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

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

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Hyoscine butylbromide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Age ≥21 and age ≤50 years BMI ≥18.5 and BMI <30 kg/m2 (Body Mass Index) Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation Exclusion Criteria: Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance Evidence of a clinically relevant concomitant disease Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders History of relevant orthostatic hypotension, fainting spells or blackouts Chronic or relevant acute infections History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) as judged clinically relevant by the investigator 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 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 Participation in another trial with an investigational drug within two months prior to randomization Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day) Inability to refrain from smoking on trial days as judged by the investigator Alcohol abuse (more than 40 g/day for males) Drug abuse Blood donation (more than 100 mL within four weeks prior to administration or during the trial) Excessive physical activities within one week prior to administration or during the trial Any laboratory value outside the reference range that is of clinical relevance Inability to comply with dietary regimen of trial site Hypersensitivity to hyoscine butylbromide and/or related drugs of these classes History of megacolon History of prostatic hyperplasia History of mechanical stenosis of the gastrointestinal (e.g. after surgery of the gastrointestinal tract) History of narrow-angle glaucoma History of tachycardic arrhythmias History of myasthenia gravis Bladder-neck obstruction

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Buscopan, single rising doses<br> | Drug: Hyoscine butylbromide<br> <br> * Other names: Buscopan®;|
| Experimental: Buscopan, multiple rising doses<br> | Drug: Hyoscine butylbromide<br> <br> * Other names: Buscopan®;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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-τ |  | up 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 electrocardiogram |  | up to 14 days after last drug administration | 
| Number of subjects with abnormal changes in laboratory parameters |  | up to 14 days after last drug administration | 
| Number of subjects with abnormal findings in physical examination |  | up to 14 days after last drug administration | 
| Occurrence of adverse events |  | up to 47 days | 
| Tolerability assessed by investigator on a 4-point scale |  | within 14 days after last drug administration |