Phase 2: EBA, Safety and Tolerability of Sanfetrinem Cilexetil

Study Director
Christelle Van Niekerk
Start Date
/ 2022
Trial Phase
Phase II
Trial Status
Current Enrollment
Target Enrollment

Brief Summary:

To evaluate the 2-week bactericidal activity, pharmacokinetics, safety and tolerability of sanfetrinem cilexetil in participants with rifampicin-susceptible pulmonary tuberculosis.

Detailed Description:

A single-centre, open-label, clinical trial in two stages. Stage 1 will recruit 20 participants followed by a recruitment pause and an interim analysis to determine if sanfetrinem cilexetil has early bactericidal activity (EBA). Should EBA be demonstrated, stage 2 will focus on optimising sanfetrinem cilexetil.

All treatments will be administered orally (PO) on days 1-14. The treatments are:

Stage 1:

  • Sanfetrinem cilexetil 1.6 g PO 12-hourly
  • Rifampicin 35 mg/kg PO once daily (OD)*

An interim analysis is planned after stage 1 to review the pharmacokinetics (PK), safety, tolerability and EBA of sanfetrinem cilexetil. Results of stage 1 will determine whether stage 2 should proceed and if any modifications in dose, duration or combinations are required for Stage 2. If deemed possible, a PK-EBA model will be derived using only stage 1 from which clinical trial simulations will be conducted to inform the design of stage 2. If EBA is not demonstrated, the study will be stopped after stage 1.

Stage 2:

  • Rifampicin 35 mg/kg po OD*
  • Sanfetrinem cilexetil 3.2 g PO OD
  • Sanfetrinem cilexetil 800 mg PO 12-hourly
  • Sanfetrinem cilexetil 800 mg PO 8-hourly
  • Sanfetrinem cilexetil 1.6 g plus amoxicillin/clavulanic acid (Amx/CA) 250mg/125 mg, PO 12-hourly
  • Sanfetrinem cilexetil 1.6 g 12-hourly plus rifampicin 35 mg/kg PO OD

    • Five of the rifampicin 35 mg/kg arm participants will be recruited in stage 1 and the remainder in stage 2.

Participants on rifampicin will serve both as control for the EBA quantitative mycobacteriology and allow evaluation of pharmacodynamic-pharmacodynamic (PD-PD) interaction between rifampicin and sanfetrinem.

The study will not be blinded but the mycobacteriology laboratory staff performing the endpoint assays will remain blinded until analysis of the EBA results.