Clinical trial NCT05340530: To Evaluate the Pharmacokinetic Effects of TQD3606 for Injection in Healthy Adult Subjects
Official title: Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Characteristics of Injectable TQD3606 in a Single Center, Randomized, Double-blind, Placebo-controlled, Single, Multiple Dosing in Healthy Subjects, and to Explore Urinary Excretion of the Product
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Infections
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-04-22
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: TQD3606 is a fixed-dose combination of meropenem and avibatam. This study is a phase I clinical study to evaluate the safety, tolerability and pharmacokinetic characteristics of TQD3606 injection in a single center, randomized, double-blind, placebo-controlled, single and multiple administration in healthy subjects, and to explore the excretion of TQD3606 in urine. To evaluate the tolerability and safety of injectable TQD3606 after single and multiple dosing in healthy subjects.


Eligibility criteria: Inclusion Criteria:

* 1 Signed the informed consent before the test and fully understood the test content, process and possible adverse reactions;
* 2 Able to complete the research according to the requirements of the test plan;
* 3 Subjects aged between 18 and 55 (including 18 and 55);
* 4 Body mass index (BMI) ≥ 18 and ≤ 28kg/m2, with male weight ≥ 50 kg and female weight ≥ 45 kg;
* 5 Health status: No mental disorders, no history of cardiovascular system, nervous system, respiratory system, digestive system, urinary system, endocrine system and metabolic abnormalities;
* 6 Subjects had no pregnancy plan and voluntarily used effective contraceptive measures for at least 6 months from 2 weeks before self-medication to the last use of study medication.

Exclusion Criteria:

* 1 Previous neuropsychiatric system, respiratory system, cardiovascular system, digestive system, hemolymph system, liver and kidney dysfunction, endocrine system, musculoskeletal system disease or other diseases, and the investigator judged that the previous history may affect drug metabolism or safety;
* 2 Known allergic history to meropenem or avitabtam, known history of anaphylactic shock to penicillin, cephalosporins, carbapenems and other β -lactam antibiotics or other severe allergic reactions (such as bullous epidermolysis atrophic dermatitis, exudative dermatitis);
* 3 Allergic constitution, including allergy to food and other drugs;
* 4 Persons with a history of epilepsy or central nervous system dysfunction;
* 5 Those with definite chronic headache or chronic diarrhea in the past;
* 6 Changes in QT interval or QT Corrected (QTc) \> 450ms were considered clinically significant by researchers;
* 7 The creatinine clearance rate was less than 50ml/min;
* 8 Taking any prescription, over-the-counter, vitamin products or herbal medicine within 2 weeks prior to screening;
* 9 Abnormal and clinically significant laboratory tests during screening period;
* 10 Blood donation or significant blood loss within 3 months prior to taking the study drug (\>450 ml);
* 11 Participated in any drug clinical trials within 3 months prior to taking the study drug;
* 12 Heavy smokers (5 cigarettes or more per day) within 3 months prior to screening;
* 13 Have a history of drug and/or alcohol abuse (14 units of alcohol per week: 1 unit =360mL beer or 45mL 40% spirits or 150mL wine);
* 14 Urine drug test positive or have a history of drug abuse or drug use in the past five years;
* 15 Unable to tolerate venipuncture blood collection or poor vascular condition;
* 16 Have taken a special diet (including dragon fruit, mango, grapefruit, grapefruit juice and/or xanthine diet) within 2 weeks prior to the trial;
* 17 Consuming chocolate, caffeinated coffee or tea within 48 hours before the trial;
* 18 Have taken any alcoholic food or beverage within 48 hours prior to the test;
* 19 The subject cannot complete the test due to personal reasons;
* 20 Conditions considered unsuitable for inclusion by other researchers.

Primary outcomes:
measure: Maximum Concentration (Cmax)
timeFrame: 1 hour before administration，to 24 hours after administration.
measure: Area under the plasma concentration-time curve from initial dosing to 24 hours (AUC0-24)
timeFrame: 1 hour before administration，to 24 hours after administration.
Secondary outcomes:
measure: Time to maximum concentration following drug administration (Tmax)
timeFrame: 1 hour before administration，to 24 hours after administration.
measure: Apparent terminal elimination half-life following drug administration (t1/2)
timeFrame: 1 hour before administration，to 24 hours after administration.
measure: Area under plasma concentration-time curve from first dosing to last measurable concentration point (AUC0-t)
timeFrame: 1 hour before administration，to 24 hours after administration.
measure: The amount of drug excreted through urine 24 hours after administration (Ae0-24)
timeFrame: 1 hour before administration，to 24 hours after administration.
measure: Cumulative excretion rate of drugs through urine
timeFrame: 1 hour before administration，to 24 hours after administration.
measure: The total clearance (CLt) The total clearance (CLt)
timeFrame: 1 hour before administration，to 24 hours after administration.
measure: Renal clearance (CLr)
timeFrame: 1 hour before administration，to 24 hours after administration.
measure: Elimination rate constant(λz)
timeFrame: 1 hour before administration，to 24 hours after administration.
measure: Apparent volume of distribution (Vd/F)
timeFrame: 1 hour before administration，to 24 hours after administration.
measure: Mean residence time (MRT)
timeFrame: 1 hour before administration，to 24 hours after administration.
measure: Valley concentration (Cmin,ss)
timeFrame: Within 60 minutes before 8th to 10th administration and 24 hours after 10th administration
measure: Accumulation index
timeFrame: Within 60 minutes before 8th to 10th administration and 24 hours after 10th administration
measure: Adverse event rate
timeFrame: Baseline up to 24 hours after administration
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: Baseline up to 24 hours after administration
measure: Body temperature
timeFrame: 1 hour before administration and 24 hours after administration
measure: Pulse
timeFrame: 1 hour before administration and 24 hours after administration
measure: Systolic and diastolic blood pressure
timeFrame: 1 hour before administration and 24 hours after administration
measure: Number of participants with abnormal laboratory test results
timeFrame: Baseline up to 24 hours after administration
Other outcomes:
Locations:
city: Changchun
country: China
facility: Affiliated Hospital of Changchun University of Traditional Chinese Medicine
state: Jilin
Study officials:
References: