Oral treatment with rodatristat ethyl is safe and well-tolerated, according to results from two completed Phase 1 clinical studies in healthy volunteers.
These positive results support advancing the investigational therapy into Phase 2 studies involving people with pulmonary arterial hypertension (PAH), the treatment’s developer says.
The most recent findings on Altavant Sciences’ lead candidate were presented at the 29th International Congress of the European Respiratory Society (ERS), held Sept. 28-Oct. 2 in Madrid, Spain.
The poster, “Safety, tolerability, pharmacokinetics and pharmacodynamics after repeated once or twice daily RVT-1201, a TPH inhibitor for treatment of PAH,” was presented by Stephen Wring, PhD, Altavant’s vice president of research and development.
Rodatristat ethyl, formerly known as RVT-1201, is a tryptophan hydroxylase (TPH) inhibitor designed to prevent the production of serotonin. Lower levels of serotonin can reduce signals known to be involved in the tightening and growth of pulmonary artery muscle cells, which are hallmark features for PAH development.
The safety and efficacy of rodatristat ethyl was first evaluated in 96 healthy volunteers, recruited at a single center, who were enrolled in two Phase 1 clinical studies — KAR5585-101 and RVT-1201-1001.
Participants were assigned to take 100, 200, 400, or 800 mg of rodatristat ethyl twice a day, 500 or 800 mg once a day, or a dose-matching placebo, for a total of 14 days of treatment.
Results showed that rodatristat ethyl is generally well-tolerated and safe, with no serious adverse events or dose-limiting toxicities being reported. The most common adverse reactions among all rodatristat-ethyl-treated groups were nausea, diarrhea, and headache. These events were, in general, all mild in severity and dose-related.
Evaluation of rodatristat ethyl stability and metabolism inside the body confirmed that it had a dose-dependent response. Higher doses of the therapy corresponded to significant reductions in serotonin production.
The inhibitory activity of rodatristat ethyl seen in these healthy volunteers exceeded that required to achieve a therapeutic effect in preclinical models of PAH.
“Once or twice daily RVT-1201 [rodatristat ethyl] was generally well-tolerated, and achieved meaningful reductions in serotonin biosynthesis supporting progression to Phase 2 studies in PAH,” the researchers said.
“The results presented at ERS indicate that we can maintain a favorable safety profile while pursuing this potentially disease-modifying treatment for PAH,” William T. Symonds, PharmD, CEO of Altavant, said in a press release. “A disease-modifying treatment option for PAH would represent a crucial advance in patient care.”
Now recruiting participants, the trial (NCT03924154) is expected to enroll approximately 36 PAH patients, ages 18 to 75, at nearly 20 centers across the U.S. and Canada. More information on sites and contacts can be found here. Participants will be randomly assigned to take rodatristat ethyl or placebo twice daily for six weeks.
The trial is expected to be completed by February 2020, and data collected will be used to inform a Phase 2b efficacy study.
“We hope [the ELEVATE 1 trial] will demonstrate changes in biomarkers of serotonin biosynthesis consistent with those associated with improvements to vessel remodeling in animal models of PAH,” Symonds said.
Phase 1 Data Shows Safety of Rodatristat Ethyl in Healthy Volunteers