Pulmonary Disease, Chronic ObstructivePhase 4ACTIVATENCT02424344

Effect of Aclidinium/Formoterol on Lung Hyperinflation, Exercise Capacity and Physical Activity in Moderate to Severe COPD Patients

A Phase 4 study testing Aclidinium/Formoterol in people with Pulmonary Disease, Chronic Obstructive, run by AstraZeneca at 26 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 40 to 130 years
Conditions the study is for: Pulmonary Disease, Chronic Obstructive
What is being tested?: Aclidinium/Formoterol
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 267 participants
Where: 26 sitesin 4 countries
Study dates: 27 Apr 2015to 25 Jul 2016
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 130 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Males and non-pregnant, non-lactating females aged ≥ 40.
Patients with a clinical diagnosis of COPD according to GOLD guidelines 2014, with a post bronchodilator FEV1 ≥ 40% and < 80% of the predicted value and FEV1/FVC < 70% at Visit 1.
Functional residual capacity (FRC) measured by body plethysmography at Visit 1 ≥ 120% of predicted value.
Patients with modified Medical Research Council dyspnea scale (mMRC) ≥ 2 at Visit 1.
Current or former cigarette smokers with a smoking history of at least 10 pack-years at Visit 1
Patients willing to participate in the telecoaching program during the four last weeks and to enhance their physical activity
Patients who understand and are able to follow the study procedures, are cooperative and are willing to participate in the study as indicated by signing the informed consent.

Who cannot join

History or current diagnosis of asthma.
Any respiratory tract infection (including upper respiratory tract) or COPD exacerbation in the 6 weeks prior to Visit 1 or during the run-in period.
Patients who have been hospitalised for an acute COPD exacerbation within 3 months prior to Visit 1 or during the run-in period.
Clinically significant respiratory conditions other than COPD.
Use of long-term oxygen therapy (≥ 15 hours/day).
Oxygen saturation ≤ 85% as measured by pulse oximetry during exercise testing at Visit 1, Visit 2 or Visit 3 prior to randomisation.

Show all 23Show fewer

Patients with a Body Mass Index (BMI) ≥ 40kg/m2.
Patient who may need to start a pulmonary rehabilitation program during the study and/or who started/finished it within 3 months prior to Visit 1 or during the run-in period.
Patients with clinically significant cardiovascular conditions.
Patients with Type I or uncontrolled Type II diabetes, uncontrolled hypo-or hyperthyroidism, hypokalaemia, or hyperadrenergic state, uncontrolled or untreated hypertension.
Patient with known non-controlled history of infection with human immunodeficiency virus (HIV) and/or active hepatitis.
Patients with clinically relevant abnormalities in the results of the blood pressure, ECG, or physical examination at Visit 1.
Patients with any serious or uncontrolled physical or mental dysfunction that could place the patient at higher risk derived from his/her participation in the study or could confound the results
Patients with conditions other than COPD that may contribute to dyspnoea and exercise limitation or with contraindications to clinical exercise testing according to ATS recommendations for CPET
Patients with other relevant comorbidities that make the patient nor suitable to follow-up study procedures and/or could affect physical activity
Patients who cycled < 2 minutes or > 15 minutes during the constant work-rate exercise tests conducted at Visit 2 (Run-in Visit) or at Visit 3 even after adjustment of the work load.
Patients with history of hypersensitivity reaction to inhaled anticholinergics, sympathomimetic amines or inhaled medication or any component thereof (including report of paradoxical bronchospasm)
Patients for whom the use of anticholinergic drugs is contraindicated (acute urinary retention, symptomatic prostatic hypertrophy, bladder neck obstruction or narrow-angle glaucoma)
Patients unable to properly use a multidose dry powder inhaler or a pressurized metered-dose inhaler (pMDI).
Patients using any prohibited medication (including IMP within 30 days (or 6 half-lives, whichever is longer) before Visit 1) or who have not undergone the required washout period.
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 who do not maintain regular day/night, waking/sleeping cycles (e.g., night shift workers, sleep apnea).
Patients unable to give their consent, or patients of consenting age but under guardianship, or vulnerable patients

Trial locations and contacts

26 sites in 4 countries.

Country

City, postcode or hospital

26 sites in 4 countries

Germany15 sites

Research Site
Berlin, 10117
Research Site
Berlin, 10717
Research Site
Berlin, 10787
Research Site
Berlin, 10969
Research Site
Berlin, 13086
Research Site
Dortmund, 44263
Research Site
Frankfurt, 60596
Research Site
Großhansdorf, 22927
Research Site
Hamburg, 20253
Research Site
Hamburg, 20354
Research Site
Hanover, 30173
Research Site
Jena, 7740
Research Site
Lübeck, 23552
Research Site
München, 80331
Research Site
Wiesbaden, 65187

Other trials in Germany

Canada4 sites

Research Site
Hamilton, Ontario, L8N 3Z5
Research Site
Kingston, Ontario, K7L 2V7
Research Site
Sainte-Foy, Quebec, G1V 4G5
Research Site
Saskatoon, Saskatchewan, S7N 0W8

Other trials in Canada

Hungary4 sites

Research Site
Budapest, 1125
Research Site
Deszk, 6772
Research Site
Nyíregyháza, 4400
Research Site
Törökbálint, 2045

Other trials in Hungary

Spain3 sites

Research Site
Alicante, 03004
Research Site
Cáceres, 10003
Research Site
Madrid, 28046

Other trials in Spain

About this study

Official title: A Multiple Dose, Randomized, Double-blind, Placebo Controlled, Parallel Clinical Trial to Assess the Effect of Aclidinium Bromide/Formoterol Fumarate Fixed-dose Combination on Lung Hyperinflation, Exercise Capacity and Physical Activity in Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

The present study is planned to evaluate the effect of the aclidinium bromide/formoterol fumarate 400/12 μg FDC BID on the hyperinflation, exercise endurance and physical activity in patients with moderate to severe COPD. Additionally, the effect of the behavioural intervention on top of aclidinium bromide/formoterol fumarate 400/12 μg will be assessed both on the exercise endurance and the physical activity.

Conditions: Pulmonary Disease, Chronic Obstructive
Being tested: Aclidinium/Formoterol, Placebo
Keywords: COPD
Medical subject headings: Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Aclidinium/FormoterolDrug
Aclidinium bromide/Formoterol fumarate FDC 400/12μg dry powder for oral inhalation twice daily via Genuair inhaler
PlaceboDrug
Dose-matched placebo dry powder for oral inhalation twice daily via Genuair inhaler

Study groups in NCT02424344
Study group	Role	What they receive
Aclidinium Bromide/Formoterol Fumarate FDC 400/12μg	Experimental	8 weeks, double blind treatment period Receives: Drug: Aclidinium/Formoterol
Placebo to Aclidinium/Formoterol	Placebo comparator	8 weeks, double blind treatment period Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Trough Functional Residual Capacity (FRC) After 4 Weeks of Treatment
Baseline values in FRC were defined as the corresponding values just before randomization on Day 1 of treatment (Week 0). Trough values were obtained prior to study drug administration.
Measured: Baseline and Week 4

Secondary outcomes (2)

Change From Baseline in Endurance Time (ET) During Constant Work Rate Cycle Ergometry at Week 8
The ET was the time from the increase in work rate to 75% Wmax to the point of symptom limitation.
Baseline measurements were taken prior to the IP dose on Day 1. Measurements at Week 8 were taken at 3 hours post-dose. Participants underwent a behavioural intervention (consisting of a telecoaching programme to enhance physical activity) between Week 4 and Week 8.
Measured: Baseline to Week 8
Percentage of Inactive Patients (Mean of <6000 Steps Per Day) at Week 8
Physical activity was assessed by means of measurement of activity parameters (e.g. number of steps) through a Dynaport MoveMonitor and completion of the Daily ProActive Physical Activity in chronic obstructive pulmonary disease (COPD) questionnaire.
Compliant criterion based on at least 8 hours per day, and at least 3 days per week. Participants underwent a behavioural intervention (consisting of a telecoaching programme to enhance physical activity) between Week 4 and Week 8.
Baseline was defined as mean of steps/day assessed during the week before the randomisation visit.
Measured: Week 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Apr 201525 Jul 2016

First posted23 Apr 2015 (estimated)
Study start27 Apr 2015
Primary completion25 Jul 2016
Study completion25 Jul 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 267 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02424344
Sponsor's protocol ID: D6570C00001
Other IDs: M-40464-33, 2014-005318-50, 2014
Acronym: ACTIVATE
Status last verified: Dec 2017
First submitted: 20 Apr 2015
Last updated: 9 Oct 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Koopman M, Franssen FME, Gaffron S, Watz H, Troosters T, Garcia-Aymerich J, Paggiaro P, Molins E, Moya M, van Burk L, Maier D, Garcia Gil E, Wouters EFM, Vanfleteren LEGW, Spruit MA. Differential Outcomes Following 4 Weeks of Aclidinium/Formoterol in Patients with COPD: A Reanalysis of the ACTIVATE Study. Int J Chron Obstruct Pulmon Dis. 2022 Mar 8;17:517-533. doi: 10.2147/COPD.S308600. eCollection 2022.
PubMed 35342289

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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The Aim of the Study is to Decipher the Alterations in Signalling Pathways of Skeletal Muscle Stem Cells (Satellite Cells (SCs)) in Individuals With COPD, as Well as to Examine the Effect of Exercise Training on SCs.
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All Pulmonary Disease, Chronic Obstructive trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multiple Dose, Randomized, Double-blind, Placebo Controlled, Parallel Clinical Trial to Assess the Effect of Aclidinium Bromide/Formoterol Fumarate Fixed-dose Combination on Lung Hyperinflation, Exercise Capacity and Physical Activity in Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
ClinicalTrials.gov ID: NCT02424344
Acronym / sponsor ID: ACTIVATE / D6570C00001
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: COPD
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 267 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Menarini Group
Study start: 27 Apr 2015 (actual)
Primary completion: 25 Jul 2016 (actual)
Study completion: 25 Jul 2016 (actual)
First posted: 23 Apr 2015 (estimated)
Results: Posted 9 Oct 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Aclidinium Bromide/Formoterol Fumarate FDC 400/12μg	Experimental	Drug: Aclidinium/Formoterol8 weeks, double blind treatment period
Placebo to Aclidinium/Formoterol	Placebo comparator	Drug: Placebo8 weeks, double blind treatment period

Who may qualify

Ages: 40 to 130 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Males and non-pregnant, non-lactating females aged ≥ 40.
Patients with a clinical diagnosis of COPD according to GOLD guidelines 2014, with a post bronchodilator FEV1 ≥ 40% and < 80% of the predicted value and FEV1/FVC < 70% at Visit 1.
Functional residual capacity (FRC) measured by body plethysmography at Visit 1 ≥ 120% of predicted value.
Patients with modified Medical Research Council dyspnea scale (mMRC) ≥ 2 at Visit 1.
Current or former cigarette smokers with a smoking history of at least 10 pack-years at Visit 1

Key exclusion criteria (23 listed)

History or current diagnosis of asthma.
Any respiratory tract infection (including upper respiratory tract) or COPD exacerbation in the 6 weeks prior to Visit 1 or during the run-in period.
Patients who have been hospitalised for an acute COPD exacerbation within 3 months prior to Visit 1 or during the run-in period.
Clinically significant respiratory conditions other than COPD.
Use of long-term oxygen therapy (≥ 15 hours/day).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Aclidinium/FormoterolAclidinium bromide/Formoterol fumarate FDC 400/12μg dry powder for oral inhalation twice daily via Genuair inhaler	Drug	Aclidinium Bromide/Formoterol Fumarate FDC 400/12μg
PlaceboDose-matched placebo dry powder for oral inhalation twice daily via Genuair inhaler	Drug	Placebo to Aclidinium/Formoterol

Primary outcome

Change From Baseline in Trough Functional Residual Capacity (FRC) After 4 Weeks of Treatment
Time frame: Baseline and Week 4
Baseline values in FRC were defined as the corresponding values just before randomization on Day 1 of treatment (Week 0). Trough values were obtained prior to study drug administration.

2 secondary outcomes

Change From Baseline in Endurance Time (ET) During Constant Work Rate Cycle Ergometry at Week 8
Time frame: Baseline to Week 8
Percentage of Inactive Patients (Mean of <6000 Steps Per Day) at Week 8
Time frame: Week 8

Results and safety

Results posted to the registry on 9 Oct 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AB/FF 400/12 μg	134	127
Placebo	133	123

Primary outcome: Change From Baseline in Trough Functional Residual Capacity (FRC) After 4 Weeks of Treatment

Time frame: Baseline and Week 4. Least squares mean (Standard Error). Unit: Liters

Measure	AB/FF 400/12 μg n = 124	Placebo n = 125
Value	-0.162 (0.050)	-0.037 (0.050)

AB/FF 400/12 μg vs Placebo: Least Square mean difference: -0.125 (95% CI -0.259 to 0.010), p = 0.069, ANCOVA

Population analysed: The intent-to-treat (ITT) population - equal to the Safety population and defined as all randomised patients who took at least one dose of investigational product (IP) - who had available trough FRC values at baseline and Week 4.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: From Screening, Week -2 (Days -17 to -11) to Follow-up, Week 10 (Day 70+3). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AB/FF 400/12 μg	2 of 134 (1.5%)	14 of 134 (10.4%)	Not reported
Placebo	3 of 133 (2.3%)	24 of 133 (18%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35342289Koopman M, Franssen FME, Gaffron S, Watz H, Troosters T, Garcia-Aymerich J, Paggiaro P, Molins E, Moya M, van Burk L, Maier D, Garcia Gil E, Wouters EFM, Vanfleteren LEGW, Spruit MA. Differential Outcomes Following 4 Weeks of Aclidinium/Formoterol in Patients with COPD: A Reanalysis of the ACTIVATE Study. Int J Chron Obstruct Pulmon Dis. 2022 Mar 8;17:517-533. doi: 10.2147/COPD.S308600. eCollection 2022.

Related trials for Pulmonary Disease, Chronic Obstructive

Active, not recruiting
Symptoms and Functions in Patients With COPD and Chronic Bronchitis Switching From CIG to THS
COPD, Smoking
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruiting
The Aim of the Study is to Decipher the Alterations in Signalling Pathways of Skeletal Muscle Stem Cells (Satellite Cells (SCs)) in Individuals With COPD, as Well as to Examine the Effect of Exercise Training on SCs.
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Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
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A Study to Investigate the Efficacy and Safety of Belumosudil Compared With Best Available Therapy in Participants Aged 12 Years or Older With Chronic Graft-versus-host Disease
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

26 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Aclidinium/Formoterol in people with Pulmonary Disease, Chronic Obstructive, run by AstraZeneca at 26 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in Germany, Canada, Hungary, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Trough Functional Residual Capacity (FRC) After 4 Weeks of Treatment (time frame: Baseline and Week 4). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02424344, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2018.