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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Lasolvan tablet; Drug: Lasolvan effervescent tablet; Drug: Lasolvan prolonged-released capsules; Drug: Lasolvan prolonged-release hard capsule

• Registration Number: NCT02036775
• Lead Sponsor: Boehringer Ingelheim

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-01-13
• Study First Submitted QC: 2014-01-13
• Study First Posted: 2014-01-15
• Study Start: 2014-03
• Primary Completion: 2014-05
• Study Completion: 2014-05
• Results First Submitted: 2015-04-17
• Status Verified: 2015-05
• Results First Submitted QC: 2015-05-12
• Last Update Submitted: 2015-05-12
• Results First Posted: 2015-05-13
• Last Update Posted: 2015-05-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment Sequence 4	Lasolvan effervescent tablet	Treatment 2, Washout 6 days, Reference product, Washout 6 days, Treatment 1
Treatment Sequence 6	Lasolvan effervescent tablet	Treatment 1, Washout 6 days, Treatment 2, Washout 6 days, Reference product
Treatment sequence 3	Lasolvan prolonged-release hard capsule	Reference product, Washout 6 days, Treatment 2, Washout 6 days, Treatment 1
Treatment sequence 5	Lasolvan prolonged-release hard capsule	Reference product, Washout 6 days, Treatment 1, Washout 6 days, Treatment 2
Treatment sequence 1	Lasolvan tablet	Treatment 1, Washout 6 days, Reference product, Washout 6 days, Treatment 2
Treatment sequence 2	Lasolvan tablet	Treatment 2, Washout period 6 days, Treatment 1, Washout 6 days, Reference product
Treatment sequence 1	Lasolvan effervescent tablet	Treatment 1, Washout 6 days, Reference product, Washout 6 days, Treatment 2
Treatment Sequence 4	Lasolvan tablet	Treatment 2, Washout 6 days, Reference product, Washout 6 days, Treatment 1
Treatment sequence 3	Lasolvan effervescent tablet	Reference product, Washout 6 days, Treatment 2, Washout 6 days, Treatment 1
Treatment Sequence 6	Lasolvan prolonged-release hard capsule	Treatment 1, Washout 6 days, Treatment 2, Washout 6 days, Reference product
Treatment sequence 5	Lasolvan tablet	Reference product, Washout 6 days, Treatment 1, Washout 6 days, Treatment 2
Treatment Sequence 6	Lasolvan tablet	Treatment 1, Washout 6 days, Treatment 2, Washout 6 days, Reference product
Treatment sequence 2	Lasolvan prolonged-release hard capsule	Treatment 2, Washout period 6 days, Treatment 1, Washout 6 days, Reference product
Treatment sequence 3	Lasolvan tablet	Reference product, Washout 6 days, Treatment 2, Washout 6 days, Treatment 1
Treatment sequence 1	Lasolvan prolonged-released capsules	Treatment 1, Washout 6 days, Reference product, Washout 6 days, Treatment 2
Treatment sequence 2	Lasolvan effervescent tablet	Treatment 2, Washout period 6 days, Treatment 1, Washout 6 days, Reference product
Treatment sequence 5	Lasolvan effervescent tablet	Reference product, Washout 6 days, Treatment 1, Washout 6 days, Treatment 2
Treatment Sequence 4	Lasolvan prolonged-release hard capsule	Treatment 2, Washout 6 days, Reference product, Washout 6 days, Treatment 1

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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)
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)
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)
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)
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)
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 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.
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))
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))

Trial Locations

Locations (1)

18.510.2 Boehringer Ingelheim Investigational Site; 🇷🇺 St. Petersburg, Russian Federation