Early Bactericidal Activity (EBA) of SQ109 in Adult Subjects With Pulmonary TB
Early Bactericidal Activity (EBA) of SQ109 in Adult Subjects With Pulmonary TB
SQ109 was developed with the aim of shortening TB treatment and providing new drugs for
 resistant TB. The drug has demonstrated efficacy in toxicology studies and an acceptable
 safety profile in first-in-man studies. The objective of this study is to evaluate the
 extended early bactericidal activity (EBA), safety, tolerability, and pharmacokinetics of
 several doses of SQ109 with or without Rifampicin (RIF) for 14 days in adults with newly
 diagnosed, uncomplicated, smear positive, pulmonary TB.
Inclusion Criteria:

 1. Provide signed written informed consent for study participation, including HIV testing
 (if HIV serostatus is not known or the last documented negative is more than four
 weeks prior to enrolment).

 2. Be eighteen (18) to 64 (inclusive) years of age.

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

 4. Have newly diagnosed, previously untreated, uncomplicated, sputum smear-positive,
 pulmonary TB.

 5. Have a chest X-ray which, in the opinion of the Investigator, is compatible with TB.

 6. Is sputum positive on direct microscopy for acid-fast bacilli (at least 1+ on the
 IUATLD/WHO scale (Appendix 3).

 7. Is able to produce an adequate spot sputum sample, indicating an overnight sputum
 volume of at least 10 mL.

 8. Female patients of childbearing potential must have a negative serum pregnancy test,
 and consent to practice two effective methods of birth control when not abstaining
 from sexual intercourse, unless she and her partner(s) are surgically sterile or she
 is post-menopausal with no menses for the last 12 months. Preferably, contraceptive
 measures should be continued until completion of TB treatment, but at least until one
 month after last dose of IMP, unless she and her partner(s) are sterile (that is,
 women who have had a bilateral oophorectomy or hysterectomy or have been
 postmenopausal for at least 12 consecutive months).

 Two of the following methods may be used, but only one may be hormonal: tubal
 ligation, vaginal diaphragm, intrauterine device, condom, oral contraceptives,
 contraceptive implant, combined hormonal patch, combined injectable contraceptive or
 depot-medroxyprogesterone acetate, partner(s) has had a vasectomy.

 9. Male participants must agree to use an adequate method of contraception when not
 abstaining from sexual intercourse throughout participation in the trial and for 12
 weeks after last dose, unless he has had bilateral orchidectomy.

 10. A Karnofsky score of at least 60 (requires occasional assistance but is able to care
 for most of his/her needs, see Appendix 5)

 Exclusion Criteria:

 1. Poor general condition where any delay in treatment cannot be tolerated per discretion
 of Investigator.

 2. Treatment with any drug active against MTB within the 3 months prior to Visit 1 (this
 includes, but is not limited to INH, EMB, RIF, PZA, amikacin, cycloserine, rifabutin,
 streptomycin, kanamycin, para-aminosalicylic acid, rifapentine, thioacetazone,
 capreomycin, fluoroquinolone, thioamides, metronidazole).

 3. Sputum isolate is resistant to RIF as detected by rapid assay from native sputum

 4. A history of allergy to the IMP or related substances.

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

 6. A history of previous TB.

 7. Evidence of serious lung conditions other than TB or uncontrolled obstructive
 bronchial disease.

 8. Laboratory parameters done at, or within 14 days prior to, screening:

 -  Serum amino aspartate transferase (AST) and/or serum alanine aminotransferase
 (ALT) activity >3 times the upper limit of normal

 -  Serum total bilirubin level >2.5 times the upper limit of normal

 -  Serum creatinine level >2 times the upper limit of normal

 -  Complete blood count with hemoglobin level <7.0 g/dL

 -  Platelet count <50,000/mm3

 -  Serum potassium <3.5 meq/L

 9. History, presence, or evidence of a neuropathy or epilepsy.

 10. Clinically relevant change s in the ECG such as atrioventricular (AV) block,
 prolongation of the QRS complex over 120 milliseconds, or of either the QTcF or QTcB
 interval over 450 milliseconds on the screening ECG.

 11. A history of, or current clinically relevant cardiovascular disorder such as
 myocardial infarction, heart failure, coronary heart disease, hypertension,
 arrhythmia, or tachyarrhythmia. Family history of sudden death of unknown or
 cardiac-related cause, or of prolonged QTc interval. Concomitant use of any drug known
 to prolong QTc interval (including amiodarone, bepridil chloroquine, chlorpromazine,
 cisapride, cisapride, clarithromycin, disopyramide dofetilide, domperidone,
 droperidol, erythromycin, halofantrine, haloperidol, ibutilide, levomethadyl,
 lumefantrine, mesoridazine, methadone, pentamidine, pimozide, procainamide, quinidine,
 sotalol, sparfloxacin, terfenadine, thioridazine).

 12. Diabetics using insulin.

 13. Evidence of clinically significant metabolic, gastrointestinal, neurological,
 psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the
 indication being studied).

 14. Any disease or condition in which the use of the standard TB drugs or any of their
 components is contraindicated, including but not limited to allergy to any TB drug,
 their components or to the IMPs.

 15. Any disease or condition in which any of the medicinal products listed in the section
 pertaining to prohibited medication (see 4.10.4) is used.

 16. 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 patient. Opiates prescribed for cough relief are not
 counted as drug abuse.

 17. Prior administration of SQ109.

 18. Is pregnant, breast-feeding, or planning to conceive or father a child within one
 month of cessation of treatment.

 19. Use of any drugs or substances within 30 days prior to dosing known to be strong
 inhibitors or inducers of cytochrome P450 enzymes (including xenobiotics, quinidine,
 tyramine, ketoconazole, testosterone, quinine, gestodene, metyrapone, phenelzine,
 doxorubicin, troleandomycin, cyclobenzaprine, erythromycin, cocaine, furafylline,
 cimetidine, dextromethorphan). Exceptions may be made for subjects that have received
 3 days or less of one of these drugs or substances, if there has been a wash-out
 period equivalent to at least 5 half-lives of that drug or substance.

 20. Use of any therapeutic agents within 30 days prior to dosing known to alter any major
 organ function (e.g., barbiturates, opiates, phenothiazines, cimetidine).

 21. Use of systemic glucocorticoids within three months prior to dosing.

 22. HIV infection with helper/inducer T lymphocyte (CD4 cell) count of 250 10-6/L.

 23. Receiving antiretroviral therapy (ART).