The following article is part of conference coverage from the Americas Committee for Treatment and Research in Multiple Sclerosis 2020 Forum in West Palm Beach, Florida. Neurology Advisor‘s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from the ACTRIMS 2020 Forum.
WEST PALM BEACH, FL — An oral formulation of VCE-004.8, EHP-101, is well tolerated by healthy participants, and it will soon be studied in multiple sclerosis (MS) and other autoimmune disorders, according to study results presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2020 Forum, held from February 27 to 29, 2020, in West Palm Beach, Florida.
Orally administered EHP-101 has been indicated to induce significant remyelination of the brain in murine cuprizone models (Navarrete C et al, unpublished data, January 2020), but these data have not yet been studied in humans. The objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of single and multiple doses of EHP-101 or placebo, and to confirm the exposure of VCE-004.8 within a therapeutic dose range in healthy volunteers.
In this randomized, double-blind, placebo-controlled phase 1 study, researchers administered EHP-101 in single ascending doses (0.91-185 mg) to 8 cohorts and in multiple ascending doses (20 mg once daily to 50 mg twice daily) to 4 cohorts over 7 days of treatment. Researchers assessed clinical safety by the incidence of treatment emergent adverse events, vital signs, laboratory, and cardiologic and ophthalmologic assessments; they also evaluated plasma pharmacokinetics, exploratory pharmacodynamics, and biomarkers. Of the randomly assigned 104 participants, 80 received the active drug, EHP-101.
Researchers revealed that EHP-101 was well tolerated at all dose levels, and caused only mild to moderate treatment emergent adverse events in study participants. The half-life of a 25-mg single dose of EHP-101 was approximately 2 hours during fasting and approximately 7 hours in a fed state. Post-administration with food, EHP-101 showed a mean increase of 1.5-fold in the maximum plasma concentration and area under the curve. The maximum plasma concentration for the predicted accelerated titration design was reached with a single dose of 20 mg, and the targeted exposure based on area under the curve was approached with a single dose of 50 mg and multiple doses of twice-daily 25 mg.
“In this first-in-human (FIH) study with EHP-101, single doses up to 185 mg and multiple doses up to [twice-daily] 50 mg for 7 days were well tolerated by healthy [participants]. No clinically significant safety signals were observed. The encouraging FIH data enable the start of clinical studies in patients [with] MS and other autoimmune disorders,” the researchers concluded.
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Schupp J, del Mar Municio M, DeMesa J, Fuller D, Snyder B, Rolland A. First-in-human study with EHP-101 oral solution of a synthetic cannabidiol derivative enables the initiation of a phase II study in multiple sclerosis. Presented at: Annual Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum; February 27-29, 2020; West Palm Beach, FL. Abstract P061.