Trial Outcomes & Findings for Effect of Aclidinium/Formoterol on Lung Hyperinflation, Exercise Capacity and Physical Activity in Moderate to Severe COPD Patients (NCT NCT02424344)

Results Overview

Baseline values in FRC were defined as the corresponding values just before randomization on Day 1 of treatment (Week 0). Trough values were obtained prior to study drug administration.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

267 participants

Primary outcome timeframe

Baseline and Week 4

Results posted on

2018-10-09

Participant Flow

This study was conducted at 26 study centers, 15 in Germany, 4 in Hungary, 3 in Spain and 4 in Canada. The first patient was enrolled in April 2015 and the last patient visit was in July 2016.

335 patients were screened; 267 were assessed as eligible and were randomized into the study. 68 patients failed screening. The main reason for screening failure was non-fulfilment of inclusion or exclusion criteria (16.7%).

Participant milestones

Participant milestones
Measure	AB/FF 400/12 μg Aclidinium Bromide/Formoterol Fumarate 400/12 μg	Placebo Placebo to Aclidinium/Formoterol
Overall Study STARTED	134	133
Overall Study COMPLETED	127	123
Overall Study NOT COMPLETED	7	10

Reasons for withdrawal

Reasons for withdrawal
Measure	AB/FF 400/12 μg Aclidinium Bromide/Formoterol Fumarate 400/12 μg	Placebo Placebo to Aclidinium/Formoterol
Overall Study Lack of Efficacy	0	1
Overall Study Withdrawal by Subject	2	1
Overall Study Lost to Follow-up	1	0
Overall Study Adverse Event	4	8

Baseline Characteristics

Effect of Aclidinium/Formoterol on Lung Hyperinflation, Exercise Capacity and Physical Activity in Moderate to Severe COPD Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AB/FF 400/12 μg n=134 Participants Aclidinium Bromide/Formoterol Fumarate 400/12 μg	Placebo n=133 Participants Placebo to Aclidinium/Formoterol	Total n=267 Participants Total of all reporting groups
Age, Continuous	62.6 Years STANDARD_DEVIATION 7.9 • n=5 Participants	62.1 Years STANDARD_DEVIATION 7.7 • n=7 Participants	62.3 Years STANDARD_DEVIATION 7.8 • n=5 Participants
Sex: Female, Male Female	53 Participants n=5 Participants	54 Participants n=7 Participants	107 Participants n=5 Participants
Sex: Female, Male Male	81 Participants n=5 Participants	79 Participants n=7 Participants	160 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 4

Population: The intent-to-treat (ITT) population - equal to the Safety population and defined as all randomised patients who took at least one dose of investigational product (IP) - who had available trough FRC values at baseline and Week 4.

Baseline values in FRC were defined as the corresponding values just before randomization on Day 1 of treatment (Week 0). Trough values were obtained prior to study drug administration.

Outcome measures

Outcome measures
Measure	AB/FF 400/12 μg n=124 Participants Aclidinium Bromide/Formoterol Fumarate 400/12 μg	Placebo n=125 Participants Placebo to Aclidinium/Formoterol
Change From Baseline in Trough Functional Residual Capacity (FRC) After 4 Weeks of Treatment	-0.162 Liters Standard Error 0.050	-0.037 Liters Standard Error 0.050

SECONDARY outcome

Timeframe: Baseline to Week 8

Population: Intention-to-treat population - which was equal to the safety population, defined as all participants who took at least one dose of investigational product - who had available ET values at baseline and Week 8.

The ET was the time from the increase in work rate to 75% Wmax to the point of symptom limitation. Baseline measurements were taken prior to the IP dose on Day 1. Measurements at Week 8 were taken at 3 hours post-dose. Participants underwent a behavioural intervention (consisting of a telecoaching programme to enhance physical activity) between Week 4 and Week 8.

Outcome measures

Outcome measures
Measure	AB/FF 400/12 μg n=124 Participants Aclidinium Bromide/Formoterol Fumarate 400/12 μg	Placebo n=121 Participants Placebo to Aclidinium/Formoterol
Change From Baseline in Endurance Time (ET) During Constant Work Rate Cycle Ergometry at Week 8	50.7 Seconds Standard Error 18.1	-4.6 Seconds Standard Error 18.2

SECONDARY outcome

Timeframe: Week 8

Population: The intent-to-treat (ITT) population - equal to the Safety population and defined as all randomised patients who took at least one dose of IP \- who had available activity data (compliant criterion).

Physical activity was assessed by means of measurement of activity parameters (e.g. number of steps) through a Dynaport MoveMonitor and completion of the Daily ProActive Physical Activity in chronic obstructive pulmonary disease (COPD) questionnaire. Compliant criterion based on at least 8 hours per day, and at least 3 days per week. Participants underwent a behavioural intervention (consisting of a telecoaching programme to enhance physical activity) between Week 4 and Week 8. Baseline was defined as mean of steps/day assessed during the week before the randomisation visit.

Outcome measures

Outcome measures
Measure	AB/FF 400/12 μg n=118 Participants Aclidinium Bromide/Formoterol Fumarate 400/12 μg	Placebo n=117 Participants Placebo to Aclidinium/Formoterol
Percentage of Inactive Patients (Mean of <6000 Steps Per Day) at Week 8	41.53 Percent of inactive participants	50.43 Percent of inactive participants

Adverse Events

AB/FF 400/12 μg

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	AB/FF 400/12 μg n=134 participants at risk Aclidinium Bromide/Formoterol Fumarate 400/12 μg	Placebo n=133 participants at risk Placebo to Aclidinium/Formoterol
General disorders Fatigue	0.75% 1/134 • Number of events 1 • From Screening, Week -2 (Days -17 to -11) to Follow-up, Week 10 (Day 70+3)	0.00% 0/133 • From Screening, Week -2 (Days -17 to -11) to Follow-up, Week 10 (Day 70+3)
Eye disorders Lens dislocation	0.00% 0/134 • From Screening, Week -2 (Days -17 to -11) to Follow-up, Week 10 (Day 70+3)	0.75% 1/133 • Number of events 1 • From Screening, Week -2 (Days -17 to -11) to Follow-up, Week 10 (Day 70+3)
Infections and infestations Diverticulitis	0.00% 0/134 • From Screening, Week -2 (Days -17 to -11) to Follow-up, Week 10 (Day 70+3)	0.75% 1/133 • Number of events 1 • From Screening, Week -2 (Days -17 to -11) to Follow-up, Week 10 (Day 70+3)
Injury, poisoning and procedural complications Pubis fracture	0.75% 1/134 • Number of events 1 • From Screening, Week -2 (Days -17 to -11) to Follow-up, Week 10 (Day 70+3)	0.00% 0/133 • From Screening, Week -2 (Days -17 to -11) to Follow-up, Week 10 (Day 70+3)
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/134 • From Screening, Week -2 (Days -17 to -11) to Follow-up, Week 10 (Day 70+3)	0.75% 1/133 • Number of events 1 • From Screening, Week -2 (Days -17 to -11) to Follow-up, Week 10 (Day 70+3)
Nervous system disorders Ataxia	0.75% 1/134 • Number of events 1 • From Screening, Week -2 (Days -17 to -11) to Follow-up, Week 10 (Day 70+3)	0.00% 0/133 • From Screening, Week -2 (Days -17 to -11) to Follow-up, Week 10 (Day 70+3)

Other adverse events

Other adverse events
Measure	AB/FF 400/12 μg n=134 participants at risk Aclidinium Bromide/Formoterol Fumarate 400/12 μg	Placebo n=133 participants at risk Placebo to Aclidinium/Formoterol
Infections and infestations Nasopharyngitis	10.4% 14/134 • Number of events 14 • From Screening, Week -2 (Days -17 to -11) to Follow-up, Week 10 (Day 70+3)	9.8% 13/133 • Number of events 13 • From Screening, Week -2 (Days -17 to -11) to Follow-up, Week 10 (Day 70+3)
Nervous system disorders Headache	3.0% 4/134 • Number of events 4 • From Screening, Week -2 (Days -17 to -11) to Follow-up, Week 10 (Day 70+3)	9.0% 12/133 • Number of events 24 • From Screening, Week -2 (Days -17 to -11) to Follow-up, Week 10 (Day 70+3)

Additional Information

Study Director

AstraZeneca

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Publication of the results by the Principal Investigator (PI) will be subject to mutual agreement between the PI and the sponsor.
Publication restrictions are in place

Restriction type: OTHER