A Study to Evaluate Pharmacokinetics, Safety and Tolerability of Single and Multiple Intravenous Doses of N-acetylcysteine (NAC) in Chinese Healthy Volunteers

NCT ID: NCT03881163

Last Updated: 2021-02-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-11
• Study Completion Date: 2020-01-18

Brief 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.

Conditions

Respiratory Tract Disorders

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Single dose regime of N-acetylcysteine (NAC)

On day 1 at 08:00 ±1 hours, one dose of 600 mg of NAC (300 + 300 mg ampoule) will be administered under fasting conditions.

Group Type: EXPERIMENTAL

N-acetylcysteine (NAC)

Intervention Type: DRUG

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.

Multiple dose regime of N-acetylcysteine (NAC)

On days 4 and 5 at 08:00 ±1 hours and 20:00 ±1 hours and at 08:00 ±1 on day 6, 5 doses of 600 mg of NAC (300 + 300 mg ampoule) will be administered.

Group Type: EXPERIMENTAL

N-acetylcysteine (NAC)

Intervention Type: DRUG

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.

Interventions

N-acetylcysteine (NAC)

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 Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Zambon SpA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, No.197 Ruijin Er Road, China

Countries

China

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Z7244J01

Identifier Type: -

Identifier Source: org_study_id