The experimental design of a phase 2b clinical trial testing the safety and efficacy of rodatristat ethyl in patients with pulmonary arterial hypertension (PAH) is described in an article published in the journal Pulmonary Circulation.

“The trial incorporates endpoints to generate essential clinical efficacy, safety, pharmacokinetic, and pharmacodynamic data needed to evaluate the ability of rodatristat ethyl to ameliorate PAH by halting or reversing pulmonary vascular remodeling through its unique mechanism of TPH1 inhibition,” the authors of the study wrote.

Rodatristat ethyl is a prodrug for rodatristat and a potent inhibitor of TPH1 or tryptophan hydroxylase 1, which is upregulated in PAH arterial endothelial cells. Previous research has shown that rodatristat ethyl can reduce levels of 5-hydroxy indole acetic acid (5-HIAA) in a dose-dependent manner. 5-HIAA is the major metabolite of serotonin, which is synthesized by TPH1, in the plasma and urine of healthy people. 

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The phase 2b trial called ELEVATE 2 is a dose-ranging, randomized, double-blind, placebo-controlled, multicenter study that will evaluate the effect of rodatristat ethyl on pulmonary vascular resistance as measured at right heart catheterization.

Read more about clinical trials for PAH.

The study is currently recruiting participants in the US, Europe, Ukraine, and the UK and aims to enroll 90 participants aged 18 years or more with PAH. Participants will either receive 300 mg or 600 mg of rodatristat ethyl or a placebo twice a day plus standard of care medication(s) for 24 weeks. 

The primary outcome measure will be the percent change from baseline of pulmonary vascular resistance between active treatment and placebo. Secondary outcome measures are the proportion of patients who improve in WHO Functional Class, change from baseline in 6-minute walk distance, and change from baseline in NT-proBNP levels.

The trial is expected to be completed in February 2023. 


Lazarus HM, Denning J, Wring S, et al. A trial design to maximize knowledge of the effects of rodatristat ethyl in the treatment of pulmonary arterial hypertension (ELEVATE 2). Pulm Circ. Published online April 29, 2022. doi:10.1002/pul2.12088

A study of rodatristat ethyl in patients with pulmonary arterial hypertension (ELEVATE 2). US National Library of Medicine. Last updated January 18, 2022. Accessed May 5, 2022.