Single-dose PK Study of Benapenem In Healthy Subjects

NCT03588156 | Completed Phase 1 DMC

• 1 other identifier: 5081-CPK-1001
• Study Type: interventional
• Target: 98
• Locations: 0 countries
• Sites: N/A

Brief Summary

To design 11 dose groups within 62.5 mg \~ 4000 mg for single-dose tolerability study. A single-center, randomized, blinded, placebo-controlled, dose escalation trial design is adopted. 8 subjects each in 62.5 mg, 125 mg, 3000 mg and 4000 mg dose groups, 10 subjects each in other groups, including 2 placebo-controlled subjects. To be carried out from low-dose group to high-dose group. The next dose group can be studied only when the observation of the previous dose group is completed and it is confirmed that the drug is safely tolerated. The test should be stopped in case of serious adverse reactions, or when more subjects experience adverse reactions and have reached termination criteria of the trial, even if the maximum dose has not been reached. Infusion time is planned to be 30 min in 62.5 mg, 125 mg and 250 mg ; two infusion time, 30 min and 60 min, in 500 mg, 1000 mg and 2000 mg groups. If subjects can tolerate 60-min infusion, the same dose group at infusion time of 30 min is added. The 3000 mg and 4000 mg dose groups only receive 60-min infusion for investigation of tolerability.

Conditions

Healthy Subject

Keywords

Healthy Subject; PK Study; Tolerability; Safety Evaluation

Outcome Measures

Primary Outcomes (3)

• Number of subjects with clinically significant findings in vital signs

  Vitals signs such as systolic and diastolic blood pressure, heart rate, and pulse rate will be measured in a semi-supine position after 5 minutes of rest.

  Change from Baseline at Day1, Day2, Day4 after dosing

• Number of subjects with clinically significant findings in laboratory parameters

  Hematology and clinical chemistry and Urine Routine abnormalities will be monitored

  Change from Baseline at Day1, Day2, Day4 after dosing

• Number of subjects with clinically significant 12-lead ECGs

  Single 12-lead ECGs will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTcF intervals

  Change from Baseline at Day1, Day2, Day4 after dosing

Secondary Outcomes (3)

• AUC(0-24) of Benapenem

  In each group: Pre dose and 0.25,0.5,0.75,1,1.5, 2, 2.5, 3, 4, 6,8,12, 24hour after dosing

• Maximum observed plasma concentration (Cmax) of Benepenem

  In each group: Pre dose and 0.25,0.5,0.75,1,1.5, 2, 2.5, 3, 4, 6,8,12, 24hour after dosing

• Time to maximum observed plasma concentration (tmax) of Benapenem

  In each group: Pre dose and 0.25,0.5,0.75,1,1.5, 2, 2.5, 3, 4, 6,8,12, 24hour after dosing

Study Arms (2)

Benapenem

EXPERIMENTAL

Investigatial Product: Benapenem: 11 group : 62.5mg one dose; 125mg one dose;250mg one dose;500mg one dose 30min infusion;500mg one dose 60min infusion ;1000mg one dose 30min infusion; 1000mg one dose 60min infusion 2000mg one dose 30min infusion;2000mg one dose 60min infusion;3000mg one dose 60min infusion;4000mg one dose 60min infusion

Drug: Benapenem

Placebo

PLACEBO COMPARATOR

Placebo control 11 group : 62.5mg one dose;125mg one dose;250mg one dose;500mg one dose 30min infusion;500mg one dose 60min infusion ;1000mg one dose 30min infusion; 1000mg one dose 60min infusion 2000mg one dose 30min infusion;2000mg one dose 60min infusion;3000mg one dose 60min infusion;4000mg one dose 60min infusion

Drug: Placebo

Interventions

Benapenem DRUG

Dose-escalation For 11 level dose groups A1 \~ A11(each 62.5mg/kg, 125mg/kg, 250mg/kg, 500mg/kg, 1000mg/kg 60min infusion, 1000mg/kg 30min infusion, 2000mg/kg 60 min infusion, 2000mg/kg 30min infusion, 3000mg/kg, 4000mg/kg), 10 subjects (8 for the study drug and 2 for placebo) are randomized to each dose group

Also known as: 5081

Benapenem

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \) Male or female healthy subjects, aged 18\~45;
• \) Body weight ≥ 50 kg and body mass index 19.0\~24.0 kg/m2;
• \) Prior to the test, physical examination, blood routine, urine routine, liver and kidney functions, and related examinations normal, or mild abnormalities in indicators while without clinical significance as indicated by the investigator;
• )Normal or mild abnormalities without clinical significance in the standard 12-lead ECG;
• )Signing informed consent form

You may not qualify if:

• \) Regular smoking, alcohol abuse, and drug abuse;
• )Use of drugs known damage to an organ within three months;
• )History of specific allergies, or history of drug allergy, especially those allergic to lactams and excipients of test drug;
• )Febrile illnesses within three days before the screening;
• )Patients with mental illness or psychotic disorder in the past;
• )Past mental and nervous system diseases (epilepsy, stroke, cerebrovascular disorder, etc.), gastrointestinal disorder (such as stomach ulcers, gastritis, etc.) or disorder of other systems (such as cardiovascular, respiratory, hematological, or endocrine system, etc.) diseases or medical history.
• )Habitually taking any medication, including traditional Chinese medicine;
• )Having taken any medication that may affect test results within two weeks before the screening, such as antibiotics, NSAIDs, aluminum- or magnesium-containing antacids, diuretics, anticoagulants, central nervous system depressants, and any drug that may affect the drug absorption;
• )Having participated in other investigational drug trial in the preceding three months;
• )Blood donation for 360 ml or more within three months before the screening;
• )Heart rate \< 50 bpm or \> 100 bpm;
• )Systolic blood pressure\<90mmHg or ≥ 140mmHg, diastolic blood pressure ≥ 90 mmHg or \< 60 mmHg;
• )Women who are pregnant or breastfeeding, or who may be pregnant without adopting acceptable contraception, or who have a positive result in serum pregnancy test;
• )Women who are planning to become pregnant within 6 months, or male subjects who are planning to make his spouse pregnant within 6 months;
• )HBsAg, HCV antibody, HIV antibody, and Treponema pallidum antibody positive;

Sponsors & Collaborators

• Sihuan Pharmaceutical Holdings Group Ltd.: lead

Related Publications (1)

• Zhao CY, Lv Y, Zhu Y, Wei MJ, Liu MY, Ji XW, Kang ZS, Xia YH, Tian JH, Ma Y, Liu Y. A First-in-Human Safety, Tolerability, and Pharmacokinetics Study of Benapenem in Healthy Chinese Volunteers. Antimicrob Agents Chemother. 2019 Feb 26;63(3):e02188-18. doi: 10.1128/AAC.02188-18. Print 2019 Mar.

  PMID: 30617093 DERIVED

MeSH Terms

Interventions

benapenem

Study Officials

• Yan Zhu, Doctor

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 11 dose groups within 62.5 mg \~ 4000 mg for single-dose tolerability study to carried out from low-dose group to high-dose group

Study Record Dates

• First Submitted: May 16, 2018
• First Posted: July 17, 2018
• Study Start: March 11, 2015
• Primary Completion: September 17, 2015
• Study Completion: September 17, 2015
• Last Updated: July 17, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share