Asthma control using fluticasone propionate/salmeterol in Asian and non-Asian populations: a post hoc analysis of the GOAL study.

BACKGROUND: To analyse the efficacy of fluticasone propionate (FP) alone and combined with salmeterol (SAL) in achieving guideline-defined asthma control in Asian patients. METHODS: A post hoc analysis of the GOAL study in which patients were stratified by prior-medication use into inhaled corticosteroid (ICS)-naïve (Stratum [S] 1), low-dose ICS (S2), and medium-dose ICS (S3), and randomised to receive FP/SAL or FP. Doses were stepped-up every 12 weeks until Totally Controlled asthma or maximum dose was reached (PhI) and then maintained until study end (PhII). The primary endpoint was the proportion of patients achieving Well-Controlled asthma during PhI. Additional endpoints included Total Control and adverse events. Asian and non-Asian patients were analysed separately. RESULTS: In Asian patients in PhI, 74% (n = 87/118) in S1 achieved Well-Controlled asthma with FP/SAL versus 74% (n = 89/121) with FP alone (p = 0.839); corresponding values were 76% (n = 81/107) versus 60% (n = 62/104; p = 0.005) in S2, and 58% (n = 59/102) versus 43% (n = 41/95; p = 0.015) in S3. More patients in all three strata achieved Totally Controlled asthma with FP/SAL versus FP alone. Control was achieved more rapidly and with lower ICS doses with FP/SAL versus FP. A high proportion of patients who achieved control during PhI maintained control during PhII. Similar trends were found in non-Asian patients. No new safety concerns were identified. CONCLUSIONS: A greater proportion of Asian patients (S2 and S3, for Well-Controlled; all strata, for Totally Controlled) achieved guideline-defined asthma control with FP/SAL versus FP alone. High proportions of Asian patients in S1 achieved Well-Controlled asthma in both treatment groups.

Randomized Trial of Once-Daily Fluticasone Furoate in Children with Inadequately Controlled Asthma.

OBJECTIVE: To evaluate the dose-response, efficacy, and safety of fluticasone furoate (FF; 25 µg, 50 µg, and 100 µg), administered once daily in the evening during a 12-week treatment period to children with inadequately controlled asthma. STUDY DESIGN: This was a Phase IIb, multicenter, stratified, randomized, double-blind, double-dummy, parallel-group, placebo- and active-controlled study in children aged 5-11 years with inadequately controlled asthma. The study comprised a 4-week run-in period, 12-week treatment period, and 1-week follow-up period. Children were randomized to receive either placebo once daily, fluticasone propionate (FP) 100 µg twice daily, FF 25 µg, FF 50 µg, or FF 100 µg each once daily in the evening. Primary endpoint was the mean change from baseline in daily morning peak expiratory flow (PEF) averaged over weeks 1-12. Adverse events (AEs) also were investigated. RESULTS: In total, 593 children were included in the intent-to-treat population. The difference vs placebo in change from baseline daily morning PEF averaged over weeks 1-12 was statistically significant for the FF 25, FF 50, FF 100, and FP 100 groups (18.6 L/min, 19.5 L/min, 12.5 L/min, and 14.0 L/min, respectively; P < .001 for all). The incidence of AEs was greater in the FF groups (32%-36%) than in the placebo group (29%); the most frequent AE was cough. CONCLUSION: FF and FP resulted in significant improvements in morning PEF compared with placebo, suggesting that they are effective treatments for children with inadequately controlled asthma. All treatments were well tolerated; no new safety concerns were identified. TRIAL REGISTRATION: ClinicalTrials.gov:NCT01563029.

Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy.

BACKGROUND: Inhaled corticosteroids (ICS) are effective maintenance treatments for childhood asthma; however, many children remain uncontrolled. Vilanterol (VI) is an inhaled long-acting beta-2 agonist which, in combination with the ICS fluticasone furoate, is being explored as a once-daily treatment for asthma in children. We evaluated the dose-response, efficacy, and safety of once-daily VI (6.25 µg, 12.5 µg and 25 µg) administered in the evening over 4 weeks, on background fluticasone propionate (FP) in children with asthma inadequately controlled on ICS. METHODS: This was a Phase IIb, multicentre, randomised, double-blind, parallel-group, placebo-controlled study in children ages 5-11 years with persistent asthma on ICS and as-needed short-acting beta-agonist. The study comprised a 4-week run-in, 4-week treatment period, and 1-week follow-up. From study start, children replaced their current ICS with open-label FP 100 µg twice daily. Children were randomised to receive placebo, VI 6.25 µg, VI 12.5 µg or VI 25 µg once daily. Primary endpoint was treatment difference between VI 25 and placebo groups in mean change from baseline in evening peak expiratory flow averaged over the 4-week treatment. Secondary endpoints included change from baseline in trough forced expiratory volume in one second (FEV1) at Week 4 and change from baseline in percentage of rescue-free and symptom-free 24-h periods. Safety assessments included incidence of adverse events (AEs) and asthma exacerbations. RESULTS: In total, 456 children comprised the intention-to-treat population. The adjusted treatment difference between VI 25 and placebo groups for the primary endpoint was not statistically significant (p = 0.227) so no statistical inference was made for other VI dose comparisons or other endpoints. No difference in change from baseline in trough FEV1 was observed for any VI treatments versus placebo; however, VI 25 resulted in an additional 0.6 rescue-free days and 0.7 symptom-free days per week versus placebo. The incidence of AEs was slightly higher in the VI groups (28-33 %) versus placebo (22 %). Nine children experienced asthma exacerbations during the treatment period. CONCLUSION: VI plus FP did not result in significant improvements in lung function versus placebo plus FP, but was well tolerated at all doses assessed. TRIAL REGISTRATION: NCT01573767 (ClinicalTrials.gov).

Preliminary safety and efficacy data of brecanavir, a novel HIV-1 protease inhibitor: 24 week data from study HPR10006.

BACKGROUND: Brecanavir, a novel protease inhibitor (PI), has sub-nM in vitro antiviral activity against multi-PI-resistant HIV-1 and in vitro is >100-fold more potent than previously marketed PIs and approx. 10-fold more potent than the recently marketed PI, darunavir. METHODS: HPR10006 is an open label, single-arm, descriptive 48 week study, with 8 and 24 week interim analyses. Thirty-one HIV-1-infected patients were enrolled and received brecanavir/ritonavir 300 mg/100 mg twice daily, with two nucleoside reverse transcriptase inhibitors, based on history and genotype. RESULTS: At baseline, 25/31 had PI-sensitive virus and 6/31 had PI-resistant virus (median of two primary PI and five secondary PI mutations). Median baseline HIV-1 RNA was 5.0 and 4.2 log(10) copies/mL, respectively. Four patients discontinued prior to Week 24. At Week 24, 77% (24/31) had HIV-1 RNA <50 copies/mL regardless of screening genotype, including 5/6 patients with PI-resistant virus (6/6 had HIV-1 RNA <400 copies/mL). Brecanavir/ritonavir was well tolerated with no serious adverse events or clinically concerning changes in laboratory parameters. Of 31 patients, 10 (32%) experienced drug-related Grade 2-4 adverse events [most frequent events were fatigue (13%), dyspepsia (10%) and nausea (10%)]. Baseline isolate brecanavir IC(50) values for all patients ranged from 0.1 to 0.2 nM. Median plasma trough concentration at Week 4 was 150 ng/mL. Correcting the IC(50) (0.2 nM) value for protein binding (6-fold increase in vitro with 50% human serum) gives a corrected inhibitory quotient of 180. CONCLUSIONS: Brecanavir/ritonavir was well tolerated and showed potent antiviral activity in HIV-1-infected patients harbouring both PI-sensitive and PI-resistant virus, following 24 weeks of dosing.