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

Pulmonary Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00125918
• Other study ID #: 10303
• Secondary ID: H6D-MC-LVGY
• Status: Completed
• Phase: Phase 3
• First received: August 1, 2005
• Last updated: February 13, 2008
• Start date: August 2005
• Est. completion date: August 2007

Study information

• Verified date: February 2008
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 406
• Est. completion date: August 2007
• Est. primary completion date: August 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

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

Locations

Country	Name	City	State
France	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lille
France	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Vandoeuvre Les Nancy
Italy	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bergamo
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Minneapolis	Minnesota
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Salt Lake City	Utah
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	ICOS Corporation

Countries where clinical trial is conducted

United States,  France,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	6 minute walk distance change from baseline to Week 16		16 weeks
Secondary	World Health Organization (WHO) functional class, Borg dyspnea, cardiopulmonary hemodynamics, quality of life - change from baseline to Week 16		16 weeks
Secondary	Time to first occurrence of clinical worsening		Not defined

External Links

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