Clinical trial NCT02796677: AMPLIFY - D6571C00001 Duaklir USA Phase III Study
Official title: A 24 Week Treatment, Multicenter, Randomized, Double Blinded, Double Dummy, Parallel-group, Clinical Trial Evaluating the Efficacy and Safety of Aclidinium Bromide 400 μg/Formoterol Fumarate 12 μg Fixed-dose Combination BID Compared With Each Monotherapy (Aclidinium Bromide 400 μg BID and Formoterol Fumarate 12 μg BID) and Tiotropium 18 μg QD When Administered to Patients With Stable Chronic Obstructive Pulmonary Disease.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: Safety
Efficacy
Aclidinium bromide
Formoterol fumarate
Tiotropium
Bronchodilation
COPD
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2016-06-13
Enrollment: 1595
Sex: ALL
Minimum age (years): 40
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multiple dose, randomized, parallel, double-blind, double-dummy, multicenter and multinational Phase III study to determine the efficacy and safety of Aclidinium bromide 400μg/Formoterol Fumarate (AB/FF) 12 μg compared to individual components and TIO (Tiotropium) 18 μg when administered to patients with stable chronic obstructive pulmonary disease (COPD).

Detailed description: This study was conducted to assess the bronchodilator efficacy and safety as well as effect on health related quality of life of AB/FF 400/12 μg compared to the individual components (AB 400 μg and FF 12 μg) in COPD patients. The trial duration of 24 weeks allows the assessment of the effect on symptoms improvement of the combined treatments versus individual components as well as the long term bronchodilation comparison between AB 400 μg and TIO 18 μg in minimizing the risk of COPD exacerbations in current or former smokers, aged ≥40 in symptomatic COPD patients.

Eligibility criteria: Inclusion Criteria:

* Adult male or non-pregnant, non-lactating female patients aged ≥40.
* Patients with diagnosis of moderate to very severe stable COPD: post-bronchodilator FEV1 \< 80% of the predicted normal and post-bronchodilator FEV1/FVC \< 70% at Screening Visit.
* Symptomatic patients with a CAT score ≥10 at Screening and Randomization visit (Visits 1 and 2).
* 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:

* 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 D6571C00001.
* Patients with predominant asthma.
* Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation (including the mild COPD exacerbation) within 6 weeks prior to screening 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 Screening Visit.
* 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 Screening.
* 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 centralised reading report assessed at Screening.
* Patients with clinically significant abnormalities in the laboratory tests, ECG parameters (other than QTc) or in the physical examination at Screening Visit that might comprise patient safety.
* Patient with known non-controlled history of infection with human immunodeficiency virus and/or active hepatitis.
* Patient with a history of hypersensitivity reaction to inhaled medication or any component thereof, including paradoxical bronchospasm.
* Patients with known narrow-angle glaucoma, symptomatic bladder neck obstruction, acute urinary retention or symptomatic non-stable 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 that cannot comply with the study procedures.
* Patients treated with any investigational drug within 30 days (or 6 half-lives, whichever is longer) prior to Screening.
* 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. Patients who demonstrate \< 80% compliance with the electronic diary during the run-in period.

Primary outcomes:
measure: Change From Baseline in 1-hour Morning Post-dose Dose Forced Expiratory Volume in 1 Second (FEV1) of AB/FF 400/12 μg Compared to AB 400 μg at Week 24
timeFrame: At baseline 1-hour postdose and Week 24
measure: Change From Baseline in Morning Predose (Trough) FEV1 of AB/FF 400/12 μg Compared to FF 12 μg at Week 24
timeFrame: At baseline morning predose and Week 24
measure: Change From Baseline in Morning Predose (Trough) FEV1 at Week 24 Comparing AB 400 μg Versus TIO 18 μg to Demonstrate Non-inferiority
timeFrame: At baseline morning predose and Week 24
Secondary outcomes:
measure: Change From Baseline in Normalized Area Under Curve 3hours Post-dose (nAUC0-3/3h) FEV1 of AB/FF 400/12 μg Compared to AB 400 μg and and FF 12 μg at Week 24
timeFrame: At Day 1 and Day 169
measure: Responder (Number of Participants) Analysis of St. George's Respiratory Questionnaire (SGRQ) Total Score With AB/FF 400/12 μg Versus AB 400 μg and FF 12 μg.
timeFrame: At baseline and Week 24
Other outcomes:
Locations:
city: Gulf Shores
country: United States
facility: Research Site
state: Alabama
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Corona
country: United States
facility: Research Site
state: California
city: Fresno
country: United States
facility: Research Site
state: California
city: Fullerton
country: United States
facility: Research Site
state: California
city: Lincoln
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Waterbury
country: United States
facility: Research Site
state: Connecticut
city: Clearwater
country: United States
facility: Research Site
state: Florida
city: Edgewater
country: United States
facility: Research Site
state: Florida
city: Hollywood
country: United States
facility: Research Site
state: Florida
city: Homestead
country: United States
facility: Research Site
state: Florida
city: Miami Lakes
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Ormond Beach
country: United States
facility: Research Site
state: Florida
city: Port Orange
country: United States
facility: Research Site
state: Florida
city: Saint Petersburg
country: United States
facility: Research Site
state: Florida
city: Saint Petersburg
country: United States
facility: Research Site
state: Florida
city: Sarasota
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Winter Park
country: United States
facility: Research Site
state: Florida
city: Blue Ridge
country: United States
facility: Research Site
state: Georgia
city: Woodstock
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Portage
country: United States
facility: Research Site
state: Indiana
city: Lafayette
country: United States
facility: Research Site
state: Louisiana
city: Fall River
country: United States
facility: Research Site
state: Massachusetts
city: Chelsea
country: United States
facility: Research Site
state: Michigan
city: Farmington Hills
country: United States
facility: Research Site
state: Michigan
city: Troy
country: United States
facility: Research Site
state: Michigan
city: Edina
country: United States
facility: Research Site
state: Minnesota
city: Fridley
country: United States
facility: Research Site
state: Minnesota
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Woodbury
country: United States
facility: Research Site
state: Minnesota
city: Saint Charles
country: United States
facility: Research Site
state: Missouri
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Fremont
country: United States
facility: Research Site
state: Nebraska
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Bronx
country: United States
facility: Research Site
state: New York
city: Brooklyn
country: United States
facility: Research Site
state: New York
city: Buffalo
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Rochester
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Gastonia
country: United States
facility: Research Site
state: North Carolina
city: Wilmington
country: United States
facility: Research Site
state: North Carolina
city: Canton
country: United States
facility: Research Site
state: Ohio
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Dublin
country: United States
facility: Research Site
state: Ohio
city: Grove City
country: United States
facility: Research Site
state: Ohio
city: Edmond
country: United States
facility: Research Site
state: Oklahoma
city: Midwest City
country: United States
facility: Research Site
state: Oklahoma
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Medford
country: United States
facility: Research Site
state: Oregon
city: Altoona
country: United States
facility: Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Wyomissing
country: United States
facility: Research Site
state: Pennsylvania
city: East Providence
country: United States
facility: Research Site
state: Rhode Island
city: Columbia
country: United States
facility: Research Site
state: South Carolina
city: Gaffney
country: United States
facility: Research Site
state: South Carolina
city: Mount Pleasant
country: United States
facility: Research Site
state: South Carolina
city: Spartanburg
country: United States
facility: Research Site
state: South Carolina
city: Union
country: United States
facility: Research Site
state: South Carolina
city: Arlington
country: United States
facility: Research Site
state: Texas
city: Baytown
country: United States
facility: Research Site
state: Texas
city: Boerne
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Fort Worth
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Lewisville
country: United States
facility: Research Site
state: Texas
city: McKinney
country: United States
facility: Research Site
state: Texas
city: Tomball
country: United States
facility: Research Site
state: Texas
city: Midvale
country: United States
facility: Research Site
state: Utah
city: Abingdon
country: United States
facility: Research Site
state: Virginia
city: Newport News
country: United States
facility: Research Site
state: Virginia
city: Dimitrovgrad
country: Bulgaria
facility: Research Site
city: Gabrovo
country: Bulgaria
facility: Research Site
city: Roman
country: Bulgaria
facility: Research Site
city: Ruse
country: Bulgaria
facility: Research Site
city: Sevlievo
country: Bulgaria
facility: Research Site
city: Sliven
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Stara Zagora
country: Bulgaria
facility: Research Site
city: Vidin
country: Bulgaria
facility: Research Site
city: Jaromer
country: Czechia
facility: Research Site
city: Jindrichuv Hradec
country: Czechia
facility: Research Site
city: Praha 8
country: Czechia
facility: Research Site
city: Rokycany
country: Czechia
facility: Research Site
city: Strakonice
country: Czechia
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bochum
country: Germany
facility: Research Site
city: Dortmund
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Grosshansdorf
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Luebeck
country: Germany
facility: Research Site
city: Marburg
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Schwerin
country: Germany
facility: Research Site
city: Balassagyarmat
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Gödöllő
country: Hungary
facility: Research Site
city: Komló
country: Hungary
facility: Research Site
city: Nyíregyháza
country: Hungary
facility: Research Site
city: Pécs
country: Hungary
facility: Research Site
city: Szigetszentmiklós
country: Hungary
facility: Research Site
city: Szombathely
country: Hungary
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Petach Tikva
country: Israel
facility: Research Site
city: Rehovot
country: Israel
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Częstochowa
country: Poland
facility: Research Site
city: Gdańsk
country: Poland
facility: Research Site
city: Gdynia
country: Poland
facility: Research Site
city: Inowrocław
country: Poland
facility: Research Site
city: Katowice
country: Poland
facility: Research Site
city: Ostrowiec Świętokrzyski
country: Poland
facility: Research Site
city: Pabianice
country: Poland
facility: Research Site
city: Szczecin
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Zabrze
country: Poland
facility: Research Site
city: Alicante
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Lleida
country: Spain
facility: Research Site
city: Ivano-Frankivsk
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Odessa
country: Ukraine
facility: Research Site
city: Poltava
country: Ukraine
facility: Research Site
city: Sumy
country: Ukraine
facility: Research Site
city: Uzhhorod
country: Ukraine
facility: Research Site
city: Vinnytsia
country: Ukraine
facility: Research Site
city: Zhytomyr
country: Ukraine
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Cardiff
country: United Kingdom
facility: Research Site
city: Chorley
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Hexham
country: United Kingdom
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
affiliation: 3495 Bailey Ave , Buffalo NY14215, USA
name: Sanjay Sethi
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sethi S, Kerwin E, Watz H, Ferguson GT, Mroz RM, Segarra R, Molins E, Jarreta D, Garcia Gil E. AMPLIFY: a randomized, Phase III study evaluating the efficacy and safety of aclidinium/formoterol vs monocomponents and tiotropium in patients with moderate-to-very severe symptomatic COPD. Int J Chron Obstruct Pulmon Dis. 2019 Mar 22;14:667-682. doi: 10.2147/COPD.S189138. eCollection 2019.