A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of the Phosphodiesterase Type 5 (PDE5) Inhibitor Tadalafil in the Treatment of Patients with Pulmonary Arterial Hypertension - LVGY

• Conditions: Pulmonary arterial hypertension (PAH) is a chronic and progressive disease characterized by elevation of pulmonary artery pressure and pulmonary vascular resistance, leading to right heart failure and death.

• Registration Number: EUCTR2005-002692-33-BE
• Lead Sponsor: illy ICOS LLC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-10-26
• Last Update Posted: 7 October 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

-=12 years of age.
-Body weight = 40 kg.
-Currently have a diagnosis of PAH that is either:
oidiopathic,
orelated to collagen vascular disease,
orelated to anorexigen use,
oassociated with an atrial septal defect (with resting arterial oxygen saturation = 88% on room air at screening), or
owith surgical repair, of at least 1 yr duration, of a congenital systemic-to-pulmonary shunt (e.g., ventricular septal defect, patent ductus arteriosus).
-Have a history of the diagnosis of PAH established by a resting mean pulmonary artery pressure =25 mm Hg, pulmonary artery wedge pressure =15 mm Hg, and a pulmonary vascular resistance (PVR) = 3 Wood units via right heart catheterization.
-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 a screening AST/ALT < 3 times upper limit of normal.
-Have a chest radiograph (CXR) within 6 months of screening that shows clear lung fields or no more than mild patchy (not diffuse) interstitial infiltrates.
-Have no evidence of significant parenchymal lung disease, as evidenced by pulmonary function tests within 6 months of screening showing total lung capacity = 60% predicted.
-Have a 6-minute walk test distance =150 and =450 meters at screening.
-Have World Health Organization (WHO) functional class I, II, III or IV status.
-A female subject of childbearing potential must have a negative serum pregnancy test at the screening visit and agree to use two medically reliable methods of contraception (e.g., barrier with either spermacide or hormonal contraception) until study completion.
-Written informed consent (and written assent for minors) will be obtained prior to any study procedure being performed.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

-Are nursing or pregnant.
-Have pulmonary hypertension related to conditions other than specified above, including but not limited to chronic thromboembolic disease, portal pulmonary hypertension, HIV infection, or left heart disease.
-For subjects with pulmonary arterial hypertension associated with an atrial septal defect, resting arterial oxygen saturation (SaO2) < 88% on room air at screening.
-History of left-sided heart disease, including any of the following:
·clinically significant aortic or mitral valve disease (i.e., aortic stenosis, aortic insufficiency, mitral stenosis, moderate or greater mitral regurgitation);
·pericardial constriction;
·restrictive or congestive cardiomyopathy;
·left ventricular ejection fraction < 40% by multigated radionucleotide angiogram (MUGA), angiography, or echocardiography;
·left ventricular shortening fraction < 22% by echocardiography;
·life-threatening cardiac arrhythmias.
-History of atrial septostomy within 3 months before administration of study drug.
-Have severe hepatic impairment, Child-Pugh Class C (see Appendix C).
-Have severe renal insufficiency, defined as receiving renal dialysis or having a measured or estimated creatinine clearance (CC) < 30 mL/min (Cockroft-Gault formula, below) at screening:
CC = [(140 – age) x weight (kg)/ serum creatinine (mg/dL) ´ 72] ´ 0.85 (female) or 1.00 (male)
-Have a systolic blood pressure >160 mm Hg or < 90 mm Hg, or diastolic blood pressure >100 mm Hg or < 50 mm Hg at screening.
-Have a history of angina pectoris or other condition that was treated with long-or short-acting nitrates within 12 weeks before administration of study drug.
-Have a musculoskeletal disorder (e.g. arthritis, artificial leg, etc.) or any other disease besides pulmonary hypertension that may significantly limit ambulation.
-Have a history of symptomatic coronary disease.
-Have a history of HIV infection.
-Have any new long-term treatment for pulmonary arterial hypertension added within 4 weeks before administration of study drug.
-Have any therapy with a prostacyclin or analogue, L-arginine, phosphodiesterase inhibitor, or investigational drug within 4 weeks before administration of study drug.
-Have any chronic PAH medication except for anticoagulants discontinued within 4 weeks prior to administration of study drug.
-Current treatment with antiretroviral therapy (protease inhibitor), ketoconazole, or itraconazole.
-Are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
-Are employed by Lilly or ICOS (that is, employees, temporary contract workers, or designees responsible for the conduct of the study). Immediate family of Lilly or ICOS employees may participate in Lilly ICOS LLC-sponsored clinical trials, but are not permitted to participate at a Lilly or ICOS facility. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified