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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

Phase 1
Completed
Conditions
Healthy
Interventions
Registration Number
NCT02199860
Lead Sponsor
Boehringer Ingelheim
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
63
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
SD I - single rising dosesSD I-
SD II - single rising doses + PlaceboPlacebo-
SD II - single rising doses + PlaceboSD II-
SD II - single rising dosesSD II-
PlaceboPlacebo-
Primary Outcome Measures
NameTimeMethod
Number of patients with adverse eventsup to 25 days
Change in lung function measurement specific conductance (SGaw)up to 5 hours after drug administration
Assessment of tolerability on a 4-point scale8 days after drug administration
Change in lunf function measurement forced expiratory volume in 1 second (FEV1)up to 5 hours after drug administration
Change in lung function measurements airway resistance (Raw)up to 5 hours after drug administration
Secondary Outcome Measures
NameTimeMethod
tmax (Time from dosing to the maximum concentration of the analyte in plasma)up to 48 hours after drug administration
λz (Terminal rate constant in plasma)up to 48 hours after drug administration
Cmax (Maximum measured concentration of the analyte in plasma)up to 48 hours after drug administration
AUC0-∞ (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)up to 48 hours after drug administration
t½ (Terminal half-life of the analyte in plasma)up to 48 hours after drug administration
MRTih (Mean residence time of the analyte in the body after inhalation)up to 48 hours after drug administration
AUC0-tz (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)up to 48 hours after drug administration
CL/F (Apparent clearance of the analyte in plasma following extravascular administration)up to 48 hours after drug administration
Vz/F (Apparent volume of distribution of the analyte during the terminal phase)up to 48 hours after drug administration
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