Denosumab, Teriparatide or Both for the Treatment of Postmenopausal Osteoporosis

NCT ID: NCT00926380

Last Updated: 2018-06-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

94 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-06-30

Study Completion Date

2016-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Osteoporosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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denosumab ONLY

Group Type EXPERIMENTAL

denosumab

Intervention Type DRUG

denosumab: 60 mg SC every 6 months

teriparatide (Forteo®) ONLY

Group Type EXPERIMENTAL

teriparatide

Intervention Type DRUG

teriparatide: 20 mcg SC QD

denosumab and teriparatide (Forteo®)

Group Type EXPERIMENTAL

denosumab

Intervention Type DRUG

denosumab: 60 mg SC every 6 months

teriparatide

Intervention Type DRUG

teriparatide: 20 mcg SC QD

Interventions

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denosumab

denosumab: 60 mg SC every 6 months

Intervention Type DRUG

teriparatide

teriparatide: 20 mcg SC QD

Intervention Type DRUG

Other Intervention Names

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Forteo®

Eligibility Criteria

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Inclusion Criteria

Must satisfy A and B and C and D below:

* (A) Women aged \> 55
* (B) Postmenopausal
* (C) Osteoporotic with high risk of fracture

Exclusion Criteria

* 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.
* Any current or previous use of strontium or any parenteral bisphosphonate.
* Known sensitivity to mammalian cell-derived drug products.
* Known sensitivity to teriparatide or any of its excipients.
Minimum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Benjamin Leder, MD

Principal Investigator, MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Benjamin Z Leder, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Robert M Neer, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

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Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 11346808 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14500804 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14500805 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11341338 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11564687 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9568710 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9520411 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18381571 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18539106 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17164314 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26964731 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26144908 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24420643 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23683600 (View on PubMed)

Other Identifiers

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2009P000525

Identifier Type: -

Identifier Source: secondary_id

20080723

Identifier Type: -

Identifier Source: org_study_id

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