Single Dose, Two-stage Bioequivalence Study of SCMC-Lys Salt 1.35 g Powder vs SCMC-Lys Salt 90 mg/mL Syrup

Bronchitis Clinical Trial

Official title: Two-way Crossover, Randomised, Single Dose and Two-stage Bioequivalence Study of Carbocysteine-L-lysine Salt 1.35 g Powder for Oral Solution Formulation vs 90 mg/mL Syrup Formulation After Oral Administration to Healthy Volunteers.

Status Completed

Clinical Trial Summary

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.

Clinical Trial Description

As a part of the Dompé farmaceutici S.p.A. extension line program, Dompé developed a new 1.35 g powder for oral solution formulation of carbocysteine L-lysine salt-monohydrate.

The present bioequivalence phase I study is needed to compare the bioavailability and the concentration-time profile of the new 1.35 g powder for oral solution formulation with the reference compound Fluifort® 90 mg/mL syrup (15 mL corresponding to 1.35 g of SCMC- lys).

The new 1.35 g powder for oral solution formulation of carbocysteine L-lysine salt- monohydrate is expected to be bioequivalent to Fluifort® 90 mg/mL syrup with the same indications: mucolytic, expectorant in acute and chronic respiratory tract disorders.

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

Secondary end-point are:

1. To describe the pharmacokinetic (PK) profile of carbocysteine after single oral administration of test and reference;

2. to collect safety and tolerability data after single oral administration of test and reference.

Study Design:

The trial has been designed in agreement with the "Guideline on the investigation of bioequivalence." 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 T/R ratio of the geometric means.

The sample size of stage 1 was calculated assuming a point estimate for the T/R ratio of the geometric means of 1.053 (i.e. μR=0.95·μT) and a multiplicative coefficient of variation (CVm) of 20% for both AUC0-t and Cmax. A power of 90% was considered and, according to the Pocock spending function and to the current European bioequivalence guideline, the α level was set to 0.0294. Fifteen (15) subjects per sequence (i.e. 30 subjects overall) will be enrolled in the first stage of the study.

After the end of study stage 1, PK parameters will be calculated and an ad interim bioequivalence test will be performed on the calculated PK parameters Cmax, AUC0-t and AUC0-∞. To safeguard the overall type I error, the α level of the bioequivalence test will be set to 0.0294 according to the Pocock spending function. Should bioequivalence be proven with the results of the subjects of the first stage, the primary objective of the study would then be satisfied and the second study stage will not take place. Should bioequivalence not be proven with the results of the subjects of the first stage and with an a posteriori calculated power > 90% for both AUC0-t and Cmax, the study will be stopped and the bioequivalence will not be proven.

Should bioequivalence not be proven with the results of the subjects of the first stage and with an a posteriori calculated power ≤ 90% for AUC0-t or Cmax, the overall sample size for the study (stage 1 plus 2) will be calculated on the basis of the ad interim bioequivalence results. The additional subjects will be enrolled into the second study stage. After completion of stage 2, the PK analysis and the bioequivalence test will be performed on the pooled subjects of the two study stages. The α level of the bioequivalence test of stage 1 plus 2 will be set to 0.0294 according to the Pocock spending function. The second stage will be performed after notification of the sample size to the local Ethics Committee and to the central Swiss authority (Swissmedic). ;

Related Conditions & MeSH terms

• Bronchitis

• NCT number: NCT02858193
• Study type: Interventional
• Source: Dompé Farmaceutici S.p.A
• Status: Completed
• Phase: Phase 1
• Start date: July 4, 2016
• Completion date: October 2016