Study to Evaluate Safety, Tolerability and Pharmacokinetics of Increasing Repeated Oral Doses of Ambroxol Lozenges in Healthy Male Volunteers

A Double-blind (at Each Dose Level), Randomised, Placebo Controlled Phase I Study to Evaluate Safety, Tolerability and Pharmacokinetics of Increasing Repeated Oral Doses of Ambroxol Lozenges (Dosage: 20, 40, 80 mg Three Times Daily) Over 4 Days in Healthy Male Volunteers

The main objectives of the present study are to determine pharmacokinetics of ambroxol in healthy male volunteers following repeated administration of lozenges of 20 mg ambroxol for four days

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Ambroxol - in single rising doses

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy males according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs, 12-lead Electrocardiogram (ECG), clinical laboratory tests
• Age ≥21 and Age ≤50 year
• 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:

• Any finding of the medical examination (including vital signs 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
• Surgery of the gastrointestinal tract (except appendectomy)
• 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)
• 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 or that prolong the QT/QTc interval 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
• Actual smoker
• Alcohol abuse (more than 40 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 trial site
• A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms)
• A history of additional risk factors for torsade de pointes (e.g., heart failure, hypokalaemia, family history of Long QT Syndrome)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo
EXPERIMENTAL: Ambroxol - in single rising doses	Drug: Ambroxol - in single rising doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax (maximum measured concentration of the analyte in plasma)	up to 24 hours after drug administration
tmax (time from dosing to the maximum concentration of the analyte in plasma)	up to 24 hours after drug administration
AUC0-24 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours)	up to 24 hours after drug administration
Ae0-24 (amount of the analyte that is eliminated in urine from the time point 0 until time point 24)	up to 24 hours after drug administration
CLR,0-24 (renal clearance of the analyte determined from the time point 0 until time point 24) using AUC0-24 and Ae0-24	up to 24 hours after drug administration
Cmax,ss (maximum concentration of the analyte in plasma at steady state)	up to 120 hours after first drug administration
tmax,ss (time from last dosing to maximum concentration at steady state)	up to 120 hours after first drug administration
Cmin,ss (minimum concentration of the analyte in plasma at steady state)	up to 120 hours after first drug administration
AUC72-96,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform 24 hour interval matching Day 1)	up to 96 hours after first drug administration
Ae72-96,ss (amount of analyte that is eliminated in urine at steady state from the time point 72 to time point 96)	up to 96 hours after first drug administration
CLR,72-96,ss (renal clearance of the analyte in plasma from the time point 72 until the time point 96 at steady state) using AUC72-96 and Ae72-96	up to 96 hours after first drug administration
λz,ss (terminal rate constant in plasma at steady state)	up to 120 hours after first drug administration
t1/2,ss (terminal half-life of the analyte in plasma at steady state)	up to 120 hours after first drug administration
RA (accumulation ratio)	up to 96 hours after first drug administration
LI (linearity index)	up to 96 hours after first drug administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with adverse events	up to 36 days
Number of patients with abnormal changes in laboratory parameters	up to 36 days
Number of patients with clinically significant changes in vital signs (blood pressure [BP], pulse rate [PR])	up to 36 days
Number of patients with clinically significant changes in 12-lead electrocardiogram (ECG)	up to 36 days
Assessment of tolerability on a 4-point scale	10 days after last drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (ACTUAL): November 1, 2009

Study Registration Dates

• First Submitted: July 17, 2014
• First Submitted That Met QC Criteria: July 17, 2014
• First Posted (ESTIMATE): July 18, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): July 23, 2014
• Last Update Submitted That Met QC Criteria: July 22, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory System Agents; Expectorants; Ambroxol
• Other Study ID Numbers: 18.493