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Pharmacokinetics, Safety and Tolerability of Rising Doses of Buscopan® in Healthy Male Volunteers

Phase 1
Completed
Conditions
Healthy
Interventions
Registration Number
NCT02261077
Lead Sponsor
Boehringer Ingelheim
Brief Summary

Study to investigate pharmacokinetics, safety and tolerability of Buscopan® after single rising dose and after multiple rising doses

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
Inclusion Criteria
  1. Healthy males based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests. There is no finding deviating from normal and of clinical relevance. There is no evidence of a clinically relevant concomitant disease.
  2. Age ≥21 and age ≤50 years
  3. BMI ≥18.5 and BMI <30 kg/m2 (Body Mass Index)
  4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation
Exclusion Criteria
  1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
  2. Evidence of a clinically relevant concomitant disease
  3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
  4. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
  5. History of relevant orthostatic hypotension, fainting spells or blackouts
  6. Chronic or relevant acute infections
  7. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) as judged clinically relevant by the investigator
  8. Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to randomization
  9. Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to enrolment in the study or during the study
  10. Participation in another trial with an investigational drug within two months prior to randomization
  11. Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day)
  12. Inability to refrain from smoking on trial days as judged by the investigator
  13. Alcohol abuse (more than 40 g/day for males)
  14. Drug abuse
  15. Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
  16. Excessive physical activities within one week prior to administration or during the trial
  17. Any laboratory value outside the reference range that is of clinical relevance
  18. Inability to comply with dietary regimen of trial site
  19. Hypersensitivity to hyoscine butylbromide and/or related drugs of these classes
  20. History of megacolon
  21. History of prostatic hyperplasia
  22. History of mechanical stenosis of the gastrointestinal (e.g. after surgery of the gastrointestinal tract)
  23. History of narrow-angle glaucoma
  24. History of tachycardic arrhythmias
  25. History of myasthenia gravis
  26. Bladder-neck obstruction

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo-
Buscopan, single rising dosesHyoscine butylbromide-
Buscopan, multiple rising dosesHyoscine butylbromide-
Primary Outcome Measures
NameTimeMethod
Maximum measured concentration of analyte in plasma (Cmax)up to 104 hours after last drug administration
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)up to 104 hours after last drug administration
Amount of analyte eliminated in urine from the time point t1 to time point t2 (Aet1-t2)up to 80 hours after last drug administration
Secondary Outcome Measures
NameTimeMethod
Time from dosing to maximum measured concentration (tmax)up to 104 hours after last drug administration
Area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ after administration of the first dose (AUCτ,1)up to 32 hours after drug administration
Terminal rate constant in plasma (λz)up to 104 hours after last drug administration
Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F)up to 104 hours after last drug administration
Amount of analyte eliminated in urine from the time point t1 to time point t2 (Aet1-t2)up to 80 hours after last drug administration
Fraction of analyte eliminated in urine from time point t1 to time point t2 (fet1-t2)up to 80 hours after last drug administration
Renal clearance of the analyte from the time point t1 until the time point t2 (CLR,t1-t2)up to 80 hours after last drug administration
Average concentration of the analyte in plasma at steady-state (Cavg)up to 104 hours after last drug administration
Terminal half-life of the analyte in plasma (t1/2)up to 104 hours after last drug administration
Mean residence time of the analyte in the body (MRTpo)up to 104 hours after last drug administration
Total/apparent clearance in plasma after extravascular administration (CL/F)up to 104 hours after last drug administration
Minimum concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmin,ss)up to 104 hours after last drug administration
Predose concentration of the analyte in plasma at steady state immediately before administration of the next dose (Cpre,ss)predose on days 1-4
Linearity index (LI)up to 104 hours after last drug administration
Accumulation ratio (RA) based on Cmax (RA,Cmax,N)up to 104 hours after last drug administration
RA,AUC,N based on AUC0-τup to 104 hours after last drug administration
Number of subjects with clinically relevant findings in vital sign parameters (blood pressure (BP), pulse rate (PR))up to 14 days after last drug administration
Number of subjects with clinically relevant findings in 12-lead electrocardiogramup to 14 days after last drug administration
Number of subjects with abnormal changes in laboratory parametersup to 14 days after last drug administration
Number of subjects with abnormal findings in physical examinationup to 14 days after last drug administration
Occurrence of adverse eventsup to 47 days
Tolerability assessed by investigator on a 4-point scalewithin 14 days after last drug administration
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