Asthma: triple-drug inhaler boosts lung function in phase 3 trials

Takeaway

• Single-inhaler extrafine triple therapy improved forced expiratory volume in 1 second (FEV₁) and exacerbation rate in 2 phase 3 trials of patients with uncontrolled asthma (TRIMARAN and TRIGGER).
• The trials showed benefit for adding the long-acting muscarinic antagonist glycopyrronium (G) to combination therapy with the corticosteroid beclomethasone dipropionate (BDP) and the long-acting beta-2-agonist formoterol fumarate (FF).

Why this matters

• First clinical trial of a single-inhaler triple therapy in asthma.
• Extrafine formulations heighten deposition of the medication in small airways.

Study design

• 2 multicentre, parallel-group, double-blind, randomised, active-controlled, phase 3 trials with 1155 patients in TRIMARAN and 1437 patients in TRIGGER.
• Doses in TRIMARAN: BDP 100 μg/FF 6 μg/G 10 μg vs BDP 100 μg/FF 6 μg.
• Doses in TRIGGER: BDP 200 μg/FF 6 μg/G 10 μg or open-label BDP 100 μg/FF 6 μg plus tiotropium vs BDP 100 μg/FF 6 μg
• Patients were required to have uncontrolled asthma, a history of ≥1 exacerbation in the previous year, and previously treated with inhaled corticosteroid.
• Coprimary outcomes: FEV₁ at week 26 and rate for moderate and severe exacerbations over the course of 52 weeks.
• Funding: Chiesi Farmaceutici.

Key results

• TRIMARAN
  • FEV₁ improved by 57 mL (P=.0080).
  • Exacerbations reduced by 15% (rate ratio [RR], 0.85; P=.033).
• TRIGGER
  • FEV₁ improved by 73 mL (P=.0025).
  • Exacerbations reduced by 12% (RR, 0.88; P=.11).

Limitations

• One open-label group.