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| __NOTOC__
| | #REDIRECT [[Tadalafil#Clinical Studies]] |
| {{Tadalafil}}
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| {{CMG}}; {{AE}} {{PB}}
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| '''''For patient information, click <u>[[Tadalafil tablet (patient information)|here]]'''''</u>
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| ==Clinical Studies==
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| ===ADCIRCA for Pulmonary Arterial Hypertension===
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| A randomized, double-blind, 16 week placebo-controlled study was conducted in 405 patients with [[pulmonary arterial hypertension]], defined as a resting mean pulmonary artery pressure (mPAP) ≥25 mm Hg, pulmonary capillary wedge pressure ([[PCWP]]) ≤15 mm Hg, and [[pulmonary vascular resistance]] ([[PVR]]) ≥3 Wood units via right heart catheterization. Allowed background therapy included [[bosentan]] (maintenance dosing up to 125 mg twice daily) and chronic [[anticoagulation]]. The use of [[prostacyclin]] or analogue, L–arginine, [[phosphodiesterase inhibitor]], or other chronic [[PAH]] medications were not permitted.
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| Subjects were randomly assigned to 1 of 5 treatment groups (tadalafil 2.5, 10, 20, 40 mg, or placebo) in a 1:1:1:1:1 ratio. Subjects had to be at least 12 years of age and had a diagnosis of [[PAH]] that was idiopathic, heritable, related to connective tissue disease, anorexigen use, [[human immunodeficiency virus]] ([[HIV]]) infection, associated with an atrial-septal defect, or associated with surgical repair of a congenital systemic-to-pulmonary shunt of least 1 year in duration (for example, [[ventricular septal defect]], [[patent ductus arteriosus]]). Patients with a history of left-sided heart disease, severe [[renal insufficiency]], or [[pulmonary hypertension]] related to conditions other than specified in the inclusion criteria were not eligible for enrollment.
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| The mean age of all subjects was 54 years (range 14 - 90 years) with the majority of subjects being Caucasian (81%) and female (78%). PAH etiologies were predominantly idiopathic or heritable [[PAH]] (61%) and related to connective tissue disease (23%). More than half (53%) of the subjects in the study were receiving concomitant [[bosentan]] therapy. The majority of subjects had a [[World Health Organization]] ([[WHO]]) Functional Class III (65%) or II (32%). The mean baseline 6-minute walk distance (6-MWD) was 343 meters. Of the 405 subjects, 341 completed the study.
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| The primary efficacy endpoint was the change from baseline at week 16 in 6-MWD (see Figure 1). In the ADCIRCA 40 mg treatment group, the placebo-adjusted mean change increase in 6-MWD was 33 meters (95% C.I. 15-50 meters; p=0.0004). The improvement in 6-MWD was apparent at 8 weeks of treatment and then maintained at week 12 and week 16.
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| Placebo-adjusted changes in 6-MWD at 16 weeks were evaluated in subgroups (see Figure 2). In patients taking only ADCIRCA 40 mg (i.e., without concomitant [[bosentan]]), the placebo-adjusted mean change in 6-MWD was 44 meters. In patients taking ADCIRCA 40 mg and concomitant [[bosentan]] therapy, the placebo adjusted mean change in 6-MWD was 23 meters.
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| |[[Image:Tadanafil4.PNG|thumb|1000px]]
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| There was less clinical worsening (defined as death, lung transplantation, atrial septostomy, hospitalization because of worsening PAH, initiation of new PAH therapy [[[prostacyclin]] or analog, [[endothelin]] receptor antagonist, [[PDE5]] inhibitor], or worsening WHO functional class) in the ADCIRCA 40 mg group compared to the placebo group and the groups that used lower doses of ADCIRCA.
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| |[[Image:Tadanafil7.PNG|thumb|1000px]]
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| The Kaplan-Meier plot of times to clinical worsening is shown below.
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| |[[Image:Tadanafil8.PNG|thumb|1000px]]
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| ===Long-Term Treatment of Pulmonary Arterial Hypertension===
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| Patients (N=357) from the placebo-controlled study entered a long-term extension study. Of these, 311 patients have been treated with tadalafil for at least 6 months and 182 for 1 year (median exposure 356 days; range 2 days to 415 days). The survival rate in the extension study was 96.5 per 100 patient years. Without a control group, these data must be interpreted cautiously.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = ADCIRCA (TADALAFIL) TABLET [UNITED THERAPEUTICS CORPORATION] | url =http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ff61b237-be8e-461b-8114-78c52a8ad0ae | publisher = | date = | accessdate = 7 February 2014 }}</ref>
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| ==References==
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| {{Reflist|2}}
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| [[Category:Drugs]]
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