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

Boehringer Ingelheim

Status and phase: Completed; Phase 2

Conditions: Asthma

Treatments: Drug: Tiotropium bromide; Drug: Placebo; Drug: tiotropium bromide

Study type: Interventional

Funder types: Industry

Identifiers

NCT01122680

205.424

2009-017745-55 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 105 patients

Sex: All

Ages: 12 to 17 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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105 participants in 4 patient groups, including a placebo group

Treatment A

Experimental group

Description:

patients inhale 2 puffs (dose of 1.25 mcg) once daily in the evening via Respimat inhaler

Treatment:

Drug: Tiotropium bromide

Treatment C

Experimental group

Description:

patients inhale 2 puffs (dose of 5 mcg) once daily in the evening via Respimat inhaler

Treatment:

Drug: tiotropium bromide

Drug: tiotropium bromide

Placebo

Placebo Comparator group

Description:

patients inhale 2 puffs of placebo matching tiotropium once daily in the evening via Respimat inhaler

Treatment:

Drug: Placebo

Treatment B

Experimental group

Description:

patients inhale 2 puffs (dose of 2.5 mcg) once daily in the evening via Respimat inhaler

Treatment:

Drug: tiotropium bromide

Drug: tiotropium bromide