AMPLIFY - D6571C00001 Duaklir USA Phase III Study

NCT02796677 | Completed Phase 3 Results FDA Drug FDA Device

• 1 other identifier: D6571C00001
• Study Type: interventional
• Target: 1,595
• Locations: 10 countries
• Sites: 163

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).

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Safety; Efficacy; Aclidinium bromide; Formoterol fumarate; Tiotropium; Bronchodilation; COPD

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (2)

• 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

  At Day 1 and Day 169

• 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.

  At baseline and Week 24

Study Arms (4)

AB/FF 400/12 μg BID

EXPERIMENTAL

Participants were administered AB/FF 400/12 μg via Pressair®/Genuair® inhaler twice daily for 24 weeks of treatment.

Drug: Aclidinium bromide 400 μg/Formoterol Fumarate 12 μg (AB/FF 400/12 μg); Other: Placebo to AB/FF 400/12 μg, AB 400 μg and FF 12 μg

AB 400 μg BID

EXPERIMENTAL

Participants were administered AB 400 μg via Pressair®/Genuair® inhaler twice daily for 24 weeks of treatment.

Drug: Aclidinium bromide 400 μg (AB 400 μg); Other: Placebo to AB/FF 400/12 μg, AB 400 μg and FF 12 μg

FF 12 μg BID

EXPERIMENTAL

Participants were administered FF 12 μg via Pressair®/Genuair® inhaler twice daily for 24 weeks of treatment.

Drug: Formoterol fumarate 12 μg (FF 12 μg); Other: Placebo to AB/FF 400/12 μg, AB 400 μg and FF 12 μg

TIO 18 μg QD

EXPERIMENTAL

Participants were administered TIO 18 μg via Handihaler® inhale once daily for 24 weeks of treatment.

Drug: Tiotropium 18 μg (TIO 18 μg); Other: Placebo to TIO 18 μg

Interventions

Aclidinium bromide 400 μg/Formoterol Fumarate 12 μg (AB/FF 400/12 μg) DRUG

Inhalation powder

Also known as: Oral Inhalation (by Pressair®/Genuair® Dry Powder Inhaler)

AB/FF 400/12 μg BID

Aclidinium bromide 400 μg (AB 400 μg) DRUG

Inhalation powder

Also known as: Oral Inhalation (by Pressair®/Genuair® Dry Powder Inhaler)

AB 400 μg BID

Formoterol fumarate 12 μg (FF 12 μg) DRUG

Inhalation powder

Also known as: Oral Inhalation (by Pressair®/Genuair® Dry Powder Inhaler)

FF 12 μg BID

Placebo to AB/FF 400/12 μg, AB 400 μg and FF 12 μg OTHER

Inhalation powder

Also known as: Oral Inhalation (by Pressair®/Genuair® Dry Powder Inhaler)

AB 400 μg BID; AB/FF 400/12 μg BID; FF 12 μg BID

Tiotropium 18 μg (TIO 18 μg) DRUG

Powder in capsules for oral inhalation

Also known as: Oral Inhalation (by Handihaler® Dry Powder Inhaler, DPI)

TIO 18 μg QD

Placebo to TIO 18 μg OTHER

Powder in capsules for oral inhalation

Also known as: Oral Inhalation (by Handihaler® Dry Powder Inhaler, DPI)

TIO 18 μg QD

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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (163)

Research Site

Gulf Shores, Alabama, 36542, United States

Location

Research Site

Phoenix, Arizona, 85018, United States

Location

Research Site

Tucson, Arizona, 85712, United States

Location

Research Site

Corona, California, 92879, United States

Location

Research Site

Fresno, California, 93702, United States

Location

Research Site

Fullerton, California, 92835, United States

Location

Research Site

Lincoln, California, 95648, United States

Location

Research Site

San Diego, California, 92120, United States

Location

Research Site

Waterbury, Connecticut, 06708, United States

Location

Research Site

Clearwater, Florida, 33765, United States

Location

Research Site

Edgewater, Florida, 32132, United States

Location

Research Site

Hollywood, Florida, 33021, United States

Location

Research Site

Homestead, Florida, 33030, United States

Location

Research Site

Miami, Florida, 33144, United States

Location

Research Site

Miami, Florida, 33186, United States

Location

Research Site

Miami Lakes, Florida, 33016, United States

Location

Research Site

Ormond Beach, Florida, 32174, United States

Location

Research Site

Port Orange, Florida, 32129, United States

Location

Research Site

Sarasota, Florida, 34233, United States

Location

Research Site

St. Petersburg, Florida, 33704, United States

Location

Research Site

St. Petersburg, Florida, 33709, United States

Location

Research Site

Tampa, Florida, 33603, United States

Location

Research Site

Winter Park, Florida, 32789, United States

Location

Research Site

Blue Ridge, Georgia, 30513, United States

Location

Research Site

Woodstock, Georgia, 30189, United States

Location

Research Site

Chicago, Illinois, 60602, United States

Location

Research Site

Portage, Indiana, 46368, United States

Location

Research Site

Lafayette, Louisiana, 70508, United States

Location

Research Site

Fall River, Massachusetts, 02720, United States

Location

Research Site

Chelsea, Michigan, 48118, United States

Location

Research Site

Farmington Hills, Michigan, 48336, United States

Location

Research Site

Troy, Michigan, 48085, United States

Location

Research Site

Edina, Minnesota, 55435, United States

Location

Research Site

Fridley, Minnesota, 55432, United States

Location

Research Site

Minneapolis, Minnesota, 55407, United States

Location

Research Site

Woodbury, Minnesota, 55125, United States

Location

Research Site

Saint Charles, Missouri, 63301, United States

Location

Research Site

St Louis, Missouri, 63117, United States

Location

Research Site

St Louis, Missouri, 63141, United States

Location

Research Site

Fremont, Nebraska, 68025, United States

Location

Research Site

Omaha, Nebraska, 68114, United States

Location

Research Site

Omaha, Nebraska, 68134, United States

Location

Research Site

Las Vegas, Nevada, 89102, United States

Location

Research Site

Brooklyn, New York, 11230, United States

Location

Research Site

Buffalo, New York, 14215, United States

Location

Research Site

New York, New York, 10036, United States

Location

Research Site

Rochester, New York, 14618, United States

Location

Research Site

The Bronx, New York, 10455, United States

Location

Research Site

Charlotte, North Carolina, 28207, United States

Location

Research Site

Charlotte, North Carolina, 28277, United States

Location

Research Site

Gastonia, North Carolina, 28054, United States

Location

Research Site

Wilmington, North Carolina, 28401, United States

Location

Research Site

Canton, Ohio, 44718, United States

Location

Research Site

Cincinnati, Ohio, 45231, United States

Location

Research Site

Cincinnati, Ohio, 45242, United States

Location

Research Site

Cincinnati, Ohio, 45246, United States

Location

Research Site

Columbus, Ohio, 43207, United States

Location

Research Site

Columbus, Ohio, 43215, United States

Location

Research Site

Dublin, Ohio, 43016, United States

Location

Research Site

Grove City, Ohio, 43123, United States

Location

Research Site

Edmond, Oklahoma, 73034, United States

Location

Research Site

Midwest City, Oklahoma, 73110, United States

Location

Research Site

Oklahoma City, Oklahoma, 73104, United States

Location

Research Site

Medford, Oregon, 97504, United States

Location

Research Site

Altoona, Pennsylvania, 16602, United States

Location

Research Site

Pittsburgh, Pennsylvania, 15243, United States

Location

Research Site

Wyomissing, Pennsylvania, 19610, United States

Location

Research Site

East Providence, Rhode Island, 02914, United States

Location

Research Site

Columbia, South Carolina, 29204, United States

Location

Research Site

Gaffney, South Carolina, 29340, United States

Location

Research Site

Mt. Pleasant, South Carolina, 29464, United States

Location

Research Site

Spartanburg, South Carolina, 29303, United States

Location

Research Site

Union, South Carolina, 29379, United States

Location

Research Site

Arlington, Texas, 76012, United States

Location

Research Site

Baytown, Texas, 77521, United States

Location

Research Site

Boerne, Texas, 78006, United States

Location

Research Site

Dallas, Texas, 75225, United States

Location

Research Site

Fort Worth, Texas, 76104, United States

Location

Research Site

Houston, Texas, 77074, United States

Location

Research Site

Lewisville, Texas, 75067, United States

Location

Research Site

McKinney, Texas, 75069, United States

Location

Research Site

Tomball, Texas, 77375, United States

Location

Research Site

Midvale, Utah, 84047, United States

Location

Research Site

Abingdon, Virginia, 24210, United States

Location

Research Site

Newport News, Virginia, 23606, United States

Location

Research Site

Dimitrovgrad, 6400, Bulgaria

Location

Research Site

Gabrovo, 5300, Bulgaria

Location

Research Site

Roman, 3130, Bulgaria

Location

Research Site

Rousse, 7002, Bulgaria

Location

Research Site

Sevlievo, 5400, Bulgaria

Location

Research Site

Sliven, 8800, Bulgaria

Location

Research Site

Sofia, 1002, Bulgaria

Location

Research Site

Sofia, 1431, Bulgaria

Location

Research Site

Stara Zagora, 6003, Bulgaria

Location

Research Site

Vidin, 3700, Bulgaria

Location

Research Site

Jaroměř, 544 01, Czechia

Location

Research Site

Jindřichův Hradec, 377 01, Czechia

Location

Research Site

Prague, 182 00, Czechia

Location

Research Site

Rokycany, 33722, Czechia

Location

Research Site

Strakonice, 38601, Czechia

Location

Research Site

Berlin, 10117, Germany

Location

Research Site

Berlin, 10629, Germany

Location

Research Site

Berlin, 10717, Germany

Location

Research Site

Berlin, 10787, Germany

Location

Research Site

Berlin, 12627, Germany

Location

Research Site

Bochum, 44787, Germany

Location

Research Site

Dortmund, 44263, Germany

Location

Research Site

Dresden, 01069, Germany

Location

Research Site

Frankfurt, 60596, Germany

Location

Research Site

Großhansdorf, 20927, Germany

Location

Research Site

Hamburg, 20253, Germany

Location

Research Site

Hamburg, 20354, Germany

Location

Research Site

Hamburg, D-22143, Germany

Location

Research Site

Hanover, 30159, Germany

Location

Research Site

Leipzig, 04103, Germany

Location

Research Site

Leipzig, 04275, Germany

Location

Research Site

Lübeck, 23552, Germany

Location

Research Site

Marburg, 35037, Germany

Location

Research Site

München, 80539, Germany

Location

Research Site

Schwerin, 19055, Germany

Location

Research Site

Balassagyarmat, 2660, Hungary

Location

Research Site

Budapest, 1036, Hungary

Location

Research Site

Debrecen, 4031, Hungary

Location

Research Site

Gödöllő, 2100, Hungary

Location

Research Site

Komló, 7300, Hungary

Location

Research Site

Nyíregyháza, 4400, Hungary

Location

Research Site

Pécs, 7635, Hungary

Location

Research Site

Szigetszentmiklós, 2310, Hungary

Location

Research Site

Szombathely, 9700, Hungary

Location

Research Site

Jerusalem, 91120, Israel

Location

Research Site

Petah Tikva, 49100, Israel

Location

Research Site

Rehovot, 76100, Israel

Location

Research Site

Bialystok, 15-003, Poland

Location

Research Site

Częstochowa, 42-200, Poland

Location

Research Site

Gdansk, 80-382, Poland

Location

Research Site

Gdynia, 81-384, Poland

Location

Research Site

Inowrocław, 88-100, Poland

Location

Research Site

Katowice, 40-040, Poland

Location

Research Site

Ostrowiec Świętokrzyski, 27-400, Poland

Location

Research Site

Pabianice, 95-200, Poland

Location

Research Site

Szczecin, 70-111, Poland

Location

Research Site

Warsaw, 01-192, Poland

Location

Research Site

Wroclaw, 50-088, Poland

Location

Research Site

Zabrze, 41-800, Poland

Location

Research Site

Alicante, 03004, Spain

Location

Research Site

Barcelona, 08830, Spain

Location

Research Site

Lleida, 25198, Spain

Location

Research Site

Ivano-Frankivsk, 76012, Ukraine

Location

Research Site

Kharkiv, 61035, Ukraine

Location

Research Site

Kharkiv, 61039, Ukraine

Location

Research Site

Odesa, 65009, Ukraine

Location

Research Site

Poltava, 36024, Ukraine

Location

Research Site

Sumy, 40030, Ukraine

Location

Research Site

Uzhhorod, 88017, Ukraine

Location

Research Site

Vinnytsia, 21018, Ukraine

Location

Research Site

Zhytomyr, 10002, Ukraine

Location

Research Site

Birmingham, B15 2SQ, United Kingdom

Location

Research Site

Cardiff, CF14 5GJ, United Kingdom

Location

Research Site

Chorley, PR7 7NA, United Kingdom

Location

Research Site

Glasgow, G20 OSP, United Kingdom

Location

Research Site

Hexham, NE46 1QJ, United Kingdom

Location

Research Site

Liverpool, L22 0LG, United Kingdom

Location

Research Site

Manchester, M15 6SX, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 30962681 DERIVED

Related Links

• Protocol
• SAP

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

aclidinium bromide; Formoterol Fumarate; Inhalation; Tiotropium Bromide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Global Clinical Leader
• Organization: AstraZeneca AB

clinicaltrialtransparency@astrazeneca.com

+46 766 346712

Study Officials

• Sanjay Sethi

  3495 Bailey Ave , Buffalo NY14215, USA

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2016
• First Posted: June 13, 2016
• Study Start: July 5, 2016
• Primary Completion: June 8, 2017
• Study Completion: June 8, 2017
• Last Updated: November 9, 2018
• Results First Posted: November 9, 2018

Record last verified: 2018-11

Locations

BU (10); CZ (5); ES (3); PL (12); US (85); HU (9); UA (9); GB (7); DE (20); IL (3)