Evaluation of the efficacy, safety and pharmacokinetic profile of oral recombinant human parathyroid hormone [rhPTH(1–31)NH2] in postmenopausal women with osteoporosis

Abstract Context Treatment of osteoporosis with subcutaneous (SC) injections of rhPTH(1–34) or rhPTH(1–84) is associated with significant improvements in BMD and reductions in osteoporotic fractures. However, subcutaneous injections can be associated with discomfort and thus deteriorating compliance. Objective The UGL-OR1001 trial aimed to establish the efficacy and safety parameters of a novel oral tablet formulation of rhPTH(1–31)NH 2 and matching placebo tablets and open-label teriparatide positive control in postmenopausal women with osteoporosis. Design 24 weeks of randomized, double-blind treatment with once daily doses of 5 mg oral treatment or corresponding placebo, or open-label subcutaneous teriparatide. Patients or other participants Women diagnosed with postmenopausal osteoporosis as detected by lumbar spine DXA, with an exclusion of those with prior treatment with bone active agents. Intervention(s) Orally formulated recombinant human PTH(1–31)NH 2 and placebo, or open-label subcutaneous teriparatide as a positive control. Main outcome measure(s) The primary endpoint was to characterize the percent change from baseline in bone mineral density (BMD) at L1–L4 axial lumbar spine after 24 weeks in the rhPTH(1–31)NH 2 arm. Secondary and exploratory endpoints included safety and tolerability of the oral formulation, measurement of biochemical markers of bone turnover, and evaluation of the PK profile at first and last dose. The study was registered at ClinicalTrials.gov with the identifier: NCT01321723. Results The oral tablet formulation of rhPTH(1–31)NH 2 resulted in similar PK profiles at both timepoints with mean C max values similar to subcutaneous administration. In the rhPTH(1–31)NH 2 arm, a 2.2% increase in lumbar spine BMD was observed compared to baseline ( p p Conclusions In summary, these data demonstrate that enteric-coated oral tablet formulation technology consistently generated robust levels of exposure of rhPTH(1–31)NH 2 leading to induction of bone formation without inducing bone resorption resulting in significantly increased levels of LS BMD. Few adverse events were observed, recommending this orally delivered drug candidate for further development.