Pharmacodynamic Effects, Safety and Tolerability of Cilobradine, Compared to Metoprolol Succinate and Placebo in Healthy Volunteers
Pharmacodynamic Effects, Safety and Tolerability of Cilobradine, Compared to Metoprolol Succinate and Placebo in Healthy Volunteers
Pharmacodynamic effects on heart rate (HR) at rest and during exercise and on flicker fusion
 frequency (FFF), FFF method evaluation

 Safety, tolerability and pharmacokinetics of cilobradine
Inclusion Criteria:

 -  All participants in the study should be healthy males and females. Volunteers will

 -  be 21 to 55 years of age

 -  have a Body Mass Index (BMI) of 19.9 to 29.9 kg/m2 and

 -  have a resting heart rate (HR) (after 10 min. in the supine position) of more
 than 55 beats per minute (bpm)

 -  Only post-menopausal females, or those who had had a hysterectomy, could participate.
 All females had to have a negative pregnancy test

 -  In accordance with good clinical practice (GCP) and the local legislation all
 volunteers had to give their written informed consent prior to admission to the study

 Exclusion Criteria:

 -  Any finding of the medical examination (including BP, HR and ECG) deviating from
 normal and of clinical relevance

 -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,
 immunological or hormonal disorders

 -  Diseases of the central nervous system or psychiatric disorders or neurological
 disorders

 -  History of relevant orthostatic hypotension, fainting spells or blackouts

 -  Chronic or relevant acute infections

 -  History of allergy/hypersensitivity (including drug allergy) which is deemed relevant
 to the trial as judged by the Investigator

 -  Intake of drugs with a long half-life (> 24 hours) within ten half-lives of the
 respective drug before enrolment in the study

 -  Use of any drugs which might influence the results of the trial within two weeks prior
 to administration or during the trial

 -  Participation in another trial with an investigational drug (≤ two months prior to
 administration or during the trial)

 -  Smoker (> 10 cigarettes or > 3 cigars of > 3 pipes/day)

 -  Inability to refrain from smoking on trial days

 -  Alcohol abuse (> 60 g/day)

 -  Drug abuse

 -  Blood donation (≥ 100 ml within four weeks prior to administration or during the
 trial)

 -  Excessive physical activities (within the last week before the study)

 -  Any laboratory value outside the reference range of clinical relevance

 Not necessarily clinically relevant abnormalities, but specific Exclusion criteria for the
 drugs under study or for the study:

 -  Consumption of more than 2 cups of coffee or black tea, or cola drinks, per day during
 the last 6 weeks. However, subjects may participate if abstinence from the before
 mentioned beverages is well tolerated during an interval of at least 2 weeks between
 screening and first treatment

 -  ECG: PQ interval > 210 ms

 -  HR at rest < 55 bpm

 -  Systolic BP < 115 mmHg

 -  Colour vision test abnormal. However, subjects may participate if they are able to
 perform the flicker fusion test without difficulty

 -  Psoriasis (own medical history or relative)

 -  Relevant ophthalmological disease

 -  History of asthma or obstructive pulmonary disease

 -  History (including childhood) of traumatic injury to the head or brain

 -  History (including childhood) of reduced seizure threshold

 -  The following subjects will not be allowed to participate in the study

 -  Any subject involved in professional transportation of human subjects

 -  Any subject involved in operating dangerous machinery