Study of Ambrisentan and Phosphodiesterase Type-5 Inhibitor (PDE-5i) to Treat Pulmonary Arterial Hypertension - Full Text View

Sponsor:	Gilead Sciences
Information provided by:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00617305

Purpose

To evaluate the change from baseline in pulmonary vascular resistance (PVR), and other hemodynamic parameters, following the addition of ambrisentan to background phosphodiesterase type-5 inhibitor (PDE-5i) therapy in subjects with pulmonary arterial hypertension (PAH) who have demonstrated a sub-optimal response to PDE-5i monotherapy.

Condition	Intervention	Phase
Pulmonary Arterial Hypertension	Drug: ambrisentan plus sildenafil or tadalafil	Phase IV

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Open-label, Multicenter Study of Ambrisentan and a Phosphodiesterase Type-5 Inhibitor Combination Therapy in Subjects With Pulmonary Arterial Hypertension Who Have Demonstrated a Sub-Optimal Response to a Phosphodiesterase Type-5 Inhibitor

Resource links provided by NLM:

Genetics Home Reference related topics: pulmonary arterial hypertension

MedlinePlus related topics: High Blood Pressure

Drug Information available for: Sildenafil Tadalafil Sildenafil citrate Ambrisentan

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

The primary efficacy endpoint is the change from baseline in PVR evaluated after 24 weeks. Efficacy endpoints supportive of the primary endpoint include other hemodynamic measures (mPAP, mean right atrial pressure [mRAP], and cardiac output). [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

A change from baseline measured at week 24 in: 6WMD, BDI immediately following exercise, CAMPHOR Quality of Life (QoL), WHO functional class, and NT-proBNP. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Time to clinical worsening of PAH evaluated for the 24-week primary endpoint period. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Survival through the 24-week primary endpoint period. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	April 2008
Estimated Study Completion Date:	July 2011
Estimated Primary Completion Date:	February 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 ambrisentan plus an approved phosphodiesterase type-5 (PDE-5) inhibitor for the treatment of PAH (sildenafil or tadalafil)	Drug: ambrisentan plus sildenafil or tadalafil ambrisentan: 5mg to 10mg, oral, once daily sildenafil: 20mg to 100mg, oral, three times daily tadalafil: not to exceed 40mg, oral, once daily Other Name: Letairis, Revatio, Viagra, Cialis, Adcirca

Detailed Description:

The primary objective of this study is to evaluate the change from baseline in pulmonary vascular resistance (PVR), and other hemodynamic parameters, following the addition of ambrisentan to background phosphodiesterase type-5 inhibitor (PDE-5i) therapy in subjects with pulmonary arterial hypertension (PAH) who have demonstrated a sub-optimal response to PDE-5i monotherapy.

The secondary objectives of this study are to evaluate the change from baseline in other clinical measures of PAH following the addition of ambrisentan to background PDE-5i therapy in subjects with PAH who have demonstrated a sub-optimal response to PDE-5i monotherapy.

The safety and tolerability of ambrisentan/PDE-5i combination therapy will be evaluated throughout the study. In addition, long-term efficacy will be examined.

Eligibility

Ages Eligible for Study:	16 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Select Inclusion Criteria

Must be between 16 and 75 years of age;
Must weigh at least 40 kg;
Have a current diagnosis of IPAH, FPAH, or PAH that is primarily due to connective tissue disease, congenital heart defects, drug or toxin use or HIV;
Have WHO functional class III symptoms;
Be receiving sildenafil or tadalafil monotherapy for the treatment of PAH for at least the past 12 weeks;
Meet all of the following hemodynamic criteria by means of a right heart; catheterization: mPAP of at least 25 mmHg; PVR of at least 400 dyne*sec/cm5; LCWP or LVEDP of not more than 15 mmHg;
Meet all of the following pulmonary function test criteria: total lung capacity at least 60% of predicted normal and forced expiratory volume in 1 second of at least 65% of predicted normal;
Able to walk at least 150 meters during a 6-minute walk test (6MWT);
If receiving CCBs or HMG-CoA reductase inhibitors (i.e., statins) must be on stable therapy for at least 4 weeks;
If diagnosed with HIV, must have stable disease status.

Selected Exclusion Criteria:

Have a current PH diagnosis other than IPAH, FPAH, or PAH;
Have left ventricular ejection fraction (LVEF) ≤40% or clinically significant ischemic, valvular, or constrictive heart disease;
Have received chronic prostanoid or ERA therapy within the past 12 weeks;
Have discontinued ERA treatment for any adverse reaction other than those associated with liver function test abnormalities;
Have received IV inotropes within 2 weeks;
Have serum ALT or AST lab value that is greater than 2.0x the upper limit of normal.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00617305

Show 30 Study Locations

Sponsors and Collaborators

Gilead Sciences

More Information

No publications provided

Responsible Party:	Hunter Gillies, MD, Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00617305 History of Changes
Other Study ID Numbers:	GS-US-300-0117
Study First Received:	February 6, 2008
Last Updated:	January 11, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Gilead Sciences:

ambrisentan
PAH
combination therapy
phosphodiesterase type-5 inhibitor (PDE-5i)

cardiovascular
endothelin receptor antagonist
ERA

Additional relevant MeSH terms:

Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases
Sildenafil
Tadalafil

Phosphodiesterase 5 Inhibitors
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012