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