Clinical trial NCT02199860: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-07-25
Enrollment: 63
Sex: ALL
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Number of patients with adverse events
timeFrame: up to 25 days
measure: Assessment of tolerability on a 4-point scale
timeFrame: 8 days after drug administration
measure: Change in lung function measurements airway resistance (Raw)
timeFrame: up to 5 hours after drug administration
measure: Change in lung function measurement specific conductance (SGaw)
timeFrame: up to 5 hours after drug administration
measure: Change in lunf function measurement forced expiratory volume in 1 second (FEV1)
timeFrame: up to 5 hours after drug administration
Secondary outcomes:
measure: Cmax (Maximum measured concentration of the analyte in plasma)
timeFrame: up to 48 hours after drug administration
measure: tmax (Time from dosing to the maximum concentration of the analyte in plasma)
timeFrame: up to 48 hours after drug administration
measure: AUC0-∞ (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
timeFrame: up to 48 hours after drug administration
measure: 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)
timeFrame: up to 48 hours after drug administration
measure: λz (Terminal rate constant in plasma)
timeFrame: up to 48 hours after drug administration
measure: t½ (Terminal half-life of the analyte in plasma)
timeFrame: up to 48 hours after drug administration
measure: MRTih (Mean residence time of the analyte in the body after inhalation)
timeFrame: up to 48 hours after drug administration
measure: CL/F (Apparent clearance of the analyte in plasma following extravascular administration)
timeFrame: up to 48 hours after drug administration
measure: Vz/F (Apparent volume of distribution of the analyte during the terminal phase)
timeFrame: up to 48 hours after drug administration
Other outcomes:
Locations:
Study officials:
References: