Treatment with udenafil (brand name Zydena) can increase exercise capacity and is well-tolerated in people with pulmonary arterial hypertension (PAH), results from a Phase 2b clinical trial show.
The trial data was reported in the study “Efficacy and Safety of Udenafil for the Treatment of Pulmonary Arterial Hypertension: a Placebo-controlled, Double-blind, Phase IIb Clinical Trial,” which was published in the journal Clinical Therapeutics.
Udenafil, which is not approved in the U.S., is a phosphodiesterase-5 (PDE-5) inhibitor that was developed by the Korean company Dong-A. It works like Revatio (sildenafil citrate, marketed by Pfizer)) and other PDE-5 inhibitors by promoting relaxation of blood vessels and allowing them to widen. But udenafil has a longer half-life and increased stability in the body than similar compounds. (Half-life refers to how long it takes the body to get rid of half the dose.)
Researchers conducted a Phase 2b clinical trial (NCT01553721) to explore the potential of this investigational PDE-5 inhibitor as treatment for PAH.
The trial enrolled 63 PAH patients who were divided randomly into two groups and treated with either udenafil (50 mg twice a day, taken orally) or a placebo.
After 16 weeks of treatment, researchers evaluated changes in patient’s exercise capacity as determined by the 6-minute walking distance (6MWD) test.
The average change from before starting the treatment was 46 meters (about 150 feet) in the udenafil group and 21 meters (almost 69 feet) in the placebo group, which represented a significant difference of 25 meters (82 feet) between the two groups.
When the team looked at the subset of patients who were being treated concurrently with an endothelin receptor antagonist (ERA) — a class of medications that includes Letairis (ambrisentan), Opsumit (macitentan), and Tracleer (bosentan) — the difference was even more pronounced. Those taking udenafil showed an improvement of 54 meters (177 feet) in the 6MWD test as compared to 20 meters (65 feet) in the placebo group.
Despite these positive results, no significant changes in the Borg Dyspnea Score (a measurement of how a person subjectively perceives his or her exertion) or clinical worsening over the 16-week trial period were reported between the two groups.
Still, compared to the placebo group, patients taking udenafil showed significantly lower levels of N-terminal pro b-type natriuretic peptide (NT-proBNP), a biomarker of stress on the heart.
Udenafil was generally well-tolerated during the trial period, with the most common side effects noted being headache and chest discomfort.
There were four patients on udenafil who reported serious side effects, two of whom dropped out of the study due to swelling, severe chills, and limb pain. Some of these serious adverse effects likely were caused by the the therapy. Other serious reactions, including muscle pain, chest pain, and difficulty breathing, were deemed unlikely to have been caused by udenafil.
“The data obtained through the study show the efficacy of udenafil for the treatment of patients with PAH; moreover, udenafil seemed to be safe and well tolerated by patients,” the researchers wrote, adding that, “further extended study of udenafil in PAH is warranted.”