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

NCT02858193 | Completed Phase 1 Results

• 1 other identifier: SCL0115
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Bronchitis

Outcome Measures

Primary Outcomes (2)

• Carbocysteine Plasma PK Parameters: Cmax

  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

  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

• Carbocysteine Plasma PK Parameters: AUC0-t

  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

  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

Secondary Outcomes (5)

• Carbocysteine Plasma PK Parameters: AUC0-∞

  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

• Carbocysteine Plasma PK Parameters: Tmax

  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

• Carbocysteine Plasma PK Parameters: t1/2

  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

• Carbocysteine Plasma PK Parameters: Frel

  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

• Number of TEAEs

  From the screening visit up to the final visit/ETV (i.e.up to 4 weeks)

Study Arms (2)

Test - Reference (1.35 g of SCMC-lys monohydrate salt powder - Fluifort® syrup 90 mg SCMC-lys/mL)

EXPERIMENTAL

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).

Drug: SCMC-lys powder 1.35 g; Drug: Fluifort® syrup

Reference - Test (Fluifort® syrup 90 mg SCMC-lys/mL-1.35 g of SCMC-lys monohydrate salt powder)

EXPERIMENTAL

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).

Drug: SCMC-lys powder 1.35 g; Drug: Fluifort® syrup

Interventions

SCMC-lys powder 1.35 g DRUG

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.

Also known as: Carbocysteine lysine salt 1.35 g powder for oral solution

Reference - Test (Fluifort® syrup 90 mg SCMC-lys/mL-1.35 g of SCMC-lys monohydrate salt powder); Test - Reference (1.35 g of SCMC-lys monohydrate salt powder - Fluifort® syrup 90 mg SCMC-lys/mL)

Fluifort® syrup DRUG

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.

Also known as: Carbocysteine lysine salt 90 mg/ml syrup

Reference - Test (Fluifort® syrup 90 mg SCMC-lys/mL-1.35 g of SCMC-lys monohydrate salt powder); Test - Reference (1.35 g of SCMC-lys monohydrate salt powder - Fluifort® syrup 90 mg SCMC-lys/mL)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• To be enrolled in this study, subjects must fulfil all these criteria:
• Sex and Age: males/females,18-55 years old inclusive
• Body Mass Index (BMI): 18.5-30 kg/m2 inclusive
• Vital signs: systolic blood pressure (SBP) 100-139 mmHg, diastolic blood pressure (DBP) 50-89 mmHg, pulse rate (PR) 50-90 bpm and body temperature (BT) 35.5 - 37.5°C, measured after 5 min of rest in the sitting position;
• Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study
• Contraception and fertility (females only): females of child-bearing potential and with an active sexual life must not wish to get pregnant within 30 days after the end of the study and must be using at least one of the following reliable methods of contraception:
• Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit until 30 days after final visit
• A non-hormonal intrauterine device \[IUD\] or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit until 30 days after final visit
• A male sexual partner who agrees to use a male condom with spermicide
• A sterile sexual partner Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year will be admitted. For all female subjects, pregnancy test result must be negative at screening.

You may not qualify if:

• Subjects meeting any of these criteria will not be enrolled in the study:
• Electrocardiogram (ECG 12-leads, supine position): clinically significant abnormalities
• Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study
• Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness
• Allergy: ascertained or presumptive hypersensitivity to the active principles (carbocysteine-L-lysine salt) and/or formulations' ingredients; history of hypersensitivity to drugs (in particular to mucolytics) or allergic reactions in general, which the Investigator considers may affect the outcome of the study
• Diseases: significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory (including asthma), skin, haematological, endocrine or neurological and autoimmune diseases that may interfere with the aim of the study
• Medications: medications, including over the counter (OTC) drugs \[in particular carbocysteine-L-lysine salt, carbocysteine and N-acetylcysteine, mucolytics and /or mucoregulators in general\], herbal remedies and food supplements taken 2 weeks before the start of the study. Hormonal contraceptives for females will be allowed
• Investigative drug studies: participation in the evaluation of any investigational product for 6 months before this study. The 6-month interval is calculated as the time between the last visit of the previous study and the first day of the present study (date of the informed consent signature)
• Blood donation: blood donations for 3 months before this study
• Drug, alcohol, caffeine, tobacco: history of drug, alcohol (\>1 drink/day for females and \>2 drinks/day for males, defined according to the USDA Dietary Guidelines 2010) caffeine (\>5 cups coffee/tea/day) or tobacco abuse (≥6 cigarettes/day)
• Drug test: positive result at the drug test at screening
• Alcohol test: positive alcohol breath test at day -1
• Diet: abnormal diets (\<1600 or \>3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians
• Pregnancy (females only): positive or missing pregnancy test at screening or day -1, pregnant or lactating women

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead
• Cross Research S.A.: collaborator

Study Sites (1)

CROSS Research S.A., Phase I Unit

Arzo, Swiss, CH-6864, Switzerland

Location

MeSH Terms

Conditions

Bronchitis

Interventions

Powders; Solutions

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Clinical Development & Operations
• Organization: Dompé farmaceutici SpA

clinical.trials@dompe.com

+39 02 583831

Study Officials

• Milko Radicioni, MD

  CROSS Research S.A., Phase I Unit

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2016
• First Posted: August 8, 2016
• Study Start: July 4, 2016
• Primary Completion: July 25, 2016
• Study Completion: October 10, 2016
• Last Updated: November 18, 2024
• Results First Posted: November 18, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)