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

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2005-002692-33-GB
• Date of registration: 12/09/2005
• Prospective Registration: Yes
• Primary sponsor: Lilly ICOS LLC
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 10/04/2006
• Target sample size: 400
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-002692-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Germany, Ireland, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
-=12 years of age.
-Body weight = 40 kg.
-Currently have a diagnosis of PAH that is either:
o idiopathic,
o related to collagen vascular disease,
o related to anorexigen use,
o related to HIV infection
o associated with an atrial septal defect (with resting arterial oxygen saturation = 88% on room air at screening), or
o with surgical repair, of at least 1-year 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.
In the event that a pulmonary artery wedge pressure is unable to be obtained during right heart catheterization, subjects with a left ventricular end diastolic pressure (LVEDP) <15 mm Hg, with normal heart function, and absence of mitral stenosis on echocardiography, can be eligible for enrollment.
-If on bosentan, must be on a maintenance dose not greater than 125 mg twice daily for at least 12 weeks prior to screening and have a screening AST/ALT < 3 times the 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, or left-sided 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; symptomatic coronary artery disease within 5 years of study entry.
-History of atrial septostomy within 3 months before administration of study drug.
-Have severe hepatic impairment, Child-Pugh Class 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 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

Intervention(s)

Product Name: Cialis
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Tadalafil
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5 or 10 or 20-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To evaluate tadalafil population pharmacokinetics.

Main Objective: To evaluate the safety and efficacy of the PDE5 inhibitor tadalafil in the treatment of patients with PAH.

Primary end point(s): 6-minute walk distance change from baseline to Week 16.

Secondary ID(s)

H6D-MC-LVGY

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 04/01/2017
• Date Completed: 16/08/2007
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-002692-33/results