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

NCT01122680 | Completed Phase 2 Results

• 2 other identifiers: 205.4242009-017745-55
• Study Type: interventional
• Target: 105
• Locations: 5 countries
• Sites: 19

Brief Summary

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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline and 4 weeks

Secondary Outcomes (13)

• Trough FEV1 Response

  Baseline and 4 weeks

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

  Baseline and 4 weeks

• FEV1 Individual Measurements Response at Each Time-point

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

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

  Baseline and 4 weeks

• FVC Trough Response

  Baseline and 4 weeks

Study Arms (4)

Treatment A

EXPERIMENTAL

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

Drug: Tiotropium bromide

Treatment C

EXPERIMENTAL

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

Drug: tiotropium bromide

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Treatment B

EXPERIMENTAL

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

Drug: tiotropium bromide

Interventions

tiotropium bromide DRUG

inhalation solution, dose of 1.25 mcg (2 puffs of 0.625 mcg)

Treatment A

Placebo DRUG

placebo inhalation solution

Placebo

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• Male or female patients between 12 and 17 years of age.
• 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.
• All patients must have been on maintenance treatment with inhaled corticosteroids at a stable medium dose for at least 4 weeks before Visit 1.
• 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.
• 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%.
• 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.
• All patients should be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment.
• Patients should be able to use the Respimat® inhaler correctly.
• 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.

You may not qualify if:

• Patients with a significant disease other than asthma.
• Patients with a history of congenital or acquired heart disease, and/or have been hospitalised for cardiac syncope or failure during the past year.
• 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.
• Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years.
• Patients with significant alcohol or drug abuse within the past two years.
• Patients with known hypersensitivity to anticholinergic drugs, benzalkonium chloride (BAC), ethylenediaminetetraacetic acid (EDTA) or any other components of the tiotropium inhalation solution.
• Pregnant or nursing adolescent female patients, including female patients with a positive Beta HCG (serum pregnancy) testing at screening (visit 1).
• Sexually active female patients of child-bearing potential not using a highly effective method of birth control.
• Patients with a known narrow-angle glaucoma, or any other disease where anticholinergic treatment is contraindicated.
• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Pfizer: collaborator

Study Sites (19)

205.424.01002 Boehringer Ingelheim Investigational Site

Denver, Colorado, United States

Location

205.424.01006 Boehringer Ingelheim Investigational Site

Columbia, Missouri, United States

Location

205.424.01007 Boehringer Ingelheim Investigational Site

Warrensburg, Missouri, United States

Location

205.424.01004 Boehringer Ingelheim Investigational Site

Boys Town, Nebraska, United States

Location

205.424.01001 Boehringer Ingelheim Investigational Site

Canton, Ohio, United States

Location

205.424.49007 Boehringer Ingelheim Investigational Site

Koblenz, Germany

Location

205.424.49004 Boehringer Ingelheim Investigational Site

Rosenheim, Germany

Location

205.424.49002 Boehringer Ingelheim Investigational Site

Wesel, Germany

Location

205.424.37104 Boehringer Ingelheim Investigational Site

Balvi, Latvia

Location

205.424.37103 Boehringer Ingelheim Investigational Site

Daugavpils, Latvia

Location

205.424.37105 Boehringer Ingelheim Investigational Site

Rēzekne, Latvia

Location

205.424.37101 Boehringer Ingelheim Investigational Site

Riga, Latvia

Location

205.424.37102 Boehringer Ingelheim Investigational Site

Riga, Latvia

Location

205.424.37001 Boehringer Ingelheim Investigational Site

Vilnius, Lithuania

Location

205.424.37003 Boehringer Ingelheim Investigational Site

Vilnius, Lithuania

Location

205.424.37004 Boehringer Ingelheim Investigational Site

Vilnius, Lithuania

Location

205.424.38604 Boehringer Ingelheim Investigational Site

Kamnik, Slovenia

Location

205.424.38605 Boehringer Ingelheim Investigational Site

Ljubljana, Slovenia

Location

205.424.38602 Boehringer Ingelheim Investigational Site

Maribor, Slovenia

Location

Related Publications (1)

• Vogelberg C, Engel M, Moroni-Zentgraf P, Leonaviciute-Klimantaviciene M, Sigmund R, Downie J, Nething K, Vevere V, Vandewalker M. Tiotropium in asthmatic adolescents symptomatic despite inhaled corticosteroids: a randomised dose-ranging study. Respir Med. 2014 Sep;108(9):1268-76. doi: 10.1016/j.rmed.2014.06.011. Epub 2014 Jul 17.

  PMID: 25081651 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

Tiotropium Bromide

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2010
• First Posted: May 13, 2010
• Study Start: May 1, 2010
• Primary Completion: April 1, 2011
• Last Updated: May 16, 2014
• Results First Posted: June 27, 2012

Record last verified: 2012-07

Locations

US (5); DE (3); LA (5); LI (3); SL (3)