PHIRST-1: Tadalafil in the Treatment of Pulmonary Arterial Hypertension

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and effectiveness of tadalafil for the treatment of pulmonary arterial hypertension.

Detailed Description
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This is a randomized, double-blind, placebo-controlled, multicenter study. The key measure of effectiveness of the study drug will be determined using a 6-minute walk test. Eligible patients will be treated for 16 weeks and may be eligible to enter a 52-week extension phase study (PHIRST-2). Study procedures for both studies (PHIRST-1 and PHIRST-2) will include routine blood tests, medical history, physical exams, questionnaire responses, and exercise tests.

Official Title
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PHIRST-1: Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of the Phosphodiesterase Type 5 (PDE5) Inhibitor Tadalafil in the Treatment in Patients With Pulmonary Arterial Hypertension

Conditions
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Pulmonary Hypertension

Intervention / Treatment
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* Drug: tadalafil
* Drug: tadalafil
* Drug: tadalafil
* Drug: tadalafil
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 12 years of age. Body weight at least 40 kg (approximately 88 pounds). Pulmonary hypertension (PAH) that is either idiopathic; related to collagen vascular disease; related to anorexigen use; associated with an atrial septal defect (resting SaO2 greater than or equal to 88%); with surgical repair, of at least 1 year duration, of a congenital systemic-to-pulmonary shunt. If on bosentan, must be at the maximal dose of 125 mg twice daily for a minimum of 12 weeks prior to screening and have an AST/ALT less than 3 times normal. History of PAH established by a resting mean pulmonary artery pressure greater than or equal to 25 mm Hg, pulmonary artery wedge pressure less than or equal to 15 mm Hg, and pulmonary vascular resistance greater than or equal to 3 Wood units via right heart catheterization Have World Health Organization functional class I, II, III or IV status. Have a qualifying 6-minute walk test distance at screening Have no evidence of significant parenchymal lung disease Exclusion Criteria: Are nursing or pregnant. PAH due to conditions other than noted in the above inclusion criteria. History of left-sided heart disease. History of atrial septostomy within 3 months before study entry History of angina pectoris or other condition that was treated with long-or short-acting nitrates within 12 weeks before administration of study drug. History of symptomatic coronary disease. Have any therapy with a prostacyclin or analogue, L-arginine, phosphodiesterase (PDE) inhibitor, or investigational drug within 4 weeks before administration of study drug.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Placebo | Drug: placebo<br>* placebo tablet taken by mouth once a day for 16 weeks<br>|
| Active Comparator: 2<br>2.5 mg tadalafil | Drug: tadalafil<br>* tadalafil 2.5 mg and placebo tablets taken by mouth once a day for 16 weeks.<br>* Other names: IC351;|
| Active Comparator: 3<br>10 mg tadalafil | Drug: tadalafil<br>* tadalafil 10 mg and placebo tablets taken by mouth once a day for 16 weeks.<br>* Other names: IC351;|
| Active Comparator: 4<br>20 mg tadalafil | Drug: tadalafil<br>* tadalafil 20 mg and placebo tablets taken by mouth once a day for 16 weeks.<br>* Other names: IC351;|
| Active Comparator: 5<br>40 mg tadalafil | Drug: tadalafil<br>* tadalafil 40 mg and placebo tablets taken by mouth once a day for 16 weeks.<br>* Other names: IC351;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 minute walk distance change from baseline to Week 16 |  | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| World Health Organization (WHO) functional class, Borg dyspnea, cardiopulmonary hemodynamics, quality of life - change from baseline to Week 16 |  | 16 weeks | 
| Time to first occurrence of clinical worsening |  | Not defined | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Pulmonary; Pulmonary Heart Disease