Clinical trial NCT02858193
Conditions: Bronchitis
Sponsor: Dompé Farmaceutici S.p.A
Start date: 2016-07-04; Completion date: 2016-10-10
Enrollment: 30 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
Objectives:

The objectives of the study was to investigate the bioequivalence between two formulations containing S-carboxymethyl-L-cysteine L-lysine monohydrate salt (SCMC-lys) when administered as single oral dose in two consecutive study periods to healthy male and female volunteers under fasting conditions.

Primary end-point: to evaluate the bioequivalent rate (Cmax) and extent (AUC0-t) of absorption of carbocysteine after single oral administration of test and reference.

Secondary end-points:

* to describe the pharmacokinetic (PK) profile of carbocysteine after single oral administration of test and reference products;
* to collect safety and tolerability data after single oral administration of test and reference products.

Detailed description:
This was a single centre, single dose, open, randomised, two-way, cross-over, two stage bioequivalence study. According to the two-stage design of the study, an initial group of subjects was treated in study stage 1 and data were analysed. If bioequivalence had been demonstrated, according to the protocol, the study would have been terminated after stage 1. Since this occurred, stage 2 was not performed.

The study was conducted as planned and consisted of a screening visit, a treatment phase of two study periods separated by a wash out interval of at least 4 days and a final visit / early termination visit (ETV).

Due to the lack of information about the PK profile of the new formulation it was decided to use a "two stage" bioequivalence study design, that allows a re-calculation of the sample size in case the number of subjects initially enrolled in the study is not large enough to provide a reliable answer to the questions addressed due to underestimation of the variability or misleading estimation of the point estimate for the Test/Reference (T/R) ratio of the geometric means.

The sequence of treatments in the two study periods was assigned to each randomised subject according to a computer generated randomisation list.

A wash-out period of at least 4 days between the two administrations is justified by the elimination half-life of the carbocysteine (1-2 h).

Arms: arm 1: In this arm, a single oral dose of test product (1 sachet; 1.35 g of SCMC-lys corresponding to 750 mg of carbocysteine-free base) was orally administered, under fasting conditions, in the first period (day 1, Visit 3, 8:00 ± 1h ), and, after a wash-out period of at least 4 days, a single dose of the reference product Fluifort® syrup 90 mg SCMC-lys/mL (15 mL of syrup, 1.35 g of SCMC-lys) was orally administered, under fasting conditions, in the second study period (day 1, visit 5, 8:00 ± 1h). arm 2: In this arm, a single oral dose of reference product Fluifort® syrup 90 mg SCMC-lys/mL (15 mL of syrup, 1.35 g of SCMC-lys) was orally administrated, under fasting conditions, in the first period (day 1, Visit 3, 8:00 ± 1h ), and, after a wash-out period of at least 4 days, a single dose of the test product 1 sachet; 1.35 g of SCMC-lys corresponding to 750 mg of carbocysteine-free base was orally administered, under fasting conditions, in the second study period (day 1, visit 5, 8:00 ± 1h).
Interventions: intervention 1: SCMC-lys powder 1.35 g intervention 2: Fluifort® syrup
Intervention descriptions: intervention 1: Powder for oral solution in sachets each containing 1.35 g of S-carboxymethyl-L-cysteine L-lysine monohydrate salt (SCMC-lys).

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. intervention 2: 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.

Protocol documents: