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

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

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 In case of using oral contraceptives, they should be withdrawn at least 2 months before the study.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