The purpose of the present study was to obtain information about the safety, tolerability and pharmacokinetics of BIBN 4096 BS after single inhalation administration of rising doses of spray-dried powder in healthy male and female volunteers. According to the original protocol, the primary objective was to investigate the safety and tolerability of single doses of a new spray-dried inhalation formulation of BIBN 4096 BS (SD I). Following implementation of Amendment 2, this objective was extended to the second spray-dried inhalation formulation SD II with and without concomitant administration of lactose

Inclusion Criteria:

Subjects could be included in the study if they met the following criteria:

• Healthy male or female volunteers
• Written informed consent in accordance with Good Clinical Practice (GCP) and the local legislation prior to admission to the study
• Age 21 - 50 years
• Body mass index (BMI): 18.5 - 29.9 kg/m2

Exclusion Criteria:

Subjects were not allowed to participate if any of the following applied:

• Any finding of the medical examination (including blood pressure, pulse rate, Respiratory rate, body temperature and ECG) deviating from normal and of clinical relevance

• Raw > 3 cm H2O • s • L-1 or FEV1 <80% of predicted

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

• Diseases of the central nervous system, 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 was deemed relevant to the trial as judged by the investigator

• Intake of drugs with a long half-life (>24 hours) within at least 1 month or less than 10 half-lives of the respective drug before enrolment in the study

• Use of any drugs which might influence the results of the trial (within 1 week prior to administration of investigational drug or during the trial)

• Participation in another trial with an investigational drug (within 2 months prior to drug administration or during the trial)

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

• Inability to refrain from smoking on trial days

• Alcohol abuse (>60 gram/day)

• Drug abuse

• Blood donation (≥100 mL within 4 weeks prior to administration of investigational drug or during the trial)

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

• Any laboratory value outside the reference range and of clinical relevance

• For female subjects:

  • Pregnancy
  • Positive pregnancy test
  • No adequate contraception e.g. oral contraceptives, sterilization, intrauterine device
  • Inability to maintain this adequate contraception during the whole study period,
  • Lactation period