First in Man Studies of Pharmacokinetic Profiles of a Novel Oral PTH(1-34)

Tang, Jonathan, Galitzer, Hillel, Washbourne, Christopher, Piec, Isabelle, Wang, Naifang, Burshtein, Gregory, Phillip Schwartz, Phillip, Caraco, Yoseph, Ehud Arbit, Ehud and Fraser, William (2014) First in Man Studies of Pharmacokinetic Profiles of a Novel Oral PTH(1-34). In: American Society of Bone and Mineral Research, 2014-09-11 - 2014-09-15, George R Bush Convention Centre.

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Abstract

Background: PTH(1-34) (Teriparatide) is an anabolic agent used in treatment of osteoporosis. It promotes bone formation and reduces the risk of vertebral and some non-vertebral fractures. The route of administration by daily subcutaneous (sc) injection can cause problems in certain patients. A new oral delivery system for human PTH(1-34) has been developed as a possible treatment option. Galitzer et al. presented pre-clinical data (ASBMR 2012, MO0402) and first-in-human results (ASBMR 2013, FR0378) on safety, tolerability and absorption dynamics of oral PTH(1-34) in various dosages. We now describe the pharmacokinetics (PK) of oral PTH(1-34) compared to sc and placebo in healthy subjects. Objective: A single-center, double blinded, triple crossover study was designed to compare the 1.8 mg optimal dose of oral PTH(1-34) against standard dosage of teriparatide injection and oral placebo. Method: The study was conducted following and in accordance with the Hadassah Medical Center ethical approval committee. 12 healthy volunteers (6m/6f), 18-50y, received three treatments: single sc injection of 20µg FORTEO®, 1.8 mg oral PTH(1-34), or placebo. Blood samples were collected at time 0, 10, 15, 20, 30, 45, 60, 75, 90, 120, 180, 240, 300 minute post dose. Plasma concentration of PTH(1-34) (IDS, Tyne and Wear, UK) and cyclic adenosine 3’,5’monophosphate (cAMP) were measured on all samples. Results: All 12 subjects on oral PTH(1-34) showed rapid, post dose increase then decrease of PTH(1-34), from baseline mean (±SD) of 5.9 (1.8) pg/mL to peak mean of 185.3 (±128.8) pg/mL. PK profiles of oral PTH(1-34) showed Cmax (pg/mL), Tmax (mins), AUC0-last of 238.3 (110.8), 17.5 (5.4) and 6161.7 (2726.7), respectively; whereas sc showed mean Cmax (pg/mL), Tmax (mins), AUC0-last of 172.3 (55.7), 20.8 (8.7) and 13965.9 (2984.8), respectively. Plasma cAMP increased in all subjects in response to oral PTH(1-34) and sc treatment. Serum adjusted calcium in all subjects remained within normal limits throughout the studies. Conclusion: PK profiles showed a single oral dose of 1.8 mg PTH(1-34) is rapidly absorbed, and no significant difference in Cmax and Tmax when compared with 20µg of sc teriparatide. A significant difference in the rate of plasma clearance and AUC0-last value was observed (fig.1). These differing profiles and modality of administration of PTH(1-34) could offer unique advantages in the treatment of calcium and metabolic bone disorders.

Item Type: Conference or Workshop Item (Poster)
Additional Information: Jonathan C. Y. Tang, Hillel Galitzer, Christopher J. Washbourne, Isabelle Piec, Naifang Wang, Gregory Burshtien, Phillip Schwartz, Yoseph Caraco, Ehud Arbit, William D. Fraser. 2014 First in Man Studies of Pharmacokinetic Profiles of a Novel Oral PTH (1-34). J Bone Miner Res 29 (Suppl 1). Available at http://www.asbmr.org/education/AbstractDetail?aid=990476c3-4440-4363-a391-6559b1e59568. Accessed September 15, 2014.
Uncontrolled Keywords: parathyroid hormone,pth assay,pth (1-34),osteoporosis
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: Pure Connector
Date Deposited: 07 Oct 2014 12:40
Last Modified: 22 Jul 2020 03:04
URI: https://ueaeprints.uea.ac.uk/id/eprint/50418
DOI:

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