Y. Kenan ¹, E. Kochba ¹, M. Shahar ¹, H. Gadasi ¹, G. Levin ¹, A. J. Foldes ², S. Ish-Shalom ³,*, T. Matsumoto ⁴, R. Lindsay ⁵, C. Christiansen ⁶, R. Neer <sup>7

1</sup>TransPharma Medical Ltd, Lod, ²Hadassah-Hebrew University Medical Center, Jerusalem, ³Metabolic Bone Diseases Unit, Rambam Health Care Center, Haifa, Israel, ⁴Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medical Sciences, Tokushima, Japan, ⁵Internal Medicine, Helen Hayes Hospital, West Haverstraw, ⁷Massachusetts General Hospital, Boston, United States, ⁶Nordic Bioscience, Herlev, Denmark

Aims: TransPharma has developed a system for transdermal (TD) delivery of teriparatide to alleviate the discomfort of subcutaneous (SC) injections and to improve acceptance and compliance. The aim was to compare the effects of TD 50,
80, and SC 20 µg teriparatide on biochemical markers of bone turnover and safety.

Methods: A 3-month, randomized, multicenter study was conducted in postmenopausal women with osteoporosis (mean ± SD, age 65.1 ± 6.8 yr). The transdermal delivery of teriparatide utilized radiofrequency ablation to create microchannels in the skin, allowing rapid diffusion into the systemic circulation from a subsequently-applied drug patch. The primary objective was percent change from baseline to day 96 in procollagen type I N-terminal propeptide (PINP), a marker of bone formation. Secondary objectives included changes from baseline in PINP and CTX (C-terminal cross- linked telopeptide of type I collagen), a marker of bone resorption, at days 48, 72, and 96, and safety monitoring of TD compared with SC teriparatide.

Results: A total of 99/104 women (95.2%) completed the study, a withdrawal rate 5%. Bone markers were measured in 33, 31, and 36 women in the TD 50, 80, and SC 20 µg groups, respectively. PINP and CTX increased significantly from baseline (Table). No clinically significant differences across study groups or time were observed for hypercalcemic, dermatologic, or other adverse events (AEs). The number of patients with predose and 4,6,8 hours postdose serum total calcium levels exceeding the upper limit of normal in the TD50, TD80, and SC20 groups were 7 (20.6%), 9 (28.1%), and 14 (38.9%), respectively. Four severe AEs were determined by investigators to be unrelated to study treatment: 1/34 (2.9%, screening AE), 2/34 (5.9%), 1/36 (2.8%) in TD50, 80 and SC20 groups, respectively.

Table: Time course of PINP and CTX median percent change from baseline by treatment group
 

	Baseline (Median µg/L)	Day 48 (%)	Day 72 (%)	Day 96 (%)
PINP       TD50	51.6	53‡	71‡	88‡c
TD80	43.4	83‡	122‡	172‡
SC20	47.0	83‡	88‡	150‡
CTX      TD50	0.432	29†a	34‡a	53‡b
TD80	0.351	72‡	99‡	116‡
SC20	0.392	11*a	34‡b	79‡

*P=0.0029, †P=0.0002, ‡P<0.0001 vs. baseline; aP<0.001; bP<0.01; cP<0.05 vs. TD80

Conclusions: Teriparatide was well tolerated by all groups. Transdermal teriparatide 50 and 80 demonstrated significant increases in PINP and CTX, similar to subcutaneous 20 teriparatide.

Acknowledgement: Funded by Eli Lilly and Company