Clinical trial NCT02796651: Formoterol Dose Ranging Study (ACHIEVE Duaklir USA Phase IIb)
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease - COPD
Keywords: Perforomist
Pressair
COPD
Cigarette smoking
Formoterol fumarate
long-acting β2-adrenergic agonists (LABA)
long-acting muscarinic antagonists (LAMA)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2016-06-13
Enrollment: 132
Sex: ALL
Minimum age (years): 40
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).

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.

Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: Day 7: 30 min, 1 to 4 hours, 6 hours, 9 hours and 12 hours post-dose
Secondary outcomes:
measure: Change From Baseline in FEV1 AUC0-6/6h at Day 1 on Treatment
timeFrame: Day 1: zero time to 6 hours post-dose
measure: Change From Baseline in FEV1 AUC0-6/6h at Day 7 on Treatment
timeFrame: Day 7: zero time to 6 hours post-dose
measure: Change From Baseline in Morning Pre-dose (Trough) FEV1 at Day 7 on Treatment
timeFrame: At baseline and Day 7
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Research Site
state: Arizona
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Tempe
country: United States
facility: Research Site
state: Arizona
city: Celebration
country: United States
facility: Research Site
state: Florida
city: Clearwater
country: United States
facility: Research Site
state: Florida
city: DeLand
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Lawrenceville
country: United States
facility: Research Site
state: Georgia
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Gastonia
country: United States
facility: Research Site
state: North Carolina
city: Medford
country: United States
facility: Research Site
state: Oregon
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Easley
country: United States
facility: Research Site
state: South Carolina
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Rock Hill
country: United States
facility: Research Site
state: South Carolina
city: Spartanburg
country: United States
facility: Research Site
state: South Carolina
city: Boerne
country: United States
facility: Research Site
state: Texas
city: Killeen
country: United States
facility: Research Site
state: Texas
Study officials:
affiliation: 1112 East McDowell Road, Phoenix, AZ 85006, United States.
name: Mark H. Gotfried, MD
role: PRINCIPAL_INVESTIGATOR
References: