Efficacy of tadalafil sustained long-term from freemexy's blog
New data from an extension study of the PHIRST trial indicate that
patients with pulmonary arterial hypertension continued to benefit from
treatment with tadalafil after an additional 52 weeks of therapy.Tadalafil powder half life
Results from the previously published, multicenter, randomized, placebo-controlled, 16-week Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) study linked treatment with tadalafil 40 mg (Adcirca, Lilly) — the highest of four doses evaluated — to significantly improved 6-minute walk distance, time to clinical worsening and quality of life.
To evaluate the long-term safety and durability of efficacy of tadalafil in patients with pulmonary arterial hypertension, researchers conducted PHIRST-2 — a double blind, uncontrolled extension study in which patients were randomly assigned to receive once-daily tadalafil 20 mg (n=63) or 40 mg (n=294) for an additional 52 weeks.
Patients who received tadalafil 20 mg or 40 mg in both PHIRST and PHIRST-2 maintained improvements in 6-minute walk distances achieved during PHIRST (406 m and 413 m, respectively) at the conclusion of the extension study (415 m and 410 m, respectively). Those previously receiving lower doses or placebo during PHIRST, however, did not experience a similar level of improvement.
A higher proportion of patients receiving tadalafil 20 mg experienced WHO functional class deterioration when compared with those assigned tadalafil 40 mg (9% vs. 6
.
Post-hoc analyses associated background bosentan (Tracleer, Actelion) use and higher 6-minute walk distance at PHIRST baseline with fewer clinical worsening events.
Safety profiles from both PHIRST and PHIRST-2 were comparable, according to the study results. Ninety-two percent of patients experienced at least one treatment-emergent adverse event during PHIRST-2, 49% of which may have been drug-related. Most adverse events, however, were mild to moderate in intensity and did not result in study discontinuation.
“These data demonstrate that the long-term safety profile of tadalafil appears similar to that in the 16-week PHIRST study and that treatment for up to 68 weeks appears safe and well tolerated,” the researchers wrote. “For patients receiving [tadalafil 20 mg] or [tadalafil 40 mg], the short-term improvements in exercise capacity observed in PHIRST appeared to be maintained for an additional 52 weeks in PHIRST-2.”
Results from the previously published, multicenter, randomized, placebo-controlled, 16-week Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) study linked treatment with tadalafil 40 mg (Adcirca, Lilly) — the highest of four doses evaluated — to significantly improved 6-minute walk distance, time to clinical worsening and quality of life.
To evaluate the long-term safety and durability of efficacy of tadalafil in patients with pulmonary arterial hypertension, researchers conducted PHIRST-2 — a double blind, uncontrolled extension study in which patients were randomly assigned to receive once-daily tadalafil 20 mg (n=63) or 40 mg (n=294) for an additional 52 weeks.
Patients who received tadalafil 20 mg or 40 mg in both PHIRST and PHIRST-2 maintained improvements in 6-minute walk distances achieved during PHIRST (406 m and 413 m, respectively) at the conclusion of the extension study (415 m and 410 m, respectively). Those previously receiving lower doses or placebo during PHIRST, however, did not experience a similar level of improvement.
A higher proportion of patients receiving tadalafil 20 mg experienced WHO functional class deterioration when compared with those assigned tadalafil 40 mg (9% vs. 6
.Post-hoc analyses associated background bosentan (Tracleer, Actelion) use and higher 6-minute walk distance at PHIRST baseline with fewer clinical worsening events.
Safety profiles from both PHIRST and PHIRST-2 were comparable, according to the study results. Ninety-two percent of patients experienced at least one treatment-emergent adverse event during PHIRST-2, 49% of which may have been drug-related. Most adverse events, however, were mild to moderate in intensity and did not result in study discontinuation.
“These data demonstrate that the long-term safety profile of tadalafil appears similar to that in the 16-week PHIRST study and that treatment for up to 68 weeks appears safe and well tolerated,” the researchers wrote. “For patients receiving [tadalafil 20 mg] or [tadalafil 40 mg], the short-term improvements in exercise capacity observed in PHIRST appeared to be maintained for an additional 52 weeks in PHIRST-2.”
The Wall