Safety, Tolerability and Pharmacokinetics of Tiotropium in Cystic Fibrosis Patients

NCT02172534 | Completed Phase 1

• 1 other identifier: 205.338
• Study Type: interventional
• Target: 113
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (8)

• Changes from baseline in physical examination

  Baseline, Day 1 and 28

• Changes from baseline in blood pressure

  Baseline, Day 1 and 28

• Changes from baseline in pulse rate

  Baseline, Day 1 and 28

• Changes from baseline in laboratory evaluation

  Baseline, Day 28

• Occurrence of Adverse Events

  up to 59 days

• Change in FEV1 (Forced expiratory volume in one second)

  Pre-dose and 0.5, 1 and 2 hours after treatment on Day1 and 28

• Change in FVC (Forced vital capacity)

  Pre-dose and 0.5, 1 and 2 hours after treatment on Day1 and 28

• Change in FEF25-75% (Forced Expiratory Flow)

  Pre-dose and 0.5, 1 and 2 hours after treatment on Day1 and 28

Secondary Outcomes (30)

• Cmax (maximum concentration of the analyte in plasma) after the first dose of 2.5 μg tiotropium bromide

  Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day1

• tmax (time from dosing to maximum concentration) after the first dose of 2.5 μg tiotropium bromide

  Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day1

• AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point within the first dosing of 2.5 μg tiotropium bromide interval)

  Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day1

• Aet1-t2 (amount of analyte that is eliminated in urine from the time point t1 to time point t2) after the first dose of 2.5 μg tiotropium bromide

  Pre-dose and 0-2, 2-4 and 4-8 hours after treatment on Day1

• fet1-t2 (fraction of analyte excreted in urine from time point t1 to t2) after the first dose of 2.5 μg tiotropium bromide

  Pre-dose and 0-2, 2-4 and 4-8 hours after treatment on Day1

Study Arms (6)

Tiotropium bromide low

EXPERIMENTAL

Single dose: 2.5 µg Tiotropium

Drug: Tiotropium bromide low

Tiotropium bromide medium

EXPERIMENTAL

Single dose: 5 µg Tiotropium

Drug: Tiotropium bromide medium

Tiotropium bromide high

EXPERIMENTAL

Single dose: 10 µg Tiotropium

Drug: Tiotropium bromide high

Tiotropium bromide low (28 days)

EXPERIMENTAL

multiple dose: 2.5 µg Tiotropium

Drug: Tiotropium bromide low

Tiotropium bromide medium (28 days)

EXPERIMENTAL

Multiple dose: 5 µg Tiotropium

Drug: Tiotropium bromide medium

Placebo

PLACEBO COMPARATOR

single or multiple dose of Placebo

Drug: Placebo

Interventions

Tiotropium bromide low DRUG

Tiotropium bromide low; Tiotropium bromide low (28 days)

Tiotropium bromide medium DRUG

Tiotropium bromide medium; Tiotropium bromide medium (28 days)

Tiotropium bromide high DRUG

Tiotropium bromide high

Placebo DRUG

Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2014
• First Posted: June 24, 2014
• Study Start: September 1, 2006
• Primary Completion: September 1, 2008
• Last Updated: June 24, 2014

Record last verified: 2014-06