SQ109 EBA

• Register: PACTR
• Last refreshed on: 27 May 2013
• Main ID: PACTR201009000252144
• Date of registration: 27/09/2010
• Primary sponsor: Prof. Burkhard G?ke, Medical Director, Klinikum of the University of Munich
• Public title: SQ109 EBA
• 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
• Date of first enrolment: 2010-12-06
• Target sample size: 90
• Recruitment status: Open to recruitment: actively recruiting participa
• URL: HTTP://www.pactr.org/ATMWeb/appmanager/atm/atmregistry?da=true&tno=PACTR201009000252144
• Study type: interventional
• Study design: Parallel: different groups receive different interventions at same time during study,; Randomised,; Permuted block randomisation with blocks of six,; Numbered containers,

Countries of recruitment

South Africa

Contacts

• Name: Sonja Henne
• Affiliation: Head of Clinical Development

• Name: Norbert Heinrich
• Affiliation: Medical Expert

Key inclusion & exclusion 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 occasi
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 b3 times the upper limit of normal
? Serum total bilirubin level b2.5 times the upper limit of normal
? Serum creatinine level b2 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

Age minimum: 18 Year
Age maximum: 64 Year
Gender: Both

Health Condition(s) or Problem(s) studied

Tuberculosis
null

Primary Outcome(s)

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).

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.

Secondary Outcome(s)

? 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).

Pharmakokinetics

The change in time to positivity (TTP) in the Mycobacterium Growth Indicator Tube (Bactec MGIT 960 system).

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).

Secondary ID(s)

20100606

Source(s) of Monetary Support

Sequella Inc.

BMBF

EDCTP