Early Bactericidal Activity (EBA) of SQ109 in Adult Subjects With Pulmonary TB

NCT ID: NCT01218217

Last Updated: 2013-01-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2012-05-31

Brief Summary

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.

Conditions

Tuberculosis, Pulmonary

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SQ109 75 mg

75 mg SQ109 monotherapy daily

Group Type: EXPERIMENTAL

SQ109

Intervention Type: DRUG

SQ109 150 mg tablet

SQ109 150 mg

150 mg SQ109 daily

Group Type: EXPERIMENTAL

SQ109

Intervention Type: DRUG

SQ109 150 mg tablet

SQ109 300 mg

300 mg SQ109 daily

Group Type: EXPERIMENTAL

SQ109

Intervention Type: DRUG

SQ109 150 mg tablet

SQ109 150 mg + RIF

150 mg SQ109 + RIF standard dose daily

Group Type: EXPERIMENTAL

SQ109

Intervention Type: DRUG

SQ109 150 mg tablet

Rifampicin

Intervention Type: DRUG

Rifampicin 150 mg capsules

SQ109 300 mg + RIF

300 mg SQ109 + RIF standard dose daily

Group Type: EXPERIMENTAL

SQ109

Intervention Type: DRUG

SQ109 150 mg tablet

Rifampicin

Intervention Type: DRUG

Rifampicin 150 mg capsules

RIF Mono

Standard dose Rifampicin monotherapy daily

Group Type: ACTIVE_COMPARATOR

Rifampicin

Intervention Type: DRUG

Rifampicin 150 mg capsules

Interventions

SQ109

SQ109 150 mg tablet

Intervention Type: DRUG

Rifampicin

Rifampicin 150 mg capsules

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sequella, Inc.

INDUSTRY

Sponsor Role: collaborator

European and Developing Countries Clinical Trials Partnership (EDCTP)

OTHER_GOV

Sponsor Role: collaborator

German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role: collaborator

Quintiles, Inc.

INDUSTRY

Sponsor Role: collaborator

CMed Technologies Inc.

INDUSTRY

Sponsor Role: collaborator

PathCare

UNKNOWN

Sponsor Role: collaborator

Parexel

INDUSTRY

Sponsor Role: collaborator

Michael Hoelscher

OTHER

Sponsor Role: lead

Responsible Party

Michael Hoelscher

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Michael Hoelscher, MD

Role: STUDY_CHAIR

Klinikum of the University of Munich

Andreas Diacon, MD

Role: PRINCIPAL_INVESTIGATOR

Task Applied Sciences

Rodney Dawson, MD

Role: PRINCIPAL_INVESTIGATOR

University of Cape Town

Locations

TASK Applied Sciences

Cape Town, , South Africa

University of Cape Town

Cape Town, , South Africa

Countries

South Africa

Other Identifiers

LMU-IMPH-SQ109-01

Identifier Type: -

Identifier Source: org_study_id