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)

Condition(s) targeted: Pulmonary Disease, Chronic Obstructive

Intervention: Ipratropium bromide HFA-134a inhalation aerosol (Drug); Atrovent CFC inhalation aerosol (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Boehringer Ingelheim

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

Official title: 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)

Study design: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Amount of unchanged ipratropium excreted in the urine from 0 to 24 h after a single dose

Amount of unchanged ipratropium excreted in the urine within 1 hour at steady state

Amount of unchanged ipratropium excreted in the urine over the 6 h dosing interval at steady state

Secondary outcome:

Area under the plasma ipratropium concentration time curve at different time points

Peak plasma ipratropium concentration at different time points

Trough plasma ipratropium concentration at different time points

Time to peak plasma ipratropium concentrations at steady state

Degree of fluctuation (DF) of the plasma ipratropium concentrations

Area under the plasma ipratropium concentration time curve

Peak plasma ipratropium concentration

Number of patients with adverse events

Changes from baseline in pulse rate and blood pressure

Number of patients with clinical significant findings in laboratory tests

Number of patients with clinical significant findings in physical examination

Number of patients with clinical significant findings in electrocardiogram (ECG)

Changes from test-day baseline in pulse rate and blood pressure

Minimum age: 40 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Starting date: October 2000
Last updated: September 9, 2014