Formoterol Dose Ranging Study (ACHIEVE Duaklir USA Phase IIb)

Chronic Obstructive Pulmonary Disease - COPD Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02796651
• Other study ID #: D6571C00002
• Status: Completed
• Phase: Phase 2
• First received: June 7, 2016
• Last updated: January 11, 2018
• Start date: June 30, 2016
• Est. completion date: December 7, 2016

Study information

• Verified date: January 2018
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 132
• Est. completion date: December 7, 2016
• Est. primary completion date: December 7, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 130 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease - COPD
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Formoterol fumarate (6 µg)
Oral Inhalation (by Pressair® Dry Powder Inhaler, DPI)
• Formoterol furmarate (20 µg)
Oral Inhalation (via a standard jet nebulizer connected to an air compressor.
• Placebo for formoterol fumarate
Oral Inhalation (by Pressair® Dry Powder Inhaler, DPI)
• Formoterol fumarate (12 µg)
Oral Inhalation (by Pressair® Dry Powder Inhaler, DPI)
• Formoterol fumarate (40 µg)
Oral Inhalation (via a standard jet nebulizer connected to an air compressor.

Locations

Country	Name	City	State
United States	Research Site	Boerne	Texas
United States	Research Site	Celebration	Florida
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Clearwater	Florida
United States	Research Site	DeLand	Florida
United States	Research Site	Easley	South Carolina
United States	Research Site	Gastonia	North Carolina
United States	Research Site	Glendale	Arizona
United States	Research Site	Greenville	South Carolina
United States	Research Site	Killeen	Texas
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lawrenceville	Georgia
United States	Research Site	Medford	Oregon
United States	Research Site	Orlando	Florida
United States	Research Site	Phoenix	Arizona
United States	Research Site	Portland	Oregon
United States	Research Site	Rock Hill	South Carolina
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	Tempe	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Parexel

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Day 7: 30 min, 1 to 4 hours, 6 hours, 9 hours and 12 hours post-dose
Secondary	Change From Baseline in FEV1 AUC0-6/6h at Day 1 on Treatment	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.	Day 1: zero time to 6 hours post-dose
Secondary	Change From Baseline in FEV1 AUC0-6/6h at Day 7 on Treatment	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	Day 7: zero time to 6 hours post-dose
Secondary	Change From Baseline in Morning Pre-dose (Trough) FEV1 at Day 7 on Treatment	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.	At baseline and Day 7