Pharmacokinetics and Safety Comparison of Tiotropium Inhalation Powder Administered as the Bromide Salt From Hard Polyethylene Capsule Via the HandiHaler® 2 and Spiriva® HandiHaler® in Patients With Chronic Obstructive Pulmonary Disease (COPD)

NCT02242266 | Completed Phase 2

• 1 other identifier: 1184.9
• Study Type: interventional
• Target: 121
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of this trial was to establish non-inferiority of lung function response to tiotropium 10 μg, formulated as inhalation powder in the polyethylene hard capsule and delivered via the HandiHaler® 2, compared to tiotropium 18 μg, formulated as inhalation powder in the hard gelatine capsule and delivered via the HandiHaler® (Spiriva®) following single dose inhalation in patients with COPD. A hard polyethylene (PE) capsule with half the strength (tiotropium 5 μg) was included to investigate a dose ordering effect. The secondary objectives were to characterize the pharmacokinetics of tiotropium inhalation powder hard PE capsule (delivered via HandiHaler® 2) and tiotropium inhalation powder hard gelatine capsule (delivered via HandiHaler®) and to compare the safety of the two pharmaceutical formulations.

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (1)

• Area under the curve for the time period 0 to 12 hours of forced expiratory volume in one second (FEV1 AUC0-12)

  pre-dose and 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing

Secondary Outcomes (17)

• Peak FEV1 on each test-day

  pre-dose and 30, 60 minutes, 2 and 3 hours post-dosing

• Peak forced vital capacity (FVC)

  pre-dose and 30, 60 minutes, 2, 3, 4, 6, 8, 10, 12, 14, 22, 23 and 24 hours post-dosing

• FVC AUC0-12

  pre-dose and 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing

• FEV1 AUC12-24

  12, 14, 22, 23 and 24 hours post-dosing

• FEV1 AUC0-24

  pre-dose and 30, 60 minutes, 2, 3, 4, 6, 8, 10, 12, 14, 22, 23 and 24 hours post-dosing

Study Arms (4)

Tiotropium low dose

EXPERIMENTAL

oral inhalation via the blue HandiHaler®

Drug: Tiotropium low dose; Drug: Placebo via the grey HandiHaler®

Tiotropium medium dose

EXPERIMENTAL

oral inhalation via the blue HandiHaler®

Drug: Tiotropium medium dose; Drug: Placebo via the grey HandiHaler®

Spiriva® HandiHaler® high dose

ACTIVE COMPARATOR

oral inhalation via the grey HandiHaler®

Drug: Spiriva® HandiHaler® high dose; Drug: Placebo via the blue HandiHaler®

Placebo

PLACEBO COMPARATOR

Drug: Placebo via the blue HandiHaler®; Drug: Placebo via the grey HandiHaler®

Interventions

Tiotropium low dose DRUG

inhalation powder, hard PE capsule

Tiotropium low dose

Tiotropium medium dose DRUG

inhalation powder, hard PE capsule

Tiotropium medium dose

Spiriva® HandiHaler® high dose DRUG

Tiotropium inhalation powder, hard gelatine capsule

Spiriva® HandiHaler® high dose

Placebo via the blue HandiHaler® DRUG

oral inhalation via the blue HandiHaler®

Placebo; Spiriva® HandiHaler® high dose

Placebo via the grey HandiHaler® DRUG

oral inhalation via the grey HandiHaler®

Placebo; Tiotropium low dose; Tiotropium medium dose

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must sign an informed consent consistent with International Conference on Harmonization Good Clinical Practice (ICH-GCP) guidelines and local legislations prior to any study-related procedures, which includes medication washout and restrictions
• All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:
• Patients must have relatively stable\* airway obstruction with a pre-dose FEV1 \<= 60% of predicted normal and FEV1 \<= 70% of FVC at Visits 1 and 2.
• \* The randomization of patients with any respiratory infection or COPD exacerbation in the 6 weeks prior to the Screening Visit (Visit 1) or during the baseline period should be postponed. Patients may be randomized 6 weeks following recovery from the infection or exacerbation
• At Visit 1, patients must demonstrate an improvement in FEV1 of \>= 12% over the baseline FEV1 value 45 minutes after inhalation of 4 puffs of 20 µg ipratropium bromide (Atrovent® MDI)
• Male or female patients 40 years of age or older
• Patients must be current or ex-smokers with a smoking history of more than 10 pack-years (Patients who had never smoked cigarettes had to be excluded)
• Patients must be able to perform technically acceptable pulmonary function tests during the study period as required in the protocol
• Patients must be able to inhale medication in a competent manner from the HandiHaler® 2 and the HandiHaler® devices

You may not qualify if:

• Patients with significant diseases other than COPD will be excluded. A significant disease is defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study
• Patients with a recent history (i.e., six months or less) of myocardial infarction
• Patients who have been hospitalized for heart failure (NYHA class III or IV) within the past year
• Patients with any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention 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 treated basal cell carcinoma are allowed
• Patients with a history of asthma, allergic rhinitis or atopy or who have a total blood eosinophil count ≥600/mm3. A repeat eosinophil count will not be conducted in these patients
• Patients with a history of life threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis
• Patients with known active tuberculosis
• Patients with significant alcohol or drug abuse within the past two years
• Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the Screening Visit (Visit 1) or patients who are currently in a pulmonary rehabilitation program that will not be maintained throughout the duration of the study
• Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy
• Patients who are being treated with cromolyn sodium or nedocromil sodium
• Patients using oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day
• Patients with known hypersensitivity to anticholinergic drugs, lactose or any other components of the inhalation capsule delivery system (Spiriva® HandiHaler®; tiotropium HandiHaler 2)
• Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception for the previous three months (i.e. oral contraceptives, intrauterine devices, diaphragm or subdermal implants, e.g.: Norplant®)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Tiotropium Bromide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

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: September 16, 2014
• First Posted: September 17, 2014
• Study Start: July 28, 2005
• Primary Completion: June 4, 2006
• Last Updated: December 1, 2023

Record last verified: 2023-11