study of the safety, tolerability, and pk of szey-2108 administered intravenously to hvs in sad and mad cohorts

Conditions: Infections

Summary: this phase 1 study was designed to evaluate the safety and tolerability of szey-2108 in single and multiple intravenous infusions, the pharmacokinetic profile of szey-2108 after single and multiple intravenous infusions, and the effect of exposure to szey-2108 after a single intravenous infusion on qt/qtc interval. metabolites in each biological matrix (blood, urine, feces) and excretion characteristics (feces) after szey-2108 were analyzed.

this is a first-in-human, randomized, double-blind, placebo-controlled study consisting of 2 parts. part 1: single-dose intravenous infusion dose-escalation trial. a total of 44 \~ 52 healthy adult subjects will be enrolled in part 1 and they will be administrated with szey-2108 or placebo by single intravenous infusion. part 1 consists of 7 cohorts: 100mg，200mg，500mg, 1000mg, 2000mg，4000mg and the dose of last cohort to be determined. four subjects will be randomized to szey-2108 or placebo at a ratio of 1:1 in the 100mg cohort and eight subjects at a ratio of 3:1 in other each cohort. time for intravenous infusion is 2h±5 min and it may be extended to 3 h±5 min if intolerance occur in 2000mg and 4000mg cohort. subjects will be randomised to receive an intravenous infusion of szey-2108 or placebo on the morning of d1, then they will still be hospitalised for safety, tolerability, pharmacokinetic and c-qtc assessment, and finally will discharge the phase i clinical study centre after completion of all assessments at d3. they are required to return to the study centre at d7 for a safety follow-up visit. part 2: multi-dose intravenous infusion dose-escalation trial according to results of part 1, administration dose and dosing interval may be adjusted in part 2. thirty healthy adult subjects will be enrolled in part 2 and they will receive multiple doses of szey-2108 or placebo by intravenous infusion. part 2 consists of 3 cohorts: 1000mg at q8h，2000mg at q8h, and one dose level of 1000mg, 1500mg or 2000mg at q6h. ten subjects will be randomized to szey-2108 or placebo at a ratio of 4:1 in each cohort. time for intravenous infusion is 2h±5 min and it may be extended to 3 h±5 min if intolerance occur in 2000mg cohort. subjects will be randomized to receive an intravenous infusion of szey-2108 or placebo at q8h or q6h on d1\~d7 and on the morning of d8. they will still be hospitalised for safety, tolerability and pharmacokinetic assessment, and finally will discharge the phase i clinical study centre after completion of all assessments at d9 or d10 (for faecal retention group). subjects are required to return to the study centre at d15 for a safety follow-up visit.

Eligibility criteria:
inclusion criteria: * age between 18 and 45 years at the time of screening; * bmi between 19 and 28 kg/m2, and weight for males and females ≥ 50kg and 45kg, respectively; * no clinical relevant abnormalities * sign informed consent exclusion criteria: * any clinical significant illness * other medical or psychiatric may inappropriate for the study * past history of allergic conditions or current comorbid allergies * use of any prescription medications within 4 weeks prior to screening or use of any over-the-counter medications, herbs, supplements, and vitamins within 7 days prior to the use of the investigational drug; * history of cigarette, alcohol or drug abuse * abnormal vital signs, such as blood pressure and pulse rate * abnormal examination results, such as 12-ecg, egfr, alt, ast and tbl * positive results of hbsag, tppa, hcv-ab, or hiv-ab * blood loss or donation \> 400ml within 3 months prior to screening * pregant or breastfeeding females or subjects unwilling to contraception

Keywords: healthy volunteers szey-2108