A Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease (TOPIC)

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease

This was a multicenter, randomized, double-blind, placebo-controlled study of patients with severe, though stable, cystic fibrosis (CF) whose routine treatment included Pulmozyme. Patients were randomized to either continue Pulmozyme or have therapy withdrawn for 2 weeks (placebo group). Patients must have had stable CF symptoms without any change in therapy for 2 weeks prior to enrollment in order to participate.

Inclusion Criteria:

• Signed Informed Consent Form and, if applicable, Assent Form
• Age ≥ 14 years old at screening
• Proven diagnosis of CF
• Ability to perform acceptable and reproducible spirometry maneuvers at screening
• FVC ≤ 45% predicted for race, height, age, and sex at screening
• Chronic use of Pulmozyme for at least 3 months in the last year and daily or twice daily use during the 14 days prior to screening
• Stable regimen of chest physiotherapy (CPT) for at least 14 days prior to screening
• Ability to complete the 6-minute walk test at screening
• Ability to complete the 6-minute walk test and spirometry at Visit 2
• If on routine tobramycin solution for inhalation (i.e., TOBI®) or other cycled antibiotic therapy, intention to either start or stop therapy at the time of Visit 2 (based on routine therapy cycle; no other planned change in this antibiotic regimen for 28 days before or 28 days after Visit 2)
• Clinically stable with no change in medications during the 14 days prior to screening

Exclusion Criteria:

• Use of an investigational drug or device within 28 days prior to screening
• Previous episode of acute respiratory failure requiring assisted ventilation within 2 years prior to screening
• Previous lung transplant
• Any cardiac disease that would contraindicate performing the 6-minute walk test
• Pregnancy or nursing
• Known hypersensitivity or other contraindication to the use of Pulmozyme
• Previous completion or premature discontinuation of study drug or withdrawal from this study
• More than one prior screening failure for this study at any time or any prior screening failure for this study within the last 28 days