Pharmacokinetics and Bioavailability Study of Lasolvan Ha... | NCT02036775

NCT02036775

Status Module

Sponsor/Collaborators Module

Oversight Module

No data available

No data is available for this block.

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
Lasolvan tablet	Drug	One Lasolvan tablet 30 mg twice daily for 5 days.	Treatment sequence 1

Outcomes Module

Primary Outcomes

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	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

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	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

Eligibility Module

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

Contacts/Locations Module

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
32372294	Derived	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.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Lasolvan 75mg / Lasolvan 30mg / Lasolvan 60mg	Patients were administered three treatments in the following order: One Lasolvan prolonged release hard capsule, 75mg, swallowed and taken with 200ml of boiled water once daily for 5 days One Lasolvan tablet, 30mg, was taken with 200mL of boiled water twice daily for 5 days (reference treatment) One-half Lasolvan effervescent tablet, 60mg, dissolved in 200mL of boiled water, taken twice daily for 5 days

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

Masking Info

FG0004 subjects
FG0014 subjects
FG0024 subjects
FG0034 subjects
FG0044 subjects
FG0054 subjects

Treated set which included all subjects who had been dispensed study medication and were documented to have taken at least one dose of study medication.

Arm/Group Information

ID	Title	Description
BG000	Study Overall	A randomised, open-label, three period, crossover study. The three treatments administered were: One Lasolvan prolonged release hard capsule, 75mg, swallowed and taken with 200ml of boiled water once daily for 5 days One-half Lasolvan effervescent tablet, 60mg, dissolved in 200mL of boiled water, taken twice daily for 5 days One Lasolvan tablet, 30mg, was taken with 200mL of boiled water twice daily for 5 days (reference treatment) Each subject received one treatment per treatment period. Each of the three treatment phases was 6 days long, where study drug was administered on day 1-5 during each treatment.

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0001182.084± 28.859 OG0011110.095± 28.292 OG0021070.909± 32.259

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002						Adjusted Geometric Mean Ratio (%)	110.68	Standard Deviation	20.42	2-Sided	90	99.84	122.69			The standard deviation is actually the intra-individual geometric coefficient of variation (gCV(%))	Yes	Non-Inferiority or Equivalence	The assessment of relative bioavailability without molar mass adjustment (dose adjustment) was based upon two-sided 90% confidence intervals (CIs) for the ratios of the geometric means (test divided by reference) of the area under the curve (AUCss 0-24) using an acceptance range of 80%-125%.

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)

PK-BA set

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

ID	Title	Description
OG000	Lasolvan 75mg	One Lasolvan prolonged release hard capsule, 75mg, swallowed and taken with 200ml of boiled water once daily for 5 days
OG001	Lasolvan 60mg	One-half Lasolvan effervescent tablet, 60mg, dissolved in 200mL of boiled water, taken twice daily for 5 days
OG002	Lasolvan 30mg	One Lasolvan tablet, 30mg, was taken with 200mL of boiled water twice daily for 5 days (reference treatment)

Units	Counts

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)

PK-BA set

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

ID	Title	Description
OG000	Lasolvan 75mg	One Lasolvan prolonged release hard capsule, 75mg, swallowed and taken with 200ml of boiled water once daily for 5 days
OG001	Lasolvan 60mg	One-half Lasolvan effervescent tablet, 60mg, dissolved in 200mL of boiled water, taken twice daily for 5 days
OG002	Lasolvan 30mg	One Lasolvan tablet, 30mg, was taken with 200mL of boiled water twice daily for 5 days (reference treatment)

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)

PK-BA set

Posted

Geometric Mean

Geometric Coefficient of Variation

1/h

ID	Title	Description
OG000	Lasolvan 75mg	One Lasolvan prolonged release hard capsule, 75mg, swallowed and taken with 200ml of boiled water once daily for 5 days
OG001	Lasolvan 60mg	One-half Lasolvan effervescent tablet, 60mg, dissolved in 200mL of boiled water, taken twice daily for 5 days
OG002	Lasolvan 30mg	One Lasolvan tablet, 30mg, was taken with 200mL of boiled water twice daily for 5 days (reference treatment)

Units	Counts

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)

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

ID	Title	Description
OG000	Lasolvan 75mg	One Lasolvan prolonged release hard capsule, 75mg, swallowed and taken with 200ml of boiled water once daily for 5 days
OG001	Lasolvan 60mg	One-half Lasolvan effervescent tablet, 60mg, dissolved in 200mL of boiled water, taken twice daily for 5 days
OG002	Lasolvan 30mg	One Lasolvan tablet, 30mg, was taken with 200mL of boiled water twice daily for 5 days (reference treatment)

Units	Counts

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)

PK-BA set

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

ID	Title	Description
OG000	Lasolvan 75mg	One Lasolvan prolonged release hard capsule, 75mg, swallowed and taken with 200ml of boiled water once daily for 5 days
OG001	Lasolvan 60mg	One-half Lasolvan effervescent tablet, 60mg, dissolved in 200mL of boiled water, taken twice daily for 5 days
OG002	Lasolvan 30mg	One Lasolvan tablet, 30mg, was taken with 200mL of boiled water twice daily for 5 days (reference treatment)

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.

PK-BA set

Posted

Median

Full Range

hours

ID	Title	Description
OG000	Lasolvan 75mg	One Lasolvan prolonged release hard capsule, 75mg, swallowed and taken with 200ml of boiled water once daily for 5 days
OG001	Lasolvan 60mg	One-half Lasolvan effervescent tablet, 60mg, dissolved in 200mL of boiled water, taken twice daily for 5 days
OG002	Lasolvan 30mg	One Lasolvan tablet, 30mg, was taken with 200mL of boiled water twice daily for 5 days (reference treatment)

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)

PK-BA set

Posted

Mean

Standard Deviation

ng/mL

ID	Title	Description
OG000	Lasolvan 75mg	One Lasolvan prolonged release hard capsule, 75mg, swallowed and taken with 200ml of boiled water once daily for 5 days
OG001	Lasolvan 60mg	One-half Lasolvan effervescent tablet, 60mg, dissolved in 200mL of boiled water, taken twice daily for 5 days
OG002	Lasolvan 30mg	One Lasolvan tablet, 30mg, was taken with 200mL of boiled water twice daily for 5 days (reference treatment)

Units

Secondary

Peak-trough Swing

Peak-trough swing (PTS) calculated as ((Cmax,ss - Cmin,ss / Cav,ss)*100)

PK-BA set

Posted

Mean

Standard Deviation

percentage of ng/mL

ID	Title	Description
OG000	Lasolvan 75mg	One Lasolvan prolonged release hard capsule, 75mg, swallowed and taken with 200ml of boiled water once daily for 5 days
OG001	Lasolvan 60mg	One-half Lasolvan effervescent tablet, 60mg, dissolved in 200mL of boiled water, taken twice daily for 5 days
OG002	Lasolvan 30mg	One Lasolvan tablet, 30mg, was taken with 200mL of boiled water twice daily for 5 days (reference treatment)

Units	Counts
Participants

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))

PK-BA set

Posted

Median

Full Range

hours

ID	Title	Description
OG000	Lasolvan 75mg	One Lasolvan prolonged release hard capsule, 75mg, swallowed and taken with 200ml of boiled water once daily for 5 days
OG001	Lasolvan 60mg	One-half Lasolvan effervescent tablet, 60mg, dissolved in 200mL of boiled water, taken twice daily for 5 days
OG002	Lasolvan 30mg	One Lasolvan tablet, 30mg, was taken with 200mL of boiled water twice daily for 5 days (reference treatment)

Units	Counts

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))

PK-BA set

Posted

Median

Full Range

hours

ID	Title	Description
OG000	Lasolvan 75mg	One Lasolvan prolonged release hard capsule, 75mg, swallowed and taken with 200ml of boiled water once daily for 5 days
OG001	Lasolvan 60mg	One-half Lasolvan effervescent tablet, 60mg, dissolved in 200mL of boiled water, taken twice daily for 5 days
OG002	Lasolvan 30mg	One Lasolvan tablet, 30mg, was taken with 200mL of boiled water twice daily for 5 days (reference treatment)

Units

Arm/Groups

ID	Title	Description	Serious Events (At Risk)	Other Events (At Risk)
EG000	Lasolvan 75mg	One Lasolvan prolonged release hard capsule, 75mg, swallowed and taken with 200ml of boiled water once daily for 5 days	24	24
EG001	Lasolvan 60mg	One-half Lasolvan effervescent tablet, 60mg, dissolved in 200mL of boiled water, taken twice daily for 5 days	24	24
EG002	Lasolvan 30mg	One Lasolvan tablet, 30mg, was taken with 200mL of boiled water twice daily for 5 days (reference treatment)	23	23

ID	Term
D000551	Ambroxol

Units	Counts
Participants	OG00023 OG00123 OG00223

ID	Term
D001964	Bromhexine
D000814	Aniline Compounds
D000588	Amines
D009930	Organic Chemicals
D003514	Cyclohexylamines