Trial to Determine the Comparability of Ipratropium Bromide Hydrofluoroalkane (HFA)-134a Inhalation Aerosol to ATROVENT® Chlorofluorocarbon (CFC) Inhalation Aerosol, in Patients With Chronic Obstructive Pulmonary Disease (COPD)

An Open-Label, Crossover, Pharmacokinetic Trial to Determine the Comparability of 84 µg Ipratropium Bromide HFA-134a Inhalation Aerosol to 84 µg ATROVENT® CFC Inhalation Aerosol, in Patients With Chronic Obstructive Pulmonary Disease (COPD)

The objective of this study was to determine the pharmacokinetic comparability of 84 µg ipratropium bromide HFA-134a inhalation aerosol and 84 µg ATROVENT® CFC Inhalation Aerosol in COPD patients

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Ipratropium bromide HFA-134a inhalation aerosol; Drug: Atrovent CFC inhalation aerosol

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 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 a stable, moderate to severe airway obstruction with an Forced Expiratory Volume in one second (FEV1) <=65% of predicted normal and FEV1 <=70% of Forced vital capacity (FVC)

  • Males: Predicted Normal FEV1 = 0.093 (height in inches)-0.032 (age)-1.343
  • Females: Predicted Normal FEV1 = 0.085 (height in inches)-0.025(age)-1.692
• Male or female age 40 years 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 cigarettes (20 cigarettes) per day for a year
• Patients must be able to satisfactorily administer the medication, perform pulmonary function tests (PFTs) and maintain records during the study period as required in the protocol
• All patients must sign an Informed Consent Form prior to participation in the trial (i.e., prior to pre-study washout of their usual pulmonary medications and prior to fasting for laboratory tests)

Exclusion Criteria:

• 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 with may influence the results of the study or patients ability to participate in the study
• Patients with clinically relevant 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 (SGOT) >80 IU/L, serum glutamic pyruvic transaminase (SGPT) >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 patients
• Patients with a history of asthma, allergic rhinitis or atopy or who have a blood eosinophil count above 600/mm3. A repeat eosinophil count will be not be conducted in these patients
• Patients with a recent (i.e., one year or less) history of myocardial infarction
• Patients with a recent history (i.e., three years or less) of cardiac failure, patients with cardiac arrhythmia requiring therapy, patients receiving any systemic beta-blockers and patients on chronic daytime oxygen therapy
• Patients with known active tuberculosis
• Patients with a history of cancer within the last 5 years. Patients with treated basal cell carcinoma are allowed
• 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 an upper respiratory tract infection or COPD exacerbation in the 6 weeks prior to the screening visit (Visit 1) or during the baseline period
• Patients with known hypersensitivity to anticholinergic drugs
• Patients with known symptomatic prostatic hypertrophy or bladder-neck obstruction
• Patients with known narrow-angle glaucoma
• Patients who are on cromolyn sodium or nedocromil sodium
• Patients who are on antihistamines
• Pregnant or nursing women and women of childbearing potential not using a medically approved means of contraception (e.g., oral contraceptive, intrauterine devices, diaphragm or Norplant®)
• Patients who have taken an investigational drug within 1 month or 6 half-lives (whichever is longer) of the drug prior to the screening visit or patients currently enrolled in another research study
• Patients with a history of and/or active alcohol or drug abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ipratropium bromide	Drug: Ipratropium bromide HFA-134a inhalation aerosol
Active Comparator: ATROVENT	Drug: Atrovent CFC inhalation aerosol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Amount of unchanged ipratropium excreted in the urine from 0 to 24 h after a single dose	Up to 24 hours (h) after single drug administration
Amount of unchanged ipratropium excreted in the urine within 1 hour at steady state	1h after drug administration
Amount of unchanged ipratropium excreted in the urine over the 6 h dosing interval at steady state	up to 6 h after drug administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma ipratropium concentration time curve at different time points	Up to 23 days after first drug administration
Peak plasma ipratropium concentration at different time points	Up to 23 days after first drug administration
Trough plasma ipratropium concentration at different time points	Up to 23 days after first drug administration
Time to peak plasma ipratropium concentrations at steady state	Up to 23 days after first drug administration
Degree of fluctuation (DF) of the plasma ipratropium concentrations	Up to 23 days after first drug administration
Area under the plasma ipratropium concentration time curve	Day 1 after first drug administration
Peak plasma ipratropium concentration	Day 1 after first drug administration
Number of patients with adverse events	Up to 23 days after first drug administration
Changes from baseline in pulse rate and blood pressure	Baseline, day 23 day after first drug administration
Number of patients with clinical significant findings in laboratory tests	Up to 23 days after first drug administration
Number of patients with clinical significant findings in physical examination	Up to 23 days after first drug administration
Number of patients with clinical significant findings in electrocardiogram (ECG)	Up to 23 days after first drug administration
Changes from test-day baseline in pulse rate and blood pressure	Up to 23 days after first drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2000
• Primary Completion (Actual): April 1, 2001

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 10, 2014
• Last Update Submitted That Met QC Criteria: September 9, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Aspiration; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anesthetics; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Bromides; Ipratropium; Norflurane
• Other Study ID Numbers: 244.2480