Efficacy and Safety of 3 Doses of Tiotropium Compared to Placebo in Adolescents (12 to 17 Yrs) With Moderate Asthma

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01122680
First received: May 11, 2010
Last updated: May 7, 2014
Last verified: July 2012
  Purpose

The primary objective of this trial is to evaluate the efficacy and safety of tiotropium 1.25 mcg (2 actuations of 0.625 mcg), tiotropium 2.5 mcg (2 actuations of 1.25 mcg) and tiotropium 5 mcg (2 actuations of 2.5 mcg) once daily in the evening delivered by the Respimat inhaler in adolescents (12 to 17 yrs) with moderate persistent asthma, compared to placebo and on top of maintenance therapy with an inhaled corticosteroid controller medication. It is a randomised, double-blind, placebo-controlled Phase II trial with incomplete cross-over design. Patients need to be still symptomatic, i. e. not fully controlled with their maintenance treatment.


Condition Intervention Phase
Asthma
Drug: Tiotropium bromide
Drug: tiotropium bromide
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase II Randomised, Double-blind, Placebo-controlled, Incomplete Crossover Trial With 4-week Treatment Periods to Evaluate Efficacy and Safety of Tiotropium Inhalation Solution (Doses of 1.25 µg, 2.5 µg and 5 µg) Delivered Via Respimat® Inhaler Once Daily in the Evening in Adolescents (12 to 17 Yrs Old) With Moderate Persistent Asthma

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Forced Expiratory Volume (FEV1) Peak (0-3h) Response [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    The FEV1 peak (0-3h) response is determined at the end of the 4 week treatment period. This is the difference between the maximum FEV1 measured within the first 3 hours post dosing and the FEV1 baseline measurement. Analysis adjusted for treatment, period, patient and baseline using a mixed model.


Secondary Outcome Measures:
  • Trough FEV1 Response [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    The trough FEV1 is defined as the pre-dose FEV1 measured just prior to the last administration of randomised treatment. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

  • FEV1 Area Under the Curve From 0 to 3 h (AUC0-3h) Response [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    FEV1 (AUC0-3h) will be calculated as the area under the curve from 0 to 3hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

  • FEV1 Individual Measurements Response at Each Time-point [ Time Frame: Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose) ] [ Designated as safety issue: No ]
    Individual FEV1 measurements at each time-point ("personal best"). Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

  • Forced Vital Capacity (FVC) Peak (0-3h) Response [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    The FVC peak (0-3h) response is determined at the end of the 4 week treatment period. This is the difference between the maximum FVC measured within the first 3 hours post dosing and the FVC baseline measurement. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

  • FVC Trough Response [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    The trough FVC response is defined as the pre-dose FVC measured just prior to the last administration of randomised treatment. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

  • FVC Area Under the Curve From 0 to 3 h (AUC0-3h) Response [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    FVC (AUC0-3h) will be calculated as the area under the curve from 0 to 3hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

  • FVC Individual Measurements at Each Time-point [ Time Frame: Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose) ] [ Designated as safety issue: No ]
    Individual FVC measurements at each time-point ("personal best"). Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

  • Forced Expiratory Flow (FEF) 25-75% Individual Measurements Response at Each Time Point [ Time Frame: Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose) ] [ Designated as safety issue: No ]
    FEF 25-75% is the mean forced expiratory flow between 25% and 75% of the FVC determined at the end of the 4-week treatment period. This is often referred to as the maximum midexpiratory flow. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

  • Mean Morning Peak Expiratory Flow (PEF) Response [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    Mean morning PEF assessed by patients at home. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

  • Mean Evening PEF Response [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    Mean evening PEF assessed by patients at home. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

  • Change From Baseline in the Number of Puffs of Rescue Medication Per Day [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    Mean number of inhalations (puffs) of unscheduled rescue salbutamol therapy during whole day. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

  • Control of Asthma as Assessed by Asthma Control Questionnaire (ACQ) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    ACQ is a questionnaire consisting of a seven point Likert scale ranging from 0 to 6, whereby 0 represents good control and 6 represents poor control of asthma. The scale describes the frequency and severity of asthma symptoms. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

  • Change From Baseline in Mean Number of Nighttime Awakenings [ Time Frame: Baseline and last week of treatment (week 4) ] [ Designated as safety issue: No ]
    Mean number of nighttime awakenings due to asthma symptoms as assessed by patients eDiary incorporated in the AM3® device. Analysis adjusted for treatment, period, patient and baseline using a mixed model.


Enrollment: 105
Study Start Date: May 2010
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A
patients inhale 2 puffs (dose of 1.25 mcg) once daily in the evening via Respimat inhaler
Drug: Tiotropium bromide
inhalation solution, dose of 1.25 mcg (2 puffs of 0.625 mcg)
Experimental: Treatment C
patients inhale 2 puffs (dose of 5 mcg) once daily in the evening via Respimat inhaler
Drug: tiotropium bromide
inhalation solution, dose of 5 mcg (2 puffs of 2.5 mcg)
Placebo Comparator: Placebo
patients inhale 2 puffs of placebo matching tiotropium once daily in the evening via Respimat inhaler
Drug: Placebo
placebo inhalation solution
Experimental: Treatment B
patients inhale 2 puffs (dose of 2.5 mcg) once daily in the evening via Respimat inhaler
Drug: tiotropium bromide
inhalation solution, dose of 2.5 mcg (2 puffs of 1.25 mcg)

  Eligibility

Ages Eligible for Study:   12 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. All patients and legally accepted caregiver(s) must sign and date an Informed Consent form consistent with Good Clinical Practice (GCP) guidelines of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and local legislation prior to participation in the trial.
  2. Male or female patients between 12 and 17 years of age.
  3. All patients must have at least a 3 months history of asthma and fulfill the diagnostic criteria of moderate persistent asthma, according to the current Global Initiative for Asthma (GINA) guidelines at the time of enrolment into the trial.
  4. All patients must have been on maintenance treatment with inhaled corticosteroids at a stable medium dose for at least 4 weeks before Visit 1.
  5. All patients must be symptomatic (partly controlled) at Visit 1 (screening) and prior to randomisation at Visit 2 as defined by an Asthma Control Questionnaire (ACQ) mean score of equal or above 1.5.
  6. All patients must have a pre-bronchodilator FEV1 above 60% and less than or equal 90% of predicted normal at Visit 1. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator) as compared to Visit 2 (pre-dose) must be within ± 30%.
  7. All patients must have an increase in FEV1 of equal or above 12% and 200 mL 15 min. after 400 mcg salbutamol (albuterol) at Visit 1. If patients in the lower age range (e.g., 12 to 14 year olds) exhibit a very small total lung volume, positive reversibility testing might be based solely on the relative (12%) post-bronchodilator response.
  8. All patients should be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment.
  9. Patients should be able to use the Respimat® inhaler correctly.
  10. Patients must be able to perform all trial related procedures including technically acceptable spirometric manoeuvres, according to American Thoracic Society (ATS) standards and the use of the electronic diary/peak flow meter.

Exclusion criteria:

  1. Patients with a significant disease other than asthma.
  2. Patients with a history of congenital or acquired heart disease, and/or have been hospitalised for cardiac syncope or failure during the past year.
  3. Patients with any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention (e. g. pacemaker implantation) or a change in drug therapy within the past year.
  4. Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years.
  5. Patients with lung diseases other than asthma, e.g. cystic fibrosis (CF). In case of ex-premature infants, a history of significant bronchopulmonary dysplasia (BPD) will be regarded as exclusion criterion
  6. Patients with significant alcohol or drug abuse within the past two years.
  7. Patients with known hypersensitivity to anticholinergic drugs, benzalkonium chloride (BAC), ethylenediaminetetraacetic acid (EDTA) or any other components of the tiotropium inhalation solution.
  8. Pregnant or nursing adolescent female patients, including female patients with a positive Beta HCG (serum pregnancy) testing at screening (visit 1).
  9. Sexually active female patients of child-bearing potential not using a highly effective method of birth control.
  10. Patients with a known narrow-angle glaucoma, or any other disease where anticholinergic treatment is contraindicated.
  11. Patients with renal impairment, as defined by a creatinine clearance less than 50 mL/min/1.73 m2 body surface area (BSA) as calculated by Schwartz Formula.
  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.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01122680

Locations
United States, Colorado
205.424.01002 Boehringer Ingelheim Investigational Site
Denver, Colorado, United States
United States, Missouri
205.424.01006 Boehringer Ingelheim Investigational Site
Columbia, Missouri, United States
205.424.01007 Boehringer Ingelheim Investigational Site
Warrensburg, Missouri, United States
United States, Nebraska
205.424.01004 Boehringer Ingelheim Investigational Site
Boys Town, Nebraska, United States
United States, Ohio
205.424.01001 Boehringer Ingelheim Investigational Site
Canton, Ohio, United States
Germany
205.424.49007 Boehringer Ingelheim Investigational Site
Koblenz, Germany
205.424.49004 Boehringer Ingelheim Investigational Site
Rosenheim, Germany
205.424.49002 Boehringer Ingelheim Investigational Site
Wesel, Germany
Latvia
205.424.37104 Boehringer Ingelheim Investigational Site
Balvi, Latvia
205.424.37103 Boehringer Ingelheim Investigational Site
Daugavpils, Latvia
205.424.37105 Boehringer Ingelheim Investigational Site
Rezekne, Latvia
205.424.37102 Boehringer Ingelheim Investigational Site
Riga, Latvia
205.424.37101 Boehringer Ingelheim Investigational Site
Riga, Latvia
Lithuania
205.424.37004 Boehringer Ingelheim Investigational Site
Vilnius, Lithuania
205.424.37003 Boehringer Ingelheim Investigational Site
Vilnius, Lithuania
205.424.37001 Boehringer Ingelheim Investigational Site
Vilnius, Lithuania
Slovenia
205.424.38604 Boehringer Ingelheim Investigational Site
Kamnik, Slovenia
205.424.38605 Boehringer Ingelheim Investigational Site
Ljubljana, Slovenia
205.424.38602 Boehringer Ingelheim Investigational Site
Maribor, Slovenia
Sponsors and Collaborators
Boehringer Ingelheim
Pfizer
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01122680     History of Changes
Other Study ID Numbers: 205.424, 2009-017745-55
Study First Received: May 11, 2010
Results First Received: April 10, 2012
Last Updated: May 7, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Slovenia: Agency for Medicinal Products - Ministry of Health
United States: Food and Drug Administration

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Bromides
Tiotropium
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Bronchodilator Agents
Anti-Asthmatic Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on July 23, 2014