Phase 1 trial of F230 oral therapy for PAH doses 1st participant
Study in China seeks 116 healthy adults to test different doses of F230
The first participant has been dosed in a Phase 1 trial testing F230, an investigational oral therapy for pulmonary arterial hypertension (PAH).
This clinical study (NCT06899815) seeks to enroll about 116 healthy individuals in China, ages 18 to 45. Around 68 participants will be randomly assigned to receive a single dose of F230 or a placebo across single-ascending dose groups testing various dose levels, from 3 mg to 40 mg. Another 36 participants will take part in multiple-ascending dose groups, where they will receive repeated doses of F230 at 6 mg, 12 mg, and 20 mg, according to preliminary results of the single-ascending dose study, or the placebo.
A third trial arm will assess the effect of food on pharmacological properties of F230, which will be given as oral tablets.
The study’s main goal is to test F230’s pharmacokinetics, or how it moves into, through, and out of the body. Assessments of safety and tolerability will also be conducted.
The clinical trial is sponsored by Gyre Therapeutics, also known as Beijing Continent Pharmaceuticals, the company developing F230.
F230 designed to reduce structural remodeling in blood vessels of lungs
The trial marks Gyre’s entry into the PAH field, an area “with limited treatment options,” according to a company press release.
PAH is a progressive disorder marked by the narrowing of pulmonary arteries, or the vessels carrying blood from the heart to the lungs, leading to high blood pressure. This structural remodeling also limits blood flow, increases resistance within pulmonary circulation, and forces the right side of the heart to pump harder, eventually leading to right heart failure if untreated. Symptoms often include shortness of breath, fatigue, chest pain, and fainting.
Increased levels of endothelin-1, a potent vasoconstrictor, are frequently found in the blood of PAH patients and are known to play a role in disease development. Endothelin-1 not only promotes vessel narrowing but also stimulates the abnormal growth of smooth muscle cells in pulmonary arteries, contributing to vessel wall thickening and remodeling. This molecule exerts its effects partly through the endothelin A (ETA) receptor, which is predominantly found on vascular smooth muscle cells.
F230, a synthetic small molecule originally developed by Eisai, is a selective inhibitor of the ETA receptor. By blocking this receptor, F230 is designed to reduce structural remodeling in the lungs’ blood vessels, thereby lowering pulmonary arterial pressure.
In animal studies, F230 lowered high blood pressure in the lungs and in the right side of the heart. Treated animals also showed reduced thickening of the heart’s right ventricle, the chamber responsible for pumping blood to the lungs, as well as thinner pulmonary arterial walls. These differences were statistically significant even at the lowest effective dose.
Building on these promising results, Gyre received approval last year from regulators in China to move forward with clinical testing of F230.
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