Healthy
Conditions
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
Interventions
DRUGLasolvan tablet
One Lasolvan tablet 30 mg twice daily for 5 days.
DRUGLasolvan effervescent tablet
One-half Lasolvan effervescent tablet 60mg twice daily for 5 days.
DRUGLasolvan prolonged-release hard capsule
One Lasolvan prolonged-release hard capsule 75 mg once daily for 5 days
DRUGLasolvan prolonged-released capsules
One Lasolvan prolonged-release hard capsule 75 mg once daily for 5 days
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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 In case of using oral contraceptives, they should be withdrawn at least 2 months before the study.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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 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 | 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) |
| Maximum Measured 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 | Maximum measured concentration of the analyte in plasma at steady state (Cmax ss) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Steady state concentration of the analyte in plasma at the end of dosing interval (Cmin ss) |
| 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 | Average concentration of the analyte in plasma in the time interval of 0 to 24 h at steady state (Cav ss) |
| 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 | 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. |
| 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 | 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) |
| Peak-trough Swing | 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 | Peak-trough swing (PTS) calculated as ((Cmax,ss - Cmin,ss / Cav,ss)\*100) |
| Time Period When Concentration of the Analyte Exceeds 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 | Time period when the concentration of the analyte exceeds Cav ss (T (C\>Cav ss)) |
| Plateau Time During Which Concentration of the Analyte in Plasma Exceeds 75% of 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 | Plateau time during which concentration of the analyte in plasma exceeds 75% of Cmax ss (T(C\>75% Cmax ss)) |
| Peak-trough Fluctuation Between Minimum and Maximum Concentration of the Analyte in Plasma | 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 | Peak-trough fluctuation between minimum and maximum concentration of the analyte in plasma (PTF) |
| 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 | Metric which characterises the rate of absorption at steady state (Cmax ss/AUCss 0-24) |
Countries
Russia
Participant flow
Pre-assignment details
A randomised, open-label, three period, crossover study. 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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Treatment Period 2 (6 Days) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Study Overall |
|---|---|
| Age, Continuous | 25.04 years STANDARD_DEVIATION 6.423 |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 24 | 0 / 24 | 0 / 23 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 23 |
Outcome results
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)
Time frame: 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
Population: Pharmacokinetic (PK) set relative bioavailability set (PK-BA set) which includes all subjects in the treated set who completed 3 periods and for whom the PK profiles in 3 periods could be adequately characterized in respect to at least 1 of the PK parameters of primary interest without important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lasolvan 75mg | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to 24 h at Steady State | 1182.084 ng*h/mL | Geometric Coefficient of Variation 28.859 |
| Lasolvan 60mg | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to 24 h at Steady State | 1110.095 ng*h/mL | Geometric Coefficient of Variation 28.292 |
| Lasolvan 30mg | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to 24 h at Steady State | 1070.909 ng*h/mL | Geometric Coefficient of Variation 32.259 |
90% CI: [99.84, 122.69]
90% CI: [96.54, 110.74]
90% CI: [100.29, 114.02]
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)
Time frame: 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
Population: PK-BA set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lasolvan 75mg | Maximum Measured Concentration of the Analyte in Plasma at Steady State | 73.510 ng/mL | Geometric Coefficient of Variation 26.927 |
| Lasolvan 60mg | Maximum Measured Concentration of the Analyte in Plasma at Steady State | 90.755 ng/mL | Geometric Coefficient of Variation 34.426 |
| Lasolvan 30mg | Maximum Measured Concentration of the Analyte in Plasma at Steady State | 87.289 ng/mL | Geometric Coefficient of Variation 34.426 |
90% CI: [76.96, 93.25]
90% CI: [95.22, 113.31]
90% CI: [73.92, 88.62]
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)
Time frame: 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
Population: PK-BA set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lasolvan 75mg | 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 | 945.667 ng*h/mL | Geometric Coefficient of Variation 28.859 |
| Lasolvan 60mg | 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 | 1110.095 ng*h/mL | Geometric Coefficient of Variation 28.292 |
| Lasolvan 30mg | 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 | 1070.909 ng*h/mL | Geometric Coefficient of Variation 32.259 |
90% CI: [79.87, 98.15]
90% CI: [96.54, 110.74]
90% CI: [80.23, 91.22]
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)
Time frame: 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
Population: PK-BA set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lasolvan 75mg | Average Concentration of the Analyte in Plasma in the Time Interval of 0 to 24 h at Steady State | 49.254 ng/mL | Geometric Coefficient of Variation 28.859 |
| Lasolvan 60mg | Average Concentration of the Analyte in Plasma in the Time Interval of 0 to 24 h at Steady State | 46.254 ng/mL | Geometric Coefficient of Variation 28.292 |
| Lasolvan 30mg | Average Concentration of the Analyte in Plasma in the Time Interval of 0 to 24 h at Steady State | 44.621 ng/mL | Geometric Coefficient of Variation 32.259 |
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)
Time frame: 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
Population: PK-BA set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lasolvan 75mg | Peak-trough Fluctuation Between Minimum and Maximum Concentration of the Analyte in Plasma | 0.994 ng/mL | Standard Deviation 0.278 |
| Lasolvan 60mg | Peak-trough Fluctuation Between Minimum and Maximum Concentration of the Analyte in Plasma | 1.482 ng/mL | Standard Deviation 0.322 |
| Lasolvan 30mg | Peak-trough Fluctuation Between Minimum and Maximum Concentration of the Analyte in Plasma | 1.483 ng/mL | Standard Deviation 0.318 |
Secondary
Peak-trough Swing
Peak-trough swing (PTS) calculated as ((Cmax,ss - Cmin,ss / Cav,ss)\*100)
Time frame: 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
Population: PK-BA set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lasolvan 75mg | Peak-trough Swing | 205.054 percentage of ng/mL | Standard Deviation 82.703 |
| Lasolvan 60mg | Peak-trough Swing | 313.106 percentage of ng/mL | Standard Deviation 113.101 |
| Lasolvan 30mg | Peak-trough Swing | 322.120 percentage of ng/mL | Standard Deviation 135.222 |
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))
Time frame: 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
Population: PK-BA set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lasolvan 75mg | Plateau Time During Which Concentration of the Analyte in Plasma Exceeds 75% of Cmax ss | 9.00 hours |
| Lasolvan 60mg | Plateau Time During Which Concentration of the Analyte in Plasma Exceeds 75% of Cmax ss | 2.25 hours |
| Lasolvan 30mg | Plateau Time During Which Concentration of the Analyte in Plasma Exceeds 75% of Cmax ss | 2.00 hours |
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)
Time frame: 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
Population: PK-BA set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lasolvan 75mg | Rate of Absorption at Steady State (Cmax ss/AUCss 0-24) | 0.062 1/h | Geometric Coefficient of Variation 13.477 |
| Lasolvan 60mg | Rate of Absorption at Steady State (Cmax ss/AUCss 0-24) | 0.082 1/h | Geometric Coefficient of Variation 14.568 |
| Lasolvan 30mg | Rate of Absorption at Steady State (Cmax ss/AUCss 0-24) | 0.082 1/h | Geometric Coefficient of Variation 13.477 |
90% CI: [71.1, 82.4]
90% CI: [94.69, 106.58]
90% CI: [69.92, 81.93]
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)
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lasolvan 75mg | Steady State Concentration of the Analyte in Plasma at the End of Dosing Interval | 24.891 ng/mL | Geometric Coefficient of Variation 39.355 |
| Lasolvan 60mg | Steady State Concentration of the Analyte in Plasma at the End of Dosing Interval | 22.740 ng/mL | Geometric Coefficient of Variation 37.26 |
| Lasolvan 30mg | Steady State Concentration of the Analyte in Plasma at the End of Dosing Interval | 21.523 ng/mL | Geometric Coefficient of Variation 40.803 |
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.
Time frame: 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
Population: PK-BA set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lasolvan 75mg | Time From Dosing to the Maximum Concentration of the Analyte in Plasma at Steady State | Tmax,ss,12-24h (N=0, 23, 23) | NA hours |
| Lasolvan 75mg | Time From Dosing to the Maximum Concentration of the Analyte in Plasma at Steady State | Tmax,ss,0-12h (N=0, 23, 23) | NA hours |
| Lasolvan 75mg | Time From Dosing to the Maximum Concentration of the Analyte in Plasma at Steady State | Tmax,ss,h (N=23, 0, 0) | 6.00 hours |
| Lasolvan 60mg | Time From Dosing to the Maximum Concentration of the Analyte in Plasma at Steady State | Tmax,ss,12-24h (N=0, 23, 23) | 13.50 hours |
| Lasolvan 60mg | Time From Dosing to the Maximum Concentration of the Analyte in Plasma at Steady State | Tmax,ss,0-12h (N=0, 23, 23) | 1.00 hours |
| Lasolvan 60mg | Time From Dosing to the Maximum Concentration of the Analyte in Plasma at Steady State | Tmax,ss,h (N=23, 0, 0) | NA hours |
| Lasolvan 30mg | Time From Dosing to the Maximum Concentration of the Analyte in Plasma at Steady State | Tmax,ss,0-12h (N=0, 23, 23) | 2.00 hours |
| Lasolvan 30mg | Time From Dosing to the Maximum Concentration of the Analyte in Plasma at Steady State | Tmax,ss,h (N=23, 0, 0) | NA hours |
| Lasolvan 30mg | Time From Dosing to the Maximum Concentration of the Analyte in Plasma at Steady State | Tmax,ss,12-24h (N=0, 23, 23) | 14.00 hours |
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))
Time frame: 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
Population: PK-BA set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lasolvan 75mg | Time Period When Concentration of the Analyte Exceeds Cav ss | 10.500 hours |
| Lasolvan 60mg | Time Period When Concentration of the Analyte Exceeds Cav ss | 8.500 hours |
| Lasolvan 30mg | Time Period When Concentration of the Analyte Exceeds Cav ss | 7.750 hours |