Phase 1 Completed N=24 Other

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

Respiratory Tract Disorders

Source: ClinicalTrials.gov NCT03881163 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Jan 2021

Primary outcomePrimary: Peak Drug Concentration (Cmax) After Single Dose of NAC — 83.30 µg/mL

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.

Outcome Measures

Outcome	Result	p-value
PRIMARY Peak Drug Concentration (Cmax) After Single Dose of NAC	83.30	—
PRIMARY Time to Achieve Cmax (Tmax) After Single Dose of NAC	0.083	—
PRIMARY Terminal Elimination Rate Constant (Kel) After Single Dose of NAC	0.09723	—
PRIMARY Half-life (t1/2) After Single Dose of NAC	7.129	—
PRIMARY Area Under the Concentration-time Curve (AUC) After Single Dose of NAC	87.16; 93.94; 81.87	—
PRIMARY Volume of Distribution (Vd) After Single Dose of NAC	65.69	—
PRIMARY Total Body Clearance (CLt) After Single Dose of NAC	6.387	—
PRIMARY Total Amount of NAC Excreted in Urine [Ae(0-t)] After Single Dose of NAC	62750; 16170; 3609; 1846; 1366; 84020	—
PRIMARY Total Fraction of NAC Dose Excreted in Urine [Fe(0-t)] After Single Dose of NAC	0.1046; 0.1400; 0.1493; 0.1534; 0.1558	—
PRIMARY Renal Clearance (CLr) After Single Dose of NAC	995.2	—
PRIMARY Percentage of the AUC(0-inf) Obtained by Extrapolation (%AUCextra)	6.967	—
PRIMARY Plasma Concentration at Steady-state After Multiple Doses of NAC	100.8; 1.899; 7.719	—
PRIMARY Time to Achieve Css_max (tss_max) After Multiple Doses of NAC	0.083	—
PRIMARY Area Under the Concentration-time Curve at Steady State After Multiple Doses of NAC	116.6; 92.63	—
PRIMARY Accumulation Ratio After Multiple Doses of NAC	1.132	—
PRIMARY Total Amount of NAC Excreted in Urine From the Last Multiple Dose to 32 h at Steady-state [Aess(0-32)]	68980	—
PRIMARY Degree of Fluctuation Over One Dosing Interval at Steady-state (DF%) After Multiple Dose of NAC	1279	—
SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs)	7; 2	—

Eligibility Criteria

Inclusion Criteria

Informed consent: signed written informed consent before inclusion in the study
Ethnicity, Sex and Age: Chinese males and females, 18-45 year old inclusive
Weight: body weight ≥50 kg
Body Mass Index: 19-26 kg/m2 inclusive
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
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
Nicotine addiction (smoker subjects only): ability to abstain from smoking for the duration of the clinical study
Contraception and fertility (women only): women of child-bearing potential must be using at least one of the following reliable methods of contraception:
Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 60 calendar days 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 60 calendar days before the screening visit
A male sexual partner who agrees to use a male condom with spermicide
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

Electrocardiogram (12-lead ECG in 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, in particular significant laboratory abnormality indicative of hepatic condition (more than 3 times the upper limit)
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
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
Virology: positive result of HIV, hepatitis B (HBV), hepatitis C (HCV) or Treponema pallidum (TP) assays
Surgery: any surgery within 60 calendar days of screening (excluding diagnostic surgery)
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
Investigative drug studies: participation in the evaluation of any investigational product for 1 month before this study
Blood donation: blood donations for 90 calendar days 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 2015-2020] caffeine (>5 cups coffee/tea/day) or tobacco abuse (≥10 cigarettes/day)
Abuse drug test: positive urine abuse drug test at screening or day -1
Alcohol test: positive alcohol breath test at day -1
Diet: abnormal diets ( 3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians; consumption of al

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Data sourced from ClinicalTrials.gov (NCT03881163). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.