Safety and Tolerability of COMBIVENT® HFA as Compared to COMBIVENT® CFC and Placebo HFA in Healthy Male and Female Subjects
Safety and Tolerability of COMBIVENT® HFA as Compared to COMBIVENT® CFC and Placebo HFA in Healthy Male and Female Subjects
Study to assess the safety and tolerability of COMBIVENT® hydrofluoroalkane (HFA) as compared
 to COMBIVENT® chlorofluorocarbons (CFC) and placebo HFA after single and repetitive dosing in
 healthy male and female subjects
Inclusion Criteria:

 -  Healthy males/females

 -  Age range from 21 to 50 years and be within 20% of their normal weight (Broca-Index)

 -  All female volunteers must use a safe contraception (i.e. oral contraceptives,
 intrauterine devices; sterilised) and must have a negative urine pregnancy test

 -  All subjects must have a negative hepatitis B, C and HIV tests as well as a negative
 drug screening

 -  Prior to admission to the treatment after giving his/her informed consent (in
 accordance with Good Clinical Practice and local legislation) in writing, each subject
 will have his/her medical history taken and will receive a complete medical
 examination (incl. blood pressure and pulse rate measurements) as well as 12-lead ECG
 within 14 days before the first administration of the test drug. Haematopoietic,
 hepatic and renal function tests will be carried out in the laboratory. The subject
 will fast for 12 hours before collection of specimens for all laboratory parameters

 -  Currently non-smoking (smoke free for >= one year and <=5 pack year smoking history)

 -  Normal spirometry as evidenced by a baseline FEV1 >= 90% of predicted normal value for
 age, height and sex

 -  Predicted normal values will be calculated according to European Community for Steel
 and Coal (ECCS)

 -  Ability to adequately use an inhalation aerosol device

 -  Ability to perform technically satisfactory pulmonary function tests

 Exclusion Criteria:

 -  Volunteers will be excluded from the study if the results of the medical examination
 or laboratory test (especially serum glutamate oxaloacetate transaminase (SGOT) >
 2-fold of upper normal range, serum glutamate pyruvate transaminase (SGPT) > 1.5 -
 fold of upper normal range) are judged by the investigator to differ significantly
 from normal clinical values

 -  Volunteers who have an eosinophil count >= 600/mm³. A repeat eosinophil count will not
 be conducted in these subjects

 -  Volunteers with a serum potassium value >+- 10% outside the normal range

 -  Volunteers with known gastrointestinal, hepatic, renal, respiratory, cardiovascular,
 metabolic immunological or hormonal disorders

 -  Volunteers with diseases of the central nervous system (such as epilepsy) or with
 psychiatric disorders

 -  Volunteers with known history of orthostatic hypotension, fainting spells or blackouts

 -  Volunteers with chronic or relevant acute infections

 -  Volunteers with upper respiratory tract infection in the past six weeks prior to the
 screening visit or between the screening visit and first test day

 -  Volunteers with a history of asthma or allergic rhinitis

 -  Volunteers with history of allergy/hypersensitivity (including drug allergy,
 especially anticholinergics and beta-agonist agents) which is deemed relevant to the
 trial as judged by the investigator

 -  Volunteers with known narrow-angle glaucoma

 -  Volunteers with disturbed micturition

 -  Volunteers who have taken a drug with a long half-life (>= 24 hours) within ten
 half-lives of the respective drug before enrolment in the study

 -  Volunteers who received any concomitant therapy, including over the counter
 medications (including vitamins, supplements and/or nonsteroidal antiinflammatory
 drugs; excluding oral or depository contraceptives) within one week of the screening
 visit

 -  Volunteers who have participated in another study with an investigational drug within
 the last two months preceding this study

 -  Volunteers who drink more than 40g of alcohol per day

 -  Volunteers who are dependent on drugs

 -  Volunteers who have donated blood (>= 100 ml ) within the last four weeks

 -  Volunteers who participated in excessive physical activities (e.g. competitive sports)
 within the last week before the study

 -  Pregnant or nursing women or women of childbearing potential not using a medically
 approved means of contraception (i.e. contraceptives, intrauterine devices,
 sterilised)

 -  Volunteers with significant tremor measured on screening visit

 -  Previous participation in this study