SAT235 An Orally Administered Robotic Pill (RP) Reliably And Safely Delivers the Human Parathyroid Hormone Analog hPTH(1-34) (Teriparatide) With High Bioavailability in Healthy Human Volunteers: A Phase 1 Study

Disclosure: J.T. Myers: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. A. Dasari: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. A. Battiwala: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. N. Patel: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. A. Toledo Vo: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. A. Yamaguchi: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. K. Horlen: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. L.C. Fung: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. B. Syed: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. S. Nguyen: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. J. Van Dam: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. M. Imran: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. M. Hashim: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. A.K. Dhalla: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. Background/Purpose: Teriparatide, an effective osteoanabolic agent, requires a chronic regimen of daily subcutaneous (SC) injections, representing a burden for patients which may interfere with compliance and quality of life. We have developed a novel oral robotic pill (RP) to deliver biotherapeutic agents with bioavailability rivaling or surpassing that of parenteral injections. Here we present data from a Phase 1 study in healthy women volunteers designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of 20- and 80 µg of hPTH (1-34) administered orally via RP (RT-102) at single doses. Methods: The study was approved by the Alfred Health HREC in Australia. Participants received a single dose of either RT-102 at 20 µg (RT-102/20 µg group; N=15) or 80 µg (RT-102/80 µg group; N=14) or a single 20 µg dose of the commercially available teriparatide (Forteo(®)) via SC injection (SC group; N=10). Fluoroscopic images were taken to track the transit/deployment of RT-102 and confirm excretion of remnants. Drug concentration in serum samples serially collected over 6 hours were measured by a validated ELISA assay. Results: All 29 participants in the RT-102 arms were able to swallow RT-102 and none experienced any adverse events (AEs) upon device deployment. Both doses of RT-102 were safe and well-tolerated with no serious adverse events (SAEs) reported. In the SC group, a total of six drug-related AEs were reported in four participants. There were no AEs reported in the RT-102/20 µg group. Mild and transient AEs attributed to the drug were observed in one participant in the RT-102/80 µg group. No AEs related to the RP were reported. Imaging confirmed excretion of all RP device remnants within an average of 2.7 ± 1.4 days. Based on serum analyses, drug was successfully delivered by RT-102 in 12 of 15 participants in the 20 µg group and in all 14 participants in the 80 µg group. PK analyses indicated that RT-102 delivered drug with more sustained peak concentrations than the SC group. The C(max) of RT-102 was 98 ± 10 pg/mL for the 20 µg dose and 971 ± 223 pg/mL for the 80µg dose compared to 128 ± 20 pg/mL for the 20 µg SC injection group. The T(max) for RT-102 delivery was 68 and 60 min for the 20 µg and 80 µg doses, respectively, compared to 13 min for the SC injection. Based on AUC calculations of the PK curves, the relative bioavailability of RT-102 dose groups was 3- to 4-fold higher compared to the SC injection group. Conclusions: This study provides the first clinical evidence of safe and successful delivery of hPTH (1-34) via an orally administered RP with high reliability and bioavailability. These data suggest that RT-102 can potentially offer an easier and more convenient treatment option to osteoporosis patients, and given the high bioavailability, RT-102 may be effective at doses lower than the currently approved 20 µg SC dose of teriparatide. Presentation: Saturday, June 17, 2023