This 2 arm study will investigate the efficacy, safety and tolerability of RAR Gamma versus placebo in ex-smokers with moderate or severe emphysema treated with optimal COPD therapy. Following optimization of COPD therapy (up to 6 weeks) patients will be randomized to receive either RAR Gamma (5mg) or placebo once daily using a 2:1 ratio (active:placebo), in addition to their standard therapy. Following the double-blind treatment period, patients will enter a 4-week follow-up period. The anticipated time on study period is 1-2 years, and the target sample size is 100-500 individuals.

Inclusion Criteria:

• patients of >44 years of age, with >10 pack-year smoking history;
• women not of child-bearing potential;
• ex-smokers (must have stopped smoking for >=12 months) with clinical diagnosis of emphysema;
• willing to be switched to optimal COPD therapy.

Exclusion Criteria:

• off oral steroids >28 days prior to enrollment;
• >2 exacerbations of pulmonary symptoms requiring outpatient treatment, or >1 exacerbation requiring hospitalization, within 12 months prior to screening;
• exposure to synthetic oral retinoids in past 12 months;
• history of allergy or sensitivity to retinoids.