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

Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT01551888
Collaborator
(none)
24
Enrollment
1
Location
2
Arms
2
Duration (Months)
12.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this Phase II study is to evaluate the pharmacokinetics, safety, and tolerability of aclidinium/formoterol fixed dose combination (FDC 400/12 μg via the Almirall Inhaler and formoterol 12 μg via the Foradil® Aerolizer®, both administered twice daily for five days to patients with moderate to severe COPD.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
24 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 2a, Randomized, Open-Label, 2-Way Crossover Study To Determine The Pharmacokinetics, Safety, And Tolerability Of Aclidinium/Formoterol 400/12 µg Fixed Dose Combination Via Almirall Inhaler And Formoterol 12 µg Via Foradil® Aerolizer® In Patients With Moderate To Severe Chronic Obstructive Pulmonary Disease
Study Start Date :
Jan 1, 2012
Actual Primary Completion Date :
Mar 1, 2012
Actual Study Completion Date :
Mar 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: Aclidinium/formoterol 400/12μg FDC

Aclidinium/formoterol 400/12μg fixed-dose combination (FDC), one inhalation twice daily (morning and evening) for 4 days, then one inhalation (morning) on Day 5 via the Almirall inhaler

Drug: Aclidinium/formoterol 400/12μg
Aclidinium/formoterol 400/12μg fixed dose combination (FDC), one inhalation twice daily (morning and evening) for 4 days, then one inhalation (morning) on Day 5 via the Almirall inhaler
Active Comparator: Formoterol

Formoterol 12μg one inhalation twice daily (morning and evening) for 4 days, then one inhalation (morning) on Day 5 via the Foradil® Aerolizer®

Drug: Formoterol
Formoterol 12 μg one inhalation twice daily (morning and evening) for 4 days, then one inhalation (morning) on Day 5 via the Foradil® Aerolizer®
Other Names:
  • Foradil® Aerolizer®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Area Under the Formoterol Plasma Concentration Versus Time Curve (AUC) Over Dosing Interval at Steady State [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)]

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

    2. Maximum Formoterol Plasma Drug Concentration (Cmax) at Steady State [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)]

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

    3. Maximum Formoterol Plasma Drug Concentration (Cmax) Following a Single Dose [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]

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

    Secondary Outcome Measures

    1. Area Under the Formoterol Plasma Concentration Versus Time Curve (AUC) Over Dosing Interval Following a Single Dose [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]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    40 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Current or former cigarette smokers with a cigarette smoking history of at least 10 pack-years

    • A diagnosis of stable moderate to severe COPD and stable airway obstruction as defined by the Global Initiative for Chronic Obstructive Lung Disease guidelines and stable airway obstruction.

    Exclusion Criteria:

    • Patients who have been hospitalized for an acute COPD exacerbation within three months prior to Screening

    • Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation in the six weeks before Screening

    • Patients with any clinically significant respiratory conditions other than COPD

    • Clinical history that suggests that the patient has asthma as opposed to COPD

    • Chronic use of oxygen therapy ≥ 15 hours/day

    • Patients with clinically significant cardiovascular conditions

    • Patients with a history of hypersensitivity reaction to inhaled anticholinergics, beta-2 agonists, sympathomimetic amines, or inhaled medications

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Forest Investigative Site 001 Spartanburg South Carolina United States 29303

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    • Study Director: Esther Garcia, MD, AstraZeneca

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT01551888
    Other Study ID Numbers:
    • LAC-PK-01
    First Posted:
    Mar 13, 2012
    Last Update Posted:
    Feb 14, 2017
    Last Verified:
    Dec 1, 2016
    Keywords provided by AstraZeneca
    COPD
    Chronic Obstructive Pulmonary Disease
    Chronic Bronchitis
    Emphysema
    Airflow Obstruction, Chronic
    Chronic Airflow Obstruction
    Chronic Obstructive Airway Disease
    Chronic Obstructive Lung Disease
    Additional relevant MeSH terms:
    Lung Diseases
    Lung Diseases, Obstructive
    Pulmonary Disease, Chronic Obstructive
    Formoterol Fumarate

    Study Results

    Participant Flow

    Recruitment Details 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
    Pre-assignment Detail
    Arm/Group Title Sequence 1 Sequence 2
    Arm/Group Description 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 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 Title: Period 1
    STARTED 12 12
    COMPLETED 12 12
    NOT COMPLETED 0 0
    Period Title: Period 1
    STARTED 12 12
    COMPLETED 12 12
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Overall Study Population
    Arm/Group Description All patients participating in the crossover study
    Overall Participants 24
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    60.9
    (7.5)
    Gender (Count of Participants)
    Female
    10
    41.7%
    Male
    14
    58.3%

    Outcome Measures

    1. Primary Outcome
    Title Area Under the Formoterol Plasma Concentration Versus Time Curve (AUC) Over Dosing Interval at Steady State
    Description The standard deviation of the measure is expressed as the coefficient of variation (%)
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic (PK) analysis population included all patients who completed the study and had evaluable PK parameters
    Arm/Group Title Formoterol 12 μg Aclidinium/Formoterol 400/12 μg FDC
    Arm/Group Description Administered via Foradil® Aerolizer® Fixed dose combination (FDC) administered via Almirall inhaler
    Measure Participants 24 24
    Mean (Standard Deviation) [pg*hr/mL]
    87.14
    (27.8)
    85.15
    (28.3)
    2. Primary Outcome
    Title Maximum Formoterol Plasma Drug Concentration (Cmax) at Steady State
    Description The standard deviation of the measure is expressed as the coefficient of variation (%)
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic (PK) analysis population included all patients who completed the study and had evaluable PK parameters
    Arm/Group Title Formoterol 12 μg Aclidinium/Formoterol 400/12 μg FDC
    Arm/Group Description Administered via Foradil® Aerolizer® Fixed dose combination (FDC) administered via Almirall inhaler
    Measure Participants 24 24
    Mean (Standard Deviation) [pg/mL]
    14.90
    (27.9)
    16.72
    (31.6)
    3. Secondary Outcome
    Title Area Under the Formoterol Plasma Concentration Versus Time Curve (AUC) Over Dosing Interval Following a Single Dose
    Description The standard deviation of the measure is expressed as the coefficient of variation (%)
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic (PK) analysis population included all patients who completed the study and had evaluable PK parameters
    Arm/Group Title Formoterol 12 μg Aclidinium/Formoterol 400/12 μg FDC
    Arm/Group Description Administered via Foradil® Aerolizer® Fixed dose combination (FDC) administered via Almirall inhaler
    Measure Participants 24 24
    Mean (Standard Deviation) [pg*hr/mL]
    41.63
    (32.2)
    42.27
    (31.3)
    4. Primary Outcome
    Title Maximum Formoterol Plasma Drug Concentration (Cmax) Following a Single Dose
    Description The standard deviation of the measure is expressed as the coefficient of variation (%)
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic (PK) analysis population included all patients who completed the study and had evaluable PK parameters
    Arm/Group Title Formoterol 12 μg Aclidinium/Formoterol 400/12 μg FDC
    Arm/Group Description Administered via Foradil® Aerolizer® Fixed dose combination (FDC) administered via Almirall inhaler
    Measure Participants 24 24
    Mean (Standard Deviation) [pg/mL]
    8.23
    (39.9)
    9.55
    (39.0)

    Adverse Events

    Time Frame Up to study Day 17
    Adverse Event Reporting Description
    Arm/Group Title Aclidinium/Formoterol 400/12 μg Formoterol 12 μg
    Arm/Group Description Fixed dose combination (FDC) administered via Almirall inhaler Administered via Foradil® Aerolizer®
    All Cause Mortality
    Aclidinium/Formoterol 400/12 μg Formoterol 12 μg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Aclidinium/Formoterol 400/12 μg Formoterol 12 μg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/24 (0%) 2/24 (8.3%)
    Cardiac disorders
    Aortic valve incompetence 0/24 (0%) 1/24 (4.2%)
    Nervous system disorders
    Lacunar infarction 0/24 (0%) 1/24 (4.2%)
    Vascular disorders
    Aortic aneurysm 0/24 (0%) 1/24 (4.2%)
    Other (Not Including Serious) Adverse Events
    Aclidinium/Formoterol 400/12 μg Formoterol 12 μg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/24 (0%) 0/24 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Publication of the results by the PI will be subject to mutual agreement between the PI and sponsor.

    Results Point of Contact

    Name/Title Study Director
    Organization AstraZeneca
    Phone
    Email ClinicalTrialTransparency@astrazeneca.com
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT01551888
    Other Study ID Numbers:
    • LAC-PK-01
    First Posted:
    Mar 13, 2012
    Last Update Posted:
    Feb 14, 2017
    Last Verified:
    Dec 1, 2016