Trial Outcomes & Findings for Crossover, Single Dose, Two-stage Bioequivalence Study of SCMC-Lys Salt 1.35 g Powder vs SCMC-Lys Salt 90 mg/mL Syrup (NCT NCT02858193)
NCT ID: NCT02858193
Last Updated: 2024-11-18
Results Overview
Cmax = maximum plasma concentration. Cmax of carbocysteine was calculated from plasma concentrations after single oral dose of test and reference products. Plasma concentrations of carbocysteine were measured in each study period at the timepoints hereunder reported. Arithmetic means+standard deviation are reported hereunder
COMPLETED
PHASE1
30 participants
pre-dose (0), 0.25 (15 min), 0.5 (30 min), 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 10 h post-dose
2024-11-18
Participant Flow
30 healthy volunteers were randomized, receiving a single dose of test and reference treatment. Based on the cross-over design, a single dose of product was given orally in one of the two possible sequences: in the "test-reference" arm, subjects received SCMC-lys 1.35 g oral powder firstly and then the product Fluifort®. In the "reference-test" arm, subjects received reference product Fluifort® first, than SCMC-lys 1.35 g oral powder. A wash-out interval separated the 2 treatments.
Participant milestones
| Measure |
Sequence "Test -Reference"
Participants first received a single oral dose of test product (1 sachet; 1.35 g of SCMC-lys) under fasting condition (day 1, Visit 3, 8:00 ± 1h ). After a wash-out period of at least 4 days the partecipants then received a single dose of the reference product Fluifort® syrup 90 mg SCMC-lys/mL (15 mL of syrup, 1.35 g of SCMC-lys) always under fasting conditions. There were no premature discontinuations during the study
|
Sequence "Reference - Test"
Participants first received a single oral dose of reference product Fluifort® syrup 90 mg SCMC-lys/mL (15 mL of syrup, 1.35 g of SCMC-lys) under fasting condition (day 1, Visit 3, 8:00 ± 1h ). After a wash-out period of at least 4 days the partecipants then received a single dose of the test product (1 sachet; 1.35 g of SCMC-lys) always under fasting conditions.
|
|---|---|---|
|
First Treatment Period
STARTED
|
15
|
15
|
|
First Treatment Period
COMPLETED
|
15
|
15
|
|
First Treatment Period
NOT COMPLETED
|
0
|
0
|
|
Washout Period (at Least 4 Days)
STARTED
|
15
|
15
|
|
Washout Period (at Least 4 Days)
COMPLETED
|
15
|
15
|
|
Washout Period (at Least 4 Days)
NOT COMPLETED
|
0
|
0
|
|
Second Treatment Period
STARTED
|
15
|
15
|
|
Second Treatment Period
COMPLETED
|
15
|
15
|
|
Second Treatment Period
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Crossover, Single Dose, Two-stage Bioequivalence Study of SCMC-Lys Salt 1.35 g Powder vs SCMC-Lys Salt 90 mg/mL Syrup
Baseline characteristics by cohort
| Measure |
All Study Partecipants
n=30 Participants
Enrolled population: all enrolled subjects. This analysis was used for the analysis of demographic, baseline and background characteristics.
Safety population: all subjects who received at least one dose of investigational product.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
30 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
|
Age, Continuous
|
38.9 years
STANDARD_DEVIATION 10.6 • n=93 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
29 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Region of Enrollment
Switzerland
|
30 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: pre-dose (0), 0.25 (15 min), 0.5 (30 min), 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 10 h post-dosePopulation: PK population: all randomised subjects who fulfilled the study protocol requirements in terms of investigational medicinal product(s) intake and had evaluable PK data readouts for the planned treatment comparisons, with no major deviations that may affect the PK results
Cmax = maximum plasma concentration. Cmax of carbocysteine was calculated from plasma concentrations after single oral dose of test and reference products. Plasma concentrations of carbocysteine were measured in each study period at the timepoints hereunder reported. Arithmetic means+standard deviation are reported hereunder
Outcome measures
| Measure |
SCMC-lys 1.35 g Oral Solution (Test Product)
n=30 Participants
SCMC-lys 1.35 g powder for oral solution in sachets each containing 1.35 g.
One sachet of the powder of the test formulation 1.35 g of SCMC-lys corresponding to 750 mg of carbocysteine-free base was dissolved in 100 mL of hot (not boiling) still mineral water. Additional 100 mL of still mineral water at room temperature were added and mixed. The solution was swallowed and the glass was rinsed with 40 mL of still mineral water that was also drunk by the subjects. The final administered volume was 240 mL. All subjects were in fasting conditions from the evening before (at least 10 h, overnight). The final administered volume was 240 mL for both the test and reference treatments.
|
Fluifort® 90 mg/mL Syrup (Reference Product)
n=30 Participants
Fluifort® 90 mg/mL syrup (15 mL corresponding to 1.35 g SCMC-lys)
Fifteen (15) mL of syrup (1.35 g of SCMC-lys corresponding to 750 mg of carbocysteine-free base) poured in a glass were drunk by the subjects. Afterward, the glass was rinsed twice with a volume of 100 mL and 125 mL of still mineral water and the rinses were drunk immediately by the subjects. The final administered volume was 240 mL for both the test and reference treatments.
|
|---|---|---|
|
Carbocysteine Plasma PK Parameters: Cmax
|
7.15 µg/mL
Standard Deviation 1.97
|
6.34 µg/mL
Standard Deviation 1.53
|
PRIMARY outcome
Timeframe: pre-dose (0), 0.25 (15 min), 0.5 (30 min), 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 10 h post-dosePopulation: PK population: all randomised subjects who fulfilled the study protocol requirements in terms of investigational medicinal product(s) intake and had evaluable PK data readouts for the planned treatment comparisons, with no major deviations that may affect the PK results
AUC0-t= area under the concentration-time curve from administration to the last observed concentration time t, calculated with the linear trapezoidal method. AUC0-t of carbocysteine was calculated from plasma concentrations after single oral dose of test and reference products. Plasma concentration of carbocysteine were measured in each study period at the timepoints hereunder specified.Arithmetic means±standard deviation are reported hereunder Please note that AUC0-t was considered a reliable estimate of the extent of absorption if the ratio AUC0-t/AUC0-∞ equalled or exceeded a factor of 0.8, i.e. if %AUCextra was \<20%. Arithmetic means±standard deviation are reported hereunder
Outcome measures
| Measure |
SCMC-lys 1.35 g Oral Solution (Test Product)
n=30 Participants
SCMC-lys 1.35 g powder for oral solution in sachets each containing 1.35 g.
One sachet of the powder of the test formulation 1.35 g of SCMC-lys corresponding to 750 mg of carbocysteine-free base was dissolved in 100 mL of hot (not boiling) still mineral water. Additional 100 mL of still mineral water at room temperature were added and mixed. The solution was swallowed and the glass was rinsed with 40 mL of still mineral water that was also drunk by the subjects. The final administered volume was 240 mL. All subjects were in fasting conditions from the evening before (at least 10 h, overnight). The final administered volume was 240 mL for both the test and reference treatments.
|
Fluifort® 90 mg/mL Syrup (Reference Product)
n=30 Participants
Fluifort® 90 mg/mL syrup (15 mL corresponding to 1.35 g SCMC-lys)
Fifteen (15) mL of syrup (1.35 g of SCMC-lys corresponding to 750 mg of carbocysteine-free base) poured in a glass were drunk by the subjects. Afterward, the glass was rinsed twice with a volume of 100 mL and 125 mL of still mineral water and the rinses were drunk immediately by the subjects. The final administered volume was 240 mL for both the test and reference treatments.
|
|---|---|---|
|
Carbocysteine Plasma PK Parameters: AUC0-t
|
26.73 µg/mL*h
Standard Deviation 5.95
|
24.36 µg/mL*h
Standard Deviation 5.35
|
SECONDARY outcome
Timeframe: pre-dose (0), 0.25 (15 min), 0.5 (30 min), 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 10 h post-dosePopulation: PK population: all randomised subjects who fulfilled the study protocol requirements in terms of investigational medicinal product(s) intake and had evaluable PK data readouts for the planned treatment comparisons, with no major deviations that may affect the PK results
AUC0-∞= Area under the concentration-time curve extrapolated to infinity, calculated, if feasible, as AUC0-t + Ct/λz, where Ct is the last measurable drug concentration. AUC0-∞of carbocysteine was calculated from plasma concentrations after single oral dose of test and reference products. Plasma concentration of carbocysteine were measured in each study period at the timepoints hereunder specified. Arithmetic means±standard deviation are reported hereunder
Outcome measures
| Measure |
SCMC-lys 1.35 g Oral Solution (Test Product)
n=30 Participants
SCMC-lys 1.35 g powder for oral solution in sachets each containing 1.35 g.
One sachet of the powder of the test formulation 1.35 g of SCMC-lys corresponding to 750 mg of carbocysteine-free base was dissolved in 100 mL of hot (not boiling) still mineral water. Additional 100 mL of still mineral water at room temperature were added and mixed. The solution was swallowed and the glass was rinsed with 40 mL of still mineral water that was also drunk by the subjects. The final administered volume was 240 mL. All subjects were in fasting conditions from the evening before (at least 10 h, overnight). The final administered volume was 240 mL for both the test and reference treatments.
|
Fluifort® 90 mg/mL Syrup (Reference Product)
n=30 Participants
Fluifort® 90 mg/mL syrup (15 mL corresponding to 1.35 g SCMC-lys)
Fifteen (15) mL of syrup (1.35 g of SCMC-lys corresponding to 750 mg of carbocysteine-free base) poured in a glass were drunk by the subjects. Afterward, the glass was rinsed twice with a volume of 100 mL and 125 mL of still mineral water and the rinses were drunk immediately by the subjects. The final administered volume was 240 mL for both the test and reference treatments.
|
|---|---|---|
|
Carbocysteine Plasma PK Parameters: AUC0-∞
|
27.23 µg/mLxh
Standard Deviation 6.06
|
24.85 µg/mLxh
Standard Deviation 5.52
|
SECONDARY outcome
Timeframe: pre-dose (0), 0.25 (15 min), 0.5 (30 min), 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 10 h post-dosePopulation: PK population: all randomised subjects who fulfilled the study protocol requirements in terms of investigational medicinal product(s) intake and had evaluable PK data readouts for the planned treatment comparisons, with no major deviations that may affect the PK results
Tmax = Time to achieve Cmax. Tmax (0-10hours) of carbocysteine was calculated from plasma concentrations after single oral dose of test and reference products. Plasma concentration of carbocysteine were measured in each study period at the timepoints hereunder specified.
Outcome measures
| Measure |
SCMC-lys 1.35 g Oral Solution (Test Product)
n=30 Participants
SCMC-lys 1.35 g powder for oral solution in sachets each containing 1.35 g.
One sachet of the powder of the test formulation 1.35 g of SCMC-lys corresponding to 750 mg of carbocysteine-free base was dissolved in 100 mL of hot (not boiling) still mineral water. Additional 100 mL of still mineral water at room temperature were added and mixed. The solution was swallowed and the glass was rinsed with 40 mL of still mineral water that was also drunk by the subjects. The final administered volume was 240 mL. All subjects were in fasting conditions from the evening before (at least 10 h, overnight). The final administered volume was 240 mL for both the test and reference treatments.
|
Fluifort® 90 mg/mL Syrup (Reference Product)
n=30 Participants
Fluifort® 90 mg/mL syrup (15 mL corresponding to 1.35 g SCMC-lys)
Fifteen (15) mL of syrup (1.35 g of SCMC-lys corresponding to 750 mg of carbocysteine-free base) poured in a glass were drunk by the subjects. Afterward, the glass was rinsed twice with a volume of 100 mL and 125 mL of still mineral water and the rinses were drunk immediately by the subjects. The final administered volume was 240 mL for both the test and reference treatments.
|
|---|---|---|
|
Carbocysteine Plasma PK Parameters: Tmax
|
1.72 h
Standard Deviation 0.43
|
1.85 h
Standard Deviation 0.60
|
SECONDARY outcome
Timeframe: pre-dose (0), 0.25 (15 min), 0.5 (30 min), 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 10 h post-dosePopulation: PK population: all randomised subjects who fulfilled the study protocol requirements in terms of investigational medicinal product(s) intake and had evaluable PK data readouts for the planned treatment comparisons, with no major deviations that may affect the PK results
t1/2= Half-life, calculated, if feasible, as ln2/λz. t1/2 (0-10 hours) of carbocysteine was calculated from plasma concentrations after single oral dose of test and reference products. Plasma concentration of carbocysteine were measured in each study period at the timepoints hereunder specified.
Outcome measures
| Measure |
SCMC-lys 1.35 g Oral Solution (Test Product)
n=30 Participants
SCMC-lys 1.35 g powder for oral solution in sachets each containing 1.35 g.
One sachet of the powder of the test formulation 1.35 g of SCMC-lys corresponding to 750 mg of carbocysteine-free base was dissolved in 100 mL of hot (not boiling) still mineral water. Additional 100 mL of still mineral water at room temperature were added and mixed. The solution was swallowed and the glass was rinsed with 40 mL of still mineral water that was also drunk by the subjects. The final administered volume was 240 mL. All subjects were in fasting conditions from the evening before (at least 10 h, overnight). The final administered volume was 240 mL for both the test and reference treatments.
|
Fluifort® 90 mg/mL Syrup (Reference Product)
n=30 Participants
Fluifort® 90 mg/mL syrup (15 mL corresponding to 1.35 g SCMC-lys)
Fifteen (15) mL of syrup (1.35 g of SCMC-lys corresponding to 750 mg of carbocysteine-free base) poured in a glass were drunk by the subjects. Afterward, the glass was rinsed twice with a volume of 100 mL and 125 mL of still mineral water and the rinses were drunk immediately by the subjects. The final administered volume was 240 mL for both the test and reference treatments.
|
|---|---|---|
|
Carbocysteine Plasma PK Parameters: t1/2
|
1.51 h
Standard Deviation 0.24
|
1.50 h
Standard Deviation 0.21
|
SECONDARY outcome
Timeframe: pre-dose (0), 0.25 (15 min), 0.5 (30 min), 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 10 h post-dosePopulation: PK population: all randomised subjects who fulfilled the study protocol requirements in terms of investigational medicinal product(s) intake and had evaluable PK data readouts for the planned treatment comparisons, with no major deviations that may affect the PK results µg/mL
Frel: Relative bioavailability, calculated as ratio AUC0-t (test)/ AUC0-t (reference)
Outcome measures
| Measure |
SCMC-lys 1.35 g Oral Solution (Test Product)
n=30 Participants
SCMC-lys 1.35 g powder for oral solution in sachets each containing 1.35 g.
One sachet of the powder of the test formulation 1.35 g of SCMC-lys corresponding to 750 mg of carbocysteine-free base was dissolved in 100 mL of hot (not boiling) still mineral water. Additional 100 mL of still mineral water at room temperature were added and mixed. The solution was swallowed and the glass was rinsed with 40 mL of still mineral water that was also drunk by the subjects. The final administered volume was 240 mL. All subjects were in fasting conditions from the evening before (at least 10 h, overnight). The final administered volume was 240 mL for both the test and reference treatments.
|
Fluifort® 90 mg/mL Syrup (Reference Product)
Fluifort® 90 mg/mL syrup (15 mL corresponding to 1.35 g SCMC-lys)
Fifteen (15) mL of syrup (1.35 g of SCMC-lys corresponding to 750 mg of carbocysteine-free base) poured in a glass were drunk by the subjects. Afterward, the glass was rinsed twice with a volume of 100 mL and 125 mL of still mineral water and the rinses were drunk immediately by the subjects. The final administered volume was 240 mL for both the test and reference treatments.
|
|---|---|---|
|
Carbocysteine Plasma PK Parameters: Frel
|
110.28 % of bioavailability
Standard Deviation 13.85
|
—
|
SECONDARY outcome
Timeframe: From the screening visit up to the final visit/ETV (i.e.up to 4 weeks)Population: Safety population: all subject who received at least one dose of investigational product.
TEAE=Treatment Emergent Adverse Events. TEAEs were assessed throughout the study, from the screening to the final visit/early termination visit (ETV) which take place after visit 5 on day 1 of period 2, more precisely after the 10h blood sampling and vital sign.
Outcome measures
| Measure |
SCMC-lys 1.35 g Oral Solution (Test Product)
n=30 Participants
SCMC-lys 1.35 g powder for oral solution in sachets each containing 1.35 g.
One sachet of the powder of the test formulation 1.35 g of SCMC-lys corresponding to 750 mg of carbocysteine-free base was dissolved in 100 mL of hot (not boiling) still mineral water. Additional 100 mL of still mineral water at room temperature were added and mixed. The solution was swallowed and the glass was rinsed with 40 mL of still mineral water that was also drunk by the subjects. The final administered volume was 240 mL. All subjects were in fasting conditions from the evening before (at least 10 h, overnight). The final administered volume was 240 mL for both the test and reference treatments.
|
Fluifort® 90 mg/mL Syrup (Reference Product)
n=30 Participants
Fluifort® 90 mg/mL syrup (15 mL corresponding to 1.35 g SCMC-lys)
Fifteen (15) mL of syrup (1.35 g of SCMC-lys corresponding to 750 mg of carbocysteine-free base) poured in a glass were drunk by the subjects. Afterward, the glass was rinsed twice with a volume of 100 mL and 125 mL of still mineral water and the rinses were drunk immediately by the subjects. The final administered volume was 240 mL for both the test and reference treatments.
|
|---|---|---|
|
Number of TEAEs
|
0 Number of events
|
0 Number of events
|
Adverse Events
SCMC-lys 1.35 g Oral Solution (Test Product)
Fluifort® 90 mg/mL Syrup (Reference Product)
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Clinical Development & Operations
Dompé farmaceutici SpA
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place