Denosumab, Teriparatide or Both for the Treatment of Postmenopausal Osteoporosis

NCT00926380 | Completed Phase 2 Results DMC

• 2 other identifiers: 200807232009P000525
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to determine whether denosumab (an FDA-approved osteoporosis therapy), in combination with teriparatide (an FDA-approved osteoporosis therapy), will increase bone mineral density more than either one alone in postmenopausal osteoporotic women.

Conditions

Osteoporosis

Keywords

osteoporosis; postmenopausal; denosumab; teriparatide; Forteo®; DXA; Bone Mineral Density; pQCT

Outcome Measures

Primary Outcomes (1)

• Change in Spine Bone Density From Baseline to 2 Years

  Baseline and 2 years

Study Arms (3)

denosumab ONLY

EXPERIMENTAL

Drug: denosumab

teriparatide (Forteo®) ONLY

EXPERIMENTAL

Drug: teriparatide

denosumab and teriparatide (Forteo®)

EXPERIMENTAL

Drug: denosumab; Drug: teriparatide

Interventions

denosumab DRUG

denosumab: 60 mg SC every 6 months

denosumab ONLY; denosumab and teriparatide (Forteo®)

teriparatide DRUG

teriparatide: 20 mcg SC QD

Also known as: Forteo®

denosumab and teriparatide (Forteo®); teriparatide (Forteo®) ONLY

Eligibility Criteria

• Age: 45 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must satisfy A and B and C and D below:
• (A) Women aged \> 55
• (B) Postmenopausal
• (C) Osteoporotic with high risk of fracture

You may not qualify if:

• Confirmed serum alkaline phosphatase above upper normal limit with no explanation
• Liver disease (AST or ALT \> 2 x upper normal limit).
• Renal disease (serum creatinine \> 2.0 mg/dl).
• Hypercalcemia (Ca \>10.5 mg/dL)
• Elevated blood PTH (intact PTH \> 65 pg/ml)
• Serum 25-OH vitamin D \< 20 ng/ml
• HCT \< 32%.
• History of malignancy (except basal cell carcinoma) or radiation therapy.
• Significant cardiopulmonary disease including unstable coronary artery disease, stage D ACC/AHA heart failure or any other condition that the investigator deems may preclude the subject from participating safely or completing the protocol procedures.
• Major psychiatric disease that in the opinion of the investigator would preclude the subject from providing adequate informed consent or completing the protocol procedures.
• Excessive alcohol use or substance abuse that in the opinion of the investigator would preclude the subject from providing adequate informed consent or completing the protocol procedures.
• Known congenital or acquired bone disease other than osteoporosis (including osteomalacia, hyperparathyroidism, Paget's disease)
• Current use or use in the past 6 months of oral bisphosphonate
• Current use or use within the past 3 months of estrogens, selective estrogen receptor modulators, or calcitonin.
• Use of oral or parenteral glucocorticoids for more than 14 days within the past 6 months.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Amgen: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (14)

• Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001 May 10;344(19):1434-41. doi: 10.1056/NEJM200105103441904.

  PMID: 11346808 BACKGROUND

• Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, Garnero P, Bouxsein ML, Bilezikian JP, Rosen CJ; PaTH Study Investigators. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med. 2003 Sep 25;349(13):1207-15. doi: 10.1056/NEJMoa031975. Epub 2003 Sep 20.

  PMID: 14500804 BACKGROUND

• Finkelstein JS, Hayes A, Hunzelman JL, Wyland JJ, Lee H, Neer RM. The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med. 2003 Sep 25;349(13):1216-26. doi: 10.1056/NEJMoa035725. Epub 2003 Sep 20.

  PMID: 14500805 BACKGROUND

• Cosman F, Nieves J, Woelfert L, Formica C, Gordon S, Shen V, Lindsay R. Parathyroid hormone added to established hormone therapy: effects on vertebral fracture and maintenance of bone mass after parathyroid hormone withdrawal. J Bone Miner Res. 2001 May;16(5):925-31. doi: 10.1359/jbmr.2001.16.5.925.

  PMID: 11341338 BACKGROUND

• Kostenuik PJ, Capparelli C, Morony S, Adamu S, Shimamoto G, Shen V, Lacey DL, Dunstan CR. OPG and PTH-(1-34) have additive effects on bone density and mechanical strength in osteopenic ovariectomized rats. Endocrinology. 2001 Oct;142(10):4295-304. doi: 10.1210/endo.142.10.8437.

  PMID: 11564687 BACKGROUND

• Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998 Apr 17;93(2):165-76. doi: 10.1016/s0092-8674(00)81569-x.

  PMID: 9568710 BACKGROUND

• Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3597-602. doi: 10.1073/pnas.95.7.3597.

  PMID: 9520411 BACKGROUND

• Bone HG, Bolognese MA, Yuen CK, Kendler DL, Wang H, Liu Y, San Martin J. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. J Clin Endocrinol Metab. 2008 Jun;93(6):2149-57. doi: 10.1210/jc.2007-2814. Epub 2008 Apr 1.

  PMID: 18381571 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

• Antoniucci DM, Sellmeyer DE, Bilezikian JP, Palermo L, Ensrud KE, Greenspan SL, Black DM. Elevations in serum and urinary calcium with parathyroid hormone (1-84) with and without alendronate for osteoporosis. J Clin Endocrinol Metab. 2007 Mar;92(3):942-7. doi: 10.1210/jc.2006-1788. Epub 2006 Dec 12.

  PMID: 17164314 BACKGROUND

• Tsai JN, Uihlein AV, Burnett-Bowie SM, Neer RM, Derrico NP, Lee H, Bouxsein ML, Leder BZ. Effects of Two Years of Teriparatide, Denosumab, or Both on Bone Microarchitecture and Strength (DATA-HRpQCT study). J Clin Endocrinol Metab. 2016 May;101(5):2023-30. doi: 10.1210/jc.2016-1160. Epub 2016 Mar 10.

  PMID: 26964731 DERIVED

• Leder BZ, Tsai JN, Uihlein AV, Wallace PM, Lee H, Neer RM, Burnett-Bowie SA. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial. Lancet. 2015 Sep 19;386(9999):1147-55. doi: 10.1016/S0140-6736(15)61120-5. Epub 2015 Jul 2.

  PMID: 26144908 DERIVED

• Yu EW, Kumbhani R, Siwila-Sackman E, DeLelys M, Preffer FI, Leder BZ, Wu JY. Teriparatide (PTH 1-34) treatment increases peripheral hematopoietic stem cells in postmenopausal women. J Bone Miner Res. 2014 Jun;29(6):1380-6. doi: 10.1002/jbmr.2171.

  PMID: 24420643 DERIVED

• Tsai JN, Uihlein AV, Lee H, Kumbhani R, Siwila-Sackman E, McKay EA, Burnett-Bowie SA, Neer RM, Leder BZ. Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial. Lancet. 2013 Jul 6;382(9886):50-6. doi: 10.1016/S0140-6736(13)60856-9. Epub 2013 May 15.

  PMID: 23683600 DERIVED

MeSH Terms

Conditions

Osteoporosis

Interventions

Denosumab; Teriparatide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Parathyroid Hormone; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides

Results Point of Contact

• Title: Natalie David
• Organization: Massachusetts General Hospital

ndavid2@mgh.harvard.edu

Study Officials

• Benjamin Z Leder, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Robert M Neer, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, MD

Study Record Dates

• First Submitted: June 19, 2009
• First Posted: June 23, 2009
• Study Start: June 1, 2009
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: June 29, 2018
• Results First Posted: May 8, 2018

Record last verified: 2018-05

Locations

US (1)