Single Rising Dose Study Investigating the Safety, Tolerability and Pharmacokinetics of Spray Dried BIBN 4096 BS After Inhalation Administration in Healthy Male and Female Volunteers

A Double-blind (at Each Dose Level), Randomised, Placebo-controlled, Single Rising Dose Study Investigating the Safety, Tolerability and Pharmacokinetics of Two Spray-dried Formulations of BIBN 4096 BS After Inhalation Administration in Healthy Male and Female Volunteers

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