Trial record 2 of 3 for:    spiriva | cystic fibrosis

Safety, Tolerability and Pharmacokinetics of Tiotropium in Cystic Fibrosis Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT02172534
First received: June 20, 2014
Last updated: NA
Last verified: June 2014
History: No changes posted
  Purpose

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


Condition Intervention Phase
Cystic Fibrosis
Drug: Tiotropium bromide low
Drug: Tiotropium bromide medium
Drug: Tiotropium bromide high
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Changes from baseline in physical examination [ Time Frame: Baseline, Day 1 and 28 ] [ Designated as safety issue: No ]
  • Changes from baseline in blood pressure [ Time Frame: Baseline, Day 1 and 28 ] [ Designated as safety issue: No ]
  • Changes from baseline in pulse rate [ Time Frame: Baseline, Day 1 and 28 ] [ Designated as safety issue: No ]
  • Changes from baseline in laboratory evaluation [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]
  • Occurrence of Adverse Events [ Time Frame: up to 59 days ] [ Designated as safety issue: No ]
  • Change in FEV1 (Forced expiratory volume in one second) [ Time Frame: Pre-dose and 0.5, 1 and 2 hours after treatment on Day1 and 28 ] [ Designated as safety issue: No ]
  • Change in FVC (Forced vital capacity) [ Time Frame: Pre-dose and 0.5, 1 and 2 hours after treatment on Day1 and 28 ] [ Designated as safety issue: No ]
  • Change in FEF25-75% (Forced Expiratory Flow) [ Time Frame: Pre-dose and 0.5, 1 and 2 hours after treatment on Day1 and 28 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cmax (maximum concentration of the analyte in plasma) after the first dose of 2.5 μg tiotropium bromide [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day1 ] [ Designated as safety issue: No ]
  • tmax (time from dosing to maximum concentration) after the first dose of 2.5 μg tiotropium bromide [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day1 ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day1 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Pre-dose and 0-2, 2-4 and 4-8 hours after treatment on Day1 ] [ Designated as safety issue: No ]
  • fet1-t2 (fraction of analyte excreted in urine from time point t1 to t2) after the first dose of 2.5 μg tiotropium bromide [ Time Frame: Pre-dose and 0-2, 2-4 and 4-8 hours after treatment on Day1 ] [ Designated as safety issue: No ]
  • AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time interval t1 to t2) after the first dose of 5 μg and 10 μg tiotropium bromide [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day1 ] [ Designated as safety issue: No ]
  • AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) after the first dose of 5 μg and 10 μg tiotropium bromide [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day1 ] [ Designated as safety issue: No ]
  • %AUCtz-∞ (the percentage of the AUC 0-∞ that is obtained by extrapolation) after the first dose of 5 μg and 10 μg tiotropium bromide [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day1 ] [ Designated as safety issue: No ]
  • λz (terminal rate constant of the analyte in plasma) after the first dose of 5 μg and 10 μg tiotropium bromide [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day1 ] [ Designated as safety issue: No ]
  • t½ (terminal half-life of the analyte in plasma) after the first dose of 5 μg and 10 μg tiotropium bromide [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day1 ] [ Designated as safety issue: No ]
  • MRTih (mean residence time of the analyte in the body after inhalation) after the first dose of 5 μg and 10 μg tiotropium bromide [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day1 ] [ Designated as safety issue: No ]
  • CL/F (apparent clearance of the analyte in the plasma after extravascular administration) after the first dose of 5 μg and 10 μg tiotropium bromide [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day1 ] [ Designated as safety issue: No ]
  • Vz/F (apparent volume of distribution of the analyte during the terminal phase λz following an extravascular dose) after the first dose of 5 μg and 10 μg tiotropium bromide [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day1 ] [ Designated as safety issue: No ]
  • CLR,t1- t2 (renal clearance of the analyte in plasma from the time point t1 to time point t2) after the first dose of 5 μg and 10 μg tiotropium bromide [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day1 ] [ Designated as safety issue: No ]
  • Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day 28 ] [ Designated as safety issue: No ]
  • tmax,ss (time from last dosing to maximum concentration of the analyte in plasma at steady state) [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day 28 ] [ Designated as safety issue: No ]
  • Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day 28 ] [ Designated as safety issue: No ]
  • Cpre,ss(predose concentration of the analyte in plasma at steady state immediately before administration of the next dose) [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day 28 ] [ Designated as safety issue: No ]
  • AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ) [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day 28 ] [ Designated as safety issue: No ]
  • λz,ss (terminal rate constant in plasma at steady state) [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day 28 ] [ Designated as safety issue: No ]
  • t1/2,ss (terminal half-life of the analyte in plasma at steady state) [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day 28 ] [ Designated as safety issue: No ]
  • MRTih,ss (mean residence time of the analyte in the body after 14 administrations at steady state) [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day 28 ] [ Designated as safety issue: No ]
  • CL/F,ss (apparent clearance of the analyte in the plasma at steady state following extravascular multiple dose administration) [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day 28 ] [ Designated as safety issue: No ]
  • Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following extravascular administration) [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day 28 ] [ Designated as safety issue: No ]
  • Aet1-t2,ss (amount of analyte that is eliminated in urine at steady state from the time point t1 to time point t2) [ Time Frame: Pre-dose and 0-2, 2-4 and 4-8 hours after treatment on Day 28 ] [ Designated as safety issue: No ]
  • fet1-t2,ss (fraction of analyte eliminated in urine at steady state from time point t1 to time point t2) [ Time Frame: Pre-dose and 0-2, 2-4 and 4-8 hours after treatment on Day 28 ] [ Designated as safety issue: No ]
  • CLR,t1-t2,ss (renal clearance of the analyte in plasma from the time point t1 until the time point t2 at steady state) [ Time Frame: Pre-dose and 5, 15, 30 min and 1, 2, 4, 6 hours after treatment on Day 28 ] [ Designated as safety issue: No ]
  • Accumulation Ratio (R)A,Cmax,28 based on Cmax [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Accumulation Ratio (R)A,AUC,28 based on AUC0-τ [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Linearity index (LI) [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Enrollment: 113
Study Start Date: September 2006
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tiotropium bromide low
Single dose: 2.5 µg Tiotropium
Drug: Tiotropium bromide low
Experimental: Tiotropium bromide medium
Single dose: 5 µg Tiotropium
Drug: Tiotropium bromide medium
Experimental: Tiotropium bromide high
Single dose: 10 µg Tiotropium
Drug: Tiotropium bromide high
Experimental: Tiotropium bromide low (28 days)
multiple dose: 2.5 µg Tiotropium
Drug: Tiotropium bromide low
Experimental: Tiotropium bromide medium (28 days)
Multiple dose: 5 µg Tiotropium
Drug: Tiotropium bromide medium
Placebo Comparator: Placebo
single or multiple dose of Placebo
Drug: Placebo

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02172534     History of Changes
Other Study ID Numbers: 205.338
Study First Received: June 20, 2014
Last Updated: June 20, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Tiotropium
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases
Bromides
Anti-Asthmatic Agents
Anticonvulsants
Autonomic Agents
Bronchodilator Agents
Central Nervous System Agents
Cholinergic Agents
Cholinergic Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Parasympatholytics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014