Abstract Details

Title Safety and Tolerability of Orally Administered RPC1063, a Novel S1P1 Receptor Modulator, in Healthy Adult Volunteers, Results of a Phase 1 Study

Topic MS and Related Diseases

Presentation(s) P01 - (-)

Poster/Presentation
Number 178

Objective

Background BACKGROUND: RPC1063 is an oral, potent, selective sphingosine-1-phosphate receptor (S1P1R) modulator. Stimulation of the S1P1R results in sequestration of lymphocytes, which improves MS.

Design/Methods DESIGN/METHODS: Randomized, double-blind, placebo-controlled, single and multiple ascending dose escalation, first-in-human study of RPC1063. Subjects were 88 healthy male and female subjects aged 18-55 years. The study included a single ascending dose (SAD) portion, multiple ascending dose portions for 7(MAD-7) and 28day(MAD-28), and a dose titration cohort. Cohorts included 8 subjects assigned to RPC1063 (6) or placebo (2). Doses were 0.3-3 mg(SAD), 0.3-2 mg(MAD-7), and 0.3-1.5 mg(MAD-28).

Results RESULTS: Generally, RPC1063 treatment was well-tolerated. The most common AEs with RPC1063 were headache(9), somnolence(6), nausea(6), dizziness(5), fatigue(4), abdominal pain(3), and pruritus(3). No severe AEs were observed. AEs were generally similar in the placebo group. One MAD-28 subject receiving 1.5 mg had second degree, Mobitz-type-1-atrioventricular block on Day 1 of dosing and was discontinued; all other subjects completed the study. In the 3 mg SAD, 2 subjects experienced 2-second-sinus-pause during periods of sinus bradycardia, and 1 subject experienced intermittent bradycardia. These AEs resolved without medical intervention. A mild dose-dependent reduction in heart rate (HR) was observed with RPC1063. Dose titration appeared to attenuate reduction in HR. Two subjects in the 2 mg MAD-7 cohort had mild asymptomatic PFT abnormalities that resolved without medical intervention. Lymphocyte counts, used as a pharmacodynamic (PD) marker, decreased from baseline by 34% and 65% at doses of 0.3 and 1 mg, respectively. No apparent drug-related effects were observed for other clinical laboratory or ophthalmologic exams.

Conclusions CONCLUSIONS: RPC1063 was generally well tolerated, with a robust PD effect on lymphocyte counts seen at all doses. The emerging favorable safety and PD profile of RPC1063 support its continued development in patients with MS.

Authors/Disclosures
PRESENTER	No disclosure on file
Jeffrey Hartung, PhD (Receptos, Inc.)	No disclosure on file
	No disclosure on file
Robert J. Peach, PhD (Receptos)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
E M. Bebin, MD, FAAN (UAB Epilepsy Center)	Dr. Bebin has received personal compensation for serving as an employee of Springworks Therapeutics. Dr. Bebin has received personal compensation for serving as an employee of Apertura Gene Therapy. Dr. Bebin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Springworks Therapeutics. Dr. Bebin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Apertura. The institution of Dr. Bebin has received research support from NINDS. The institution of Dr. Bebin has received research support from FDA Orphan Drug Program.
	No disclosure on file
Sheila Gujrathi (Receptos)	No disclosure on file

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