Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


A Novel Oral Parathyroid Hormone Formulation, PTH134, Demonstrated a Potential Therapeutically Relevant Pharmacokinetic and Safety Profile Compared with Teriparatide s.c. in Healthy Postmenopausal Women After a Single Dose

John,  Markus R., Haemmerle,  Sibylle, Launonen,  Aino, Harfst,  Evita, Azria,  Moise, Arnold,  Michel, Mindeholm,  Linda

Purpose:

Parathyroid hormone (PTH), currently the only anabolic treatment for osteoporosis, is available as the full-length hormone, PTH1–84, or as the PTH1–34 fragment (teriparatide). Both must be given subcutaneously (s.c.). A new oral formulation of PTH1–34 (PTH134) is being developed as a more convenient option for patients. In this single-centre, partially-blinded, incomplete cross-over study, the safety, tolerability, and exposure of oral PTH134 (teriparatide combined with 2 different quantities of the absorption enhancer 5-CNAC) were assessed in 32 healthy postmenopausal women.

Method:

16 subjects were randomized to receive single doses of up to six different treatments: placebo, teriparatide 20mg s.c., or 1, 2.5, 5 or 10mg of oral PTH134 formulated with 200mg 5-CNAC. Subsequently, another 16 subjects were randomized to receive up to six different treatments: placebo, teriparatide 20mg s.c, or 2.5 or 5mg of oral PTH134 formulated with either 100 or 200mg 5-CNAC. Doses were given >= 6 days apart.

Results:

All doses of PTH134 were rapidly absorbed, and showed robust blood concentrations in a dose-dependent manner. Interestingly, PTH1–34 was eliminated faster after oral versus s.c. administration. Specifically, 2.5 and 5 mg PTH134 (containing 200 mg 5-CNAC) demonstrated Cmax and AUC0-last values closest to those of s.c. teriparatide 20mg. The geometric mean estimate for PTH134 2.5mg/200mg 5-CNAC was 98.7 pg/ml (90% CI 67.3–144.7) for Cmax and 28.3 hr*pg/ml (90% CI 16.4–49.0) for AUC(0-last), while for PTH134 5mg/200mg 5-CNAC the estimated geometric mean values were 502.7 pg/ml (90% CI 304.5–829.6) for Cmax and 175.4 hr*pg/ml (90% CI 86.0–358.0) for AUC(0-last). The corresponding estimates for teriparatide 20 mg s.c. were 143.6 pg/ml (90% CI 123.7–166.7) for Cmax and 229.9 hr*pg/ml (90% CI 198.9–263.7) for AUC(0-last).

Ionized calcium remained within normal limits in all treatment groups. Nine subjects withdrew due to treatment-related AEs. Of those, seven were taking PTH134 2.5 or 5mg: three withdrew for symptomatic hypotension (two of whom were in the 200mg 5-CNAC group), three because of delayed vomiting (two from the 200mg 5-CNAC group), one withdrew for symptomatic, but unconfirmed, hypercalcemia (receiving 2.5mg/100mg 5-CNAC). One subject receiving teriparatide and one receiving placebo withdrew for symptomatic hypotension. No serious AEs were reported.

Conclusion:

The study demonstrated potential therapeutically relevant PTH1–34 systemic exposure levels after oral administration of PTH1–34 formulated with the absorption enhancer 5-CNAC. Doses of 2.5 and 5mg of oral PTH134 achieved exposure levels closest to those of teriparatide 20mg s.c., with a comparable incidence of AEs in healthy postmenopausal women. PTH134 warrants further investigation

To cite this abstract, please use the following information:
John, Markus R., Haemmerle, Sibylle, Launonen, Aino, Harfst, Evita, Azria, Moise, Arnold, Michel, et al; A Novel Oral Parathyroid Hormone Formulation, PTH134, Demonstrated a Potential Therapeutically Relevant Pharmacokinetic and Safety Profile Compared with Teriparatide s.c. in Healthy Postmenopausal Women After a Single Dose [abstract]. Arthritis Rheum 2009;60 Suppl 10 :887
DOI: 10.1002/art.25967

Abstract Supplement

Meeting Menu

2009 ACR/ARHP