Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome

INCLUSION CRITERIA For the portion of the protocol involving continuations of pirfenidone treatment, the criteria are simply previous enrollment in 97-HG-0085. For enrollment in the new clinical trial, the inclusion criteria involve enrollment in protocol 95-HG-0193, "Clinical and Basic Investigations into Hermansky-Pudlak Syndrome". This itself requires a diagnosis of HPS based upon molecular grounds or the electron microscopic demonstration of deficiency of platelet dense bodies. In addition, for protocol 97-HG-0085, patients must: Be over 18 years of age. Have an FVC greater than 50 percent and less than or equal to 85 percent of predicted OR a hemoglobin-corrected DL(co) greater than 35 percent and less than or equal to 80 percent of predicted, with no evidence of a pulmonary embolism. Have evidence of reduced exercise tolerance lasting longer than one week on either the St. George's Hospital Respiratory Questionnaire or the Dyspnea Perception Scale. FEV(1)/FVC greater than 80 percent of predicted after bronchodilators. No evidence of improvement in pulmonary fibrosis within the past year defined as an FVC increased by 10 percent or a DL(co) increased by 15 percent. Distance walked greater than or equal to 150 meters (492 feet) with oxygen saturation greater than or equal to 83 percent on less than or equal to 6 L/min. of oxygen during the 6-Minute Walk Test (6MWT). Be available, willing, and able to come to the NIH Clinical Center for admission every 4 months for three years. EXCLUSION CRITERIA History of clinically significant environmental exposure known to cause pulmonary fibrosis (including but not limited to drugs, asbestos, beryllium, radiation, domestic birds). An explanation for interstitial lung disease other than HPS, including but not limited to radiation, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans organizing pneumonia, cancer. Diagnosis of any connective tissue disease including but not limited to scleroderma, systemic lupus erythematosus, rheumatoid arthritis. Listing on a lung transplantation waiting list. Pregnancy or lactation Cigarette smoking in the past 6 months History of ethanol abuse or recreational drug use in the past two years History of human immunodeficiency virus (HIV) or chronic viral hepatitis infection Chronic use of high-dose steroids (greater than 10 mg prednisone/day) Prior use of pirfenidone Use of any of the following within 28 days of enrollment: investigational therapy, cytotoxic/immunosuppressive agents other than corticosteroids (including but not limited to azathioprine, cyclosphosphamide, methotrexate, cyclosporine); cytokine modulators (including but not limited to etanercept and infliximab); therapies targeted to treat pulmonary fibrosis (including but not limited to D-penicillamine, colchicine, interferon gamma-1b, bosentan, N-acetylcysteine Any severe medical complication including but not be limited to uncontrolled seizures, repeated transient ischemic attacks, abnormal mental status, severe ataxia, uncontrolled migraine headaches, diplopia, repeated episodes of syncope, untreated clinical depression, recent myocardial infarction (past 6 months), unstable angina, clinically relevant arrhythmias, uncontrolled hypotension or hypertension (systolic blood pressure less than 80 or greater than 180 mm Hg), myocarditis, hepatomegaly (liver greater than 3 cm below the right costal margin), renal glomerular impairment (creatinine clearance less than 35 ml/min/1.73 m2, pancreatitis, toxic thyroiditis, malignancy (except basal cell carcinoma) Medications with a high frequency of life threatening side effects Significant laboratory abnormalities, including but not limited to serum potassium less than 3.0 or greater than 5.4 mEq/L, SGPT greater than 100 U/L, CK greater than 700 U/L, hemoglobin less than 9.0 g/dL, platelets less than 70 k/mm3, leucocyte count less than 2.0 k/microliter, or cholesterol greater than 400 mg/dL. For women of child bearing age, failure to have an effective method of birth control.