Effect of tiotropium + olodaterol on breathlessness in COPD patients

• Register: EUCTR
• Last refreshed on: 30 October 2017
• Main ID: EUCTR2015-002974-20-BE
• Date of registration: 03/06/2016
• Prospective Registration: Yes
• Primary sponsor: SCS Boehringer Ingelheim Comm. V
• Public title: Effect of tiotropium + olodaterol on breathlessness in COPD patients
• Scientific title: A randomised, double-blind, cross-over study to evaluate the effect of 6 weeks treatment of orally inhaled tiotropium + olodaterol fixed dose combination (5/5 µg) compared with tiotropium (5 µg), both delivered by the Respimat® Inhaler, on breathlessness during the three minute Constant Speed Shuttle Test (3min CSST) in patients with Chronic Obstructive Pulmonary Disease (COPD). - OTIVATO TM
• Date of first enrolment: 04/08/2016
• Target sample size: 102
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002974-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Belgium, Canada, Germany, Netherlands

Contacts

• Name: QRPE PSC CT Information Disclosure
• Affiliation: Boehringer Ingelheim

• Name: QRPE PSC CT Information Disclosure
• Affiliation: Boehringer Ingelheim

Key inclusion & exclusion criteria

Inclusion criteria:
- All patients must sign an informed consent consistent with International Conference on Harmonization - Good Clinical Practice (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:
Patients must have relatively stable airway obstruction with a post-bronchodilator 30% <= FEV1 <80% of predicted normal (ECSC); GOLD 2 - 3, and a postbronchodilator FEV1/FVC <0.70 at visit 1.
- Male or female patients, between 40 and 75 years of age (inclusive) on day of signing informed consent.
- Patients must be current or ex-smokers with a smoking history of more than 10 pack-years. Patients who have never smoked cigarettes must be excluded.
- Patients with a score on the Baseline Dyspnea Index (BDI) < 8 at visit 0.
- Patients with hyperinflation at rest, defined as FRC > 120% predicted at visit 1.
- BORG dyspnea score >=4 at the end of 3min CSST at visit 2
- Patients must be able to perform technically acceptable pulmonary function tests (spirometry and body plethysmography), must be able to complete multiple shuttle walk tests during the study period as required in the protocol.
- Patients must be able to inhale medication in a competent manner from the Respimat® inhaler and from a metered dose inhaler (MDI).

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 71
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 31

Exclusion criteria:
- Patients with a significant disease other than COPD; a significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the study, (ii) influence the results of the study, or (iii) cause concern regarding the patient's ability to participate in the study
- Patients with a, in the opinion of the investigator, clinically relevant abnormal baseline haematology, blood chemistry, or creatinine >x2 ULN will be excluded regardless of clinical condition.
- Patients with a current documented diagnosis of asthma. For patients with allergic rhinitis or atopy, source documentation is required to verify that the patient does not have asthma.
- Patients with a COPD exacerbation in the 6 weeks prior to screening (visit 1).
- A diagnosis of thyrotoxicosis (due to the known class side effect profile of B2-agonists)
- A history of myocardial infarction within 6 months of screening visit (visit 1)
- Life-threatening cardiac arrhythmia as judged by the Investigator.
- Known active tuberculosis
- Any malignancy unless free of disease for at least 5 years (patients with treated basal cell carcinoma or squamous cell skin cancers are allowed)
- A history of cystic fibrosis
- Clinically relevant bronchiectasis, as judged by the Investigator.
- Patients with severe emphysema requiring endobronchial interventions within 6 months prior to screening.
- A history of significant alcohol or drug abuse, as judged by the investigator.
- Any contraindications for exercise testing as outlined below.
- Patients who have undergone thoracotomy with pulmonary resection (patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1).
- Patients being treated with any oral or patch ß-adrenergics
- Patients being treated with oral corticosteroid medication at unstable doses (i.e., less than four 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 (not limited to exacerbation infection) 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 regularly use daytime oxygen therapy for more than one hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy during clinic visits
- Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the screening visit (visit 1) or patients who are currently in a pulmonary rehabilitation program.
- Patients who have a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnea, such as arthritis in the leg, angina pectoris or claudication or morbid obesity.
- Patients with an endurance time >=12 minutes during the incremental shuttle walk test (visit1).
- Patients with oxygen saturation < 85% (on room air) at rest or during exercise.
- Patients who have taken an investigational drug within one month or six half-lives (whichever is greater) or in case the investigational drug (sub) class is listed within the washout period specified prior to screening visit (visit 1)
- Patients with known hypersensitivity to ß-adrenergics and/or anticholinergic drugs, BAC,

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with moderate to severe Chronic Obstructive Pulmonary Disease according to the GOLD guidelines.
MedDRA version: 19.0 Level: LLT Classification code 10009026 Term: Chronic obstructive airways disease System Organ Class: 100000004855

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Trade Name: Spiolto Respimat 2.5 microgram/2.5 microgram, inhalation solution
Product Name: Tiotropium 2.5 µg/Olodaterol 2.5µg Fixed dose combination
Pharmaceutical Form: Inhalation solution
INN or Proposed INN: Tiotropium
CAS Number: 186691-13-4
Other descriptive name: TIOTROPIUM
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 2.5-
INN or Proposed INN: Olodaterol
CAS Number: 868049-49-4
Other descriptive name: OLODATEROL
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 2.5-

Trade Name: Spiriva Respimat 2.5 microgram, inhalation solution
Product Name: Tiotropium 2.5 µg
Pharmaceutical Form: Inhalation solution
INN or Proposed INN: Tiotropium
CAS Number: 186691-13-4
Other descriptive name: TIOTROPIUM
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 2.5-

Primary Outcome(s)

Main Objective: To evaluate the effect of tiotropium + olodaterol FDC compared to tiotropium monotherapy on the intensity of breathlessness during the 3 min CSST.

Primary end point(s): 1: The change from baseline in intensity of breathlessness measured using the Modified Borg Scale (MBS-S) at the end of the 3 minute Constant Speed Shuttle Test

Timepoint(s) of evaluation of this end point: 1: 6 weeks

Secondary Objective: To explore the relationship between reductions in breathlessness during the 3min CSST and reductions in breathlessness during activities of everyday living as measured by the dyspnea domain of the Chronic Respiratory Questionnaire (CRQ) following bronchodilator therapy.

Secondary Outcome(s)

Secondary end point(s): 1: Change from baseline in 1 hour post-dose FEV1

2: Change from baseline in 1 hour post-dose FVC

3: Change from baseline in Inspiratory capacity (IC) measured prior to exercise

4: Change in Chronic Respiratory Questionnaire - Self Administered Individualized (CRQ-SAI) dyspnea domain score

5: Change from baseline in intensity of Breathlessness (MBS-S) at 1min, 2min and 2.5min during the 3min CSST

6: Change in Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS) dyspnea domain score

7: Change from baseline in IC measured at the end of exercise

Timepoint(s) of evaluation of this end point: 1: 6 weeks

2: 6 weeks

3: 6 weeks

4: 6 weeks

5: 6 weeks

6: 6 weeks

7: 6 weeks

Secondary ID(s)

1237.28

Source(s) of Monetary Support

SCS Boehringer Ingelheim Comm. V