Clinical safety Studies providing evaluable safety data Pivotal studies that assessed safety as the sole primary outcome AC-052-367 (FUTURE-2) Study AC-052-374 (FUTURE-3) Extension Study AC-052-392 (FUTURE-4) Extension. Pivotal and/or main efficacy studies Study AC-052-391 (FUTURE-4). Other studies AC-052-116 Study AC-052-365 (FUTURE-1) AC-052-373 (FUTURE-3). Studies that assessed safety as the sole primary outcome Study AC-052-367 (FUTURE-2) Study design, objectives, locations and dates Study AC-053-367 (FUTURE-2) was a multicentre, multinational, open label, non comparative, Phase III extension study of a 12 week open label, single arm study (FUTURE-1). The primary objective was to assess the long term safety and tolerability of the paediatric formulation of bosentan in children with idiopathic or familial PAH. Secondary objectives included an exploratory evaluation of functional capacity, QoL, physicians’ and parents’ GCIS, time to PAH worsening, time to initiation of new therapy for PAH and time to new onset or worsening of right heart failure. Another objective was to assess long term vital status. Figure 22: Study AC-053-367 (FUTURE-2) design Inclusion and exclusion criteria The inclusion and exclusion criteria for the FUTURE-1 Study were provided. Study treatments All patients received a paediatric oral formulation of bosentan. The drug was to be administered orally, irrespective of meals, and dispersed in a teaspoon of water before being administered (not mixed with food). It was to be taken in the morning and approximately 12 hours later in the evening. The treatment dose of bosentan in FUTURE-2 was to be 4 mg/kg BD until the end of the study. If this dose was not well tolerated, it could be down-titrated to 2 mg/kg BD. Patients weighing 30 kg or over were to receive a maximum dose of 120 mg BD and a maximum of 64 mg BD if down titration was necessary. Safety variables and outcomes The tolerability and safety endpoints were:
Clinical safety Studies providing evaluable safety data Pivotal studies that assessed safety as the sole primary outcome AC-052-367 (FUTURE-2) Study AC-052-374 (FUTURE-3) Extension Study AC-052-392 (FUTURE-4) Extension. Pivotal and/or main efficacy studies Study AC-052-391 (FUTURE-4). Other studies AC-052-116 Study AC-052-365 (FUTURE-1) AC-052-373 (FUTURE-3). Studies that assessed safety as the sole primary outcome Study AC-052-367 (FUTURE-2) Study design, objectives, locations and dates Study AC-053-367 (FUTURE-2) was a multicentre, multinational, open label, non comparative, Phase III extension study of a 12 week open label, single arm study (FUTURE-1). The primary objective was to assess the long term safety and tolerability of the paediatric formulation of bosentan in children with idiopathic or familial PAH. Secondary objectives included an exploratory evaluation of functional capacity, QoL, physicians’ and parents’ GCIS, time to PAH worsening, time to initiation of new therapy for PAH and time to new onset or worsening of right heart failure. Another objective was to assess long term vital status. Figure 22: Study AC-053-367 (FUTURE-2) design Inclusion and exclusion criteria The inclusion and exclusion criteria for the FUTURE-1 Study were provided. Study treatments All patients received a paediatric oral formulation of bosentan. The drug was to be administered orally, irrespective of meals, and dispersed in a teaspoon of water before being administered (not mixed with food). It was to be taken in the morning and approximately 12 hours later in the evening. The treatment dose of bosentan in FUTURE-2 was to be 4 mg/kg BD until the end of the study. If this dose was not well tolerated, it could be down-titrated to 2 mg/kg BD. Patients weighing 30 kg or over were to receive a maximum dose of 120 mg BD and a maximum of 64 mg BD if down titration was necessary. Safety variables and outcomes The tolerability and safety endpoints were:
auspar-bosentan-180625-cer.docx