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AMPLIFY - D6571C00001 Duaklir USA Phase III Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02796677
Recruitment Status : Completed
First Posted : June 13, 2016
Results First Posted : November 9, 2018
Last Update Posted : November 9, 2018
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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).

Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease Drug: Aclidinium bromide 400 μg/Formoterol Fumarate 12 μg (AB/FF 400/12 μg) Drug: Aclidinium bromide 400 μg (AB 400 μg) Drug: Formoterol fumarate 12 μg (FF 12 μg) Other: Placebo to AB/FF 400/12 μg, AB 400 μg and FF 12 μg Drug: Tiotropium 18 μg (TIO 18 μg) Other: Placebo to TIO 18 μg Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1595 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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.
Actual Study Start Date : July 5, 2016
Actual Primary Completion Date : June 8, 2017
Actual Study Completion Date : June 8, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: COPD Lung Diseases

Arm Intervention/treatment
Experimental: AB/FF 400/12 μg BID
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)
Inhalation powder
Other Name: Oral Inhalation (by Pressair®/Genuair® Dry Powder Inhaler)

Other: Placebo to AB/FF 400/12 μg, AB 400 μg and FF 12 μg
Inhalation powder
Other Name: Oral Inhalation (by Pressair®/Genuair® Dry Powder Inhaler)

Experimental: AB 400 μg BID
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)
Inhalation powder
Other Name: Oral Inhalation (by Pressair®/Genuair® Dry Powder Inhaler)

Other: Placebo to AB/FF 400/12 μg, AB 400 μg and FF 12 μg
Inhalation powder
Other Name: Oral Inhalation (by Pressair®/Genuair® Dry Powder Inhaler)

Experimental: FF 12 μg BID
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)
Inhalation powder
Other Name: Oral Inhalation (by Pressair®/Genuair® Dry Powder Inhaler)

Other: Placebo to AB/FF 400/12 μg, AB 400 μg and FF 12 μg
Inhalation powder
Other Name: Oral Inhalation (by Pressair®/Genuair® Dry Powder Inhaler)

Experimental: TIO 18 μg QD
Participants were administered TIO 18 μg via Handihaler® inhale once daily for 24 weeks of treatment.
Drug: Tiotropium 18 μg (TIO 18 μg)
Powder in capsules for oral inhalation
Other Name: Oral Inhalation (by Handihaler® Dry Powder Inhaler, DPI)

Other: Placebo to TIO 18 μg
Powder in capsules for oral inhalation
Other Name: Oral Inhalation (by Handihaler® Dry Powder Inhaler, DPI)




Primary Outcome Measures :
  1. 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 [ Time Frame: At baseline 1-hour postdose and 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.


  2. Change From Baseline in Morning Predose (Trough) FEV1 of AB/FF 400/12 μg Compared to FF 12 μg at Week 24 [ Time Frame: At baseline morning predose and 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.


  3. Change From Baseline in Morning Predose (Trough) FEV1 at Week 24 Comparing AB 400 μg Versus TIO 18 μg to Demonstrate Non-inferiority [ Time Frame: At baseline morning predose and Week 24 ]
    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.


Secondary Outcome Measures :
  1. 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 [ Time Frame: At Day 1 and Day 169 ]
    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.

  2. 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. [ Time Frame: At baseline and Week 24 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02796677


  Show 163 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Sanjay Sethi 3495 Bailey Ave , Buffalo NY14215, USA
  Study Documents (Full-Text)

Documents provided by AstraZeneca:
Study Protocol  [PDF] March 21, 2016
Statistical Analysis Plan  [PDF] July 4, 2017


Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02796677     History of Changes
Other Study ID Numbers: D6571C00001
First Posted: June 13, 2016    Key Record Dates
Results First Posted: November 9, 2018
Last Update Posted: November 9, 2018
Last Verified: November 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by AstraZeneca:
Safety
Efficacy
Aclidinium bromide
Formoterol fumarate
Tiotropium
Bronchodilation
COPD

Additional relevant MeSH terms:
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Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Bromides
Formoterol Fumarate
Tiotropium Bromide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents
Anticonvulsants