A Double-Blind Placebo-controlled Efficacy and Sarety Study of RO3300074 (5 mg/day) in the Treatment of Moderate-Severe COPD with Emphysema
Emphysema confirmed by low-dose spiral CT
Post-bronchodilator FEV1/FVC < 70%.
Post-bronchodilator FEV1 >/=35% and </=60% of predicted.
DLCO <70% of predicted.
Following screening to randomization: no exacerbation of pulmonary symptoms requiring hospitalization, oral steroids or antibiotics.
Following screening to randomization: off oral steroids.
Able to perform 6-minute walk test.
Following screening to randomization: no change in medication or treatment for COPD.
Within 12 months prior to screening: more than 2 exacerbations of pulmonary symptoms requiring treatment with oral steroids or antibiotics, or more than 1 exacerbation requiring hospitalization.
Solitary nodule in the lung >8 mm.
Giant bullous disease >1/3 of a hemithorax.
Predominant diagnosis of bronchiectasis, tuberculosis, interstitial fibrosis, asbestosis, cystic fibrosis.
On lung transplant waiting list.
Previous lung volume reduction surgery.
Significant other medical conditions that would interfere with ability to perform the study tests.
Current use of vitamin A, beta-carotene or herbal preparations.
Exposure to synthetic oral retinoids in past 12 months.
Hypertriglyceridemia >/= 300 mg/dl with or without therapy.
Unexplained weight loss >/=10% of total body weight over the last 6 months, or BMI <19 kg/m2.
History of allergy to retinoids.
Concurrent enrollment in another therapeutic clinical trial within the last 30 days.
Medical history or active conditions likely to compromise the safety of the subject, or the absorption, metabolism, or excretion of the study medication.
History of substance abuse other than nicotine.
Elevated ALT >2.5x the upper limit of normal.
Elevated amylase >1.5x the upper limit of normal.
Elevated lipase >1.5x the upper limit of normal.
Concomitant medications that are inhibitors or inducers of CYP450 3A4.