Official Title: “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”

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

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: August 2007

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.

Intervention(s) in this Clinical Trial

• Drug: tadalafil
  • tadalafil 2.5 mg and placebo tablets taken by mouth once a day for 16 weeks.
• Drug: tadalafil
  • tadalafil 10 mg and placebo tablets taken by mouth once a day for 16 weeks.
• Drug: tadalafil
  • tadalafil 20 mg and placebo tablets taken by mouth once a day for 16 weeks.
• Drug: tadalafil
  • tadalafil 40 mg and placebo tablets taken by mouth once a day for 16 weeks.
• Drug: placebo
  • placebo tablet taken by mouth once a day for 16 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: 1
  • Placebo
• Active Comparator: 2
  • 2.5 mg tadalafil
• Active Comparator: 3
  • 10 mg tadalafil
• Active Comparator: 4
  • 20 mg tadalafil
• Active Comparator: 5
  • 40 mg tadalafil

Primary Measures

• 6 minute walk distance change from baseline to Week 16
  • Time Frame: 16 weeks
    

Secondary Measures

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

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 12 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Eli Lilly and Company

Overall Clinical Trial Officials and Contacts

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Study Director Eli Lilly and Company  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00125918

Study ID Number: 10303

ClinicalTrials.gov Identifier: NCT00125918

Health Authority: United States: Food and Drug Administration

The Pulmonary Hypertension Association (PHA) is an organization that provides support, education, advocacy, and awareness about pulmonary hypertension.

Lilly Clinical Trial Registry