caa a22 4500 445311657 CHVBK 20180317142632.0 cr unu---uuuuu 170323e20110101xx s 000 0 eng 10.1007/s11095-010-0192-9 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0192-9 Parathyroid Hormone (1-34)-Coated Microneedle Patch System: Clinical Pharmacokinetics and Pharmacodynamics for Treatment of Osteoporosis [Elektronische Daten] [Peter Daddona, James. Matriano, Jaap Mandema, Yuh-Fun Maa] ABSTRACT: Objectives: To evaluate the clinical PK/PD of PTH(1-34) delivered by a novel transdermal drug-coated microneedle patch system (ZP-PTH) for the treatment of osteoporosis. Methods: Phase 1 PK studies evaluated the effect of site of administration, patch wear time and dose in normal volunteers, ages 40-85yrs. Phase 2 was conducted in post-menopausal women with osteoporosis to determine the patch dose response compared to placebo patch and FORTEO® injection. Results: Phase 1 ZP-PTH patch delivery demonstrated a rapid PTH plasma pulse profile with Tmax 3 times shorter and apparent T1/2 2 times shorter than FORTEO®. In Phase 2, ZP-PTH 20, 30 and 40µg doses showed a proportional increase in plasma PTH AUC. Inter-subject and intra-subject AUC variability was similar for all patch doses and comparable to injection. All patch doses produced a significant increase in spine bone mineral density. Unexpectedly, ZP-PTH also produced an early increase in hip bone mineral density, an effect not observed with the injection. Conclusions: These studies suggest that this novel ZP-PTH patch system can deliver a consistent and therapeutically relevant PTH PK profile. Based on encouraging Phase 2 safety and efficacy data, the program is advancing into a pivotal Phase 3 clinical study. Springer Science+Business Media, LLC, 2010 Parathyroid hormone nationallicence PTH (1-34) nationallicence teriparatide nationallicence osteoporosis nationallicence transdermal microneedle patch nationallicence pharmacokinetics nationallicence pharmacodynamics nationallicence Macroflux nationallicence Daddona Peter Zosano Pharma, Inc., 34790 Ardentech Court, Fremont, California, 94555 aut Matriano James Zosano Pharma, Inc., 34790 Ardentech Court, Fremont, California, 94555 aut Mandema Jaap Quantitative Solutions, Inc., 845 Oak Grove Avenue, Suite 100, 94025, Menlo Park, California, USA aut Maa Yuh-Fun Zosano Pharma, Inc., 34790 Ardentech Court, Fremont, California, 94555 aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/1(2011-01-01), 159-165 0724-8741 28:1<159 2011 28 11095 https://doi.org/10.1007/s11095-010-0192-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0192-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Daddona Peter Zosano Pharma, Inc., 34790 Ardentech Court, Fremont, California, 94555 aut NATIONALLICENCE 700 1- Matriano James Zosano Pharma, Inc., 34790 Ardentech Court, Fremont, California, 94555 aut NATIONALLICENCE 700 1- Mandema Jaap Quantitative Solutions, Inc., 845 Oak Grove Avenue, Suite 100, 94025, Menlo Park, California, USA aut NATIONALLICENCE 700 1- Maa Yuh-Fun Zosano Pharma, Inc., 34790 Ardentech Court, Fremont, California, 94555 aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/1(2011-01-01), 159-165 0724-8741 28:1<159 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer