Study 351

Tracleer improves exercise capacity, hemodynamics, and functional class status and reduces rate of clinical worsening¹

Design	Dosing and duration
Randomized, double-blind, placebo-controlled trial in adult patients with PAH WHO functional class III (N=32)	Tracleer 62.5 mg BID first 4 weeks   Tracleer 125 mg BID following 8 weeks
Primary endpoint	Secondary endpoints
Change in exercise capacity at week 12 (6MWD)	Change in hemodynamics   Change in functional status   Clinical worsening
PAH etiology (Tracleer treatment group)	Background therapies
IPAH: 17 (81%)   SSc: 4 (19%) Baseline functional class status   100% FC III	Anticoagulants   Calcium channel blockers   Supplemental oxygen
Results
Significant increase in walk distance at week 121,2
*Placebo corrected.
Significantly improved 4 key hemodynamic parameters1,2
CI Cardiac index	RAP Right atrial pressure
†Parameter not available at baseline in 1 patient.
PVR Pulmonary vascular resistance	PAP Pulmonary arterial pressure
†Parameter not available at baseline in 1 patient.
100% of Tracleer patients were event-free at week 321,2
	Clinical worsening defined as1:   Right ventricular heart failure   Aggravated pulmonary hypertension
100% of Tracleer patients maintained or improved functional class status by week 121,2

Tracleer is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in patients with WHO Class II-IV symptoms, to improve exercise ability and decrease the rate of clinical worsening. Patients with WHO Class II symptoms showed reduction in the rate of clinical deterioration and a trend for improvement in walk distance. Physicians should consider whether these potential benefits are sufficient to offset liver injury in WHO Class II patients, which may preclude future use as their disease progresses.

Important safety information

Because of the associated risks, Tracleer may be prescribed only through the Tracleer Access Program.

Potential for serious liver injury (including, after prolonged treatment, rare cases of liver failure and unexplained hepatic cirrhosis in a setting of close monitoring)—Liver monitoring of all patients is essential prior to initiation of treatment and monthly thereafter.

High potential for major birth defects—Pregnancy must be excluded and prevented through the use of reliable forms of birth control; monthly pregnancy tests should be obtained.

Contraindicated for use with cyclosporine A and glyburide.

Please see full prescribing information including BOXED WARNING.

Review BREATHE-1 results

1. Channick RN, Simonneau G, Sitbon O, et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet. 2001;358:1119-1123.
2. Tracleer (bosentan) full prescribing information. Actelion Pharmaceuticals US, Inc. August 2009.