AMPLIFY - D6571C00001 Duaklir USA Phase III Study

Chronic Obstructive Pulmonary Disease Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02796677
• Other study ID #: D6571C00001
• Status: Completed
• Phase: Phase 3
• Start date: July 5, 2016
• Est. completion date: June 8, 2017

Study information

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

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1595
• Est. completion date: June 8, 2017
• Est. primary completion date: June 8, 2017
• 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 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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Aclidinium bromide 400 µg/Formoterol Fumarate 12 µg (AB/FF 400/12 µg)
Inhalation powder
• Aclidinium bromide 400 µg (AB 400 µg)
Inhalation powder
• Formoterol fumarate 12 µg (FF 12 µg)
Inhalation powder

Other:
• Placebo to AB/FF 400/12 µg, AB 400 µg and FF 12 µg
Inhalation powder

Drug:
• Tiotropium 18 µg (TIO 18 µg)
Powder in capsules for oral inhalation

Other:
• Placebo to TIO 18 µg
Powder in capsules for oral inhalation

Locations

Country	Name	City	State
Bulgaria	Research Site	Dimitrovgrad
Bulgaria	Research Site	Gabrovo
Bulgaria	Research Site	Roman
Bulgaria	Research Site	Ruse
Bulgaria	Research Site	Sevlievo
Bulgaria	Research Site	Sliven
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Stara Zagora
Bulgaria	Research Site	Vidin
Czechia	Research Site	Jaromer
Czechia	Research Site	Jindrichuv Hradec
Czechia	Research Site	Praha 8
Czechia	Research Site	Rokycany
Czechia	Research Site	Strakonice
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Bochum
Germany	Research Site	Dortmund
Germany	Research Site	Dresden
Germany	Research Site	Frankfurt
Germany	Research Site	Grosshansdorf
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	Leipzig
Germany	Research Site	Leipzig
Germany	Research Site	Luebeck
Germany	Research Site	Marburg
Germany	Research Site	München
Germany	Research Site	Schwerin
Hungary	Research Site	Balassagyarmat
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Gödöllo
Hungary	Research Site	Komló
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Pécs
Hungary	Research Site	Szigetszentmiklós
Hungary	Research Site	Szombathely
Israel	Research Site	Jerusalem
Israel	Research Site	Petach Tikva
Israel	Research Site	Rehovot
Poland	Research Site	Bialystok
Poland	Research Site	Czestochowa
Poland	Research Site	Gdansk
Poland	Research Site	Gdynia
Poland	Research Site	Inowroclaw
Poland	Research Site	Katowice
Poland	Research Site	Ostrowiec Swietokrzyski
Poland	Research Site	Pabianice
Poland	Research Site	Szczecin
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Poland	Research Site	Zabrze
Spain	Research Site	Alicante
Spain	Research Site	Barcelona
Spain	Research Site	Lleida
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Odessa
Ukraine	Research Site	Poltava
Ukraine	Research Site	Sumy
Ukraine	Research Site	Uzhhorod
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Zhytomyr
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Cardiff
United Kingdom	Research Site	Chorley
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Hexham
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	Manchester
United States	Research Site	Abingdon	Virginia
United States	Research Site	Altoona	Pennsylvania
United States	Research Site	Arlington	Texas
United States	Research Site	Baytown	Texas
United States	Research Site	Blue Ridge	Georgia
United States	Research Site	Boerne	Texas
United States	Research Site	Bronx	New York
United States	Research Site	Brooklyn	New York
United States	Research Site	Buffalo	New York
United States	Research Site	Canton	Ohio
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chelsea	Michigan
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Clearwater	Florida
United States	Research Site	Columbia	South Carolina
United States	Research Site	Columbus	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	Corona	California
United States	Research Site	Dallas	Texas
United States	Research Site	Dublin	Ohio
United States	Research Site	East Providence	Rhode Island
United States	Research Site	Edgewater	Florida
United States	Research Site	Edina	Minnesota
United States	Research Site	Edmond	Oklahoma
United States	Research Site	Fall River	Massachusetts
United States	Research Site	Farmington Hills	Michigan
United States	Research Site	Fort Worth	Texas
United States	Research Site	Fremont	Nebraska
United States	Research Site	Fresno	California
United States	Research Site	Fridley	Minnesota
United States	Research Site	Fullerton	California
United States	Research Site	Gaffney	South Carolina
United States	Research Site	Gastonia	North Carolina
United States	Research Site	Grove City	Ohio
United States	Research Site	Gulf Shores	Alabama
United States	Research Site	Hollywood	Florida
United States	Research Site	Homestead	Florida
United States	Research Site	Houston	Texas
United States	Research Site	Lafayette	Louisiana
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lewisville	Texas
United States	Research Site	Lincoln	California
United States	Research Site	McKinney	Texas
United States	Research Site	Medford	Oregon
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami Lakes	Florida
United States	Research Site	Midvale	Utah
United States	Research Site	Midwest City	Oklahoma
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Mount Pleasant	South Carolina
United States	Research Site	New York	New York
United States	Research Site	Newport News	Virginia
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Omaha	Nebraska
United States	Research Site	Omaha	Nebraska
United States	Research Site	Ormond Beach	Florida
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Port Orange	Florida
United States	Research Site	Portage	Indiana
United States	Research Site	Rochester	New York
United States	Research Site	Saint Charles	Missouri
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Petersburg	Florida
United States	Research Site	Saint Petersburg	Florida
United States	Research Site	San Diego	California
United States	Research Site	Sarasota	Florida
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	Tampa	Florida
United States	Research Site	Tomball	Texas
United States	Research Site	Troy	Michigan
United States	Research Site	Tucson	Arizona
United States	Research Site	Union	South Carolina
United States	Research Site	Waterbury	Connecticut
United States	Research Site	Wilmington	North Carolina
United States	Research Site	Winter Park	Florida
United States	Research Site	Woodbury	Minnesota
United States	Research Site	Woodstock	Georgia
United States	Research Site	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Bulgaria,  Czechia,  Germany,  Hungary,  Israel,  Poland,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	To assess the bronchodilatory effect by evaluating the mean changes from baseline in FEV1 at 1 hour post-dose of AB/FF 400/12 µg compared to AB 400 µg after administration of oral inhalation powder BID via DIP to participants with COPD.; Baseline was defined as the average of the two FEV1 values measured just prior to the administration of the first dose of investigational product (IP) at randomization Visit. If one of the two was missing, then the available one would be used as baseline value.	At baseline 1-hour postdose and Week 24
Primary	Change From Baseline in Morning Predose (Trough) FEV1 of AB/FF 400/12 µg Compared to FF 12 µg at Week 24	To assess the bronchodilatory effect by evaluating the mean changes from baseline in FEV1 in morning pre-dose (trough) of AB/FF 400/12 µg compared to FF 12 µg after administration of oral inhalation powder BID via DPI to participants with COPD.; Morning pre-dose (trough) FEV1 was defined as the average of the corresponding -30 minute and 0 minute before the morning study medication at Week 24. If one time-point was missing then the available one would be used as morning pre-dose.	At baseline morning predose and Week 24
Primary	Change From Baseline in Morning Predose (Trough) FEV1 at Week 24 Comparing AB 400 µg Versus TIO 18 µg to Demonstrate Non-inferiority	To assess the non-inferior bronchodilatory effect by evaluating the mean changes from baseline in FEV1 in morning pre-dose (trough)of AB 400 µg compared to TIO 18 µg after administration of oral inhalation powder BID via DPI to participants with COPD.	At baseline morning predose and Week 24
Secondary	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	To assess the bronchodilatory effect by evaluating the mean changes from baseline in nAUC0-3/3h FEV1 of AB/FF 400/12 µg compared to AB 400 µg and and FF 12 µg after administration of oral inhalation powder BID via DPI to participants with COPD.	At Day 1 and Day 169
Secondary	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.	SGRQ was a A standardized self-completed tool used to measure impaired health and perceived well-being ("quality of life") in respiratory diseases. The questionnaire contained 50 items divided into 3 (symptoms, activity and impacts) dimensions. Each of the three dimensions of the questionnaire is scored separately in the range from 0 to 100%, zero score indicating no impairment of life quality. A summary score utilizing responses to all items is the total SGRQ score which also ranges from 0 to 100%. The SGRQ scores are calculated using weights attached to each item of the questionnaire which provides an estimate of the distress associated with the symptoms or state described in each item. Higher scores indicate poorer health. A decrease of at least 4 units in the SGRQ total score has been established as the criterion for minimal meaningful improvement. SGRQ responders will be those with a decrease in SGRQ total score of at least 4 units from baseline.	At baseline and Week 24

External Links

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