Alendronate in an Weekly Effervescent Tablet Formulation Following Denosumab Discontinuation

NCT04338529 | Completed DMC

• 2 other identifiers: F076/AD1704/S606/18-2-20202550/14-2-20
• Study Type: observational
• Target: 92
• Locations: 1 country
• Sites: 1

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

Conditions

Postmenopausal Osteoporosis

Keywords

Denosumab; Alendronate; osteoporosis; discontinuation of treatment

Outcome Measures

Primary Outcomes (1)

• Bone Mineral Density LS

  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.

  12 months

Secondary Outcomes (5)

• Bone Mineral Density FN

  12 months

• Serum levels of bone turnover markers (BTMs): P1NP, CTX and TRAP5b

  12 months

• Comparison of Bone Mineral Density LS

  12 months

• Comparison of Bone Mineral Density FN

  12 months

• Comparison of changes in: the serum levels of bone turnover markers (BTMs) P1NP, CTX and TRAP5b; the 24-hours urine levels of calcium

  12 months

Study Arms (2)

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. In case serum P1NP levels are \> 35μg/L and/or serum CTX levels are \> 280 ng/L at 9 months (3 months following alendronate discontinuation) the patients would be strongly advised to restart alendronate treatment.

Drug: Binosto 70Mg Effervescent Tablet

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

Interventions

Binosto 70Mg Effervescent Tablet DRUG

As discussed in group descriptions

Also known as: calcium carbonate 1000 mg/d and cholecalciferol 800 IU/d

Group Alendronate 12m; Group Alendronate 6m

Eligibility Criteria

• Age: Up to 90 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study will include 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 either 6 months (Group 6, n=46) and then followed for another 6 months without medication, or 12 months of continuous treatment with alendronate (Group 12, n=46). As this is an observational study, patients could be either referred from their treating physicians or could be actually followed by the investigators themselves in case the investigator is the treating physician

You may qualify if:

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

You may not qualify if:

• i) 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

Sponsors & Collaborators

• 251 Hellenic Air Force & VA General Hospital: lead
• Laikο General Hospital, Athens: collaborator
• 424 General Military Hospital: collaborator

Study Sites (1)

251 Hellenic Air Force & VA General Hospital

Athens, Attica, 11525, Greece

Location

Related Publications (11)

• Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C; FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009 Aug 20;361(8):756-65. doi: 10.1056/NEJMoa0809493. Epub 2009 Aug 11.

  PMID: 19671655 BACKGROUND

• Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone. 2008 Aug;43(2):222-229. doi: 10.1016/j.bone.2008.04.007. Epub 2008 Apr 26.

  PMID: 18539106 BACKGROUND

• Bone HG, Bolognese MA, Yuen CK, Kendler DL, Miller PD, Yang YC, Grazette L, San Martin J, Gallagher JC. Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab. 2011 Apr;96(4):972-80. doi: 10.1210/jc.2010-1502. Epub 2011 Feb 2.

  PMID: 21289258 BACKGROUND

• McClung MR, Wagman RB, Miller PD, Wang A, Lewiecki EM. Observations following discontinuation of long-term denosumab therapy. Osteoporos Int. 2017 May;28(5):1723-1732. doi: 10.1007/s00198-017-3919-1. Epub 2017 Jan 31.

  PMID: 28144701 BACKGROUND

• Anastasilakis AD, Polyzos SA, Makras P, Aubry-Rozier B, Kaouri S, Lamy O. Clinical Features of 24 Patients With Rebound-Associated Vertebral Fractures After Denosumab Discontinuation: Systematic Review and Additional Cases. J Bone Miner Res. 2017 Jun;32(6):1291-1296. doi: 10.1002/jbmr.3110. Epub 2017 Mar 13.

  PMID: 28240371 BACKGROUND

• Cummings SR, Ferrari S, Eastell R, Gilchrist N, Jensen JB, McClung M, Roux C, Torring O, Valter I, Wang AT, Brown JP. Vertebral Fractures After Discontinuation of Denosumab: A Post Hoc Analysis of the Randomized Placebo-Controlled FREEDOM Trial and Its Extension. J Bone Miner Res. 2018 Feb;33(2):190-198. doi: 10.1002/jbmr.3337. Epub 2017 Nov 22.

  PMID: 29105841 BACKGROUND

• Black DM, Bauer DC, Schwartz AV, Cummings SR, Rosen CJ. Continuing bisphosphonate treatment for osteoporosis--for whom and for how long? N Engl J Med. 2012 May 31;366(22):2051-3. doi: 10.1056/NEJMp1202623. Epub 2012 May 9. No abstract available.

  PMID: 22571169 BACKGROUND

• Anastasilakis AD, Polyzos SA, Makras P. THERAPY OF ENDOCRINE DISEASE: Denosumab vs bisphosphonates for the treatment of postmenopausal osteoporosis. Eur J Endocrinol. 2018 Jul;179(1):R31-R45. doi: 10.1530/EJE-18-0056. Epub 2018 Apr 24.

  PMID: 29691303 BACKGROUND

• Tsourdi E, Langdahl B, Cohen-Solal M, Aubry-Rozier B, Eriksen EF, Guanabens N, Obermayer-Pietsch B, Ralston SH, Eastell R, Zillikens MC. Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS. Bone. 2017 Dec;105:11-17. doi: 10.1016/j.bone.2017.08.003. Epub 2017 Aug 5.

  PMID: 28789921 BACKGROUND

• Freemantle N, Satram-Hoang S, Tang ET, Kaur P, Macarios D, Siddhanti S, Borenstein J, Kendler DL; DAPS Investigators. Final results of the DAPS (Denosumab Adherence Preference Satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women. Osteoporos Int. 2012 Jan;23(1):317-26. doi: 10.1007/s00198-011-1780-1. Epub 2011 Sep 17.

  PMID: 21927922 BACKGROUND

• Anastasilakis AD, Papapoulos SE, Polyzos SA, Appelman-Dijkstra NM, Makras P. Zoledronate for the Prevention of Bone Loss in Women Discontinuing Denosumab Treatment. A Prospective 2-Year Clinical Trial. J Bone Miner Res. 2019 Dec;34(12):2220-2228. doi: 10.1002/jbmr.3853. Epub 2019 Oct 14.

  PMID: 31433518 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Morning (8-9 am) fasting blood samples will be obtained at baseline and at 3, 6, 9 and 12 months. Blood samples will be centrifuged immediately and serum will be separated and stored at -80 ºC; 24hours urine specimens will be collected at 6 and 12 months. All study parameters will be measured in one batch at the end of the study.

MeSH Terms

Conditions

Osteoporosis, Postmenopausal; Osteoporosis

Interventions

Alendronate; Calcium Carbonate; Cholecalciferol

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Maria Yavropoulou, MD, PhD

  LAIKO General Hospital, Athens, Greece

  STUDY CHAIR

• Polyzois Makras, MD, PhD

  251 Hellenic Airforce Gen. Hospital, Athens, Greece

  PRINCIPAL INVESTIGATOR

• Athanasios D Anastasilakis, MD, PhD

  424 Gen. Military Hospital Thessaloniki, Greece

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2020
• First Posted: April 8, 2020
• Study Start: April 1, 2020
• Primary Completion: September 25, 2024
• Study Completion: November 1, 2024
• Last Updated: December 2, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)