EBA, Safety and Tolerability of Sanfetrinem Cilexetil

• Status: Recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: TASK Applied Science
• Collaborators: European and Developing Countries Clinical Trials Partnership (EDCTP); GlaxoSmithKline
• Treatments: Amoxicillin; Clavulanic Acid; Clavulanic Acids; Rifampin

Criteria

Inclusion Criteria:

• Participants are required to meet all of the following criteria in order to be randomized.

1. Provide written, informed consent prior to all trial-related procedures.

2. Male or female, aged between 18 and 65 years, inclusive.

3. Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.

4. Newly diagnosed, previously untreated, rifampicin-susceptible pulmonary TB.

5. A chest X-ray picture taken at screening which, in the opinion of the investigator, is consistent with TB.

6. 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.

7. Ability to produce an adequate volume of sputum as estimated from an overnight sputum collection sample (estimated 10 ml or more).

8. 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:

1. Participant is not heterosexually active or practicing sexual abstinence

2. 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

3. Barrier method combined with hormone-based contraceptives or an intra-uterine device for the female partner.

Exclusion Criteria:

• Participants will be excluded from participation if they fulfil any of the following criteria.

1. 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.

2. Poor general condition where any delay in treatment cannot be tolerated per discretion of the investigator.

3. Clinically significant evidence of extrathoracic TB, as judged by the investigator.

4. 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.

5. Alcohol or drug abuse, that in the opinion of the investigator, is sufficient to compromise the safety or cooperation of the participant.

6. HIV positive ONLY IF:

• CD4 < 250cells/mm3

• On ART

7. Participation in other clinical studies with investigational agents within 8 weeks prior to trial start (with the exception of COVID-19 vaccines).

8. 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.

9. 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.

10. Participants with the following toxicities at screening as defined by the enhanced CTCEA toxicity table

1. creatinine >1.5 times upper limit of normal [ULN];

2. haemoglobin <8.0 g/dL;

3. platelets <50x109 cells/L;

4. serum potassium <3.0 mmol/L;

5. aspartate aminotransferase (AST) ≥3.0 x ULN;

6. alanine aminotransferase (ALT) ≥3.0 x ULN;

7. Total white cell count <1.5 cells/L

11. For participants undergoing PET/CT, the following are excluded:

1. Participants with diabetes (Type 1 or 2) with point of care HbA1c above 6.5, or random glucose over 11.1 mmol/L.