Effect of Ensifentrine on Sputum Markers of Inflammation in COPD

This is a randomized, double-blind, placebo-controlled, two-period cross-over study of nebulized ensifentrine (3 mg) or placebo administered BID for two 8-week Treatment Periods. All participants with receive both ensifentrine and placebo during participation.

Participants will be randomized 1:1 to receive ensifentrine or placebo first in Treatment Period 1 followed by the opposite treatment in Treatment Period 2:

1. Treatment Period 1: Ensifentrine; Treatment Period 2: Placebo. 2. Treatment Period 1: Placebo; Treatment Period 2: Ensifentrine.

All participants will take study supplied albuterol (to use as-needed) as well as a once daily COPD Maintenance Therapy during study participation.

The total duration of study participation is 22-24 weeks:

* Screening and Run-in Period: 2-4 weeks; participants will be screened for eligibility before entering a run-in period to ensure a stable background on a once daily COPD Maintenance Therapy. * Treatment Period 1: 8 weeks; participants completing the Run-in Period and meeting all entry and Randomization Criteria will be randomized to 8 weeks of treatment with blinded, nebulized ensifentrine or placebo + once daily COPD Maintenance Therapy. * Washout Period: 4 weeks; patients will only take once daily COPD Maintenance Therapy. There will be a follow-up phone call about 1 week after finishing Treatment Period 1. * Treatment Period 2: 8 weeks of treatment with Study Medication (opposite of Treatment Period 1) + once daily COPD Maintenance Therapy. * Safety follow-up: 1 week after Treatment Period 2

There are 7 scheduled in-clinic visits: Screening visit + three visits within each treatment period. There is an end of treatment safety telephone follow-up call about 1 week after each treatment period. Participants will have telephone reminders between in-clinic visits.