GSK Says Advair Diskus Achieves Primary Endpoint in LABA Safety Study of Children Aged 4-11 Years with Asthma

GlaxoSmithKline plc

today announced results from the paediatric ‘LABA' (long acting beta2-agonist) safety study. VESTRI (SAS115358) compared Advair® Diskus® (FSC), a combination of the LABA, salmeterol, and the inhaled corticosteroid (ICS), fluticasone propionate (FP), to FP monotherapy in children aged 4 – 11 years. The study assessed the composite endpoint of serious asthma-related events (deaths, intubations or hospitalisations). The VESTRI study randomised 6,250 children aged 4 – 11 years into the six month study, across 31 countries. The primary safety endpoint of the study showed FSC twice-daily (100/50mcg, 250/50mcg) demonstrated non-inferiority compared to corresponding doses of FP twice-daily (100mcg, 250mcg), on the risk of serious asthma-related events, Hazard Ratio (HR) 1.285, (95% CI 0.726, 2.272) p=0.006. All serious asthma-related events were hospitalisations (n=48), and there were no asthma-related deaths or intubations seen in either arm of the study. In the study a non-statistically significant reduction of 14% was observed in the risk of time-to-first asthma exacerbation for FSC compared to FP (HR 0.859; 95% CI 0.729, 1.012). VESTRI is the second study undertaken by GSK as a post-marketing requirement of the US Food and Drug Administration (FDA). The first study, AUSTRI, carried out with adolescent and adult patients with asthma,demonstrated non-inferiority of FSC compared to FP and these data have been published in the New England Journal of Medicine1. GSK was one of four manufacturers of LABA-containing products indicated for the treatment of asthma, required to undertake equivalent studies designed to evaluate whether the addition of a LABA to an ICS increased the risk of an event in the composite endpoint of serious asthma-related events (deaths, intubations or hospitalisations) in adolescents and adults. GSK was the only manufacturer to conduct a study in children aged 4-11 years of age, as it is the only manufacturer with a licence to treat this age group in the US. The FSC 250/50mcg dose is not licensed for the treatment of paediatrics with asthma. Study Design VESTRI Study (SAS115358) A global, multicentre, randomised stratified, double-blind, parallel-group active comparator, six-month study in paediatric patients (4 – 11 years of age) with asthma. Patients were required to have a history of persistent asthma and a history of an asthma exacerbation in the year prior to study randomisation. Eligibility for participation into the study was based on a review of pre-study asthma medications, assessment of asthma control, based on the Childhood-Asthma Control Test 2 and a history of an asthma exacerbation requiring a systemic corticosteroid in the previous year. Patients were screened at visit one to assess eligibility and subsequently randomised 1:1 to either FSC (100/50 mcg, 250/50 mcg) or FP (100mcg, 250 mcg) at visit two. Patients returned to the clinic after two weeks (visit three) and then at two-monthly intervals up to the final end of treatment clinic visit at six months. Patients' status in the months where there was not a visit was assessed by telephone contact. A follow-up phone call to query serious adverse events was made approximately one-week after end of treatment for both patients completing 6-month study treatment and those who ended study treatment prematurely. Patients were permitted to use albuterol/salbutamol rescue medication throughout the study. FSC 250/50 mcg and FP 250 mcg are not currently indicated in children 4 – 11 years of age according to US-approved product information. The primary analysis was to determine whether the addition of LABA to ICS therapy (FSC) is non-inferior to ICS therapy alone (FP) in terms of the risk of a composite of serious asthma-related events (asthma-related hospitalisation, intubation and death). To demonstrate non-inferiority, a predefined margin of 2.675 was required, meaning the upper limit of the 95% confidence interval needed to be less than 2.675 to rule out an increase in the risk of a serious asthma related event on FSC compared with FP. All serious asthma related events were adjudicated by an independent committee. The full results for this study will be posted on the GSK Clinical Study Register and published in a peer-reviewed forum.