Pharmacokinetics and Bioavailability Study of Lasolvan Hard Capsules and Effervescent Tablets in Healthy Volunteers
Condition: Healthy
Intervention: Lasolvan tablet; Lasolvan tablet; Lasolvan tablet; Lasolvan tablet; Lasolvan effervescent tablet; Lasolvan effervescent tablet; Lasolvan effervescent tablet; Lasolvan prolonged-release hard capsule; Lasolvan prolonged-release hard capsule; Lasolvan prolonged-released capsules; Lasolvan tablet; Lasolvan tablet; Lasolvan prolonged-release hard capsule; Lasolvan effervescent tablet; Lasolvan prolonged-release hard capsule; Lasolvan prolonged-release hard capsule; Lasolvan effervescent tablet; Lasolvan effervescent tablet
Intervention description: One Lasolvan tablet 30 mg twice daily for 5 days.; One Lasolvan tablet 30 mg twice daily for 5 days.; One Lasolvan tablet 30 mg twice daily for 5 days.; One Lasolvan tablet 30 mg twice daily for 5 days.; One-half Lasolvan effervescent tablet 60mg twice daily for 5 days.; One-half Lasolvan effervescent tablet 60mg 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; One Lasolvan prolonged-release hard capsule 75 mg once daily for 5 days; One Lasolvan prolonged-release hard capsule 75 mg once daily for 5 days; One Lasolvan tablet 30 mg twice daily for 5 days.; One Lasolvan tablet 30 mg twice daily for 5 days.; One Lasolvan prolonged-release hard capsule 75 mg once 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; One Lasolvan prolonged-release hard capsule 75 mg once daily for 5 days; One-half Lasolvan effervescent tablet 60mg twice daily for 5 days.; One-half Lasolvan effervescent tablet 60mg twice daily for 5 days.
Intervention MeSH terms: Ambroxol
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers

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
    

Eligibility criteria:

        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