Bioequivalence Study of Two Different Formulations of N-acetyl-cysteine (NAC)
Condition: no Condition
Intervention: N-acetylcysteine
Intervention description: The product was administered according to the randomisation list and cross-over design, with 150 mL of still mineral water under fasting conditions on study day 1 of periods 1 or 2 at 8:00±1 h.
Intervention MeSH terms: Acetylcysteine; N-monoacetylcystine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: healthy volunteers

Summary:

      Study primary Objective:

      - To evaluate the bioequivalent rate (Cmax) and extent (AUC0-t) of absorption of
      N-acetyl-cysteine 600 mg uncoated tablets vs. N-acetyl-cysteine 600 mg film-coated tablets
      (NAC) in healthy male and female volunteers.

      Study secondary objectives:

        -  To describe the pharmacokinetic (PK) profile of NAC in plasma after single dose
           administration of NAC 600 mg uncoated tablets vs. NAC 600 mg film-coated tablets;

        -  to collect safety and tolerability data after single dose administration of NAC 600 mg
           uncoated tablets vs. NAC 600 mg film-coated tablets.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Informed consent: signed written informed consent before inclusion in the study

          2. Sex and age: males and females,18-55 years old, inclusive

          3. Body Mass Index (BMI): 18.5-30 kg/m2, inclusive

          4. Vital signs: systolic blood pressure (SBP) 100-139 mmHg, diastolic blood pressure
             (DBP) 50-89 mmHg, heart rate (HR) 50-90 bpm, measured after 5 min of rest in the
             sitting position

          5. 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

          6. Contraception and fertility (females only): females of child-bearing potential and
             with an active sexual life 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

               -  A non-hormonal intrauterine device 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

               -  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 (serum β-HCG
        test) and day -1 (urine test).

        Exclusion Criteria:

          1. Electrocardiogram (ECG 12-leads, supine position): clinically significant
             abnormalities

          2. Physical findings: clinically significant abnormal physical findings which could
             interfere with the objectives of the study

          3. Laboratory analyses: clinically significant abnormal laboratory values indicative of
             physical illness

          4. Allergy: ascertained or presumptive hypersensitivity to the active principle and/or
             formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in
             general, which the investigator considers may affect the outcome of the study

          5. Diseases: significant history of renal, hepatic, gastrointestinal, cardiovascular,
             respiratory, skin, haematological, endocrine or neurological diseases that may
             interfere with the aim of the study

          6. Medications: medications, including over the counter (OTC) medications and herbal
             remedies for 2 weeks before the start of the study. Hormonal contraceptives for
             females will be allowed

          7. Investigative drug studies: participation in the evaluation of any investigational
             product for 3 months before this study. The 3-month interval is calculated as the time
             between the first calendar day of the month that follows the last visit of the
             previous study and the first day of the present study

          8. Blood donation: blood donations for 3 months before this study

          9. 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)

         10. Drug test: positive result at the drug test at screening or day-1

         11. Alcohol test: positive alcohol breath test at day -1

         12. Diet: abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating habits
             in the 4 weeks before this study; vegetarians

         13. Pregnancy (females only): positive or missing pregnancy test at screening or day -1,
             pregnant or lactating women