Date: 2013-05-01
Type of information:
phase: 3
Announcement: results
Company: Forest Laboratories (USA) Almirall (Spain)
Product: aclidinium bromide (LAMA) and formoterol fumarate (LABA), delivered in the Pressair®(Genuair® outside the USA) inhaler
Action mechanism:
Disease: chronic obstructive pulmonary disease (COPD)
Therapeutic area: Respiratory diseases
Country: USA, Australia and New Zealand
Trial
details: AUGMENT (Aclidinium/formoterol FUmurate Combination for InvestiGative use in the TreatMENT of Moderate to Severe COPD) was a 24-week randomized double-blind trial evaluating the 400/12mcg and 400/6mcg fixed dose combinations of aclidinium bromide/formoterol fumarate compared with aclidinium bromide 400mcg, formoterol fumarate 12mcg and placebo administered BID through the Pressair inhaler (Genuair outside the USA) in 1692 patients with moderate to severe COPD in the USA, Australia and New Zealand.Two co-primary endpoints, designed to take in account the different contributions of the individual components in terms of efficacy, were developed in consultation with FDA/EMA to meet the “Combination Rule” (i.e., showing superiority in FEV1 at week 24 of the fixed dose combination over aclidinium at one hour post-dose and over formoterol at morning pre-dose trough):1. The first co-primary endpoint consisted of the comparison between the fixed dose combinations of aclidinium/formoterol 400/12mcg and 400/6mcg versus aclidinium alone in change from baseline in FEV1 at 1 hour post-dose at week 24. The aclidinium/formoterol 400/12mcg and 400/6mcg achieved statistically significant improvements compared with aclidinium 400mcg (108mL and 87mL, respectively).2. The second co-primary endpoint consisted of the comparison between the fixed dose combinations of aclidinium/formoterol 400/12mcg and 400/6mcg versus formoterol alone in change from baseline in morning pre-dose trough FEV1 at week 24. The aclidinium/formoterol 400/12mcg demonstrated statistically significant improvement versus formoterol 12mcg (45mL). Aclidinium/formoterol 400/6mcg did not demonstrate statistically significant improvement versus formoterol 12mcg (26mL).
Latest
news: * On May 1, 2013, Forest Laboratories and Almirall have announced positive topline results from AUGMENT COPD, the second six-month pivotal phase III clinical trial evaluating the efficacy and safety of investigational fixed dose combinations of aclidinium bromide (LAMA) and formoterol fumarate (LABA), delivered in the Pressair®(Genuair® outside the USA) inhaler.The 400/12mcg combination of aclidinium/formoterol demonstrated statistically significant improvements in change from baseline for the co-primary endpoints of Forced Expiratory Volume (FEV1) at 1 hour post-dose versus aclidinium 400mcg (P<0.0001) and morning predose trough FEV1 versus formoterol 12mcg at week 24 (P<0.05). The 400/6mcg combination demonstrated statistically significant improvements in (FEV1) at 1 hour post-dose versus aclidinium 400mcg (p<0.0001). For the change from baseline in morning pre-dose trough FEV1, the 400/6mcg combination did not reach significance versus formoterol 12mcg at week 24 (p>0.05).Both combinations of aclidinium/formoterol (400/12mcg and 400/6mcg) provided statistically significant improvements versus placebo in the above two comparisons (both p<0.0001).The positive results of the aclidinium/formoterol 400/12mcg combination in this study are consistent with the statistically significant improvement in lung function demonstrated by aclidinium/formoterol 400/12mcg in the previously completed ACLIFORM/COPD Phase III study. In both studies, the 400/12mcg dose successfully met the required regulatory “Combination Rule” for testing two or more drugs combined in a single dosage form.Both studies included secondary end points. The end points analyzed to date are change from baseline vs placebo at 24 weeks in TDI (Transitional Dyspnea Index, which measures breathlessness) and in SGRQ (St. George’s Respiratory Questionnaire, a respiratory-specific disease-related quality of life assessment). Positive outcomes were seen with the two combinations achieving the MCID (Meaningful Clinical Important Difference) of a one point change (p<0.0001) in TDI in both studies, and a four point change (p<0.0001) in SGRQ in the AUGMENT/COPD study. Additional analyses, including those on pooled data, will be presented at future scientific meetings.Additionally, both aclidinium/formoterol treatment arms were well-tolerated in this study. The most common adverse events (greater than or equal to 3% and reported more frequently with either aclidinium/formoterol 400/12mcg or aclidinium/formoterol 400/6mcg than placebo respectively) were: cough (5.1%, 3.9% and 3.6%); nasopharyngitis (4.8%, 5.1% and 3.6%); headache (4.8%, 4.2% and 3.3%); urinary tract infection (4.5%, 2.1% and 3.0%); upper respiratory tract infection (3.0%, 3.9% and 1.5%); back pain (3.0%, 1.5% and 2.7%);diarrhea (2.7% 3.0% and 2.4%); nausea (1.5%, 4.5% and 1.2%); and dyspnea (1.5%, 3.3% and 1.8%).Regulatory filings in the USA (FDA) and Europe (EMA) are planned in Q4 2013.
