Phase III Randomized Study of the Inhalation of Tobramycin in Patients With Cystic Fibrosis
Phase III Randomized Study of the Inhalation of Tobramycin in Patients With Cystic Fibrosis
OBJECTIVES: I. Determine the safety and efficacy of tobramycin in patients with cystic
 fibrosis who are chronically colonized with Pseudomonas aeruginosa.

 II. Determine whether this treatment produces tobramycin-resistant bacteria at a frequency
 different from the placebo group and whether the emergence of resistance is associated with a
 lack of clinical response.
PROTOCOL OUTLINE: This is a randomized, double blind, placebo controlled, multicenter study.

 Patients receive tobramycin or placebo by inhalation twice daily for 28 days followed by 28
 days of rest. This treatment is repeated twice, for a total of 3 courses of therapy.

 Patients are followed every 2 weeks for the first 8 weeks, then every 4 weeks, and then at 4
 weeks after the last treatment.
PROTOCOL ENTRY CRITERIA:

 --Disease Characteristics--

 Documented cystic fibrosis with Pseudomonas aeruginosa present in a sputum or throat
 culture within 6 months prior to screening

 Sweat chloride at least 60 mEq/L

 --Prior/Concurrent Therapy--

 At least 14 days since prior intravenous or aerosolized tobramycin or other antipseudomonal
 antibiotic

 At least 4 weeks since prior administration of any investigational drug

 No concurrent antibiotics by aerosol

 --Patient Characteristics--

 Renal:

 -  Creatinine less than 2 mg/dL

 -  BUN less than 40 mg/dL

 -  No proteinuria of 2+ or greater

 Pulmonary:

 -  FEV1 at least 75% and at least 25% of predicted

 -  Room air oximetry at least 88% saturation

 -  Able to perform pulmonary function tests

 -  No hemoptysis of 60 mL or greater within 30 days prior to study

 -  No abnormal chest X-ray

 Other:

 -  Not pregnant

 -  Fertile females must use effective contraception

 -  No history of positive culture with Burkholderia cepacia

 -  No history of glucose-6-phosphate dehydrogenase deficiency

 -  No known local or systemic hypersensitivity to aminoglycosides, albuterol, or other
 beta-2 agonists