Tracleer and exercise capacity

EARLY (FC II) Trend toward improvement in walk distance¹

	19-m mean placebo-corrected 6MWD increase in Tracleer group (not significant, p=0.08)1,2
	In the EARLY study, patients taking Tracleer had a baseline 6MWD of 438 m and patients taking placebo had a baseline 6MWD of 431 m.

Study 351 (FC III) Significant increase in walk distance at week 12^2,3

Tracleer baseline: 360 m; placebo baseline: 355 m.

BREATHE-1 (FC III-IV) Significant increase in walk distance at week 16^2,4

Tracleer baseline: 438 m; placebo baseline: 431 m.

Improvements in walk distance were apparent by week 4 and maintained for up to 7 months.2

*Placebo corrected.

FC functional class.

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 how Tracleer improves hemodynamics

EARLY Endothelin Antagonist tRial in miLdlY symptomatic PAH patients. The first and only randomized, double-blind, placebo-controlled trial conducted solely in mildly symptomatic (functional class II) patients with PAH (N=185). Patients were randomized to Tracleer (62.5 mg BID, 125 mg BID) or placebo. Trial duration was 6 months. Concomitant use of anticoagulants and calcium channel blockers was allowed. Both the Tracleer group and the placebo group included some patients on sildenafil at baseline (Tracleer, n=14; placebo, n=15).¹

Study 351 Randomized, double-blind, placebo-controlled study of Tracleer 125 mg BID vs placebo in patients with WHO functional class III or IV pulmonary arterial hypertension (N=32).³

BREATHE-1 Multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of Tracleer (125 mg BID, 250 mg BID) in patients with WHO functional class III or IV pulmonary arterial hypertension (N=213). All patients (n=144 in the Tracleer group and n=69 in the control group) participated in the first 16 weeks. A subset of this population (n=35 in the Tracleer group and n=13 in the control group) continued for up to 28 weeks.⁴

1. Galiè N, Rubin LJ, Hoeper MM, et al. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial. Lancet. 2008;371:2093-2100.
2. Tracleer (bosentan) full prescribing information. Actelion Pharmaceuticals US, Inc. August 2009.
3. 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.
4. Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002;346:896-903.