Benapenem PK Phase Ib Multiple-dose Study

NCT03578588 | Completed Phase 1

• 1 other identifier: 5081-CPK-1002
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

A single-center, randomized, open-label, three-period and three-crossover trial design is adopted in the single-dose pharmacokinetic study. 12adult volunteers, are assigned to 3 groups, B1（250mg), B2 (500mg), and B3 (1000mg). Each group of subjects receive single-dose test drug at different dosages in each period. The tolerability and pharmacokinetic studies are performed simultaneously. Two doses, 250 mg and 500 mg, are proposed for multiple-dose tolerability and pharmacokinetic studies. The subjects are divided into two groups, C1 and C2, 12 subjects in each group, half males and half females. 250 mg group is performed first. Each subject receives only one dose, intravenous drip, once daily, for 7 consecutive days

Conditions

Health, Subjective

Keywords

single dose; multiple dose; Pharmacokinetic; Tolerability; Healthy Subject; Benapenem

Outcome Measures

Primary Outcomes (4)

• AUC(0-24) of Benapenem

  AUC(0-24) is the area under the curve from time 0 to 24 hours

  Pre dose and 0.25,0.5,0.75,1,1.5, 2, 2.5, 3, 4, 6,8,12, 24,36,48 hours after Dosing

• Maximum observed plasma concentration (Cmax) of Benapenem

  Maximum observed plasma concentration (Cmax) of following in healthy subjects

  Pre dose and 0.25,0.5,0.75,1,1.5, 2, 2.5, 3, 4, 6,8,12, 24,36,48 hours after Dosing

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

  Time to maximum observed plasma concentration (tmax)

  Pre dose and 0.25,0.5,0.75,1,1.5, 2, 2.5, 3, 4, 6,8,12, 24,36,48 hours after Dosing

• Time to elimination half-life (t1/2) of Benapenem

  Time to elimination half-life (t1/2)

  Pre dose and 0.25,0.5,0.75,1,1.5, 2, 2.5, 3, 4, 6,8,12, 24,36,48 hours after Dosing

Secondary Outcomes (4)

• Number of subjects with clinically significant findings in vital signs

  Screening and Day1, Day 2, Day4 after dosing

• Number of subjects with clinically significant findings in laboratory parameters

  Screening and Day1, Day 2, Day4 after dosing

• Number of subjects with adverse events and serious adverse events

  Screening and Day1, Day 2, Day4 after dosing

• Number of subjects with clinically significant 12-lead ECGs

  Screening and Day1, Day 2, Day4 after dosing

Study Arms (5)

Banapenem B1 group

EXPERIMENTAL

Dose in the 1st period 250mg; Dose in the 2nd period 500mg; Dose in the 3rd period 1000mg

Drug: Banapenem

Banapenem B2group

EXPERIMENTAL

Dose in the 1st period 500mg; Dose in the 2nd period 1000mg; Dose in the 3rd period 250mg

Drug: Banapenem

Banapenem B3group

EXPERIMENTAL

Dose in the 1st period 1000mg; Dose in the 2nd period 250mg; Dose in the 3rd period 500mg

Drug: Banapenem

Banapenem C1group

EXPERIMENTAL

250mg Once daily for 7 consecutive days

Drug: Banapenem

Banapenem C2group

EXPERIMENTAL

500mg Once daily for 7 consecutive days

Drug: Banapenem

Interventions

Banapenem DRUG

Twelve healthy adult volunteers, half male and female, are enrolled and randomly assigned to three groups, B1, B2, and B3. The subjects in three groups receive three doses, 250 mg, 500 mg and 1000 mg. Each group of subjects receive single-dose test drug at different dosages in each period. The subjects are divided into two groups, C1 and C2, 12 subjects in each group, half males and half females. 250 mg group is performed first. After completion of observation and confirming that the drug can be safely tolerated, study on 500 mg group is then performed

Also known as: 5081

Banapenem B1 group; Banapenem B2group; Banapenem B3group; Banapenem C1group; Banapenem C2group

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 with 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.
• 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 \< 90 mmHg or ≥ 140 mmHg, 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

Study Officials

• Yuan Lv, PhD

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A single-center, randomized, open-label, three-period and three-crossover trial design is adopted in the single-dose pharmacokinetic study; A single-center, randomized, open- label, and dose escalation trial design is used in the multiple-dose tolerability and pharmacokinetic studies

Study Record Dates

• First Submitted: May 17, 2018
• First Posted: July 6, 2018
• Study Start: December 14, 2015
• Primary Completion: January 13, 2016
• Study Completion: January 13, 2016
• Last Updated: July 6, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share