EBA, Safety and Tolerability of Sanfetrinem Cilexetil

Laborértékek

• Participants will be excluded from participation if they fulfil any of the following criteria.
  • Evidence of clinically significant conditions or findings, other than TB, that might compromise safety or the interpretation of trial endpoints, per discretion of the investigator.
  • Poor general condition where any delay in treatment cannot be tolerated per discretion of the investigator.
  • Clinically significant evidence of extrathoracic TB, as judged by the investigator.
  • History of allergy to any of the trial IP/s or related substances i.e. β-lactams and penicillin, as confirmed by the clinical judgement of the investigator.
  • Alcohol or drug abuse, that in the opinion of the investigator, is sufficient to compromise the safety or cooperation of the participant.
  • HIV positive ONLY IF:
  • CD4 < 250cells/mm3
  • On ART
  • Participation in other clinical studies with investigational agents within 8 weeks prior to trial start (with the exception of COVID-19 vaccines).
  • Female participant who is pregnant, breast-feeding, or planning to conceive a child within the anticipated period of trial participation. Male participant planning to conceive a child within the anticipated period of participating in the trial.
  • Treatment received with any drug active against M.tb (including but not limited to isoniazid, ethambutol, amikacin, cycloserine, fluoroquinolones, rifabutin, rifampicin, streptomycin, kanamycin, para-aminosalicylic acid, rifapentine, pyrazinamide, thioacetazone, capreomycin, thioamides), or with immunosuppressive medications such as TNF-alpha inhibitors within 2 weeks prior to screening, or systemic corticosteroids for more than 7 days within 2 weeks prior to screening.
  • Participants with the following toxicities at screening as defined by the enhanced CTCEA toxicity table
  • creatinine >1.5 times upper limit of normal [ULN];
  • haemoglobin <8.0 g/dL;
  • platelets <50x109 cells/L;
  • serum potassium <3.0 mmol/L;
  • aspartate aminotransferase (AST) ≥3.0 x ULN;
  • alanine aminotransferase (ALT) ≥3.0 x ULN;
  • Total white cell count <1.5 cells/L
  • For participants undergoing PET/CT, the following are excluded:
  • Participants with diabetes (Type 1 or 2) with point of care HbA1c above 6.5, or random glucose over 11.1 mmol/L.

• Participants are required to meet all of the following criteria in order to be randomized.
  • Provide written, informed consent prior to all trial-related procedures.
  • Male or female, aged between 18 and 65 years, inclusive.
  • Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
  • Newly diagnosed, previously untreated, rifampicin-susceptible pulmonary TB.
  • A chest X-ray picture taken at screening which, in the opinion of the investigator, is consistent with TB.
  • Sputum positive on direct microscopy for acid-fast bacilli on at least one sputum sample (at least 1+ on the IUATLD/WHO scale) or GeneXpert cycle threshold of medium or high.
  • Ability to produce an adequate volume of sputum as estimated from an overnight sputum collection sample (estimated 10 ml or more).
  • Be of non-childbearing potential or using effective methods of birth control, as defined below:
  • Non-childbearing potential:
  • Female participant/ female sexual partner - bilateral oophorectomy
• bilateral tubal ligation
• hysterectomy
• postmenopausal with no menses for at least 12 consecutive months Male participant/ male sexual partner - vasectomy
• bilateral orchidectomy more than three months prior to screening
  • Effective birth control methods:
• Participant is not heterosexually active or practicing sexual abstinence
• Double barrier method which can include a male condom, diaphragm, cervical cap, or female condom (male and female condoms should not be used together); or
• Barrier method combined with hormone-based contraceptives or an intra-uterine device for the female partner.