- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02036775
Pharmacokinetics and Bioavailability Study of Lasolvan Hard Capsules and Effervescent Tablets in Healthy Volunteers
May 12, 2015 updated by: Boehringer Ingelheim
An Open-label, Randomised, Multiple-dose, Three-period Crossover Study in Healthy Male and Female Volunteers to Characterise Pharmacokinetics and Assess the Relative Bioavailability of Two New Oral Formulations of Ambroxol Hydrochloride as Lasolvan® Prolonged-release Hard Capsules 75 mg and Lasolvan® Effervescent Tablets 60 mg Compared to Lasolvan® Tablets 30 mg.
To characterise pharmacokinetics and assess the relative bioavailability of two new oral formulations of ambroxol hydrochloride as Lasolvan® prolonged-release hard capsules 75 mg and Lasolvan® effervescent tablets 60 mg compared to Lasolvan® tablets 30 mg
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
24
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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St. Petersburg, Russian Federation
- 18.510.2 Boehringer Ingelheim Investigational Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 45 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion criteria:
- Given written informed consent for participation in the study.
- Male and female subjects aged 18-45, inclusive.
- Body mass index by Quetelet 18.50 - 24.99 kg/m2, inclusive.
- Judged by the investigator to be in good health as documented by the medical history, physical examination (including but may not be limited to an evaluation of the cardiovascular, gastrointestinal, and renal systems), vital signs assessments, 12-lead electrocardiogram (ECG), clinical laboratory assessments, and by general observations. Any abnormalities outside normal ranges for any clinical testing (laboratory tests, ECG, vital signs) can be repeated at the discretion of the investigator and judged to be not clinically significant for the study participation.
- Female subjects of childbearing potential who agree on using double-barrier contraception during the study. If female is postmenopausal (no menses for at least 1 year) or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) she will be exempt from the requirement. In case of using oral contraceptives, they should be withdrawn at least 2 months before the study.
- Male subjects who agree on using effective contraception during the study (barrier contraceptive methods).
Exclusion criteria:
- Known hypersensitivity to ambroxol hydrochloride, or other constituents of the test and reference products.
- Known rare hereditary conditions (Stevens-Johnson syndrome, toxic epidermal necrolysis, galactose intolerance, Lapp-lactase deficiency, glucose-galactose malabsorption).
- Pregnancy or breastfeeding.
- Chronic hepatic, renal, cardiovascular, respiratory, gastrointestinal, neuroendocrine diseases and blood disorders.
- Positive results of blood tests for current infections (HIV, syphilis, hepatitis B or C).
- Surgery of gastro-intestinal tract (except of appendectomy) within the past 8 weeks.
- Acute infections occurred within 4 weeks before inclusion into the study.
- Regular drug intake within 2 weeks before inclusion into the study.
- Intake of systemic drugs known to affect cytochrome P450 system (induce or inhibit) within 4 weeks before inclusion into the study.
- Blood donation (greater or equal 450 ml) within 2 months before inclusion into the study.
- Alcohol intake greater than or equal to 10 units of alcohol per week (1 unit of alcohol equals one 50 ml single measure of whisky (ABV - alcohol by volume 40%), or 0.5 litre of beer (ABV 5%), or 200 ml glass of red wine (ABV 12%) or history of alcohol abuse, narcomania, or other drug abuse.
- A positive urine drug test (cannabis, benzodiazepines, barbiturates, opiates, cocaine, amphetamines) at screening and before the first dosing in each study period.
- A positive alcohol test at screening and before the first dosing in each study period
- Participation in another phase I clinical study within 3 months before inclusion into the study.
- Known lactose intolerance.
- Known phenylketonuria
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment sequence 1
Treatment 1, Washout 6 days, Reference product, Washout 6 days, Treatment 2
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One Lasolvan tablet 30 mg twice daily for 5 days.
One-half Lasolvan effervescent tablet 60mg twice daily for 5 days.
One Lasolvan prolonged-release hard capsule 75 mg once daily for 5 days
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Experimental: Treatment sequence 2
Treatment 2, Washout period 6 days, Treatment 1, Washout 6 days, Reference product
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One Lasolvan tablet 30 mg twice daily for 5 days.
One-half Lasolvan effervescent tablet 60mg twice daily for 5 days.
One Lasolvan prolonged-release hard capsule 75 mg once daily for 5 days
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Experimental: Treatment sequence 3
Reference product, Washout 6 days, Treatment 2, Washout 6 days, Treatment 1
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One Lasolvan tablet 30 mg twice daily for 5 days.
One-half Lasolvan effervescent tablet 60mg twice daily for 5 days.
One Lasolvan prolonged-release hard capsule 75 mg once daily for 5 days
|
Experimental: Treatment Sequence 4
Treatment 2, Washout 6 days, Reference product, Washout 6 days, Treatment 1
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One Lasolvan tablet 30 mg twice daily for 5 days.
One-half Lasolvan effervescent tablet 60mg twice daily for 5 days.
One Lasolvan prolonged-release hard capsule 75 mg once daily for 5 days
|
Experimental: Treatment sequence 5
Reference product, Washout 6 days, Treatment 1, Washout 6 days, Treatment 2
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One Lasolvan tablet 30 mg twice daily for 5 days.
One-half Lasolvan effervescent tablet 60mg twice daily for 5 days.
One Lasolvan prolonged-release hard capsule 75 mg once daily for 5 days
|
Experimental: Treatment Sequence 6
Treatment 1, Washout 6 days, Treatment 2, Washout 6 days, Reference product
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One Lasolvan tablet 30 mg twice daily for 5 days.
One-half Lasolvan effervescent tablet 60mg twice daily for 5 days.
One Lasolvan prolonged-release hard capsule 75 mg once daily for 5 days
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to 24 h at Steady State
Time Frame: Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 h at steady state (AUCss 0-24)
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Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Maximum Measured Concentration of the Analyte in Plasma at Steady State
Time Frame: Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Maximum measured concentration of the analyte in plasma at steady state (Cmax ss)
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Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State During 0-24 h, Adjusted to a Daily Dose of 60 mg
Time Frame: Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Area under the concentration-time curve of the analyte in plasma at steady state during 0-24 h, adjusted to a daily dose of 60 mg (AUCss 0-24 norm)
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Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Rate of Absorption at Steady State (Cmax ss/AUCss 0-24)
Time Frame: Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Metric which characterises the rate of absorption at steady state (Cmax ss/AUCss 0-24)
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Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Steady State Concentration of the Analyte in Plasma at the End of Dosing Interval
Time Frame: Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Steady state concentration of the analyte in plasma at the end of dosing interval (Cmin ss)
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Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Average Concentration of the Analyte in Plasma in the Time Interval of 0 to 24 h at Steady State
Time Frame: Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Average concentration of the analyte in plasma in the time interval of 0 to 24 h at steady state (Cav ss)
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Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Time From Dosing to the Maximum Concentration of the Analyte in Plasma at Steady State
Time Frame: Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Time from dosing to the maximum concentration of the analyte in plasma at steady state (tmax ss).
For Lasolvan 30mg and Lasolvan 60mg, tmax ss was determined as tmax ss 0-12 and tmax ss 12-24.
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Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Peak-trough Fluctuation Between Minimum and Maximum Concentration of the Analyte in Plasma
Time Frame: Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Peak-trough fluctuation between minimum and maximum concentration of the analyte in plasma (PTF)
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Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Peak-trough Swing
Time Frame: Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Peak-trough swing (PTS) calculated as ((Cmax,ss - Cmin,ss / Cav,ss)*100)
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Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Time Period When Concentration of the Analyte Exceeds Cav ss
Time Frame: Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Time period when the concentration of the analyte exceeds Cav ss (T (C>Cav ss))
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Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Plateau Time During Which Concentration of the Analyte in Plasma Exceeds 75% of Cmax ss
Time Frame: Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Plateau time during which concentration of the analyte in plasma exceeds 75% of Cmax ss (T(C>75% Cmax ss))
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Pre-dose, 30min, 1h, 1h 30min, 2h, 3h, 4h, 5h, 6h, 7h 30min, 9h, 10h 30min, 12h, 14h, 17h, 20h, 24h after the morning dose for all treatments; also 15min, 45min, 12h 15min, 12h 30min, 12h 45min, 13h, 13h 30min, 15h, 16h for Lasolvan 60mg and Lasolvan 30mg
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2014
Primary Completion (Actual)
May 1, 2014
Study Completion (Actual)
May 1, 2014
Study Registration Dates
First Submitted
January 13, 2014
First Submitted That Met QC Criteria
January 13, 2014
First Posted (Estimate)
January 15, 2014
Study Record Updates
Last Update Posted (Estimate)
May 13, 2015
Last Update Submitted That Met QC Criteria
May 12, 2015
Last Verified
May 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 18.510
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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