Formoterol Dose Ranging Study (ACHIEVE Duaklir USA Phase IIb)

NCT02796651 | Completed Phase 2 Results FDA Drug

• 1 other identifier: D6571C00002
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 20

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).

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)

Outcome Measures

Primary Outcomes (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

  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 Outcomes (3)

• Change From Baseline in FEV1 AUC0-6/6h at Day 1 on Treatment

  Day 1: zero time to 6 hours post-dose

• Change From Baseline in FEV1 AUC0-6/6h at Day 7 on Treatment

  Day 7: zero time to 6 hours post-dose

• Change From Baseline in Morning Pre-dose (Trough) FEV1 at Day 7 on Treatment

  At baseline and Day 7

Study Arms (6)

Formoterol 6 μg

EXPERIMENTAL

Participants received formoterol fumarate 6 μg administered via Pressair twice daily (BID).

Drug: Formoterol fumarate (6 μg)

Formoterol 12 μg

EXPERIMENTAL

Participants received formoterol fumarate 12 μg administered via Pressair BID.

Drug: Formoterol fumarate (12 μg)

Formoterol 24 μg

EXPERIMENTAL

Participants received formoterol fumarate 24 μg administered via Pressair BID.

Drug: Formoterol fumarate (12 μg)

Placebo

PLACEBO COMPARATOR

Participants received placebo to formoterol fumarate administered via Pressair BID.

Drug: Placebo for formoterol fumarate

Formoterol 20 μg

EXPERIMENTAL

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)

Formoterol 40 μg

EXPERIMENTAL

Participants received Perforomist 40 μg (2 vials of Performist 20 μg) as a single dose of administration.

Drug: Formoterol fumarate (40 μg)

Interventions

Formoterol fumarate (6 μg) DRUG

Oral Inhalation (by Pressair® Dry Powder Inhaler, DPI)

Also known as: Formoterol (Pressair®)

Formoterol 6 μg

Formoterol furmarate (20 μg) DRUG

Oral Inhalation (via a standard jet nebulizer connected to an air compressor.

Also known as: Perforomist® Inhalation Solution

Formoterol 20 μg

Placebo for formoterol fumarate DRUG

Oral Inhalation (by Pressair® Dry Powder Inhaler, DPI)

Also known as: Placebo (Pressair®)

Placebo

Formoterol fumarate (12 μg) DRUG

Oral Inhalation (by Pressair® Dry Powder Inhaler, DPI)

Also known as: Formoterol (Pressair®)

Formoterol 12 μg; Formoterol 24 μg

Formoterol fumarate (40 μg) DRUG

Oral Inhalation (via a standard jet nebulizer connected to an air compressor.

Also known as: Perforomist® Inhalation Solution

Formoterol 40 μg

Eligibility Criteria

• Age: 40 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (20)

Research Site

Glendale, Arizona, 85306, United States

Location

Research Site

Phoenix, Arizona, 85006, United States

Location

Research Site

Tempe, Arizona, 85283, United States

Location

Research Site

Celebration, Florida, 34747, United States

Location

Research Site

Clearwater, Florida, 33756, United States

Location

Research Site

DeLand, Florida, 32720, United States

Location

Research Site

Orlando, Florida, 32825, United States

Location

Research Site

Lawrenceville, Georgia, 30046, United States

Location

Research Site

St Louis, Missouri, 63141, United States

Location

Research Site

Las Vegas, Nevada, 89102, United States

Location

Research Site

Charlotte, North Carolina, 28207, United States

Location

Research Site

Gastonia, North Carolina, 28054, United States

Location

Research Site

Medford, Oregon, 97504, United States

Location

Research Site

Portland, Oregon, 97202, United States

Location

Research Site

Easley, South Carolina, 29640, United States

Location

Research Site

Greenville, South Carolina, 29615, United States

Location

Research Site

Rock Hill, South Carolina, 29372, United States

Location

Research Site

Spartanburg, South Carolina, 29303, United States

Location

Research Site

Boerne, Texas, 78006, United States

Location

Research Site

Killeen, Texas, 76543, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Cigarette Smoking

Interventions

Formoterol Fumarate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Tobacco Smoking; Smoking; Behavior; Tobacco Use

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Results Point of Contact

• Title: Global Clinical Leader
• Organization: AstraZeneca AB

clinicaltrialtransparency@astrazeneca.com

+46 766 346712

Study Officials

• Mark H. Gotfried, MD

  1112 East McDowell Road, Phoenix, AZ 85006, United States.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2016
• First Posted: June 13, 2016
• Study Start: June 30, 2016
• Primary Completion: December 7, 2016
• Study Completion: December 7, 2016
• Last Updated: February 7, 2018
• Results First Posted: February 7, 2018

Record last verified: 2018-01

Locations

US (20)