Phase 1b Evaluation of Abaloparatide Solid Microstructured Transdermal System (Abaloparatide-sMTS) in Postmenopausal Women with Low Bone Mineral Density

Abstract

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 μg 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 (Tmax) for abaloparatide-sMTS was 0.33 h and geometric mean (CV %) maximum concentration (Cmax) and area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC0-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.

Conflict of interest statement

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.

Figures

Fig. 1

Study design. ABL-sMTS abaloparatide-solid Microstructured Transdermal System, D day

Fig. 2

Mean (±SD) plasma concentrations of 300 μg abaloparatide-sMTS over time (N = 22) on a linear scale (a) and logarithmic scale (b). h hour, LLOQ lower limit of quantitation, SD standard deviation, sMTS solid Microstructured Transdermal System

Fig. 3

Median (interquartile range) s-PINP (ng/mL) at Days 15 and 29 (N = 22). Baseline is defined as the last non-missing measurement taken prior to first dose. BL baseline, s-PINP serum procollagen type I N-terminal propeptide