The first participant has been dosed in a Phase 1 American study evaluating TopiVert Pharma‘s oral version of TOP1288 as a treatment for ulcerative colitis (UC).
The study will assess TOP1288’s safety, tolerability, pharmacokinetics and pharmacodynamics in healthy volunteers. Pharmacokinetics refers to the body’s absorption, distribution, metabolism, and excretion of a substance. Pharmacodynamics refers to its biological and physiological effects.
TopiVert is also conducting a randomized, double-blind, placebo-controlled Phase 2a trial (NCT02888379) in Europe. It will evaluate the effectiveness, safety, and tolerability of a 200-mg rectal formulation of TOP1288 administered once a day for four weeks to 60 people with moderate to severe symptomatic ulcerative colitis.
The rectal-formulation study is aimed at guiding the development of the oral formulation that TopiVert hopes to market.
The company expects results from both the oral and rectal studies in the second half of the year.
“We are delighted to have commenced the clinical evaluation of an oral formulation of TOP1288 as our intended commercial presentation,” Ajay Duggal, TopiVert’s chief medical officer, said in a press release. “The Phase 1 study will evaluate the ability to deliver TOP1288 to the colon by the oral route, as well as assessing safety and tolerability of the formulation. In parallel, a rectal formulation of TOP1288 is being evaluated in a Phase 2a study to demonstrate proof of concept in UC patients.”
“Both studies will report [results] in the second half of this year. Given the pressing need for improved treatments in UC, we are eager to see if TOP1288’s potent anti-inflammatory properties can bring clinical benefit to UC patients,” Duggal added.
TopiVert noted that first-line UC treatments fail in an about half of patients. Despite the number of treatment options available today, about 20 percent of patients end up requiring a partial or total colectomy, or surgical removal of the colon.
TOP1288 is a narrow-spectrum protein kinase inhibitor (NSKI). TopiVert hopes it proves to be a potent inhibitor of kinases — a type of enzyme — involved in inflammation, and that its therapeutic activity remains confined to the colon area.
A previous phase 1 study (NCT02463045) evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple ascending doses of TOP1288’s rectal formulation in healthy subjects, and multiple doses in ulcerative colitis patients.
Results of the study, which was completed in 2016, demonstrated that the rectal formulation was safe and tolerable in healthy volunteers. Participants received up to 200 mg of the formulation once or twice daily for five days.