Pharmacokinetics and Bioavailability Study of Lasolvan Hard Capsules and Effervescent Tablets in Healthy Volunteers

Healthy Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02036775
• Other study ID #: 18.510
• Status: Completed
• Phase: Phase 1
• First received: January 13, 2014
• Last updated: May 12, 2015
• Start date: March 2014
• Est. completion date: May 2014

Study information

• Verified date: May 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Russia: Pharmacological Committee, Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Lasolvan tablet
One Lasolvan tablet 30 mg twice daily for 5 days.
• Lasolvan tablet
One Lasolvan tablet 30 mg twice daily for 5 days.
• Lasolvan tablet
One Lasolvan tablet 30 mg twice daily for 5 days.
• Lasolvan tablet
One Lasolvan tablet 30 mg twice daily for 5 days.
• Lasolvan effervescent tablet
One-half Lasolvan effervescent tablet 60mg twice daily for 5 days.
• Lasolvan effervescent tablet
One-half Lasolvan effervescent tablet 60mg twice daily for 5 days.
• Lasolvan effervescent tablet
One-half Lasolvan effervescent tablet 60mg twice daily for 5 days.
• Lasolvan prolonged-release hard capsule
One Lasolvan prolonged-release hard capsule 75 mg once daily for 5 days
• Lasolvan prolonged-release hard capsule
One Lasolvan prolonged-release hard capsule 75 mg once daily for 5 days
• Lasolvan prolonged-released capsules
One Lasolvan prolonged-release hard capsule 75 mg once daily for 5 days
• Lasolvan tablet
One Lasolvan tablet 30 mg twice daily for 5 days.
• Lasolvan tablet
One Lasolvan tablet 30 mg twice daily for 5 days.
• Lasolvan prolonged-release hard capsule
One Lasolvan prolonged-release hard capsule 75 mg once daily for 5 days
• Lasolvan effervescent tablet
One-half Lasolvan effervescent tablet 60mg twice daily for 5 days.
• Lasolvan prolonged-release hard capsule
One Lasolvan prolonged-release hard capsule 75 mg once daily for 5 days
• Lasolvan prolonged-release hard capsule
One Lasolvan prolonged-release hard capsule 75 mg once daily for 5 days
• Lasolvan effervescent tablet
One-half Lasolvan effervescent tablet 60mg twice daily for 5 days.
• Lasolvan effervescent tablet
One-half Lasolvan effervescent tablet 60mg twice daily for 5 days.

Locations

Country	Name	City	State
Russian Federation	18.510.2 Boehringer Ingelheim Investigational Site	St. Petersburg

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to 24 h at Steady State	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)	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	No
Primary	Maximum Measured Concentration of the Analyte in Plasma at Steady State	Maximum measured concentration of the analyte in plasma at steady state (Cmax ss)	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	No
Secondary	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	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)	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	No
Secondary	Rate of Absorption at Steady State (Cmax ss/AUCss 0-24)	Metric which characterises the rate of absorption at steady state (Cmax ss/AUCss 0-24)	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	No
Secondary	Steady State Concentration of the Analyte in Plasma at the End of Dosing Interval	Steady state concentration of the analyte in plasma at the end of dosing interval (Cmin ss)	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	No
Secondary	Average Concentration of the Analyte in Plasma in the Time Interval of 0 to 24 h at Steady State	Average concentration of the analyte in plasma in the time interval of 0 to 24 h at steady state (Cav ss)	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	No
Secondary	Time From Dosing to the Maximum Concentration of the Analyte in Plasma at Steady State	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.	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	No
Secondary	Peak-trough Fluctuation Between Minimum and Maximum Concentration of the Analyte in Plasma	Peak-trough fluctuation between minimum and maximum concentration of the analyte in plasma (PTF)	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	No
Secondary	Peak-trough Swing	Peak-trough swing (PTS) calculated as ((Cmax,ss - Cmin,ss / Cav,ss)*100)	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	No
Secondary	Time Period When Concentration of the Analyte Exceeds Cav ss	Time period when the concentration of the analyte exceeds Cav ss (T (C>Cav ss))	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	No
Secondary	Plateau Time During Which Concentration of the Analyte in Plasma Exceeds 75% of Cmax ss	Plateau time during which concentration of the analyte in plasma exceeds 75% of Cmax ss (T(C>75% Cmax ss))	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	No

External Links

•   Link