Safety, Tolerability and Pharmacokinetics of Tiotropium in Cystic Fibrosis Patients

A Randomized, Double-blind Within Dose, Placebo-controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of Increasing Single and Multiple Doses (28-day Dosing) of Tiotropium Bromide Administered Once Daily Via the Respimat® Device in Cystic Fibrosis Patients

Study to obtain information about the safety and tolerability of tiotropium bromide administered via the Respimat® inhalation device in pediatric (≤11 y.o.) and adolescent/adult (≥12 y.o.) cystic fibrosis (CF) patients after single and multiple doses as well as to obtain pharmacokinetic data for tiotropium in CF patients after single and multiple doses

Inclusion Criteria:

• Male or female patients (pediatric ≤11 years; adolescent / adult ≥12 years)

• 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

• Able to perform acceptable spirometric maneuvers, according to ATS (American Thoracic Society) standards

• FEV1 >25% of predicted values

• Patients must be able to inhale medication in a reproducible manner from the Respimat® inhaler and from a metered dose inhaler (MDI)

• Clinical stability:

  • no evidence of acute upper or lower respiratory tract infection within 4 weeks of screening
  • no pulmonary exacerbation requiring use of i.v./oral/inhaled antibiotics, or oral corticosteroids within 4 weeks of screening
  • FEV1 at Visit 2 must be within 10% of FEV1 at Visit 1. If FEV1 at Visit 2 is not within 10% of FEV1 at Visit 1, Visit 2 may be re-scheduled once within 7 days

• 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

• Patients taking a chronic medication must be willing to continue this therapy for the entire duration of the study

Exclusion Criteria:

• Patients with a significant history of allergy / hypersensitivity (including medication allergy) which is deemed relevant to the trial as judged by the Investigator. "Relevance" in this context refers to any increased risk of hypersensitivity reaction to trial medication
• Patients with a known hypersensitivity to study drug or its components
• Patients who have participated in another study with an Investigational drug within one month or six half-lives (whichever is greater) preceding the screening visit
• Patients who are currently participating in another trial. Observational studies are allowed. Permission should be obtained from the sponsor of the study
• Patients with known relevant substance abuse, including alcohol or drug abuse. The intention of this criterion was to exclude patients who are considered to be at risk of not complying with or abusing the trial medication administration directives.
• Female patients who are pregnant or lactating, including females who have a positive urine pregnancy test at screening (pregnancy tests were performed for all females of child bearing potential)
• Female patients of child bearing potential who are not using a medically approved form of contraception.
• Patients with documented persistent colonization with B. cepacia (defined as more than one positive culture within the past year). The intention of this exclusion criterion is to be consistent with the current policy within the CF community for reducing the risk of B. cepacia cross infection.
• Patients who have started a new chronic medication for CF within four (4) weeks of screening. Patients who are on a cycling TOBI® (Tobramycin treatment) regimen must have completed at least three (3) cycles of every other month TOBI® administration prior to the screening visit. As there are other cycles used with TOBI®, the clinical monitor should be consulted before the patient was enrolled.
• 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 included significant hematological, hepatic, renal, cardiovascular, and neurologic disease. Patients with diabetes could 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.