Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis (CL-010)

The planned sample size of 15 participants per treatment group is in keeping with other Phase II trials of this type and accounts for the possibility of up to 3 drop-outs per arm, which based on previous studies of this type conducted at these sites, represents a conservative estimate of the expected drop-out rate.

Inclusion criteria

• Informed Consent
• Body weight between 40 and 90 kg, inclusive.
• Newly diagnosed, previously untreated, uncomplicated, sputum smear-positive, pulmonary TB.
• A chest X-ray compatible with TB.
• Sputum positive
• Adequate volume of sputum
• Female participants of childbearing potential negative serum pregnancy and agree to use birth control
• Male participants must agree to use contraception throughout participation in the trial and for 12 weeks after last dose.

Exclusion criteria

• Poor general condition
• Rifampicin-resistant and/or Isoniazid-resistant
• MTB Treatment received within the 3 months prior
• Allergy to the IMP or related substances
• Evidence of extrathoracic TB
• A history of previous TB
• Evidence of serious lung conditions other than TB or uncontrolled obstructive bronchial disease
• History of lens opacity or evidence of lens opacity on slit lamp ophthalmologic examination
• Any evidence of renal impairment
• For males, any evidence or history of abnormality in the reproductive system
• History and/or presence (or evidence) of neuropathy or epilepsy.
• Clinically relevant changes in the ECG
• A history of or current clinically relevant cardiovascular disorder
• Concomitant use of any drug known to prolong QTc interval
• Diabetics using insulin
• Evidence of clinically significant metabolic, gastrointestinal, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied).
• Any diseases or conditions in which the use of the standard TB drugs or any of their components is contra-indicated, including but not limited to allergy to any TB drug, their component or to the IMP.
• Any disease or conditions in which any of the medicinal products listed in the section pertaining to prohibited medication is used.
• alcohol or drug abuse
• Administration of an IMP prior to Visit 1, within 5 half-lives for that IMP if known. If the half-life of the IMP is unknown within 1 month.
• Pregnant, breast-feeding, or planning to conceive or father a child within twelve weeks of cessation of treatment for males and within one week of cessation of treatment for females.
• Use of any drugs or substances within 30 days prior to dosing known to be strong inhibitors or inducers of cytochrome P450 enzymes
• Any therapeutic agents known to alter any major organ function (e.g., barbiturates, opiates, phenothiazines, cimetidine) within 30 days prior to dosing.
• glucocorticoids within one year prior to dosing.
• HIV infection with helper/inducer T lymphocyte (CD4 cell) count of less than or equal to 300x10-6/L.
• Receiving antiretroviral therapy (ART).