What are the inclusion criteria for Ensifentrine (PDE4 inhibitor) clinical trials in patients with Chronic Obstructive Pulmonary Disease (COPD)?

Inclusion Criteria for Ensifentrine Clinical Trials in COPD Patients

The typical inclusion criteria for Ensifentrine (PDE3/4 inhibitor) clinical trials in COPD patients include moderate to severe COPD with post-bronchodilator FEV1 between 30-80% predicted, FEV1/FVC ratio <0.70, age 40-80 years, and symptomatic disease despite maintenance therapy. 1, 2

Key Inclusion Criteria

Demographic and Disease Characteristics

• Age range: 40-80 years 1, 2
• COPD diagnosis: Confirmed by spirometry
• Disease severity:
  • Post-bronchodilator FEV1/FVC ratio <0.70 3
  • Post-bronchodilator FEV1 between 30-80% predicted (moderate to severe COPD) 1
  • Symptomatic disease (typically assessed using validated tools like CAT or mMRC) 3

Lung Function Parameters

• Airflow limitation:
  • Moderate COPD: FEV1 50-80% predicted with FEV1/FVC ≤0.7 3
  • Severe COPD: FEV1 30-50% predicted with FEV1/FVC ≤0.7 3
  • Post-bronchodilator values are required (typically measured after administration of 400μg salbutamol or 80μg ipratropium) 3

Symptom Requirements

• Symptomatic disease despite current therapy:
  • mMRC dyspnea score ≥2 3
  • CAT score ≥10 3
  • Evaluating Respiratory Symptoms (E-RS) score indicating significant symptom burden 4

Treatment History

• Background therapy:
  • Many trials allowed concomitant LAMA or LABA therapy (62% of patients in ENHANCE trials) 2
  • Some trials specifically studied Ensifentrine as add-on to tiotropium 5
  • Inhaled corticosteroid use was permitted in some trials (18% of patients in ENHANCE) 2

Exacerbation History

• Recent exacerbations:
  • Some trials required history of exacerbations (e.g., at least one moderate or severe exacerbation in the previous year) 3
  • The ENHANCE trials included both frequent and infrequent exacerbators 2

Exclusion Criteria Often Applied

• Unstable disease: Exacerbation within 4 weeks prior to screening 4
• Significant comorbidities: Particularly those that might affect lung function assessment or increase risk
• Contraindications to PDE inhibitors: Based on the mechanism of action of Ensifentrine

Clinical Relevance

Ensifentrine's dual PDE3/4 inhibition provides both bronchodilator and anti-inflammatory effects, making it potentially valuable for:

• Patients with persistent symptoms despite LAMA/LABA therapy 5
• Patients at risk of exacerbations 2
• Patients who may benefit from non-steroidal anti-inflammatory effects 4

The ENHANCE trials demonstrated that Ensifentrine significantly improved lung function (FEV1) and reduced exacerbation rates across a broad range of COPD patients, including those on background maintenance therapy 1, 2.

Important Considerations

• Spirometry must be performed according to ATS/ERS standards 3
• Post-bronchodilator values should be used for classification of airflow limitation severity 3
• Patient selection should consider both symptoms and exacerbation risk, as these factors influence treatment response 3
• The pharmacokinetics of Ensifentrine may be affected by moderate renal impairment (25% reduction in clearance) 6

When designing or evaluating clinical trials of Ensifentrine in COPD, these inclusion criteria help identify patients most likely to benefit from this dual PDE3/4 inhibitor while maintaining appropriate safety parameters.