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

Boehringer Ingelheim105 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

105

Conditions

Asthma

Interventions

Eligibility

Sex: ALLMin age: 12 YearsMax age: 17 Years

Medical Language ↔ Plain English

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.

Locations (19)

205.424.01002 Boehringer Ingelheim Investigational Site

Denver, Colorado, United States

205.424.01006 Boehringer Ingelheim Investigational Site

Columbia, Missouri, United States

205.424.01007 Boehringer Ingelheim Investigational Site

Warrensburg, Missouri, United States

205.424.01004 Boehringer Ingelheim Investigational Site

Boys Town, Nebraska, United States

205.424.01001 Boehringer Ingelheim Investigational Site

Canton, Ohio, United States

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

205.424.37104 Boehringer Ingelheim Investigational Site

Balvi, Latvia

205.424.37103 Boehringer Ingelheim Investigational Site

Daugavpils, Latvia

...and 9 more locations

Outcomes

Primary Outcomes

Forced Expiratory Volume (FEV1) Peak (0-3h) Response

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.

Time frame: Baseline and 4 weeks

Secondary Outcomes

Trough FEV1 Response

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.

Time frame: Baseline and 4 weeks

FEV1 Area Under the Curve From 0 to 3 h (AUC0-3h) Response

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.

Time frame: Baseline and 4 weeks

FEV1 Individual Measurements Response at Each Time-point

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.

Time frame: Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)

Forced Vital Capacity (FVC) Peak (0-3h) Response

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.

Time frame: Baseline and 4 weeks

FVC Trough Response

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.

Time frame: Baseline and 4 weeks

FVC Area Under the Curve From 0 to 3 h (AUC0-3h) Response

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.

Time frame: Baseline and 4 weeks

FVC Individual Measurements at Each Time-point

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.

Time frame: Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)

Forced Expiratory Flow (FEF) 25-75% Individual Measurements Response at Each Time Point

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.

Time frame: Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)

Mean Morning Peak Expiratory Flow (PEF) Response

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.

Time frame: Baseline and 4 weeks

Mean Evening PEF Response

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.

Time frame: Baseline and 4 weeks

Change From Baseline in the Number of Puffs of Rescue Medication Per Day

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.

Time frame: Baseline and 4 weeks

Control of Asthma as Assessed by Asthma Control Questionnaire (ACQ)

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.

Time frame: 4 weeks

Change From Baseline in Mean Number of Nighttime Awakenings

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.

Time frame: Baseline and last week of treatment (week 4)