Pharmacodynamic and Pharmacokinetic Dose Ranging Study of Tiotropium Bromide Administered Via Respimat Device in Patients With Chronic Obstructive Pulmonary Disease (COPD)

NCT02175342 | Completed Phase 2

• 1 other identifier: 205.127
• Study Type: interventional
• Target: 202
• Locations: 0 countries
• Sites: N/A

Brief Summary

This pharmacodynamic and pharmacokinetic dose-ranging study aims to determine the optimal dose of tiotropium inhaled as a solution from a Respimat device once a day for three weeks in patients with COPD.

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (1)

• Forced expiratory volume in one second (FEV1) with emphasis on the last two hours of the 24-hour dosing interval (trough FEV1)

  last two hours of the 24-hour dosing interval

Secondary Outcomes (7)

• Forced expiratory volume in one second (FEV1)

  during the first four hours post dose

• Forced Vital Capacity (FVC)

  during first four hours post dose

• Pharmacokinetic evaluation: 2-hours urine sampling pre- and post-dose (10 patients per group)

  before and after last drug administration at day7,14 and 21.

• Chronic obstructive pulmonary disease symptom scores, physician's global evaluation, sleep question and use of rescue medication

  3 weeks treatment period

• Changes in ECG, pulse rate (PR) and blood pressure (BP) from the pre-dose values recorded on test day

  Day 0, day 7, day 14, day 21

Study Arms (8)

Tiotropium-1.25 Respimat

EXPERIMENTAL

Two puffs of tiotropium inhalation solution from a Respimat device, 0.625 mcg/puff

Drug: Tiotropium 0.625 mcg/puff; Device: Respimat

Tiotropium-2.5 Respimat

EXPERIMENTAL

Two puffs of tiotropium inhalation solution from a Respimat device, 1.25 mcg/puff

Drug: Tiotropium 1.25 mcg/puff; Device: Respimat

Tiotropium-5 Respimat

EXPERIMENTAL

Two puffs of tiotropium inhalation solution from a Respimat device, 2.5 mcg/puff

Drug: Tiotropium 2.5 mcg/puff; Device: Respimat

Tiotropium-10 Respimat

EXPERIMENTAL

Two puffs of tiotropium inhalation solution from a Respimat device, 5 mcg/puff

Drug: Tiotropium 5 mcg/puff; Device: Respimat

Tiotropium-20 Respimat

EXPERIMENTAL

Two puffs of tiotropium inhalation solution from a Respimat device, 10 mcg/puff

Drug: Tiotropium 10 mcg/puff; Device: Respimat

Placebo Respimat

PLACEBO COMPARATOR

Drug: Placebo solution; Device: Respimat

Tiotropium-18 lactose powder Handihaler

ACTIVE COMPARATOR

Drug: Tiotropium-18 lactose powder; Device: Handihaler

Placebo lactose powder Handihaler

PLACEBO COMPARATOR

Drug: Placebo lactose powder; Device: Handihaler

Interventions

Tiotropium 0.625 mcg/puff DRUG

Tiotropium-1.25 Respimat

Tiotropium 1.25 mcg/puff DRUG

Tiotropium-2.5 Respimat

Tiotropium 2.5 mcg/puff DRUG

Tiotropium-5 Respimat

Tiotropium 5 mcg/puff DRUG

Tiotropium-10 Respimat

Placebo solution DRUG

Placebo Respimat

Tiotropium-18 lactose powder DRUG

Tiotropium-18 lactose powder Handihaler

Placebo lactose powder DRUG

Placebo lactose powder Handihaler

Tiotropium 10 mcg/puff DRUG

Tiotropium-20 Respimat

Respimat DEVICE

Placebo Respimat; Tiotropium-1.25 Respimat; Tiotropium-10 Respimat; Tiotropium-2.5 Respimat; Tiotropium-20 Respimat; Tiotropium-5 Respimat

Handihaler DEVICE

Placebo lactose powder Handihaler; Tiotropium-18 lactose powder Handihaler

Eligibility Criteria

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

You may qualify if:

• Age: ≥ 40 years;
• Diagnosis of COPD and met the following criteria:
• Relatively stable, moderate to severe airway obstruction,
• Baseline 30% ≤ FEV1 ≤ 65% of predicted normal value, predicted normal values are based on the guidelines for standardized lung function testing of the European Community for Coal and Steel (ECCS) ,
• Baseline FEV1/ forced expiratory vital capacity (FEVC) ≤ 70%;
• Smoking history ≥ 10 pack-years (p.y.). A p.y. is defined as the equivalent of smoking one pack of cigarettes per day for one year;
• Male of female;
• Ability to be trained in the proper use of Respimat and Handihaler;
• Ability to be trained in the performance of technically satisfactory pulmonary function tests;
• Ability to provide written informed consent
• Patient affiliated to the Social Security System

You may not qualify if:

• History of asthma, allergic rhinitis or atopy or who have a blood eosinophil count above 600/mm³
• Changes in the therapeutic (pulmonary) plan within the last six weeks prior to the Screening Visit;
• Treatment by cromolyn/nedocromil sodium;
• Treatment by antihistamines (H1 receptor antagonists);
• A lower respiratory tract infection or any exacerbation in the past six weeks prior to the Screening Visit;
• Regular use of daytime oxygen therapy;
• Treatment by oral corticosteroid medication if initiated or modified within the last six weeks or if daily dose \> 10 mg prednisone equivalent;
• History of life threatening pulmonary obstruction, cystic fibrosis or bronchiectasis
• Patients who have undergone thoracotomy with pulmonary resection;
• History of clinically significant cardiovascular, renal neurologic, liver or endocrine dysfunction. A clinically significant disease was defined as one 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 (≤ one year) history of myocardial infarction, of heart failure or patients with any cardiac arrhythmia requiring drug therapy;
• Tuberculosis with indication for treatment;
• History of cancer within the last five years. Patients with treated basal cell carcinoma were allowed:
• Current psychiatric disorders;
• Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction;

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2014
• First Posted: June 26, 2014
• Study Start: March 1, 1998
• Primary Completion: April 1, 1999
• Last Updated: January 31, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share