Table 3.

Recent clinical trials of aclidinium/formoterol fixed-dose combination therapies

Study	Dosage	Primary end point	Coprimary end points	Study period and present status
Interventional pilot study (Phase II) [NCT00706914]	Aclidinium bromide/formoterol fumerate FDC QD	Symptomatic differences between treatment groups after 4 weeks of treatment	Differences between groups in change in pulmonary function test results after 4 weeks of treatment	June 2008–September 2011; results not published
Dose-finding clinical trial (Phase II) [NCT00626522]	Aclidinium bromide/formoterol fumerate FDC QD	Pulmonary function tests	Pharmacokinetics and safety	February 2008–July 2010; results not published
Interventional efficacy trial [NCT01049360]	2 FDCs of aclidinium bromide/formoterol fumerate BID	Change from baseline in normalized FEV1 after 14 days of treatment AUC0–12 measurement over 12 h after morning dose of drug at day 14	The secondary efficacy assessments were the change from baseline in morning predose FEV1 and the change from baseline in morning peak FEV1, both at day 14 on treatment	January 2010–September 2011; results not published
Interventional dose-finding study [NCT01078623]	2 FDCs of aclidinium bromide/formoterol fumerate BID	FEV1 AUC 0–12 h after day 14	Morning predose FEV1 and morning peak FEV1 after day 14	March 2010–November 2010; study not published
Interventional study [NCT01551888]	Aclidinium/formoterol 400 μg/12 μg FDC (BID) for 4 days, then QD on day 5 via the Genuair®	Area under the formoterol plasma concentration–time curve over the dosing interval at steady state Maximum formoterol plasma concentration at steady state	Area under the formoterol plasma concentration–time curve over the dosing interval following a single dose Maximum plasma concentration of formoterol following a single dose	March 2012–August 2012; no study result published
Interventional study (Phase III) [NCT01437540]	FDCs of aclidinium bromide/formoterol fumerate BID (high dose)	AE recording: number of patients to experience a TEAE Vital signs: number of patients to experience a PCS change in pulse rate, systolic and diastolic blood pressure, body temperature, or body weight ECGs: number of patients to experience potentially clinically significant changes in ECG from baseline Clinical laboratory measures: number of patients to experience a PCS change in clinical laboratory values for hematology, chemistry, urinalysis, or theophylline	Not listed	September 2011–April 2013; results not published
Interventional study (Phase III) [NCT01572792]	2 FDCs of aclidinium bromide/formoterol fumerate (low-dose ACL200/FOR12 μg; high-dose ACL400/FOR12 μg, BID)	Safety and tolerability: AE, clinical laboratory parameters, vital sign measurement, and ECG parameters	Not listed	April 2012–June 2013; results not published
Interventional study (Phase III) [NCT01908140]	Aclidinium bromide 400 μg/formoterol fumarate 12 μg BID for 24 weeks	Peak FEV1 at week 24	TDI focal score at week 24	July 2013–September 2014; results not published

Notes: Information of the clinical trials was obtained from the United States clinical trial registry (available at https://clinicaltrials.gov; last accessed on February 2, 2015). Searching of clinical trial database with the keywords – aclidinium + formoterol + COPD yielded 12 results, and among those aclidinium-formoterol FDC was used in ten studies only. We selected those ten studies and incorporated eight unpublished studies into this table. The other two studies are published (viz, the AUGMENT-COPD Study and the ACLIFORM-COPD Study).

Abbreviations: FDC, fixed-dose combinations; QD, once a day; FEV₁, forced expiratory volume in 1 second; ACL, aclidinium; BID, twice a day; AE, adverse event; TEAE, treatment emergent adverse event; PCS, potentially clinically significant; ECGs, electrocardiograms; FOR, formoterol; TDI, Transition Dyspnea Index; COPD, Chronic obstructive pulmonary disease; AUC, area under the curve.