Study of the Safety, Tolerability, and PK of SZEY-2108 Administered Intravenously to HVs in SAD and MAD Cohorts

NCT ID: NCT06055777

Last Updated: 2024-12-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-07
• Study Completion Date: 2024-05-31

Brief 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.

Detailed Description

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.

Conditions

Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Single intravenous doses of SZEY-2108

Single escalating doses of SZEY-2108

Group Type: ACTIVE_COMPARATOR

SZEY-2108 for injetion

Intervention Type: DRUG

Part1（Single-dose intravenous infusion dose-escalation trial）:100mg，200mg，500mg, 1000mg, 2000mg，4000mg and the dose of last cohort to be determined. Single intravenous doses on D1；Part 2（Multi-dose intravenous infusion dose-escalation trial）：1000mg at Q8h，2000mg at Q8h, and one dose level of 1000mg, 1500mg or 2000mg at Q6h. Multiple intravenous doses of SZEY-2108 at Q8h or Q6h on D1\~D7 and on the morning of D8.

Single intravenous doses of placebo

Single intravenous doses of placebo to match SZEY-2108

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Part1（Single-dose intravenous infusion dose-escalation trial）:250mL/500mL，Single intravenous doses on D1；Part 2（Multi-dose intravenous infusion dose-escalation trial）：250mL,Multiple intravenous doses of placebo at Q8h or Q6h on D1\~D7 and on the morning of D8.

Multiple intravenous doses of SZEY-2108

Multiple intravenous doses of SZEY-2108 at Q8h or Q6h on D1\~D7 and on the morning of D8.

Group Type: ACTIVE_COMPARATOR

SZEY-2108 for injetion

Intervention Type: DRUG

Part1（Single-dose intravenous infusion dose-escalation trial）:100mg，200mg，500mg, 1000mg, 2000mg，4000mg and the dose of last cohort to be determined. Single intravenous doses on D1；Part 2（Multi-dose intravenous infusion dose-escalation trial）：1000mg at Q8h，2000mg at Q8h, and one dose level of 1000mg, 1500mg or 2000mg at Q6h. Multiple intravenous doses of SZEY-2108 at Q8h or Q6h on D1\~D7 and on the morning of D8.

Multiple intravenous doses of placebo

Multiple intravenous doses of placebo at Q8h or Q6h on D1\~D7 and on the morning of D8.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Part1（Single-dose intravenous infusion dose-escalation trial）:250mL/500mL，Single intravenous doses on D1；Part 2（Multi-dose intravenous infusion dose-escalation trial）：250mL,Multiple intravenous doses of placebo at Q8h or Q6h on D1\~D7 and on the morning of D8.

Interventions

SZEY-2108 for injetion

Part1（Single-dose intravenous infusion dose-escalation trial）:100mg，200mg，500mg, 1000mg, 2000mg，4000mg and the dose of last cohort to be determined. Single intravenous doses on D1；Part 2（Multi-dose intravenous infusion dose-escalation trial）：1000mg at Q8h，2000mg at Q8h, and one dose level of 1000mg, 1500mg or 2000mg at Q6h. Multiple intravenous doses of SZEY-2108 at Q8h or Q6h on D1\~D7 and on the morning of D8.

Intervention Type: DRUG

Placebo

Part1（Single-dose intravenous infusion dose-escalation trial）:250mL/500mL，Single intravenous doses on D1；Part 2（Multi-dose intravenous infusion dose-escalation trial）：250mL,Multiple intravenous doses of placebo at Q8h or Q6h on D1\~D7 and on the morning of D8.

Intervention Type: DRUG

Other Intervention Names

Novel monocyclic β-lactam antibiotics; 0.9% Sodium Chloride Injection

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

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

Sponsors

Suzhou Erye Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xiaojie Wu

Role: PRINCIPAL_INVESTIGATOR

Huashan Hospital

Locations

Huashan Hospital Fudan University

Shanghai, Shanghai Municipality, China

Countries

China

Other Identifiers

SZEY-2108-I-01

Identifier Type: -

Identifier Source: org_study_id