Tiotropium-bromide in cystic fibrosis

• Register: EUCTR
• Last refreshed on: 9 October 2012
• Main ID: EUCTR2010-019802-17-GB
• Date of registration: 10/08/2010
• Prospective Registration: Yes
• Primary sponsor: Boehringer Ingelheim Limited
• Public title: Tiotropium-bromide in cystic fibrosis
• Scientific title: A randomised, double-blind, placebo-controlled parallel-group trial to confirm the efficacy after 12 weeks and the safety of tiotropium 5 µg administered once daily via the Respimat® device in patients with cystic fibrosis. -
• Date of first enrolment: 22/10/2010
• Target sample size: 471
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019802-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Hungary, Ireland, Israel, Italy, Poland, Portugal, Russian Federation, Slovakia, South Africa, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: Processes and Systems Coordination
• Affiliation: Boehringer Ingelheim Pharma GmbH & Co KG

• Name: Processes and Systems Coordination
• Affiliation: Boehringer Ingelheim Pharma GmbH & Co KG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients with a documented diagnosis of CF (positive sweat chloride =60 mEq/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF phenotype.
2. Male or female patients (children less than 12 years and adolescents = 12 years). Patients below 1 year of age, if eligible, can be included in the trial only for safety assessment.
3. Patients = 5 years of age must be able to perform acceptable spirometric maneuvers, according to the American Thoracic Society (ATS) standards.
4. Pre-bronchodilator FEV1 >25% of predicted values:
•pediatric/adolescent (= 5 years up to 18 years of age, inclusive) predicted equations from: Wang X et al.
•adult (>18 years) predicted equations from: Knudson RJ et al. Changes in normal maximal expiratory flow-volume curve with growth.
5. Patients must be able to inhale medication in a reproducible manner from the Respimat® inhaler and from a metered dose inhaler (MDI) for children of 5 years and above. For children below 5 years, patients must be able to inhale medication in a reproducible manner from the Respimat® inhaler with spacer (the Aerochamber plus® holding chamber with facemask).
6. Pre-bronchodilator FEV1 at Visit 2 must be within 15% of FEV1 at Visit 1. If pre-bronchodilator FEV1 at Visit 2 is not within 15% of FEV1 at Visit 1, Visit 2 can be repeated within 7 days and rescheduled once.
7. Investigator should also ascertain that the patient is symptomatically stable as defined by:
•no evidence of acute upper or lower respiratory tract infection within 2 weeks of screening (Visit 1).
. no pulmonary exacerbation requiring use of i.v./oral/inhaled antibiotics, or oral corticosteroids within 2 weeks of screening (Visit 1).
8. The patient or the patient’s legally acceptable representative must be able to give informed consent in accordance with International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines and local regulation prior to participation in the trial (i.e. prior to any study procedures, including any pre-study washout of medication and medication restrictions for pulmonary function test at Visit1).
9. Patients who are on a cycling TOBI® regimen must have completed at least 2 cycles every other month TOBI® administration prior to the screening visit. The last TOBI® cycle should have been completed 2 weeks before randomisation visit (visit 2). For other inhaled antibiotics (e.g., colistin, aztreonam), please contact the local clinical monitor (CML) for guidance. For TOBI® cycling during the trial please refer to section 4.2.1.2.
10. Patients who are on daily inhaled antibiotic use must be stabilized for at least 6 weeks prior to Visit 1 (screening).
11. Patients having previously participated in study 205.339 can also be selected.

Are the trial subjects under 18? yes
Number of subjects for this age range: 180
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 275
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion criteria:
1. Patients with a known hypersensitivity to study drug or its components
2. Patients who have participated in another study with an Investigational drug within one month preceding the screening visit.
3. Patients who are currently participating in another trial. Observational studies are allowed. Permission should be obtained from sponsor of other study.
4. Patients with known relevant substance abuse, including alcohol or drug abuse. The intention of this criterion is to exclude patients who are considered to be at risk of not complying with or abusing the trial medication administration directives.
5. Adolescent and adult female patients who are pregnant or lactating, including females who have a positive serum pregnancy test at screening (pregnancy tests will be performed for all adolescent and adult females of child bearing potential).
6. Female patients of child bearing potential who are not using a medically approved form of contraception. The ICH (M3) defined highly effective methods of birth control as those, alone or in combination, that result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. For patients using a hormonal contraceptive method, information regarding the product under evaluation and its potential effect on the contraceptive should be addressed. Barrier contraceptives (e.g. male condom or diaphragm) are acceptable if used in combination with spermicides (e.g. foam gel).Refer to ICH Topic M3 provided in the ISF.
7. Patients who have started a new chronic medication for CF within 2 weeks before the screening visit (Visit 1).
8. Clinically significant disease or medical condition other than CF or CF-related conditions that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data. This includes but is not limited to significant haematological, hepatic, renal, cardiovascular, and neurologic disease. Patients with diabetes may participate if their disease is under good control prior to screening. This criterion provides an opportunity for the investigator to exclude patients based on clinical judgment, even if other eligibility criteria are satisfied.



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

Health Condition(s) or Problem(s) studied

Cystic Fibrosis
MedDRA version: 14.1 Level: SOC Classification code 10010331 Term: Congenital, familial and genetic disorders System Organ Class: 10010331 - Congenital, familial and genetic disorders

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

Intervention(s)

Trade Name: Spiriva Respimat 2.5 microgram, solution for inhalation
Product Name: Spiriva Respimat 2.5 mcg
Product Code: Tiotropium Respimat
Pharmaceutical Form: Inhalation vapour, solution
CAS Number: 411207313
Current Sponsor code: Ba 679 Br
Other descriptive name: TIOTROPIUM BROMIDE MONOHYDRATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 3.124-
Pharmaceutical form of the placebo: Inhalation vapour
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Main Objective: The primary objective is to confirm the 12-week efficacy and superiority of tiotropium 5 µg compared to placebo and to provide safety data over a minimum of 6 months.

Secondary Objective: • Change from baseline in percent predicted forced vital capacity (FVC) (AUC0-4H) at 12 weeks.
• Change from baseline in percent predicted trough FVC at 12 weeks.
• Change from baseline in pre-bronchodilator mean forced expiratory flow between 25 -75% of FVC (FEF25-75) at 12 weeks.
• Proportion of patients with at least 1 pulmonary exacerbation during the treatment period as assessed by the Respiratory and Systemic Symptoms Questionnaire (RSSQ); using the definition as given in Fuchs et al.
•Change from baseline in Cystic fibrosis Questionnaire revised (CFQ-R) at 12 weeks.

Timepoint(s) of evaluation of this end point: •at 12 weeks
•at 12 weeks

Primary end point(s): The co-primary endpoints for this trial are:

•Change from baseline in percent predicted forced expiratory volume in one second (FEV1) area under the curve (AUC0-4H) after 12 weeks.

•Change from baseline in percent predicted trough FEV1at 12 weeks.

Secondary Outcome(s)

Secondary end point(s): • Change from baseline in percent predicted forced vital capacity (FVC) (AUC0-4H) at 12 weeks.
• Change from baseline in percent predicted trough FVC at 12 weeks.
• Change from baseline in pre-bronchodilator mean forced expiratory flow between 25 -75% of FVC (FEF25-75) at 12 weeks.
• Proportion of patients with at least 1 pulmonary exacerbation during the treatment period as assessed by the Respiratory and Systemic Symptoms Questionnaire (RSSQ)
• Change from baseline in Cystic fibrosis Questionnaire revised (CFQ-R) at 12 weeks.

Timepoint(s) of evaluation of this end point: • at 12 weeks.
• at 12 weeks.
• at 12 weeks.
• between randomization visit and last patient last visit
• at 12 weeks.

Secondary ID(s)

205.438

2010-019802-17-PT

Source(s) of Monetary Support

Boehringer Ingelheim Limited