Formoterol Dose Ranging Study (ACHIEVE Duaklir USA Phase IIb)

NCT ID: NCT02796651

Last Updated: 2018-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 132 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2016-12-07

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.

Conditions

Chronic Obstructive Pulmonary Disease - COPD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Formoterol 6 μg

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

Group Type: EXPERIMENTAL

Formoterol fumarate (6 μg)

Intervention Type: DRUG

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

Formoterol 12 μg

Participants received formoterol fumarate 12 μg administered via Pressair BID.

Group Type: EXPERIMENTAL

Formoterol fumarate (12 μg)

Intervention Type: DRUG

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

Formoterol 24 μg

Participants received formoterol fumarate 24 μg administered via Pressair BID.

Group Type: EXPERIMENTAL

Formoterol fumarate (12 μg)

Intervention Type: DRUG

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

Placebo

Participants received placebo to formoterol fumarate administered via Pressair BID.

Group Type: PLACEBO_COMPARATOR

Placebo for formoterol fumarate

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Formoterol furmarate (20 μg)

Intervention Type: DRUG

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

Formoterol 40 μg

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

Group Type: EXPERIMENTAL

Formoterol fumarate (40 μg)

Intervention Type: DRUG

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

Interventions

Formoterol fumarate (6 μg)

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

Intervention Type: DRUG

Formoterol furmarate (20 μg)

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

Intervention Type: DRUG

Placebo for formoterol fumarate

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

Intervention Type: DRUG

Formoterol fumarate (12 μg)

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

Intervention Type: DRUG

Formoterol fumarate (40 μg)

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

Intervention Type: DRUG

Other Intervention Names

Formoterol (Pressair®); Perforomist® Inhalation Solution; Placebo (Pressair®); Formoterol (Pressair®); Perforomist® Inhalation Solution

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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark H. Gotfried, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Research Site

Glendale, Arizona, United States

Research Site

Phoenix, Arizona, United States

Research Site

Tempe, Arizona, United States

Research Site

Celebration, Florida, United States

Research Site

Clearwater, Florida, United States

Research Site

DeLand, Florida, United States

Research Site

Orlando, Florida, United States

Research Site

Lawrenceville, Georgia, United States

Research Site

St Louis, Missouri, United States

Research Site

Las Vegas, Nevada, United States

Research Site

Charlotte, North Carolina, United States

Research Site

Gastonia, North Carolina, United States

Research Site

Medford, Oregon, United States

Research Site

Portland, Oregon, United States

Research Site

Easley, South Carolina, United States

Research Site

Greenville, South Carolina, United States

Research Site

Rock Hill, South Carolina, United States

Research Site

Spartanburg, South Carolina, United States

Research Site

Boerne, Texas, United States

Research Site

Killeen, Texas, United States

Countries

United States

Other Identifiers

D6571C00002

Identifier Type: -

Identifier Source: org_study_id