Caucasian women who were treated with denosumab and became osteopenic (BMD T-score of > -2.5 at the LS and the non-dominant FN) and were assigned from their treating physician to receive treatment with alendronate in an effervescent tablet formulation for 6 months and then followed for another 6 months without medication.

Drug: Binosto 70Mg Effervescent Tablet

As discussed in group descriptions

Other Names:

calcium carbonate 1000 mg/d and cholecalciferol 800 IU/d

Group Alendronate 12m

Drug: Binosto 70Mg Effervescent Tablet

As discussed in group descriptions

Other Names:

calcium carbonate 1000 mg/d and cholecalciferol 800 IU/d

Outcome Measures

Primary Outcome Measures

Bone Mineral Density LS [12 months]
Changes in the BMD of the lumbar spine 12 months after transitioning from denosumab to oral alendronate 70 mg in a weekly effervescent tablet formulation.

Secondary Outcome Measures

Bone Mineral Density FN [12 months]
Changes in the BMD of the femoral neck (FN) of the non-dominant hip 12 months after transitioning from denosumab to oral alendronate 70 mg in a weekly effervescent tablet formulation
Serum levels of bone turnover markers (BTMs): P1NP, CTX and TRAP5b [12 months]
Changes in BTMs 12 months after transitioning from denosumab to oral alendronate 70mg in a weekly effervescent tablet formulation.
Comparison of Bone Mineral Density LS [12 months]
Comparison of changes in the BMD of the LS after transitioning from denosumab to 12 months versus 6 months of treatment with oral alendronate 70 mg in a weekly effervescent tablet formulation.
Comparison of Bone Mineral Density FN [12 months]
Comparison of changes in the BMD of the FN of the non-dominant hip after transitioning from denosumab to 12 months versus 6 months of treatment with oral alendronate 70mg in a weekly effervescent tablet formulation.
Comparison of changes in the serum levels of bone turnover markers (BTMs): P1NP, CTX and TRAP5b [12 months]
Comparison of changes in the levels of BTMs after 12 months versus 6 months treatment with oral alendronate 70mg in a weekly effervescent tablet formulation in patients previously treated with denosumab

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 90 Years

Sexes Eligible for Study:

Female

Inclusion Criteria:

osteopenic postmenopausal Caucasian women following Dmab treatment ii) assignment to treatment with alendronate in an effervescent tablet formulation following Dmab discontinuation

Exclusion Criteria:

secondary osteoporosis; ii) diseases that could affect bone metabolism iii) medications that could affect bone metabolism iv) chronic kidney disease (stage >3b) and/or liver failure v) neoplastic disease vi) hypersensitivity to alendronate or to any of the excipients vii) abnormalities of the esophagus and other factors which delay esophageal emptying such as stricture or achalasia viii) inability to stand or sit upright for at least 30 minutes ix) hypocalcaemia x) confirmed esophagitis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	251 Hellenic Air Force & VA General Hospital	Athens	Attiki	Greece	11525

Sponsors and Collaborators

251 Hellenic Air Force & VA General Hospital
Laikο General Hospital, Athens
424 General Military Hospital

Investigators

Study Chair: Maria Yavropoulou, MD, PhD, LAIKO General Hospital, Athens, Greece
Principal Investigator: Polyzois Makras, MD, PhD, 251 Hellenic Airforce Gen. Hospital, Athens, Greece
Study Director: Athanasios D Anastasilakis, MD, PhD, 424 Gen. Military Hospital Thessaloniki, Greece