Eighteen Months of Treatment With Subcutaneous Abaloparatide Followed by 6 Months of Treatment With Alendronate in Postmenopausal Women With Osteoporosis: Results of the ACTIVExtend Trial

doi:10.1016/j.mayocp.2016.10.009

Mayo Clinic Proceedings

Volume 92, Issue 2, February 2017, Pages 200-210

https://doi.org/10.1016/j.mayocp.2016.10.009 Get rights and content

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Abstract

Objective

To assess the efficacy and safety of 18 months of subcutaneous abaloparatide (ABL-SC) or placebo (PBO) followed by 6 months of alendronate (ALN) (preplanned interim analysis).

Patients and Methods

ACTIVExtend, an extension of ACTIVE, enrolled patients who completed 18 months of ABL-SC or PBO in ACTIVE to receive up to 24 additional months of open-label ALN; there was 1 month between the studies to re-consent patients.

Results

Of 1243 eligible ACTIVE patients, 1139 (92%) were enrolled in ACTIVExtend beginning November 20, 2012. These results are from a prespecified 6-month interim analysis (cutoff date, June 2, 2015); the study is ongoing. Findings indicated percentages of patients with new morphometric vertebral fractures: PBO/ALN, 4.4% vs ABL-SC/ALN, 0.55%; relative risk reduction, 87% (relative risk, 0.13; 95% CI, 0.04-0.41; P<.001). Kaplan-Meier estimated rates of nonvertebral fractures were PBO/ALN, 5.6% vs ABL-SC/ALN, 2.7%; risk reduction, 52% (hazard ratio [HR], 0.48; 95% CI, 0.26-0.89; log-rank P=.02). There was also a 58% risk reduction of major osteoporotic fractures (HR, 0.42; 95% CI, 0.21-0.85; log-rank P=.01) and a 45% risk reduction of clinical fractures (HR, 0.55; 95% CI, 0.33-0.92; log-rank P=.02) in the ABL-SC/ALN group vs the PBO/ALN group. At 25 months, bone mineral density percentage change from ACTIVE baseline for ABL-SC/ALN vs PBO/ALN was as follows: lumbar spine, 12.8%; total hip, 5.5%; femoral neck, 4.5% vs 3.5%, 1.4%, 0.5%, respectively (group differences at all sites P<.001).

Conclusion

Use of ABL-SC for 18 months followed by ALN for 6 months improved bone mineral density and reduced fracture risk throughout the skeleton and may be an effective treatment option for postmenopausal women with osteoporosis.

Trial Registration

clinicaltrials.gov Identifier: NCT01657162.

Abbreviations and Acronyms

ABL-SC

subcutaneous abaloparatide

ACTIVE

Abaloparatide Comparator Trial In Vertebral Endpoints

ACTIVExtend

extension trial of the Abaloparatide Comparator Trial In Vertebral Endpoints

adverse event

ALN

alendronate

BMD

bone mineral density

femoral neck

hazard ratio

ITT

intention-to-treat

lumbar spine

mITT

modified ITT

PBO

placebo

PTH

parathyroid hormone

s-CTX

serum carboxy-terminal cross-linking telopeptide of type 1 collagen

s-PINP

serum procollagen type I N-terminal propeptide

TEAE

treatment-emergent adverse event

total hip

TPTD

teriparatide

Cited by (0)

: Potential Competing Interests: Dr Cosman has been a consultant, adviser, and collaborator to Radius Health Inc; a consultant, adviser, research grant recipient, and speaker for Amgen and Eli Lilly; and an adviser for Merck, Tarsa, and Sermonix. Dr Miller is a consultant to Radius Health Inc; has participated on scientific advisory boards for AgNovos, Alexion, Amgen, Eli Lilly, Merck, Radius Health Inc, and Roche; and has received research grants from Alexion, Amgen, Boehringer Ingelheim, Immunodiagnostics, Eli Lilly, Merck, Merck Serrano, National Bone Health Alliance, Novartis, Novo Nordisk, Roche Diagnostics, and Takeda. Drs Williams, Hattersley, Hu, and Fitzpatrick are employees of and own stock in Radius Health Inc. Dr Valter is an employee of the Center for Clinical and Basic Research. Drs Riis and Christiansen are major stockholders of Nordic Bioscience and own stock in Radius Health Inc. Dr Bilezikian is a consultant for Amgen, Radius Health Inc, Shire, and Merck and receives research support from Shire Pharmaceuticals. Dr Black has been a consultant to Radius Health Inc and an adviser to Merck and has performed data analyses for Asahi-Kasei.

: ACTIVExtend Sites and Principal Investigators: Argentina: Buenos Aires, José R. Zanchetta, MD; Brazil: Brasilia, João Lindolfo Borges, MD; Curitiba, Carolina A. Moirera Kulak, MD; Rio de Janeiro, Luis Russo, MD; Sao Paolo, Cristiano A. F. Zerbini, MD; and Vitória, Ben Hur Albergaria, MD; Czech Republic: Brno, Jan Slesinger, MD; Pardubice, Tomas Hala, MD; and Prague, Martina Machková, MD; Denmark: Aalborg, Aina Sætre Lihn, MD; Ballerup, Line Markdanner Lindgren, MD; and Vejle, Peter Alexandersen, MD; Estonia: Tallinn, Ivo Valter, MD; and Tartu, Katre Maasalu, MD; Hong Kong: Edith Lau, MD; Lithuania: Vilnius, Zydrune Visockiene, MD, PhD; Poland: Bialystok, Jerzy Supronik, MD, PhD; Kielce, Mirella Wojtecka-Grabka, MD; Warsaw and Lodz, Beata Jendrych, MD; and Zgierz, Eugenia Czajkowska-Kaczmarek, MD; Romania: Bucharest, Sorica Mustatea, MD; and United States: Lakewood, CO, Paul Miller, MD; North Miami, FL, Jose Cardona, MD; and Bethesda, MD, Michael A. Bolognese, MD.