A First-in-Human Phase 1 Randomized Single and Multiple Ascending Dose Study of RPh201 in Healthy Volunteers

Zadik Hazan, Konstantin Adamsky, Andre Lucassen, Leonard A Levin, Zadik Hazan, Konstantin Adamsky, Andre Lucassen, Leonard A Levin

Abstract

RPh201 is a drug extracted from gum mastic that has been studied for its anti-inflammatory and antibacterial properties. Preclinical studies of RPh201 demonstrated neuroprotective and neuroenhancing effects. Toxicology studies in animals did not reveal safety concerns or genotoxic effects. This single-center, phase 1, randomized, placebo-controlled, double-masked study in healthy volunteers assessed the safety and tolerability of RPh201, and determined the highest tolerated dose. There were 2 parts: a single ascending dose (SAD) stage, followed by a multiple ascending dose (MAD) stage. Three dosing arms were included in each stage (5 mg, 10 mg, and 20 mg). Safety data in the lower dosing arms were evaluated before higher doses were initiated. Eighteen participants were randomized in the SAD stage: 12 to RPh201 (4 at each dose) and 4 to placebo. Twenty-one participants were randomized in the MAD stage, of which 13 received RPh201. All 18 participants in the SAD stage completed treatment. Sixteen of the 21 participants in the MAD stage completed treatment. The most frequently reported adverse events were local injection site pain and erythema. No deaths or adverse events related to changes in vital signs or electrocardiograms were reported. No occurrences of suicidal behavior or ideation were reported.

Keywords: RPh201; gum mastic; neuroprotection; phase 1.

Conflict of interest statement

Z.H., K.A., and A.L. are employees of Regenera Pharma Limited, the company that funded these studies. L.A.L. is a consultant to Regenera, and has served as consultant on neuroprotection to Aerie, Allergan, Evevensys, Galimedix, Prilenia, and Quark. He is a recipient of funding from the Canadian Research Chairs program, National Institutes of Health (R21 EY025074), Canada Institutes for Health Research (PJT‐162396), and Research to Prevent Blindness.

© 2019 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Figures

Figure 1
Figure 1
Molecular structures of masticadienonic acid (MDA) and isomasticadienonic acid (IMDA), 2 of the main constituents of gum mastic.
Figure 2
Figure 2
Flowchart displaying details of participation in the single ascending dose (SAD) and multiple ascending dose (MAD) stages of the study.

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Source: PubMed

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