Phase II Study of Amithiozone (Thiacetazone) for Patients With Mycobacterium Avium Complex Pulmonary Disease
Phase II Study of Amithiozone (Thiacetazone) for Patients With Mycobacterium Avium Complex Pulmonary Disease
OBJECTIVES: I. Determine the bacteriological activity of amithiozone against Mycobacterium
 avium complex (MAC) pulmonary disease.

 II. Define the ability of amithiozone to improve clinical outcomes in patients with MAC
 infection.

 III. Determine the safety and tolerance of amithiozone with chronic dosing in these patients.

 IV. Assess the contribution of clarithromycin, streptomycin, rifampin, ethambutol, kanamycin,
 and amithiozone in the treatment of pulmonary MAC infection.
PROTOCOL OUTLINE: The is a randomized, open label study. All patients receive a core regimen
 of clarithromycin and streptomycin. Patients are randomized into two treatment arms. Arm I
 patients receive rifampin and ethambutol. Arm II patients receive amithiozone.

 Patients are followed for one year to detect any relapse or other complications.

 Patients not eligible for this randomized study may be entered on a short open label study
 with amithiozone.

 Completion date provided represents the completion date of the grant per OOPD records
PROTOCOL ENTRY CRITERIA:

 --Disease Characteristics--

 -  Progressive pulmonary disease due to Mycobacterium avium complex (MAC) as defined by:
 Three of more sputum culture(s) positive for MAC Change in serial chest roentgenograms
 consistent with active mycobacterial disease over a 12 week period No other obvious
 cause of pulmonary disease

 -  Patients must have organisms that are: Susceptible to amithiozone AND Susceptible or
 moderately susceptible to the combination of rifampin and ethambutol, and to
 clarithromycin and streptomycin

 --Prior/Concurrent Therapy--

 -  No likelihood of resectional thoracic surgery within 24 weeks of evaluation

 --Patient Characteristics--

 -  Age: 18 and over

 -  Performance status: Not specified

 -  Hematopoietic: Not specified

 -  Hepatic: Bilirubin less than 3 times normal SGOT/SGPT less than 3 times normal
 Alkaline phosphatase less than 3 times normal

 -  Renal: Creatinine clearance at least 30 mL/min

 -  Cardiovascular: No New York Heart Association class III or IV heart failure

 -  Other: No optic disease that precludes the use of ethambutol No hypersensitivity to
 rifampin, ethambutol, clarithromycin, streptomycin, or amithiozone HIV negative Not
 pregnant or nursing