Clinical trial NCT02261077: Pharmacokinetics, Safety and Tolerability of Rising Doses of Buscopan® in Healthy Male Volunteers
Official title: A Randomised, Double-blind, Placebo-controlled Study to Assess Pharmacokinetics, Safety and Tolerability of Single Rising Oral Doses (20 mg, 60 mg, 100 mg, 200 mg and 400 mg) and Multiple Rising Oral Doses (3 x 20 mg, 3 x 60 mg and 3 x 100 mg Per Day) of Buscopan® in Healthy Male Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-10-10
Enrollment: 60
Sex: ALL
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Maximum measured concentration of analyte in plasma (Cmax)
timeFrame: up to 104 hours after last drug administration
measure: Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)
timeFrame: up to 104 hours after last drug administration
measure: Amount of analyte eliminated in urine from the time point t1 to time point t2 (Aet1-t2)
timeFrame: up to 80 hours after last drug administration
Secondary outcomes:
measure: Time from dosing to maximum measured concentration (tmax)
timeFrame: up to 104 hours after last drug administration
measure: 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)
timeFrame: up to 32 hours after drug administration
measure: Terminal rate constant in plasma (λz)
timeFrame: up to 104 hours after last drug administration
measure: Terminal half-life of the analyte in plasma (t1/2)
timeFrame: up to 104 hours after last drug administration
measure: Mean residence time of the analyte in the body (MRTpo)
timeFrame: up to 104 hours after last drug administration
measure: Total/apparent clearance in plasma after extravascular administration (CL/F)
timeFrame: up to 104 hours after last drug administration
measure: Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F)
timeFrame: up to 104 hours after last drug administration
measure: Amount of analyte eliminated in urine from the time point t1 to time point t2 (Aet1-t2)
timeFrame: up to 80 hours after last drug administration
measure: Fraction of analyte eliminated in urine from time point t1 to time point t2 (fet1-t2)
timeFrame: up to 80 hours after last drug administration
measure: Renal clearance of the analyte from the time point t1 until the time point t2 (CLR,t1-t2)
timeFrame: up to 80 hours after last drug administration
measure: Average concentration of the analyte in plasma at steady-state (Cavg)
timeFrame: up to 104 hours after last drug administration
measure: Minimum concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmin,ss)
timeFrame: up to 104 hours after last drug administration
measure: Predose concentration of the analyte in plasma at steady state immediately before administration of the next dose (Cpre,ss)
timeFrame: predose on days 1-4
measure: Linearity index (LI)
timeFrame: up to 104 hours after last drug administration
measure: Accumulation ratio (RA) based on Cmax (RA,Cmax,N)
timeFrame: up to 104 hours after last drug administration
measure: RA,AUC,N based on AUC0-τ
timeFrame: up to 104 hours after last drug administration
measure: Number of subjects with clinically relevant findings in vital sign parameters (blood pressure (BP), pulse rate (PR))
timeFrame: up to 14 days after last drug administration
measure: Number of subjects with clinically relevant findings in 12-lead electrocardiogram
timeFrame: up to 14 days after last drug administration
measure: Number of subjects with abnormal changes in laboratory parameters
timeFrame: up to 14 days after last drug administration
measure: Number of subjects with abnormal findings in physical examination
timeFrame: up to 14 days after last drug administration
measure: Occurrence of adverse events
timeFrame: up to 47 days
measure: Tolerability assessed by investigator on a 4-point scale
timeFrame: within 14 days after last drug administration
Other outcomes:
Locations:
Study officials:
References: