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Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834     Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za     Website: www.pactr.org

Trial no.: PACTR201009000252144 Date registered: 2010/09/27
TRIAL DESCRIPTION
Public title SQ109 EBA
Official scientific title A Phase 2A Trial to Evaluate the Extended Early Bactericidal Activity, Safety, Tolerability, and Pharmacokinetics of SQ109 in Adult Subjects with Newly Diagnosed, Uncomplicated, Smear-Positive, Pulmonary Tuberculosis
Brief summary describing the background
and objectives of the trial
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.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) LMU-IMPH-SQ109-01
Disease(s) or condition(s) being studied Tuberculosis ,
Purpose of the trial Treatment
Anticipated trial start date 2010-11-01
Actual trial start date 2010-12-06
Anticipated date of last follow up 2011-09-19
Actual date of last follow up
Anticipated target sample size (number of participants) 90   
Actual target sample size (number of participants)   
Recruitment status Open to recruitment: actively recruiting participants
Secondary Ids Issuing authority/Trial register Links to Secondary ID
20100606 Medicines Control Council South Africa
20100606 Medicines Control Council South Africa

STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person
allocating the participants to the intervention arms
Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomisation with blocks of six Numbered containers Masking/blinding used

INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental group SQ109 monotherapy daily 75 mg 14 days 15
Experimental group 150mg SQ109 monotherapy daily 150 mg daily 14 days 15
Experimental group 300 mg SQ109 monotherapy daily 300mg daily 14 days 15
Experimental group 150mg SQ109 +RIF std dose daily 150 mg daily + RIF 14 days 15
Experimental group 300 mg SQ109 +RIF std dose daily 300 mg daily + RIF 14 days 15
Control group Std dose RIF monotherapy daily Std dose RIF monotherapy daily 14 days Standard dose Rifampicin 15 Active

ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Min age Max age Gender
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 occasi 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, chlorpromaz 18 Years 64 Years Both

ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval
Name of the ethics committee
Yes 2010/07/15 PharmaEthics
Ethics Committee Address
Street address City Postal code Country
123 Arrncor Road Lyttelton Manor 0157 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval
Name of the ethics committee
Yes 2010/08/16 Health Sciences Faculty, Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Room E52-24, Groote Schuur Hospital Old Main Building, Observatory 7925 Cape Town South Africa

OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Descriptive analyses will be used to assess safety and tolerability of subjects in each dose group. Data will be presented by the proportion of subjects with serious adverse events and subjects who discontinue due to adverse event(s). Daily during first two weeks On follow-up visits 17 and 28
Primary Outcome The extended EBA of 14 days of daily 75 mg, 150 mg, and 300 mg SQ109, and of daily 150 mg or 300 mg SQ109 with daily RIF standard dose will be described with linear, bi-linear or non-linear regression of logCFU over time. Daily during first two weeks and
Secondary Outcome The standard EBA (EBA 0-2) of each treatment group, as determined by the rate of change of logCFU in sputum over the period Day 0-2 (linear, bi-linear or non-linear regression of logCFU over time). Day 0 Day 1 Day 2
Secondary Outcome The standard EBA (EBA 0-2) of each treatment group, as determined by the rate of change of logCFU in sputum over the period Day 0-2 (linear, bi-linear or non-linear regression of logCFU over time). Day 0-2
Secondary Outcome ¿ Extended EBA (EBA 2-14) of each treatment group, as determined by the rate of change of logCFU in sputum over the periods Day 2-14 (linear, bi-linear or non-linear regression of logCFU over time). Day 2-14
Secondary Outcome The change in time to positivity (TTP) in the Mycobacterium Growth Indicator Tube (Bactec MGIT 960 system). Days 0-14
Secondary Outcome Pharmakokinetics Days 1,2,7,8,14,15

RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
TASK Applied Science, Karl Bremer Hospital M2 c/o Mike Pienaar Boulevard and Frans Conradie Avenue Bellville 7530 South Africa
Centre for Tuberculosis Research Innovation, University of Cape Town Lung Institute George Street Mowbray, Cape Town 7700 South Africa

FUNDING SOURCES
Name of source Street address City Postal code Country
BMBF Hannoversche Straße 28-30 Berlin 10115 Germany
EDCTP P.O. Box 93015 2509 AA The Hague Netherlands
Sequella Inc. 9610 Medical Center Drive, Suite 200 Rockville, MD Rockville, MD 20850 United States of America
BMBF Hannoversche Straße 28-30 Berlin 10115 Germany
EDCTP P.O. Box 93015 2509 AA The Hague Netherlands
Sequella Inc. 9610 Medical Center Drive, Suite 200 Rockville, MD Rockville, MD 20850 United States of America

SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Prof. Burkhard Göke, Medical Director, Klinikum of the University of Munich Marchioninistr. 15 Munich 81377 Germany University
Primary Sponsor Prof. Burkhard Göke, Medical Director, Klinikum of the University of Munich Marchioninistr. 15 Munich 81377 Germany University

COLLABORATORS
Name Street address City Postal code Country
Prof. Andreas Diacon, Principal Investigator c/o Mike Pienaar Boulevard and Frans Conradie Avenue Bellville 7530 South Africa
Michael Hoelscher, Chief Investigator, Klinikum of the University of Munich Georgenstr. 5 Munich 80799 Germany
Dr Rodney Dawson, Co-PI Fancie van Zyl Drive, Tygerberg 7550 South Africa
Prof. Andreas Diacon, Principal Investigator c/o Mike Pienaar Boulevard and Frans Conradie Avenue Bellville 7530 South Africa
Michael Hoelscher, Chief Investigator, Klinikum of the University of Munich Georgenstr. 5 Munich 80799 Germany
Dr Rodney Dawson, Co-PI Fancie van Zyl Drive, Tygerberg 7550 South Africa

CONTACT PEOPLE
Role Name Email Phone Fax
Principal Investigator Prof Andreas Diacon ahd@sun.ac.za +27219389392 +27219389476
Street address City Postal code Country Position / Affiliation
c/o Mike Pienaar Boulevard and Frans Conradie Avenue Bellville 7530 South Africa Principal Investigator
Role Name Email Phone Fax
Public Enquiries Ms Sonja Henne henne@lrz.uni-muenchen.de +49 89 2180 17604 +49 89 336038
Street address City Postal code Country Position / Affiliation
Georgenstr. 5 Munich 80799 Germany Head of Clinical Development
Role Name Email Phone Fax
Scientific Enquiries Dr Norbert Heinrich heinrich@ lrz.uni-muenchen.de +49 89 2180 17605 +49 89 336038
Street address City Postal code Country Position / Affiliation
Georgenstr. 5 Munich 80799 Germany Medical Expert