Study to Evaluate EBA, Safety and Tolerability of Carbapenems in Adults With Pulmonary Tuberculosis

• Status: Completed
• Trial end date: 2021-01-04
• Target enrollment: 0
• Participant gender: All

Summary

The goal of this single-center, open-labelled, clinical trial in two groups aims to proof that a specific group of antibiotics (carbapenems) can be used to treat pulmonary tuberculosis if it is combined with another antibiotic (amoxicillin/clavulanate). A total of 113 male or female participants (8 groups and 9 treatment regimens as group 8 was split into 2 groups of 4 participants receiving Rifafour e-275), aged between 18 and 65 years (inclusive), with newly diagnosed, smear-positive, pulmonary TB.

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

Details

• Lead Sponsor: TASK Applied Science
• Treatments: Amoxicillin; Ertapenem; Meropenem; Rifampin

Criteria

Inclusion Criteria:

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

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 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).

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:

1. Participant - not heterosexually active or practicing sexual abstinence; or

2. Female participant/sexual partner - bilateral oophorectomy, bilateral tubal ligation and/or hysterectomy or has been postmenopausal with a history of no menses for at least 12 consecutive months; or

3. Male participant/sexual partner - vasectomised or has had a bilateral orchidectomy minimally three month prior to screening;

Effective birth control methods:

1. 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

2. Barrier method combined with hormone-based contraceptives or an intra-uterine device for the female partner; and are willing to continue practicing birth control methods throughout participation in the study until Visit 19 (day 28).

(Note: hormone-based contraception alone may not be reliable when taking IP; therefore, hormone-based contraceptives alone cannot be used by female participants to prevent pregnancy).

Exclusion Criteria:

1. Evidence of clinically significant conditions or findings, other than the indication being studied, particularly epilepsy, 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. A history of TB less than 3 years ago.

4. Clinically significant evidence of extrathoracic TB (miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis), as judged by the Investigator.

5. 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.

6. Known or suspected, current or history of within the past 2 years, alcohol or drug abuse, that is, in the opinion of the Investigator, sufficient to compromise the safety or cooperation of the participant.

7. HIV infected participants.

8. Having participated in other clinical studies with investigational agents within 8 weeks prior to trial start.

9. Female participant who is pregnant, breast-feeding, or planning to conceive a child within the anticipated period of participating in the trial. Male participant planning to conceive a child within the anticipated period of participating in the trial.

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

11. Hypersensitivity to local anaesthesia of amide type.

12. Treatment received with any drug active against MTB (including but not limited to isoniazid, ethambutol, amikacin, cycloserine, fluoroquinolones, rifabutin, rifampicin, streptomycin, kanamycin, para-aminosalicylic acid, rifapentine, pyrazinamide, thioacetazone, capreomycin, thioamides, metronidazole), or with immunosuppressive medications such as TNF-alpha inhibitors or systemic or inhaled corticosteroids, within 2 weeks prior to screening

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

1. creatinine grade 2 or greater (>1.5 times upper limit of normal [ULN]);

2. haemoglobin <7.5 g/dL;

3. platelets grade 2 or greater (under 50x109 cells/L);

4. serum potassium grade 2 or greater (<3.0 mEq/L);

5. aspartate aminotransferase (AST) grade 3 (≥3.0 x ULN) to be excluded;

6. alanine aminotransferase (ALT) grade 3 (≥3.0 x ULN) to be excluded;

7. APTT grade 3

8. INR grade 3

9. Total white cell count grade 3