Investigation of the Metabolism and Pharmacokinetics of Ambroxol in Healthy Male Volunteers

NCT02194257 | Completed Phase 1

• 1 other identifier: 18.494
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

Study to determine the basic pharmacokinetics of ambroxol and \[14C\]-radioactivity including mass balance, excretion pathways and complete metabolism in healthy male volunteers following administration of a lozenge of 20 mg ambroxol together with an oral solution of 0.4 mg \[14C\]-ambroxol labelled in two different positions

Conditions

Healthy

Outcome Measures

Primary Outcomes (22)

• Individual time course profiles of [14C]-radioactivity (in nmoleq/L or nmoleq/kg for faeces) in plasma

  up to 120 hours after drug administration

• Individual time course profiles of ambroxol in plasma

  up to 120 hours after drug administration

• Rate and extent of excretion mass balance based on the total radioactivity in urine and faeces

  up to 216 hours after drug administration

• Identification of major metabolites in urine, feces and plasma in comparison with various animal species

  up to 48 hours after drug administration

• Cblood cells/Cplasma ratio of [14C]-radioactivity and Cblood /Cplasma ratio of [14C]-radioactivity

  up to 120 hours after drug administration

• Cmax (maximum concentration of the analyte(s) in plasma)

  up to 120 hours after drug administration

• tmax (time from dosing to the maximum concentration of the analyte(s) in plasma)

  up to 120 hours after drug administration

• AUC0-tz (area under the concentration-time curve of the analyte(s) in plasma over the time interval from 0 to the time of the last quantifiable data point)

  up to 120 hours after drug administration

• AUC0-∞ (area under the concentration-time curve of the analyte(s) in plasma over the time interval from 0 to infinity)

  up to 120 hours after drug administration

• λz (terminal rate constant in plasma)

  up to 120 hours after drug administration

• t1/2 (terminal half-life of the analyte(s) in plasma)

  up to 120 hours after drug administration

• MRTpo (mean residence time of the analyte(s) in the body after oral administration)

  up to 120 hours after drug administration

• CL/F (total clearance of the analyte in plasma after oral administration)

  up to 120 hours after drug administration

• Vz/F (apparent volume of distribution during the terminal phase λz following an oral dose)

  up to 120 hours after drug administration

• Ae0-tz (amount of analyte that is eliminated in urine within the time interval zero to tz)

  up to 216 hours after drug administration

• Aefaeces,0-tz (amount of analyte excreted in faeces within the time interval zero to tz)

  up to 216 hours after drug administration

• fefaeces,0-tz (fraction of analyte excreted in faeces within the time interval zero to tz in % of dose)

  up to 216 hours after drug administration

• CLR,t1-t2 (renal clearance of analyte from the within the time interval t1 to t2)

  up to 216 hours after drug administration

• fe0-tz (fraction of analyte excreted in urine within the time interval zero to tz in % of dose)

  up to 216 hours after drug administration

• Individual time course profiles of [14C]-radioactivity (in nmoleq/L or nmoleq/kg for faeces) in urine

  up to 216 hours after drug administration

• Individual time course profiles of [14C]-radioactivity (in nmoleq/L or nmoleq/kg for faeces) in faeces

  up to 216 hours after drug administration

• Individual time course profiles of ambroxol in urine

  up to 216 hours after drug administration

Secondary Outcomes (5)

• Number of patients with clinically significant changes vital signs (blood pressure [BP], pulse rate [PR])

  up to 39 days

• Number of patients with adverse events

  up to 39 days

• Number of patients with clinically significant changes in 12-lead electrocardiogram (ECG)

  up to 39 days

• Number of patients with abnormal changes in laboratory parameters

  up to 39 days

• Assessment of tolerability on a 4-point scale

  Day 14

Study Arms (2)

[14C]-cyclohexane ambroxol oral solution + ambroxol lozenge

EXPERIMENTAL

Drug: [14C]-cyclohexane ambroxol oral solution; Drug: Ambroxol lozenge

[14C]-benzyl ambroxol oral solution + ambroxol lozenge

EXPERIMENTAL

Drug: [14C]-benzyl ambroxol oral solution; Drug: Ambroxol lozenge

Interventions

[14C]-cyclohexane ambroxol oral solution DRUG

[14C]-cyclohexane ambroxol oral solution + ambroxol lozenge

[14C]-benzyl ambroxol oral solution DRUG

[14C]-benzyl ambroxol oral solution + ambroxol lozenge

Ambroxol lozenge DRUG

[14C]-benzyl ambroxol oral solution + ambroxol lozenge; [14C]-cyclohexane ambroxol oral solution + ambroxol lozenge

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy males 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
• Age ≥18 and ≤65 years
• Body mass index (BMI) ≥18.5 and BMI ≤29.9 kg/m2
• Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation

You may not qualify if:

• Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
• Any 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 study drug or its excipients)
• Intake of drugs with a long half-life (\> 24 hours) within at least one month or less than ten 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 ten days prior to administration until after the last sample from Visit 2 is collected
• Participation in another trial with an investigational drug within two months prior to administration or during the trial
• Smoker (\> 10 cigarettes or \> 3 cigars or \> 3 pipes/day)
• Inability to refrain from smoking during the stay in the trial centre
• Alcohol abuse (more than on average two units of alcoholic beverages per day or more than 14 units per week (one unit equals one pint \[285 mL\] of beer or lager, one glass \[125 mL\] of wine, 25 mL shot of 40% spirit)).
• Drug abuse
• Blood donation (more than 100 mL within 60 days prior to study drug administration or during the trial)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2014
• First Posted: July 18, 2014
• Study Start: October 1, 2008
• Primary Completion: December 1, 2008
• Last Updated: July 18, 2014

Record last verified: 2014-07