The aim of this study is to demonstrate that once daily treatment with tiotropium + olodaterol fixed dose combination will reduce the number of exacerbations over tiotropium 5 µg monotherapy.A secondary aim of the study is an assessment of a…
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Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint:
- Annualised rate of moderate to severe COPD exacerbation during the treatment
period (within 1 day after the last drug administration date).
Secondary outcome
Key secondary endpoint
- Time to first moderate to severe COPD exacerbation during the treatment
period (within 1 day after the last drug administration date)
Other secondary endpoints
- Annualised rate of exacerbation leading to hospitalisation during the
treatment period (within 1 day after the last drug administration date)
- Time to first COPD exacerbations leading to hospitalisation during the
treatment period (within 1 day after the last drug administration date)
- Time to all-cause mortality (within 1 day after the last drug administration
date)
Other endpoints
- Time to first moderate to severe COPD exacerbation requiring treatment with
systemic corticosteroids (within 1 day after the last drug administration date).
- Time to first moderate to severe COPD exacerbation requiring treatment with
antibiotics (within 1 day after the last drug administration date).
- Time to first moderate to severe COPD exacerbation requiring treatment with
ystemic corticosteroids and antibiotics (within 1 day after the last drug
administration date).
- Annualised rate of COPD exacerbation requiring systemic corticosteroids
(within 1 day after the last drug administration date).
- Annualised rate of COPD exacerbation requiring antibiotics (within 1 day
after the last drug administration date).
- Annualised rate of COPD exacerbation requiring systemic corticosteroids and
antibiotics (within 1 day after the last drug administration date).
- Annualised rate of all COPD exacerbation (within 1 day after the last drug
administration date).
- COPD Assessment Test* (CAT) score at clinic visits
Background summary
According to the GOLD guidelines, exacerbations are important events in the
course of COPD as they have major impact on the patient`s quality of life and
cause an increase in symptoms and a deterioration of lung function that may
take several weeks to recover from.
Moreover an exacerbation will accelerate the decline of lung function and is
associated with significant mortality, especially if a hospitalisation is
needed. It is without doubt, that exacerbations are associated with significant
socioeconomic costs.
The benefits of tiotropium + olodaterol FDC that have been studied in the Phase
III program include improvements in lung function, quality of life, dyspnea and
exercise endurance time, but the benefit on exacerbations has not formally been
assessed.
Study objective
The aim of this study is to demonstrate that once daily treatment with
tiotropium + olodaterol fixed dose combination will reduce the number of
exacerbations over tiotropium 5 µg monotherapy.
A secondary aim of the study is an assessment of a potential impact of
tiotropium + olodaterol FDC on hospitalisation associated with exacerbations
and survival, as compared to tiotropium 5 µg monotherapy. The latter will be
included as secondary endpoints.
Study design
This is a randomised, double-blind, active-controlled parallel group study to
evaluate the effect of 52 weeks of once daily treatment of orally inhaled
tiotropium + olodaterol fixed dose combination compared with tiotropium on
Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with
severe to very severe COPD and with one or more moderate to severe COPD
exacerbation during the previous 12 months.
The study is multinational and involves at least 55 participating countries.
The recruitment period is approximately 12 to 14 months.
The trial consists of three consecutive study periods including the screening,
the treatment and follow-up periods.
Having obtained the signed informed consent, the patient will be entered in a 2
to 7-day screening period to confirm the patient*s eligibility. At Visit 2
after a successful review of the inclusion and exclusion criteria, the patient
will be randomly allocated in equal ratio to receive once daily study treatment:
i. Tiotropium + olodaterol FDC (2.5 µg / 2.5 µg per actuation) inhalation
solution
ii. Tiotropium (2.5 µg / per actuation) inhalation solution (control group)
and will then enter the 52-week treatment phase. The randomised treatment
period consists of 5 every 3-month clinic visits and in the interim a telephone
contact will be scheduled every 6 weeks.
The treatment period will be achieved with the completion of visit 6 including
the End of Treatment (EoT) information.
The patient*s trial participation will be concluded with the completion of the
follow-up visit 21 days (3 weeks) after V6/EoT visit.
In Addition a sub-study will be done.
In total 854 patients will participate, with 20 patients in the Netherlands at
5 sites.
Participating sites in The Netherlands are:
* Amphia Ziekenhuis in Breda, PI dr. Djamin
* Catharina Ziekenhuis in Eindhoven, PI dr. Wielders
* Gelre Ziekenhuis in Zutphen, PI dr. Goosens
* Westfriesgasthuis in Hoorn, PI dr. Roeleveld
* ZGT Almelo in Almelo, PI dr. Sinninghe Damste
Patients will come for 2 additional visits to site; visit 0 and visit 6a.
Visit 0 will be used to inform patients and to instruct them on the
requirements for the spirometry at visit 1.
At visits 2, 3, 4, 5, en 6 spirometry will be done 5 minutes before inhalation
of trial medication and 1, 2 and 3 uur after inhalation. At the extra visit 6A
an additional spirometry will be done at 23 hours and 55 minutes after
inhalatie (at visit 6).
Intervention
Bronchodilator therapy; during 52 weeks a once daily inhalation of
studymedication with the Respimat® Inhaler with one of the following treatments:
1. tiotropium + olodaterol (5 µg/5 µg) fixed dose combination inhalation
solution
2. tiotropium (5 µg) inhalation solution
Patients will also undergo/ need to:
- Laboratory tests
- Completing several different patient questionnaires during study visits
- ECG
- 3- monthly telephone calls to check on health status
Patienten participating in the sub-study will have additional spirometry tests.
Study burden and risks
Tiotropium monotherapy is a well established maintenance treatment for patients
with COPD across all severities. The clinical trials conducted to date have
shown tiotropium + olodaterol FDC to be a safe, well tolerated and efficacious
combination therapy according to treatment guidelines in a moderate to very
severe COPD patient population (including patients with concomitant
cardiovascular diseases). The observed incremental bronchodilator response for
the
combination compared to the individual components translated into benefits that
were meaningful to the patient, with improvements in several patient centred
outcomes. Potential risks associated with administration of tiotropium include
the listed (expected) adverse events for tiotropium monoproduct.
Potential risks associated with administration of the combination of tiotropium
and olodaterol include the listed (expected) adverse events for tiotropium +
olodaterol FDC. Women of childbearing potential may be included in clinical
trials for tiotropium + olodaterol provided appropriate precautions are taken
to minimize the risk of pregnancy. These precautions include pregnancy testing
and use of a highly effective method of birth control. Continued testing and
monitoring during the trial should be sufficient to ensure compliance with the
measures not to become pregnant during the period of drug exposure (which may
exceed the length of study until the follow-up visit at 21 days after
discontinuation of study
medication).
Comeniusstraat 6
Alkmaar 1817 MS
NL
Comeniusstraat 6
Alkmaar 1817 MS
NL
Listed location countries
Age
Inclusion criteria
- All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions.
- All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:
* stable airway obstruction with a post-bronchodilator FEV1< 60% of predicted normal
* and a postbronchodilator FEV1/FVC <70% documented at Visit 1
- Patients with a documented history of at least one moderate to severe COPD exacerbation in the previous 12 months requiring treatment with systemic corticosteroids and/or antibiotics and/or related hospitalization.
- Investigator should also ascertain that the patient is symptomatically stable as defined by:
* no evidence of COPD exacerbation requiring use of either antibiotics and/or steroids 4
weeks prior to visit 1,
* no evidence of change in their usual COPD medication 4 weeks prior to visit 1.
- Male or female patients, 40 years of age or older.
- Patients must be current or ex-smokers with a smoking history of more than 10 pack years.
- Patients must be able to perform all trial related procedures at the investigator discretion
including:
* technically acceptable and eligible pulmonary function test (if performed at site)
* vital status follow-up in case of discontinuation until the predicted exit date (i.e.: 52 weeks from first intake of randomised treatment + 21 days).
* COPD exacerbation interview every 6 weeks in case of premature discontinuation until the predicted exit date (i.e.: 52 weeks from first intake of randomised treatment + 21 days).
- Patients must be able to inhale medication in a competent manner from the Respimat®
inhaler (Appendix 10.1), and from a metered dose inhaler (MDI) in the opinion of the
investigator.
Exclusion criteria
- Patients with a significant disease other than chronic obstructive pulmonary disease.
- Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis.
- Patients with a corrent documented diagnosis of asthma.;Patients with one of the following conditions:
- A diagnosis of thyrotoxicosis (due to the known class side effect profile of ß2-agonists)
- A history of myocardial infarction within 6 months of screening visit.
- Life-threatening cardiac arrhythmia.
- Known active tuberculosis.
- A malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years.
- A history of cystic fibrosis.
- Clinically relevant bronchiectasis.
- Patients with severe emphysema requiring endobronchial interventions within 6 months
prior to screening
- A history of significant alcohol or drug abuse.
- Patients who have undergone thoracotomy with pulmonary resection.;- Patients being treated with any oral ß-adrenergics.
- Patients being treated with oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day.
- Patients being treated with antibiotics for any reason within 4 weeks of screening visit
- Patients being treated with PDE4 inhibitors within 3 months of screening visit (e.g. roflumilast) should not be enrolled and PDE4 inhibitors should not be withdrawn for the purpose of enrolling in this study.
- Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to screening visit.
- Patients with known hypersensitivity to ß-adrenergics drugs, anticholinergic drugs, benzalkonium chloride, disodium edentat, or any other component of the Respimat® inhalation solution delivery system.
- Pregnant or nursing women.
- Women of childbearing potential not using highly effective methods of birth control.
- Patients who have previously been randomized in this study or are currently participating in another study.
- Patients who are unable to comply with pulmonary medication restrictions prior to randomization.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-002275-28-NL |
| ClinicalTrials.gov | NCT02296138 |
| CCMO | NL50456.060.14 |