A Study to Evaluate Pharmacokinetics, Safety and Tolerability of Single and Multiple Intravenous Doses of N-acetylcysteine (NAC) in Chinese Healthy Volunteers
Condition: Respiratory Tract Disorders
MeSH terms: Respiratory Tract Diseases
Intervention: N-acetylcysteine (NAC)
Intervention description: Two ampoules of IMP (300 + 300 mg) corresponding to a total dose of 600 mg of NAC diluted in 10 mL of NaCl 0.9% sterile saline solution, will be administered by a 5-minute i.v. infusion.
Intervention MeSH terms: Acetylcysteine; N-monoacetylcystine
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Factorial Assignment
Intervention model description: All the subjects enrolled in the study will receive the same treatment with the investigational medicinal product (IMP), i.e. NAC, 300 mg/ 3 mL solution injection as single dose and multiple dose regime. Single dose of IMP will be administered under fasting conditions on day 1 at 08:00 ±1 h. Multiple doses (5) of IMP will be administered twice a day (b.i.d.) on days 4 and 5 at 08:00 ±1 h and 20:00 ±1 h and one dose will be administered on day 6 at 08:00 ±1.
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This is a single and multiple dose, single centre, open-label, one-way, pharmacokinetics,
      safety and tolerability clinical trial of Phase I to be performed in Chinese healthy male and
      female volunteers. Twenty-four (24) healthy male and female Chinese volunteers will be
      included in the study. Drop-out subjects will not be replaced. The study has been designed in
      agreement with the Chinese Technical Guideline on Clinical Pharmacokinetic Research of
      Chemical Drugs, 18 March 2005 and the European Guideline on the Investigation of
      Bioequivalence. No randomisation will take place in this study. All the participant will
      receive the same treatment with the investigational medicinal product (IMP), i.e. NAC, 300
      mg/ 3 mL solution for injection.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Informed consent: signed written informed consent before inclusion in the study

          2. Ethnicity, Sex and Age: Chinese males and females, 18-45 year old inclusive

          3. Weight: body weight ≥50 kg

          4. Body Mass Index: 19-26 kg/m2 inclusive

          5. Vital signs: systolic blood pressure 100-139 mmHg, diastolic blood pressure 50-89
             mmHg, heart rate 50-90 bpm, measured after 5 min at rest in the sitting/supine
             position

          6. 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

          7. Nicotine addiction (smoker subjects only): ability to abstain from smoking for the
             duration of the clinical study

          8. Contraception and fertility (women only): women of child-bearing potential must be
             using at least one of the following reliable methods of contraception:

               1. Hormonal oral, implantable, transdermal, or injectable contraceptives for at
                  least 60 calendar days before the screening visit

               2. 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 60 calendar days before the screening visit

               3. A male sexual partner who agrees to use a male condom with spermicide

               4. A sterile sexual partner

        Women of non-child-bearing potential or in post-menopausal status for at least 1 year will
        be admitted. Women of childbearing potential should be willing to adopt abstinence or
        contraception measures during the study and two weeks post-dose. For all women, pregnancy
        test result must be negative at screening and day -1.

        Exclusion Criteria:

          1. Electrocardiogram (12-lead ECG in 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, in particular significant laboratory abnormality indicative of
             hepatic condition (more than 3 times the upper limit)

          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, urologic, metabolic, neurological or
             psychiatric diseases, as determined by the investigator, that may interfere with the
             aim of the study; history of carcinoma in situ and malignant disease; active bacterial
             or viral infection and fever >38°C within 48 h prior to study treatment administration

          6. Virology: positive result of HIV, hepatitis B (HBV), hepatitis C (HCV) or Treponema
             pallidum (TP) assays

          7. Surgery: any surgery within 60 calendar days of screening (excluding diagnostic
             surgery)

          8. Medications: medications, including over the counter (OTC) medications, herbal
             remedies and traditional Chinese remedies for 2 weeks before the start of the study.
             Hormonal contraceptives for women will be allowed

          9. Investigative drug studies: participation in the evaluation of any investigational
             product for 1 month before this study

         10. Blood donation: blood donations for 90 calendar days before this study

         11. 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
             2015-2020] caffeine (>5 cups coffee/tea/day) or tobacco abuse (≥10 cigarettes/day)

         12. Abuse drug test: positive urine abuse drug test at screening or day -1

         13. Alcohol test: positive alcohol breath test at day -1

         14. Diet: abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating habits
             in the 4 weeks before this study; vegetarians; consumption of alcohol, grapefruit,
             products containing grapefruit, or beverages containing xanthines (coffee, tea, soda,
             coffee with milk, energy drinks) within 48 hours prior to the enrolment

         15. Pregnancy (females only): positive or missing pregnancy test at screening or day -1,
             pregnant or lactating women

         16. Vaccination within 4 weeks of study treatment

         17. Other unspecified reasons that, in the opinion of the investigator, make the subject
             unsuitable for enrolment.