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

NCT02036775 | Completed Phase 1 Results

• 1 other identifier: 18.510
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (9)

• 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

  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

• 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

• Steady State Concentration of the Analyte in Plasma at the End of Dosing Interval

  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

• Average Concentration of the Analyte in Plasma in the Time Interval of 0 to 24 h at Steady State

  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

• Time From Dosing to the Maximum Concentration of the Analyte in Plasma at Steady State

  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

Study Arms (6)

Treatment sequence 1

EXPERIMENTAL

Treatment 1, Washout 6 days, Reference product, Washout 6 days, Treatment 2

Drug: Lasolvan tablet; Drug: Lasolvan prolonged-released capsules; Drug: Lasolvan effervescent tablet

Treatment sequence 2

EXPERIMENTAL

Treatment 2, Washout period 6 days, Treatment 1, Washout 6 days, Reference product

Drug: Lasolvan tablet; Drug: Lasolvan effervescent tablet; Drug: Lasolvan prolonged-release hard capsule

Treatment sequence 3

EXPERIMENTAL

Reference product, Washout 6 days, Treatment 2, Washout 6 days, Treatment 1

Drug: Lasolvan effervescent tablet; Drug: Lasolvan tablet; Drug: Lasolvan prolonged-release hard capsule

Treatment Sequence 4

EXPERIMENTAL

Treatment 2, Washout 6 days, Reference product, Washout 6 days, Treatment 1

Drug: Lasolvan tablet; Drug: Lasolvan effervescent tablet; Drug: Lasolvan prolonged-release hard capsule

Treatment sequence 5

EXPERIMENTAL

Reference product, Washout 6 days, Treatment 1, Washout 6 days, Treatment 2

Drug: Lasolvan tablet; Drug: Lasolvan prolonged-release hard capsule; Drug: Lasolvan effervescent tablet

Treatment Sequence 6

EXPERIMENTAL

Treatment 1, Washout 6 days, Treatment 2, Washout 6 days, Reference product

Drug: Lasolvan tablet; Drug: Lasolvan effervescent tablet; Drug: Lasolvan prolonged-release hard capsule

Interventions

Lasolvan tablet DRUG

One Lasolvan tablet 30 mg twice daily for 5 days.

Treatment sequence 1

Lasolvan effervescent tablet DRUG

One-half Lasolvan effervescent tablet 60mg twice daily for 5 days.

Treatment sequence 3

Lasolvan prolonged-release hard capsule DRUG

One Lasolvan prolonged-release hard capsule 75 mg once daily for 5 days

Treatment Sequence 4

Lasolvan prolonged-released capsules DRUG

One Lasolvan prolonged-release hard capsule 75 mg once daily for 5 days

Treatment sequence 1

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.
• 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
• Known lactose intolerance.
• Known phenylketonuria

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

18.510.2 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

Related Publications (1)

• Ollier C, Sent U, Mesquita M, Michel MC. Pharmacokinetics of Ambroxol Sustained Release (Mucosolvan(R) Retard) Compared with Other Formulations in Healthy Volunteers. Pulm Ther. 2020 Jun;6(1):119-130. doi: 10.1007/s41030-020-00116-7. Epub 2020 May 5.

  PMID: 32372294 DERIVED

MeSH Terms

Interventions

Ambroxol

Intervention Hierarchy (Ancestors)

Bromhexine; Aniline Compounds; Amines; Organic Chemicals; Cyclohexylamines

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2014
• First Posted: January 15, 2014
• Study Start: March 1, 2014
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: May 13, 2015
• Results First Posted: May 13, 2015

Record last verified: 2015-05

Locations

RU (1)