Trimbow is approved as maintenance treatment in adults with moderate to severe COPD who are not adequately treated by the combination of an inhaled corticosteroid and a long-acting beta2-agonist. The effects of the triple combination on symptom control and prevention of exacerbations are described in section 5.1 of the SPC and summarised below.
As patients with COPD tend to deteriorate with time, treatment often needs to be progressively increased. Patients may require several drugs that need to be taken through two or three inhalers. By allowing patients to take three drugs via a single inhaler, Trimbow could simplify treatment regimens, decreasing the burden on patients and improving adherence.
Trimbow is supplied as a pressurised metered dose inhaler, which may be used with the AeroChamber Plus spacer device. The active components of Trimbow are formulated as extrafine particles. For beclometasone, this results in a more potent effect than non-extrafine formulations.
Each delivered dose of Trimbow (the dose leaving the mouthpiece) contains 87 micrograms of beclometasone dipropionate, 5 micrograms of formoterol fumarate and 9 micrograms of glycopyrronium. Each metered dose (the dose leaving the valve) contains 100 micrograms of beclometasone dipropionate, 6 micrograms of formoterol fumarate and 10 micrograms of glycopyrronium.
The recommended dose is two inhalations of Trimbow twice daily.
The phase III clinical development programme for the triple combination inhaler included two 52-week active-controlled studies.
TRILOGY was a randomised, double-blind, two-arm, parallel-group, 52-week study in 1368 patients with COPD, which compared beclometasone/formoterol/glycopyrronium to beclometasone/formoterol (Fostair). At week 26, the triple combination significantly improved pre-dose FEV1 by 0.081L (95% CI 0.052–0.109, p<0.001) and 2-hour post-dose FEV1 by 0.117L (95% CI 0.086–0.147, p<0.001) compared with beclometasone/formoterol. Mean transition dyspnoea index (TDI) focal scores at week 26, the third co-primary endpoint, were not significantly different (p=0.160).
TRINITY was a randomised, double-blind, double-dummy, three-arm parallel-group, 52-week study in 2691 patients with COPD, which evaluated the superiority of beclometasone/formoterol/glycopyrronium to tiotropium (Spiriva Handihaler) in terms of effect on COPD exacerbations. The triple combination reduced the incidence of moderate and severe exacerbations (the primary endpoint) by 20% (95% CI 8–31, p=0.0025) and significantly improved pre-dose FEV1 by 0.061L (95% CI 0.037–0.086, p<0.0001), demonstrating superiority to tiotropium.
Pneumonia was reported in a small number of patients, with similar incidence in the three treatment groups.
The most frequently reported adverse reactions with the triple combination were oral candidiasis (affecting 0.5% of the exposed individuals), which is normally associated with inhaled corticosteroids; muscle spasms (0.5%), which can be attributed to the long-acting beta2-agonist component; and dry mouth (0.5%), which is a typical anticholinergic effect.