Study to Assess the Safety of Ipratropium Bromide, in Patients With Chronic Obstructive Pulmonary Disease (COPD)

A Double-blind, Placebo Controlled Trial to Assess the Safety of Two-week Administration of 80 mcg q.i.d. and 160 mcg q.i.d. of Ipratropium Bromide, as Delivered by the RESPIMAT® Device, in Patients With Chronic Obstructive Pulmonary Disease

Study to assess the safety of two-week administration of 80 and 160 mcg of ipratropium bromide as delivered by the RESPIMAT® device and as determined by 24 hours ambulatory ECG monitoring in COPD patients. To assess the overall safety of the two doses of ipratropium bromide as delivered by the RESPIMAT® device when administered over a two-week period.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Placebo; Drug: Ipratropium Bromide low dose; Drug: Ipratropium Bromide high dose

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All patients must have a diagnosis of COPD and must meet the following spirometric criteria:

• Patients must have relatively stable, moderate to severe airway obstruction with an FEV1 <=65% of predicted normal and FEV1 <=70% of forced vital capacity (FVC). Predicted normal value will be calculated according to Morris

  • Males: FEV1 = 0.093 (Height in inches)-0.032 (age)-1.343
  • Females: FEV1 = 0.085 (Height. in inches)-0.025(age)-1.692
• Male or female patients 40 years of age or older
• Patients must have a smoking history of more than 10 pack-years. A pack-year is defined as the equivalent of smoking one pack of 20 cigarettes per day for a year
• Patients must be able to perform pulmonary function tests (PFTs) and maintain records during the study period as required in the protocol
• Patients must be able to be trained in the proper use of an inhalation aerosol and the RESPIMAT™ device
• Patients must have a baseline electrocardiogram (ECG) with no clinical relevant arrhythmias or conduction system disease (e.g. right or left bundle branch block, second degree AV block or higher)
• Patients must have an oxygen saturation of >=90% for >=92% of the recording time on overnight oximetry
• All patients must sign an Informed Consent Form prior to participation in the trial (i.e., at least 24 hours (h) prior to the screening visit (Visit 1))

Exclusion Criteria:

• Patients with clinically relevant diseases other than COPD will be excluded. A clinically relevant 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 with may influence the results of the study or patient's ability to participate in the study
• Patients with a recent history (i.e. one year or less) of myocardial infarction
• Patients with a recent history (i.e. one year or less) of heart failure or patients with any past history or active cardiac arrhythmia requiring drug therapy
• Patients who have a pacemaker
• Patients with clinically relevant abnormal baseline hematology, blood chemistry or urinalysis. If the abnormality defines a disease listed as an exclusion criterion the patient is excluded
• All patients with serum glutamic oxaloacetic transaminase / Aspartate aminotransferase (SGOT/AST) >80 IU/L, serum glutamic pyruvic transaminase / Alanine transaminase (SGPT/ALT) >80 IU/L, bilirubin >2.0 mg/dl, or creatinine >2.0 mg/dl will be excluded regardless of the clinical condition. Repeat laboratory evaluation will be not be conducted in these subjects
• Patients who have a blood eosinophil count >=600/mm3. A Repeat eosinophil count will be not be conducted in these patients
• Patients with a history of cancer, other than treated basal cell carcinoma, within the last 5 years
• Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis
• Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reason should be evaluated per exclusion criterion No. 1
• Patients with a history of asthma, allergic rhinitis or atopy
• Patients with a history of and/or active alcohol or drug abuse
• Patients with known active tuberculosis
• Patients with an upper respiratory tract infection or COPD exacerbation in the past 6 weeks prior to the screening visit (Visit 1) or during the baseline period
• Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction
• Patients with known narrow-angle glaucoma
• Patients with current significant psychiatric disorders
• Patients with regular use of daytime oxygen therapy
• Patients who are being treated with cromolyn sodium or nedocromil sodium
• Patients who are being treated with antihistamines
• Patients using oral corticosteroid medication at unstable doses (i.e. less than six weeks on a stable dose) or at a dose in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day
• Patients who are being treated with beta-blocker medication
• Patients who have had changes in their therapeutic plan within the last six weeks prior to the screening visit (visit 1)
• Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (e.g., oral contraceptive, intrauterine devices, diaphragm or Norplant®)
• Patients with known hypersensitivity to ant cholinergic drugs or any other components of the ATROVENT® RESPIMAT™ solution including bacteriostatic agent benzalkonium chlorid (BAC) and edetic acid (EDTA)
• Patients who have taken an investigational drug within 1 month or 6 half-lives (whichever is longer) prior to the screening visit (visit1)
• Previous participation in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ipratropium Bromide low; delivered via RESPIMAT®	Drug: Ipratropium Bromide low dose
Experimental: Ipratropium Bromide high; delivered via RESPIMAT®	Drug: Ipratropium Bromide high dose
Placebo Comparator: Placebo; delivered via RESPIMAT®	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assessment of clinical significant findings in 24-hour ambulatory ECG monitoring	Pre-treatment, on Day 7 and 13
Number of patients with adverse events	Up to 15 days after first drug administration
Number of patients with clinical significant findings in ECG	Up to 15 days after first drug administration
Number of patients with clinical significant findings in vital signs	Up to 15 days after first drug administration
Number of patients with clinical significant findings in laboratory tests	Up to day 15 after drug administration
Number of patients with paradoxical bronchospasm	Up to 15 days after first drug administration

Secondary Outcome Measures

Outcome Measure	Time Frame
FEV1 (forced expiratory volume in the first second) AUC0-4 (Area under the curve from 0 to 4 hours)	Pre-treatment, up to 4 h after drug administration on Day 1 and 14
Peak FEV1	On Day 1 and 14
Onset of therapeutic FEV1 response	On Day 1 and 14
Time to peak FEV1 response	On Day 1 and 14
AUC(0-6h) (Area under the plasma concentration-time curve from 0 to 6 h)	Day 14
Cmax (maximum plasma concentration)	Day 14
Cmin(0h) (minimum plasma concentration before inhalation)	Day 14
Cmin(6h) (minimum plasma concentration at 6 hours after inhalation)	Day 14
Ae(0-2h) (urine excretion between 0 to 2 h)	Day 14
Ae(0-6h) (urine excretion between 0 to 6 h)	Day 14

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: July 1, 1998
• Primary Completion (Actual): February 1, 1999

Study Registration Dates

• First Submitted: September 9, 2014
• First Submitted That Met QC Criteria: September 9, 2014
• First Posted (Estimate): September 10, 2014

Study Record Updates

• Last Update Posted (Estimate): September 12, 2014
• Last Update Submitted That Met QC Criteria: September 11, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Bromides; Ipratropium
• Other Study ID Numbers: 244.2489