Denosumab, Teriparatide or Both for the Treatment of Postmenopausal Osteoporosis - Full Text View

Purpose

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.

Condition	Intervention	Phase
Osteoporosis	Drug: denosumab Drug: teriparatide	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	The Denosumab And Teriparatide Administration Study (DATA)

Resource links provided by NLM:

MedlinePlus related topics: Bone Density Minerals Osteoporosis

Drug Information available for: Teriparatide Teriparatide acetate Denosumab

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

Bone Mineral Density by Dual X-ray Absorptiometry (DXA) [ Time Frame: 06/2009-02/2015 ] [ Designated as safety issue: No ]


Estimated Enrollment:	90
Study Start Date:	June 2009
Estimated Study Completion Date:	February 2016
Estimated Primary Completion Date:	February 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: denosumab ONLY	Drug: denosumab denosumab: 60 mg SC every 6 months
Experimental: teriparatide (Forteo®) ONLY	Drug: teriparatide teriparatide: 20 mcg SC QD Other Name: Forteo®
Experimental: denosumab and teriparatide (Forteo®)	Drug: denosumab denosumab: 60 mg SC every 6 months Drug: teriparatide teriparatide: 20 mcg SC QD Other Name: Forteo®

Eligibility


Ages Eligible for Study:	45 Years and older (Adult, Senior)
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00926380

Locations


United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

Amgen

Investigators


Principal Investigator:	Benjamin Z Leder, MD	Massachusetts General Hospital
Principal Investigator:	Robert M Neer, MD	Massachusetts General Hospital

More Information

Publications:

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.

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. Epub 2003 Sep 20.

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. Epub 2003 Sep 20.

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.

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.

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.

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.

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.

Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J; Amg Bone Loss Study Group. 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):222-9. doi: 10.1016/j.bone.2008.04.007. Epub 2008 Apr 26.

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. Epub 2006 Dec 12.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.


Responsible Party:	Benjamin Leder, MD, Principal Investigator, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00926380 History of Changes
Other Study ID Numbers:	20080723 2009P000525
Study First Received:	June 19, 2009
Last Updated:	September 22, 2015
Health Authority:	United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:


osteoporosis postmenopausal denosumab teriparatide	Forteo® DXA Bone Mineral Density pQCT

Additional relevant MeSH terms:


Osteoporosis Osteoporosis, Postmenopausal Bone Diseases, Metabolic Bone Diseases Musculoskeletal Diseases	Denosumab Teriparatide Bone Density Conservation Agents Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 29, 2016

Denosumab, Teriparatide or Both for the Treatment of Postmenopausal Osteoporosis (DATA)