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Formoterol Dose Ranging Study (ACHIEVE Duaklir USA Phase IIb)

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ClinicalTrials.gov Identifier: NCT02796651
Recruitment Status : Completed
First Posted : June 13, 2016
Results First Posted : February 7, 2018
Last Update Posted : February 7, 2018
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
To assess the bronchodilation of three doses of formoterol fumarate (6 μg, 12 μg and 24 μg) twice daily (BID) administered via Pressair® compared to placebo and to open-label nebulized formoterol fumarate (20 μg and 40 μg).

Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease - COPD Drug: Formoterol fumarate (6 μg) Drug: Formoterol furmarate (20 μg) Drug: Placebo for formoterol fumarate Drug: Formoterol fumarate (12 μg) Drug: Formoterol fumarate (40 μg) Phase 2

Detailed Description:
This is a prospective, randomized, double-blind, 5-period incomplete unbalanced crossover, placebo and active comparator (open-label) controlled, multicenter clinical trial to assess the efficacy and safety of three doses of formoterol fumarate (6 μg, 12 μg and 24 μg) BID administered via Pressair® compared to placebo and to open-label formoterol fumarate (20 μg BID and 40 μg single dose) administered as an inhalation solution via a standard jet nebulizer (with a mouthpiece) connected to an air compressor (Perforomist® Inhalation Solution). The drug product is an inhalation powder comprising of micronized aclidinium bromide and micronized formoterol fumarate with α-lactose monohydrate as the carrier, presented in a breathactuated device-metered dry-powder inhaler (DPI). It has been approved under the trademarks of Genuair® and/or Pressair® in some territories.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 132 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Incomplete Unbalanced, Crossover Study to Assess the Efficacy and Safety of Three Doses of Formoterol Fumarate in Pressair® Compared With Perforomist® Inhalation Solution (20 and 40 μg Open-label) in Moderate to Severe COPD Patients With Reversible Airway Disease.
Actual Study Start Date : June 30, 2016
Actual Primary Completion Date : December 7, 2016
Actual Study Completion Date : December 7, 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Formoterol 6 μg
Participants received formoterol fumarate 6 μg administered via Pressair twice daily (BID).
Drug: Formoterol fumarate (6 μg)
Oral Inhalation (by Pressair® Dry Powder Inhaler, DPI)
Other Name: Formoterol (Pressair®)

Experimental: Formoterol 12 μg
Participants received formoterol fumarate 12 μg administered via Pressair BID.
Drug: Formoterol fumarate (12 μg)
Oral Inhalation (by Pressair® Dry Powder Inhaler, DPI)
Other Name: Formoterol (Pressair®)

Experimental: Formoterol 24 μg
Participants received formoterol fumarate 24 μg administered via Pressair BID.
Drug: Formoterol fumarate (12 μg)
Oral Inhalation (by Pressair® Dry Powder Inhaler, DPI)
Other Name: Formoterol (Pressair®)

Placebo Comparator: Placebo
Participants received placebo to formoterol fumarate administered via Pressair BID.
Drug: Placebo for formoterol fumarate
Oral Inhalation (by Pressair® Dry Powder Inhaler, DPI)
Other Name: Placebo (Pressair®)

Experimental: Formoterol 20 μg
Participants received Perforomist inhalation solution and were instructed to take one puff from each of the two Pressair inhalers or to inhale one vial from the Perforomist 20 μg inhalation solution BID for 7 ± 1 consecutive days.
Drug: Formoterol furmarate (20 μg)
Oral Inhalation (via a standard jet nebulizer connected to an air compressor.
Other Name: Perforomist® Inhalation Solution

Experimental: Formoterol 40 μg
Participants received Perforomist 40 μg (2 vials of Performist 20 μg) as a single dose of administration.
Drug: Formoterol fumarate (40 μg)
Oral Inhalation (via a standard jet nebulizer connected to an air compressor.
Other Name: Perforomist® Inhalation Solution




Primary Outcome Measures :
  1. Change From Baseline in Normalized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) Over the 12 h Period Immediately After Morning Study Drug Administration, AUC0-12/12h at Day 7 on Treatment [ Time Frame: Day 7: 30 min, 1 to 4 hours, 6 hours, 9 hours and 12 hours post-dose ]

    To assess the bronchodilation of 3 doses of formoterol fumarate (6 μg, 12 μg and 24 μg) twice daily (BID administered via Pressair® compared to placebo and to open-label nebulised formoterol fumarate(20 μg).

    Pre-dose spirometry was performed before the morning daily dose at Day 1 and Day 7 of each treatment period. Two sets of measurements were performed during the hour preceding the scheduled morning study drug administration, allowing approximately 30 minutes between them.

    Note: Perforomist® 40 μg treatment periods lasted for 1 day only. Hence, was not included in the calculation.



Secondary Outcome Measures :
  1. Change From Baseline in FEV1 AUC0-6/6h at Day 1 on Treatment [ Time Frame: Day 1: zero time to 6 hours post-dose ]
    To assess the bronchodilation of 3 doses of formoterol fumarate (6 μg, 12 μg and 24 μg) BID administered via Pressair® compared to placebo and to open-label nebulised formoterol fumarate (20 μg and 40 μg). 6-hour serial spirometry was performed at Day 1 of each treatment period: spirometry was performed post-dose at 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours and 6 hours post-dose.

  2. Change From Baseline in FEV1 AUC0-6/6h at Day 7 on Treatment [ Time Frame: Day 7: zero time to 6 hours post-dose ]
    To assess the bronchodilation of 3 doses of formoterol fumarate (6 μg, 12 μg and 24 μg) BID administered via Pressair® compared to placebo and to open-label nebulised formoterol fumarate (20 μg). 6-hour serial spirometry was performed at Day 7 of each treatment period: spirometry was performed post-dose at 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours and 6 hours post-dose Note: Perforomist® 40 μg treatment periods lasted for 1 day only. Hence, was not included in the calculation

  3. Change From Baseline in Morning Pre-dose (Trough) FEV1 at Day 7 on Treatment [ Time Frame: At baseline and Day 7 ]

    To assess the bronchodilation of 3 doses of formoterol fumarate (6 μg, 12 μg and 24 μg) BID administered via Pressair® compared to placebo and to open-label nebulised formoterol fumarate (20 μg). Trough value was defined as the mean of the 2 pre-dose measurements on Day 7. If 1 of the 2 measurements was missing, the non-missing measurement was used as the trough value.

    Note: Perforomist® 40 μg treatment periods lasted for 1 day only. Hence, was not included in the calculation.




Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult male or non-pregnant, non-lactating female patients aged ≥40.
  • Patients with a diagnosis of COPD (GOLD guidelines, 2016) for a period of at least 6 months prior to Visit 1.
  • Patients with moderate to severe stable COPD: post-bronchodilator FEV1 ≥ 30% and <80% of the predicted normal and post-bronchodilator FEV1/FVC < 70% at Visit 1.
  • Patients with reversible airway obstruction defined as an increase in FEV1 of at least 12% and 200 mL over the baseline value after four inhalations of albuterol sulfate 108 µg via a pMDI at Visit 1.
  • Current or former-smokers, with a smoking history of ≥ 10 pack-years.
  • Patients able to perform acceptable and repeatable pulmonary function testing for FEV1 according to the American Thoracic Society (ATS)/European Respiratory Society (ERS) 2005 criteria at Visit 1.
  • Patients eligible and able to participate in the study and who had signed an Informed Consent Form prior to initiation of any study-related procedures.

Exclusion Criteria:

  • Patients with asthma.
  • Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation (including the mild COPD exacerbation) within 6 weeks prior to Visit 1 or during the run-in period.
  • Patients hospitalized for a COPD exacerbation (an emergency room visit for longer than 24 hours is considered a hospitalization) within 3 months prior to Visit 1.
  • Clinically significant respiratory conditions other than COPD.
  • Patients who in the investigator's opinion may need to start a pulmonary rehabilitation program during the study and/or patients who started/finished it within 3 months prior to Visit 1.
  • Use of long-term oxygen therapy (≥ 15 hours/day).
  • Patients who do not maintain regular day/night, waking/sleeping cycles including night shift workers.
  • Clinically significant cardiovascular conditions.
  • Patients with uncontrolled Type I or Type II diabetes, uncontrolled hypo-or hyperthyroidism, hypokalaemia, or hyperadrenergic state, uncontrolled hypertension.
  • Patients with history of long QT syndrome or whose QTc (calculated according to Fridericia's Formula QTc=QT/RR1/3) > 470 ms as indicated in the centralized reading report assessed at Visit 1.
  • Patients with clinically significant abnormalities in the laboratory tests, ECG parameters (other than QTc) or in the physical examination at Visit 1 that might compromise patient safety.
  • Patients with a history of hypersensitivity reaction to an inhaled medication or any component thereof, including paradoxical bronchospasm.
  • Patients with known narrow-angle glaucoma, symptomatic bladder neck obstruction, acute urinary retention or symptomatic unstable prostate hypertrophy.
  • History of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years other than basal or squamous cell skin cancer.
  • Patients with any other serious or uncontrolled physical or mental dysfunction.
  • Patients with a history (within 2 years prior to screening) of drug and/or alcohol abuse that may prevent study compliance based on the Investigator judgment.
  • Patients unlikely to be cooperative or who cannot comply with the study procedures.
  • Patients treated with any investigational drug within 30 days (or 6 half-lives, whichever is longer) prior to Visit 1.
  • Patients who intended to use any concomitant medication not permitted by this protocol or who had not undergone the required washout period for a particular prohibited medication.
  • Patients unable to give consent, or patients of consenting age but under guardianship, or vulnerable patients.
  • Any other conditions that, in the investigator's opinion, might render the patient to be unsuitable for the study.
  • Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff and/or site staff), or patients employed by or relatives of the employees of the site or sponsor.
  • Previous randomization in the present study D6571C00002.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02796651


Locations
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United States, Arizona
Research Site
Glendale, Arizona, United States, 85306
Research Site
Phoenix, Arizona, United States, 85006
Research Site
Tempe, Arizona, United States, 85283
United States, Florida
Research Site
Celebration, Florida, United States, 34747
Research Site
Clearwater, Florida, United States, 33756
Research Site
DeLand, Florida, United States, 32720
Research Site
Orlando, Florida, United States, 32825
United States, Georgia
Research Site
Lawrenceville, Georgia, United States, 30046
United States, Missouri
Research Site
Saint Louis, Missouri, United States, 63141
United States, Nevada
Research Site
Las Vegas, Nevada, United States, 89102
United States, North Carolina
Research Site
Charlotte, North Carolina, United States, 28207
Research Site
Gastonia, North Carolina, United States, 28054
United States, Oregon
Research Site
Medford, Oregon, United States, 97504
Research Site
Portland, Oregon, United States, 97202
United States, South Carolina
Research Site
Easley, South Carolina, United States, 29640
Research Site
Greenville, South Carolina, United States, 29615
Research Site
Rock Hill, South Carolina, United States, 29372
Research Site
Spartanburg, South Carolina, United States, 29303
United States, Texas
Research Site
Boerne, Texas, United States, 78006
Research Site
Killeen, Texas, United States, 76543
Sponsors and Collaborators
AstraZeneca
Parexel
Investigators
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Principal Investigator: Mark H. Gotfried, MD 1112 East McDowell Road, Phoenix, AZ 85006, United States.

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02796651     History of Changes
Other Study ID Numbers: D6571C00002
First Posted: June 13, 2016    Key Record Dates
Results First Posted: February 7, 2018
Last Update Posted: February 7, 2018
Last Verified: January 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:
Perforomist
Pressair
COPD
Cigarette smoking
Formoterol fumarate
long-acting β2-adrenergic agonists (LABA)
long-acting muscarinic antagonists (LAMA)

Additional relevant MeSH terms:
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Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Pharmaceutical Solutions
Formoterol Fumarate
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action