PMID- 33638863 OWN - NLM STAT- MEDLINE DCOM- 20210504 LR - 20240331 IS - 1179-1918 (Electronic) IS - 1173-2563 (Print) IS - 1173-2563 (Linking) VI - 41 IP - 3 DP - 2021 Mar TI - Phase 1b Evaluation of Abaloparatide Solid Microstructured Transdermal System (Abaloparatide-sMTS) in Postmenopausal Women with Low Bone Mineral Density. PG - 277-285 LID - 10.1007/s40261-021-01008-7 [doi] AB - BACKGROUND AND OBJECTIVE: Abaloparatide, an anabolic osteoporosis treatment administered by subcutaneous (SC) injection, increases bone mineral density (BMD) and reduces fracture risk in postmenopausal women with osteoporosis. The abaloparatide-solid Microstructured Transdermal System [abaloparatide-sMTS (Kindeva, St Paul, MN, USA)], which delivers abaloparatide intradermally, is in development to provide an alternative method for abaloparatide delivery. The objective of this study was to evaluate the ability of subjects to self-administer abaloparatide-sMTS, based on pharmacokinetic and pharmacodynamic markers. METHODS: In this single-arm, open-label, Phase 1b study, 22 healthy postmenopausal women aged 50-85 years with low BMD were trained to self-administer abaloparatide-sMTS 300 mug once daily to the thigh for 5 min for 29 days. The primary endpoint was systemic exposure to abaloparatide. Secondary endpoints included percent change from baseline in serum procollagen type I N-terminal propeptide (s-PINP), patient experience, and safety. RESULTS: All 22 subjects completed the study. At baseline, mean age was 65.2 years, mean total hip T-score was - 1.32, and mean lumbar spine T-score was - 1.98. On Day 1, the median time to reach maximum concentration (T(max)) for abaloparatide-sMTS was 0.33 h and geometric mean (CV %) maximum concentration (C(max)) and area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC(0-t)) were 447 (38.0) pg/mL and 678 (45.3) pg.h/mL, respectively; the pharmacokinetic profile was similar on Days 15 and 29. Median percentage change in s-PINP was 45.4% and 64.4% at Days 15 and 29, respectively. The most common adverse events (AEs) were application site erythema, pain, and swelling, which were mostly of mild or moderate severity. No AEs led to study drug withdrawal and no serious AEs were reported. The success rate for self-administration at first application was 99.7%, and subject acceptability was high (~ 4.5 on a 5-point Likert Scale). CONCLUSIONS: Subjects successfully self-administered abaloparatide-sMTS, which provided a consistent pharmacokinetic profile over 29 days and produced s-PINP increases from baseline similar to that observed in the pivotal trial with abaloparatide-SC. Observed patient experience along with the clinical data support continued clinical development of abaloparatide-sMTS. TRIAL REGISTRATION NUMBER: NCT04366726, Date of registration 04/29/2020, retrospectively registered. FAU - Miller, Paul D AU - Miller PD AUID- ORCID: 0000-0002-5347-7457 AD - Colorado Center for Bone Health, (Director), Lakewood, CO, USA. FAU - Troy, Steven AU - Troy S AUID- ORCID: 0000-0002-9535-7293 AD - Radius Health, Inc., (Clinical Pharmacology), Boston, MA, USA. FAU - Weiss, Richard J AU - Weiss RJ AUID- ORCID: 0000-0002-0095-2410 AD - Radius Health, Inc., (Global Medical Affairs), Boston, MA, USA. FAU - Annett, Miriam AU - Annett M AUID- ORCID: 0000-0002-4520-6841 AD - Radius Health, Inc., (Biometrics), Boston, MA, USA. FAU - Schense, Jason AU - Schense J AUID- ORCID: 0000-0001-5691-6817 AD - Astra Healthcare Advisers (Clinical Development), Milan, Lombardy, Italy. FAU - Williams, Setareh A AU - Williams SA AUID- ORCID: 0000-0002-6795-2677 AD - Radius Health, Inc., (Health Economics and Outcomes Research), Boston, MA, USA. FAU - Mitlak, Bruce AU - Mitlak B AUID- ORCID: 0000-0001-7050-0703 AD - Radius Health, Inc., (Clinical Development), 22 Boston Wharf Road, Boston, MA, 02210, USA. bmitlak@radiuspharm.com. LA - eng SI - ClinicalTrials.gov/NCT04366726 PT - Clinical Trial, Phase I PT - Journal Article DEP - 20210227 PL - New Zealand TA - Clin Drug Investig JT - Clinical drug investigation JID - 9504817 RN - 0 (Bone Density Conservation Agents) RN - 0 (Parathyroid Hormone-Related Protein) RN - 0 (Peptide Fragments) RN - 0 (Procollagen) RN - 0 (procollagen Type I N-terminal peptide) RN - AVK0I6HY2U (abaloparatide) SB - IM MH - Aged MH - Aged, 80 and over MH - Bone Density/*drug effects MH - Bone Density Conservation Agents/*therapeutic use MH - Female MH - Humans MH - Injections, Subcutaneous MH - Lumbar Vertebrae/drug effects MH - Middle Aged MH - Osteoporosis, Postmenopausal/*drug therapy MH - Parathyroid Hormone-Related Protein/*administration & dosage MH - Peptide Fragments/blood MH - Procollagen/blood PMC - PMC7946681 OAB - Osteoporosis is a serious health condition that causes more than 2 million fractures in the USA annually. Treatment options for osteoporosis include drugs that prevent bone resorption and anabolic agents that build new bone. Bone anabolic agents, such as abaloparatide, have been shown to increase bone mineral density and reduce the risk of fracture in postmenopausal women with osteoporosis. Currently, all bone anabolic agents are delivered by subcutaneous injection. However, some patients do not like injectable treatments, which can negatively impact patients' adherence to prescribed medication. In this study, we describe a novel mode of administration, the abaloparatide-solid Microstructured Transdermal System (abaloparatide-sMTS), which is applied to the thigh for 5 min and delivers abaloparatide intradermally. The study showed that this new method delivered abaloparatide into the blood as effectively as subcutaneous injections and demonstrated signs of activity in the body. Study participants were satisfied with abaloparatide-sMTS and found it easy to use. The most common side effects were skin related, including redness, pain, and swelling, which resolved shortly after dosing. OABL- eng COIS- PDM has received research support from and is a member of an advisory board for Radius Health, Inc. JS is a paid consultant for Radius Health, Inc. and he has also received reimbursement for travel related to this study. ST, RJW, MA, SAW, and BM are employees of and own company stock in Radius Health, Inc. EDAT- 2021/02/28 06:00 MHDA- 2021/05/05 06:00 PMCR- 2021/02/27 CRDT- 2021/02/27 12:08 PHST- 2021/01/27 00:00 [accepted] PHST- 2021/02/28 06:00 [pubmed] PHST- 2021/05/05 06:00 [medline] PHST- 2021/02/27 12:08 [entrez] PHST- 2021/02/27 00:00 [pmc-release] AID - 10.1007/s40261-021-01008-7 [pii] AID - 1008 [pii] AID - 10.1007/s40261-021-01008-7 [doi] PST - ppublish SO - Clin Drug Investig. 2021 Mar;41(3):277-285. doi: 10.1007/s40261-021-01008-7. Epub 2021 Feb 27.