Safety, Tolerability and Pharmacokinetics of Oral BIBP 5371 CL in Healthy Male and Female Volunteers

Study Overview
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Brief Summary
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Safety, tolerability and pharmacokinetics (including comparisons of different formulations and investigation of food effect)

Official Title
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Safety, Tolerability and Pharmacokinetics of BIBP 5371 CL Following Oral Administration to Healthy Male and Female Volunteers (Dose Range: 10 - 350 mg). A Double-blind (Within Treatment Groups), Randomised, Placebo-controlled, Single Rising Dose Study, Including Comparisons of 50 mg vs. 100 mg Tablet and Tablet vs. Drinking Solution, and Investigation of Food Effect

Conditions
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Healthy

Intervention / Treatment
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* Drug: BIBP 5371 CL tablet
* Drug: BIBP 5371 CL solution
* Other: High fat, high caloric breakfast
* Drug: Placebo tablet
* Drug: BIBP 5371 CL tablet high dose
* Drug: Placebo drinking solution
* Drug: BIBP 5371 CL tablet low dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female volunteers Age 21 - 50 years Body mass index (BMI) 18.5 - 29.9 kg/m2 Exclusion Criteria: Any finding of the medical examination (including blood pressure, pulse rate, respiratory rate, body temperature and ECG) deviating from normal Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Diseases of the central nervous system or 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 is 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 or during the trial) Participation in another trial with an investigational drug (within 2 months prior to administration or during the trial) Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day) Inability to refrain from smoking on trial days Alcohol abuse (> 60 grams/day) Drug abuse Blood donation (≥ 100 mL within 4 weeks prior to administration or during the trial) Excessive physical activities (within the last week before the study) Any laboratory value outside the reference range of clinical relevance In addition, for female subjects: Pregnancy Positive pregnancy test No adequate contraception e.g. oral contraceptives, intrauterine device, sterilisation Females, who are not surgically sterile will be asked to additionally use barrier contraception methods (e.g. condoms) prior to administration of study medication, during the study and at least 1 month after release from the study Inability to maintain this adequate contraception during the whole study period Lactation period

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: single rising dose BIBP 5371 CL<br> | Drug: BIBP 5371 CL tablet<br>* single rising daily doses<br>|
| Experimental: BIBP 5371 CL tablet high dose<br>to be compared with same daily dose level from single rising dose arm | Drug: BIBP 5371 CL tablet high dose<br> <br> |
| Experimental: BIBP 5371 CL tablet low dose<br>to be compared with same daily dose level from single rising dose arm | Drug: BIBP 5371 CL tablet low dose<br> <br> |
| Placebo Comparator: Placebo drinking solution<br> | Drug: Placebo drinking solution<br> <br> |
| Experimental: BIBP 5371 CL drinking solution<br> | Drug: BIBP 5371 CL solution<br> <br> |
| Experimental: BIBP 5371 CL tablet high dose with food<br> | Other: High fat, high caloric breakfast<br> <br> Drug: BIBP 5371 CL tablet high dose<br> <br> |
| Experimental: BIBP 5371 CL tablet low dose with food<br> | Other: High fat, high caloric breakfast<br> <br> Drug: BIBP 5371 CL tablet low dose<br> <br> |
| Placebo Comparator: Placebo tablet<br> | Drug: Placebo tablet<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with changes in vital signs | blood pressure, pulse rate, respiratory rate, body temperature | baseline, up to 8 days after drug administration | 
| Number of patients with changes in electrocardiogram (ECG) |  | baseline, up to 8 days after drug administration | 
| Number of patients with changes in safety laboratory parameters |  | baseline, up to 8 days after drug administration | 
| Number of patients with adverse events |  | baseline, up to 8 days after drug administration | 
| Global tolerability assessment by the investigator on a verbal rating scale |  | up to 8 days after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (maximum concentration of the analyte in plasma) |  | up to 32 hours after drug administration | 
| tmax (time from dosing to maximum concentration) |  | up to 32 hours after drug administration | 
| AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |  | up to 32 hours after drug administration | 
| %AUC0-tz (the percentage of the AUC0-∞ that is obtained by extrapolation) |  | up to 32 hours after drug administration | 
| λz (terminal rate constant in plasma) |  | up to 32 hours after drug administration | 
| t1/2 (terminal half-life of the analyte in plasma) |  | up to 32 hours after drug administration | 
| MRTpo (mean residence time of the analyte in the body after po administration) |  | up to 32 hours after drug administration | 
| CL/F (apparent clearance of the analyte in the plasma after extravascular administration) |  | up to 32 hours after drug administration | 
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) |  | up to 32 hours after drug administration | 
| Aet1-t2 (amount of analyte eliminated in urine from the time point t1 to time point t2) |  | up to 32 hours after drug administration | 
| fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2) |  | up to 32 hours after drug administration | 
| CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2) |  | up to 32 hours after drug administration |