Status:
COMPLETED
Phase 2a EBA Trial of AZD5847
Lead Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)
Conditions:
Tuberculosis
Eligibility:
All Genders
18-65 years
Phase:
PHASE2
Brief Summary
The purpose of this study is to assess the early bacterial activity (EBA) from day 0 to day 14 of Astra Zeneca Drug (AZD5847) at four different doses and schedules (500 mg once daily, 500 mg twice dai...
Detailed Description
This is a study of early bactericidal activity (EBA) in treatment-naïve patients with active pulmonary tuberculosis. This prospective, randomized, open-label study that will compare the effect of mono...
Eligibility Criteria
Inclusion
- \- Adults, male or female, age 18 to 65 years - Post-menopausal women under the age of 65 years will be included in the study. Women of childbearing potential must be using or agree to use an adequate method of birth control through the end of study follow up. These methods include: total sexual abstinence; a single male partner who has been vasectomized combined with use of a condom; a combination of two effective birth control methods from the following list: a. an intrauterine device plus a condom; b. a tubal ligation (tubes tied) plus a condom; c. Depo-provera injections plus a condom; d. Intravaginal ring plus a condom - Newly diagnosed sputum smear-positive pulmonary tuberculosis as confirmed by at least one sputum AFB + smear (at least grade 1+ using the WHO/IUATLD grading scale) - Willing and able to provide informed consent - Hemoglobin \>/= 8 gm/dL - Serum creatinine \< 2 mg/dL (\<176.8 umol/L) - Serum AST \< 3.0 times the upper limit of normal for the testing laboratory and total bilirubin \< 1.3 mg/dL - Random blood glucose \< 150 mg/dL (\< 8.32 mmol/L) - If HIV-positive, not currently on ART, CD4 count\> 350 muL\^-1 and/or no need to start ART in the opinion of the local investigator - Cough productive of at least 10 ml (two teaspoons) of sputum daily per patient report over the week prior to enrollment. - Chest radiograph compatible with pulmonary TB. - Negative sputum Xpert™ MTB/RIF test for rifampin resistance. - Negative urine pregnancy test
Exclusion
- \- HIV infection with CD4 count of \</=350muL\^-1 and/or the need to start ART in the opinion of the local investigator. - Weight less than 40 kg or greater than 90 kg - Presence of hemoptysis. Subjects who cough up frank blood (more than blood streaked sputum) will not be eligible for enrollment. - Subjects with rifampin resistance as determined by the Xpert test as screening. - Pregnant or breastfeeding women - Presence of pneumothorax on pretreatment chest radiograph - Clinical suspicion of disseminated tuberculosis or tuberculous meningitis or pulmonary TB requiring immediate start of standard chemotherapy in the opinion of the local investigator - Presence of serious underlying medical illness, such as liver failure, renal failure,any diabetes mellitus, chronic alcoholism (\> 3 alcoholic drinks per day), decompensated heart failure, cardiac arrhythmias, hematologic malignancy or subjects receiving myelosuppressive chemotherapy. - Allergy or contraindication to study drugs - Prior treatment for TB with antituberculous medications (isoniazid, rifampin, pyrazinamide, ethambutol or streptomycin or those treated with other antibiotics with known activity against MTB during the preceding 6 months (for example aminoglycosides, fluoroquinolones, carbapenems and linezolid) - Subjects taking monoamine oxidase (MAO) inhibitors or selective serotonin release inhibitor (SSRI) medications - Total white blood cell count less than 3000/mm\^3 - Platelet count less than 150,000/mm\^3 - Subjects with QTcF\> 450 msec, QTcF \< 340 msec, and/or family history of long QT syndrome - Subjects unlikely in the opinion of the local investigator to be able to comply with the requirements of the study protocol - Subjects whose urine tests positive for INH metabolites, indicating they are already receiving anti-TB treatment. - History of tuberculosis less than 5 years ago, history of more than one episode of tuberculosis, history of drug resistant tuberculosis, or household contact with an individual who has confirmed drug-resistant tuberculosis. - Known arrhythmias or other cardiac conditions - Active severe dermatologic disease (Grade 3 or Grade 4 per DMID Adult Toxicity Table) - Immunosuppressive conditions or receiving immunosuppressive medications - A history of optic neuritis. - Subjects on antiretroviral therapy for HIV (including AZT, 3TC, FTC, D4T, ddI, ddC, tenofovir, abacavir, nevirapine, efavirenz, ritonavir, lopinavir, atazanavir, saquinavir, darunavir, indinavir, raltegravir) - Subjects taking drugs capable of prolonging the QTc interval, such as type Ia and III anti-arrhythmics - Random urine toxicology screen positive for cocaine or methamphetamines.
Key Trial Info
Start Date :
December 5 2012
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 24 2013
Estimated Enrollment :
75 Patients enrolled
Trial Details
Trial ID
NCT01516203
Start Date
December 5 2012
End Date
December 24 2013
Last Update
October 15 2018
Active Locations (1)
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1
Task Clinical Research Centre
Ekurhuleni, Gauteng, South Africa, 7530