Trial Outcomes & Findings for Pharmacokinetic, Safety and Tolerability Study of Aclidinium/Formoterol Fixed Dose Combination and Formoterol in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT01551888)

Results Overview

The standard deviation of the measure is expressed as the coefficient of variation (%)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose; Days 2-4: 0, 5 and 15 min post dose; Day 5: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (post AM dose)

Results posted on

2017-02-14

Participant Flow

The study was conducted in a single center in the United States First patient visit was in January 2012 and last patient visit was in March 2012

Participant milestones

Participant milestones
Measure	Sequence 1 Aclidinium/formoterol 400 μg/12 μg FDC (via the Almirall inhaler) one inhalation twice daily (morning and evening) for 4 days, then one inhalation (morning) for 1 day in Period 1 and, in Period 2, Formoterol 12 μg via the Foradil® Aerolizer®, one inhalation twice daily (morning and evening) for 4 days, then one inhalation (morning) for 1 day	Sequence 2 Formoterol 12 μg via the Foradil® Aerolizer®, one inhalation twice daily (morning and evening) for 4 days, then one inhalation (morning) for 1 day in Period 1 and, in Period 2, Aclidinium/formoterol 400 μg/12 μg FDC (via the Almirall inhaler) one inhalation twice daily (morning and evening) for 4 days, then one inhalation (morning) for 1 day
Period 1 STARTED	12	12
Period 1 COMPLETED	12	12
Period 1 NOT COMPLETED	0	0
Period 2 STARTED	12	12
Period 2 COMPLETED	12	12
Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetic, Safety and Tolerability Study of Aclidinium/Formoterol Fixed Dose Combination and Formoterol in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall Study Population n=24 Participants All patients participating in the crossover study
Age, Continuous	60.9 Years STANDARD_DEVIATION 7.5 • n=5 Participants
Gender Female	10 Participants n=5 Participants
Gender Male	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose; Days 2-4: 0, 5 and 15 min post dose; Day 5: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (post AM dose)

Population: The pharmacokinetic (PK) analysis population included all patients who completed the study and had evaluable PK parameters

The standard deviation of the measure is expressed as the coefficient of variation (%)

Outcome measures

Outcome measures
Measure	Formoterol 12 μg n=24 Participants Administered via Foradil® Aerolizer®	Aclidinium/Formoterol 400/12 μg FDC n=24 Participants Fixed dose combination (FDC) administered via Almirall inhaler
Area Under the Formoterol Plasma Concentration Versus Time Curve (AUC) Over Dosing Interval at Steady State	87.14 pg*hr/mL Standard Deviation 27.8 • Interval 0.08 to 2.0	85.15 pg*hr/mL Standard Deviation 28.3 • Interval 0.08 to 2.0

PRIMARY outcome

Timeframe: Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose; Days 2-4: 0, 5 and 15 min post dose; Day 5: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (post AM dose)

Population: The pharmacokinetic (PK) analysis population included all patients who completed the study and had evaluable PK parameters

The standard deviation of the measure is expressed as the coefficient of variation (%)

Outcome measures

Outcome measures
Measure	Formoterol 12 μg n=24 Participants Administered via Foradil® Aerolizer®	Aclidinium/Formoterol 400/12 μg FDC n=24 Participants Fixed dose combination (FDC) administered via Almirall inhaler
Maximum Formoterol Plasma Drug Concentration (Cmax) at Steady State	14.90 pg/mL Standard Deviation 27.9 • Interval 27.9 to	16.72 pg/mL Standard Deviation 31.6

PRIMARY outcome

Timeframe: Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose

Population: The pharmacokinetic (PK) analysis population included all patients who completed the study and had evaluable PK parameters

The standard deviation of the measure is expressed as the coefficient of variation (%)

Outcome measures

Outcome measures
Measure	Formoterol 12 μg n=24 Participants Administered via Foradil® Aerolizer®	Aclidinium/Formoterol 400/12 μg FDC n=24 Participants Fixed dose combination (FDC) administered via Almirall inhaler
Maximum Formoterol Plasma Drug Concentration (Cmax) Following a Single Dose	8.23 pg/mL Standard Deviation 39.9 • Interval 27.9 to	9.55 pg/mL Standard Deviation 39.0

SECONDARY outcome

Timeframe: Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose

Population: The pharmacokinetic (PK) analysis population included all patients who completed the study and had evaluable PK parameters

The standard deviation of the measure is expressed as the coefficient of variation (%)

Outcome measures

Outcome measures
Measure	Formoterol 12 μg n=24 Participants Administered via Foradil® Aerolizer®	Aclidinium/Formoterol 400/12 μg FDC n=24 Participants Fixed dose combination (FDC) administered via Almirall inhaler
Area Under the Formoterol Plasma Concentration Versus Time Curve (AUC) Over Dosing Interval Following a Single Dose	41.63 pg*hr/mL Standard Deviation 32.2 • Interval 0.08 to 2.0	42.27 pg*hr/mL Standard Deviation 31.3 • Interval 0.08 to 2.0

Adverse Events

Aclidinium/Formoterol 400/12 μg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Formoterol 12 μg

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Aclidinium/Formoterol 400/12 μg n=24 participants at risk Fixed dose combination (FDC) administered via Almirall inhaler	Formoterol 12 μg n=24 participants at risk Administered via Foradil® Aerolizer®
Cardiac disorders Aortic valve incompetence	0.00% 0/24 • Up to study Day 17	4.2% 1/24 • Up to study Day 17
Nervous system disorders Lacunar infarction	0.00% 0/24 • Up to study Day 17	4.2% 1/24 • Up to study Day 17
Vascular disorders Aortic aneurysm	0.00% 0/24 • Up to study Day 17	4.2% 1/24 • Up to study Day 17

Other adverse events

Adverse event data not reported

Additional Information

Study Director

AstraZeneca

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER