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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: SD I; Drug: SD II

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: SD I - single rising doses	Drug: SD I
Experimental: SD II - single rising doses	Drug: SD II
Experimental: SD II - single rising doses + Placebo	Drug: Placebo; Drug: SD II

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in lung function measurement specific conductance (SGaw)	up to 5 hours after drug administration
Assessment of tolerability on a 4-point scale	8 days after drug administration
Number of patients with adverse events	up to 25 days
Change in lung function measurements airway resistance (Raw)	up to 5 hours after drug administration
Change in lunf function measurement forced expiratory volume in 1 second (FEV1)	up to 5 hours after drug administration

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Cmax (Maximum measured concentration of the analyte in plasma)	up to 48 hours after drug administration
tmax (Time from dosing to the maximum concentration of the analyte in plasma)	up to 48 hours after drug administration
t½ (Terminal half-life of the analyte in plasma)	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
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
λz (Terminal rate constant 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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: May 1, 2003
• Primary Completion (Actual): February 1, 2004

Study Registration Dates

• First Submitted: July 24, 2014
• First Submitted That Met QC Criteria: July 24, 2014
• First Posted (Estimate): July 25, 2014

Study Record Updates

• Last Update Posted (Estimate): July 25, 2014
• Last Update Submitted That Met QC Criteria: July 24, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Respiratory Aspiration
• Other Study ID Numbers: 1149.44