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Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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ClinicalTrials.gov |
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Last refreshed on:
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19 February 2015 |
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Main ID: |
NCT01218217 |
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Date of registration:
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08/10/2010 |
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Prospective Registration:
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Yes |
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Primary sponsor: |
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Public title:
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Early Bactericidal Activity (EBA) of SQ109 in Adult Subjects With Pulmonary TB
SQ109EBA |
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Scientific title:
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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 |
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Date of first enrolment:
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November 2010 |
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Target sample size:
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90 |
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Recruitment status: |
Completed |
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URL:
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http://clinicaltrials.gov/show/NCT01218217 |
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Study type:
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Interventional |
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Study design:
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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Phase:
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Phase 2
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Countries of recruitment
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South Africa
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Contacts
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Name:
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Michael Hoelscher, MD |
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Address:
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Telephone:
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Email:
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Affiliation:
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Klinikum of the University of Munich |
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Name:
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Rodney Dawson, MD |
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Address:
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Telephone:
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Email:
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Affiliation:
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University of Cape Town |
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Name:
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Andreas Diacon, MD |
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Address:
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Telephone:
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Email:
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Affiliation:
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Task Applied Sciences |
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Key inclusion & exclusion criteria
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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 antiret
Age minimum:
18 Years
Age maximum:
64 Years
Gender:
Both
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Health Condition(s) or Problem(s) studied
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Tuberculosis, Pulmonary
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Intervention(s)
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Drug: SQ109
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Drug: Rifampicin
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Primary Outcome(s)
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The extended early bactericidal activity (EBA)of daily 75 mg, 150 mg, and 300 mg SQ109, and of daily 150 mg or 300 mg SQ109 with daily RIF standard dose in adults with newly diagnosed, uncomplicated, smear positive, pulmonary TB.
[Time Frame: Daily during first two weeks]
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Secondary Outcome(s)
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Proportion of subjects with serious adverse events and proportion of subjects who discontinue due to an adverse event in each experimental arm.
[Time Frame: Entire study period]
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The change in time to positivity (TTP) in the Mycobacterium Growth Indicator Tube (Bactec MGIT 960 system).
[Time Frame: Days 0-14]
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The standard EBA (EBA 0-2) of each treatment group, as determined by the rate of change of log Colony Forming Units (logCFU) in sputum over the period Day 0-2 (linear, bi-linear or non-linear regression of logCFU over time).
[Time Frame: Day 0 - Day 2]
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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).
[Time Frame: Days 2-14]
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Pharmacokinetics
[Time Frame: Days 1,2,7,8,14,15]
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Secondary ID(s)
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LMU-IMPH-SQ109-01
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Source(s) of Monetary Support
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Please refer to primary and secondary sponsors
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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