Indications for: INCRUSE ELLIPTA
Maintenance treatment of COPD.
The safety and efficacy of umeclidinium 62.5 mcg were evaluated in 3 dose-ranging trials, 2 placebo-controlled clinical trials (one 12-week trial and one 24-week trial), and a 12-month long-term safety trial. The efficacy of Incruse Ellipta is based primarily on the dose-ranging trials and the 2 placebo-controlled confirmatory trials in patients with COPD, including chronic bronchitis and/or emphysema.
In the dose-ranging trials, dose selection for umeclidinium in COPD was supported by a 7-day, randomized, double-blind, placebo-controlled, crossover study evaluating 4 doses of umeclidinium (15.6 to 125 mcg) or placebo dosed once daily in the morning in 163 patients with COPD. A dose ordering was observed, with the 62.5- and 125-mcg doses demonstrating larger improvements in FEV1 over 24 hours compared with the lower doses of 15.6 and 31.25 mcg.
The differences in trough FEV1 from baseline after 7 days for placebo and the 15.6-, 31.25-, 62.5-, and 125-mcg doses were -74 mL (95% CI: -118, -31), 38 mL (95% CI: -6, 83), 27 mL (95% CI: -18, 72), 49 mL (95% CI: 6, 93), and 109 mL (95% CI: 65, 152), respectively. Two additional dose-ranging trials in subjects with COPD demonstrated minimal additional benefit at doses above 125 mcg. The dose-ranging results supported the evaluation of 2 doses of umeclidinium, 62.5 and 125 mcg, in the confirmatory COPD trials to further assess dose response.
The clinical development program for Incruse Ellipta included 2 randomized, double-blind, placebo-controlled, parallel-group confirmatory trials in patients with COPD designed to evaluate the efficacy of Incruse Ellipta on lung function. Trial 1 (NCT #01313650) was a 24-week placebo-controlled trial, and Trial 2 (NCT #01772147) was a 12-week placebo-controlled trial. These trials treated patients that had a clinical diagnosis of COPD, were 40 years of age or older, had a history of smoking ≥10 pack-years, had a post-albuterol FEV1 ≤70% of predicted normal values, had a ratio of FEV1/FVC of <0.7, and had a Modified Medical Research Council (mMRC) score ≥2. The majority of subjects (72%) reported not having a COPD exacerbation in the prior 12 months.
Patient demographics: (n=1738)
Mean age: 63 years
Average smoking history: 46 pack-years (with 50% identified as current smokers)
Mean FEV1 (predicted): 47% (range: 13 to 74%)
Mean FEV1/FVC ratio: 0.47 (range: 0.20 to 0.74)
Mean percent reversibility: 15% (range: -35 to 109%)
Trial 1 (n=418) evaluated umeclidinium 62.5 mcg and placebo. The primary endpoint was change from baseline in trough (predose) FEV1 at Day 169 (defined as the mean of the FEV1 values obtained at 23 and 24 hours after the previous dose on Day 168) compared with placebo. Incruse Ellipta 62.5 mcg demonstrated a larger increase in mean change from baseline in trough (predose) FEV1 relative to placebo (n=280; difference from placebo: 115 [95% CI: 76, 155]). Similar results were obtained from Trial 2.
The safety and efficacy of Incruse Ellipta in combination with an ICS/LABA were also evaluated in 4 randomized, double-blind, parallel-group trials involving 1,637 patients with COPD. These trials had similar study design and were of 12-weeks’ treatment duration. Patients were randomized to Incruse Ellipta 62.5 mcg + ICS/LABA or placebo + ICS/LABA. The primary endpoint for these trials was change from baseline in trough (predose) FEV1 at Day 85 (defined as the mean of the FEV1 values obtained at 23 and 24 hours after the previous dose on Day 84). Baseline FEV1 was measured while patients were on background ICS/LABA.
In the combination with Fluticasone Furoate + Vilanterol (Trial 4 [NCT #01957163] and Trial 5 [NCT #02119286]):
Patients were randomly assigned to Incruse Ellipta 62.5 mcg + FF/VI 100 mcg/25 mcg given once daily or placebo + FF/VI 100 mcg/25 mcg given once daily.
Results in trial 4 (n=206), showed that Incruse Ellipta + FF/VI demonstrated a larger mean change from baseline in trough (predose) FEV1 relative to placebo + FF/VI (n=206; difference from placebo: 124 [95% CI: 93, 154]). Trial 5 results were similar.
In the combination with Fluticasone Propionate + Salmeterol (Trial 6 [NCT #01772134] and Trial 7 [NCT #01772147]):
Patients were randomly assigned to Incruse Ellipta 62.5 mcg + FP/SAL 250 mcg/50 mcg or placebo + FP/SAL 250 mcg/50 mcg. The treatments with Incruse Ellipta and placebo were given once daily, while the FP/SAL treatment was given twice daily.
Results in trial 6 (n=204), showed that Incruse Ellipta + FP/SAL demonstrated a larger mean change from baseline in trough (predose) FEV1 relative to placebo + FP/SAL (n=205; difference from placebo: 147 [107, 187]). Results for Trial 7 were similar.
Take at same time every day. 1 inhalation every 24hrs.
INCRUSE ELLIPTA Contraindications:
Severe hypersensitivity to milk proteins.
INCRUSE ELLIPTA Warnings/Precautions:
Not indicated for relief of acute bronchospasm. Do not initiate in rapidly or acutely deteriorating COPD. Do not exceed recommended dose. Reevaluate periodically. Prescribe a short-acting, inhaled β2-agonist for acute symptoms; monitor for increased need. Discontinue if paradoxical bronchospasm (use alternatives) or hypersensitivity reactions occur. Narrow-angle glaucoma. Urinary retention. Prostatic hyperplasia. Bladder-neck obstruction. Severe hepatic impairment. Pregnancy. Nursing mothers.
INCRUSE ELLIPTA Classification:
INCRUSE ELLIPTA Interactions:
Additive effects with concomitant other anticholinergic-containing drugs; avoid.
Nasopharyngitis, URTI, cough, arthralgia; visual disturbances, paradoxical bronchospasm.
The effective half-life of umeclidinium after once-daily inhaled dosing is 11 hours. Following intravenous dosing with radiolabeled umeclidinium, mass balance showed 58% of the radiolabel in the feces and 22% in the urine. Following oral dosing to healthy male patients, radiolabel recovered in feces was 92% of the total dose and that in urine was <1% of the total dose, suggesting negligible oral absorption.
Generic Drug Availability:
Dry pwd inhaler—30 doses