Relative Bioavailability of Ambroxol Hydrochloride of Soft Pastilles Compared to Ambroxol Hydrochloride Syrup in Healthy Male and Female Volunteers

Study Overview
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Brief Summary
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Study to investigate the relative bioavailability of ambroxol hydrochloride soft pastilles 15 mg vs. ambroxol hydrochloride (HCL) 15 mg of syrup (15mg/5mL, Reference I) and ambroxol hydrochloride 15 mg of syrup (30mg/5mL, Reference II) in a fasted state

Official Title
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Relative Bioavailability of Ambroxol Hydrochloride Following Oral Administration of Soft Pastilles 15 mg (Test) Compared to 15 mg of Syrup (15mg/5mL, Reference I) and Compared to 15 mg of Syrup (30mg/5mL) (Reference II) in Healthy Male and Female Volunteers. An Open-label, Randomised, Single-dose, 3-way Crossover Study

Conditions
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Healthy

Intervention / Treatment
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* Drug: Ambroxol hydrochloride - soft pastille
* Drug: Ambroxol hydrochloride - syrup - low dose
* Drug: Ambroxol hydrochloride - syrup - high dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males and females according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead Electrocardiogram (ECG), clinical laboratory tests No finding deviating from normal and of clinical relevance No evidence of a clinically relevant concomitant disease Age ≥18 and Age ≤55 years BMI ≥18.5 and BMI ≤29.9 kg/m2 (Body Mass Index) Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation Exclusion Criteria: 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 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 one month or less than 10 half-lives of the respective drug prior to administration or during the trial 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 administration or during the trial Participation in another trial with an investigational drug within two months prior to administration or during the trial Smoker (more than 10 cigarettes or 3 cigars or 3 pipes/day) Alcohol abuse (more than 60 g/day) 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 study centre For female subjects: Pregnancy Positive pregnancy test No adequate contraception e.g. oral contraceptives, sterilization, intrauterine device (IUD) Inability to maintain this adequate contraception during the whole study period Lactation period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ambroxol hydrochloride - soft pastille<br> | Drug: Ambroxol hydrochloride - soft pastille<br> <br> |
| Active Comparator: Ambroxol hydrochloride - syrup - low dose<br> | Drug: Ambroxol hydrochloride - syrup - low dose<br> <br> |
| Active Comparator: Ambroxol hydrochloride - syrup - high dose<br> | Drug: Ambroxol hydrochloride - syrup - high dose<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 30 hours after each drug administration | 
| Cmax (maximum concentration of the analyte in plasma) |  | up to 30 hours after each drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point) |  | up to 30 hours after each drug administration | 
| tmax (time from dosing to the maximum concentration of the analyte in plasma) |  | up to 30 hours after each drug administration | 
| λz (terminal rate constant in plasma) |  | up to 30 hours after each drug administration | 
| t1/2 (terminal half-life of the analyte in plasma) |  | up to 30 hours after each drug administration | 
| MRTpo (mean residence time of the analyte in the body after p.o. (oral) administration) |  | up to 30 hours after each drug administration | 
| CL/F (apparent clearance of the analyte in the plasma after extravascular administration) |  | up to 30 hours after each drug administration | 
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) |  | up to 30 hours after each drug administration | 
| Number of patients with adverse events |  | up to 40 days | 
| Number of patients with abnormal changes in laboratory parameters |  | up to 40 days | 
| Number of patients with clinically significant changes in vital signs (BP (Blood pressure), PR (Pulse rate)) |  | up to 40 days | 
| Assessment of tolerability by investigator on a 4-point scale |  | within 8 days after last administration |