Arcapta is specifically approved for the treatment of airflow
obstruction in patients with chronic obstructive pulmonary disease,
including chronic bronchitis and/or emphysema.
Arcapta is supplied with inhalation powder capsules and an inhaler. The
recommended dose is the once-daily inhalation of the contents of one 75
mcg Arcapta capsule using the Neohaler inhaler. Arcapta should be
administered once daily every day at the same time of the day by the
orally inhaled route only.
Dose selection for Arcapta for COPD was based on three dose-ranging
trials: Trial 1, a two-week dose-ranging trial in an asthma population;
Trial 2, a two-week dose-ranging trial in a COPD population; and Trial
3, a 26-week adaptive seamless design trial that included an initial
two-week dose ranging phase. Although Arcapta is not indicated for
asthma, dose selection was primarily based upon the results from the
dose-ranging trial in asthma patients (Trial 1) as an asthma population
is the most responsive to beta-agonist bronchodilation and is most
likely to demonstrate a dose response. Trial 2 and 3 evaluated
dose-ranging in COPD patients and provided supportive information.
Dose-Ranging in Asthma
Trial 1 was a two-week, randomized, double-blinded, placebo-controlled
design that enrolled 511 adults with persistent asthma. Trial 1 included
Arcapta doses of 18.75, 37.5, 75, and 150 mcg once daily, a salmeterol
active control group, and placebo. The trial showed that the effect on
FEV1 in subjects treated with Arcapta 18.75 and 37.5 mcg doses was lower
compared to subjects treated with other Arcapta doses, particularly
after the first dose. The effect did not clearly differ between the 75
and 150 mcg doses.
Dose-ranging in COPD
Trial 2 was a two-week, randomized, double-blinded, placebo-controlled
design that enrolled 552 subjects with a clinical diagnosis of COPD, who
were 40 years or older, had a smoking history of at least 10 pack
years. The subjects received Arcapta doses of 18.75, 37.5, 75 and 150
mcg once daily, a salmeterol active control group, and placebo. The
effect on FEV1 in subjects treated with Arcapta 18.75 mcg dose was lower
compared to subjects treated with other Arcapta doses. Although a
dose-response relationship was observed at Day 1, the effect did not
clearly differ among the 37.5, 75 and 150 mcg doses by Day 15. Trial 3
evaluated doses of 75, 150, 300, and 600 mcg once daily, placebo, and
two active comparators. Although a dose-response relationship was
observed at week 2, the effect did not clearly differ among the Arcapta
doses.
Six confirmatory randomized, double-blinded placebo and active-controlled trials were conducted:
Trial 3 was a 26-week seamless adaptive design trial that included an
initial two week dose-ranging phase. The trial evaluated Arcapta doses
of 150 mcg and 300 mcg once daily, placebo, and an active comparator;
Trials 4 and 5 were 12-week trials and evaluated Arcapta 75 mcg once daily, and placebo;
Trial 6 was a 12-week trial that evaluated Arcapta 150 mcg once daily and placebo;
Trial 7 was a 26-week trial that evaluated Arcapta 150 mcg once daily, an active comparator, and placebo, and
Trial 8 was a 52 week trial that evaluated Arcapta 300 mcg and 600 mcg once daily, an active comparator, and placebo.
A total of 5,474 subjects were enrolled. All subjects had a clinical
diagnosis of COPD, were 40 years or older, had a smoking history of at
least 10 pack years, had a post-bronchodilator FEV1 less than 80% and at
least 30% of the predicted normal value and a post-bronchodilator ratio
of FEV1 over FVC of less than 70%. The primary efficacy endpoint was
24-hour post-dose trough FEV1 after 12 weeks of treatment. In all six
confirmatory COPD trials, all doses of Arcapta tested (75 mcg, 150 mcg,
300 mcg, and 600 mcg) showed significantly greater 24-hour post-dose
trough FEV1 compared to placebo at 12 weeks. In addition, serial FEV1
measurements in patients treated with Arcapta demonstrated a
bronchodilatory treatment effect after the first dose compared to
placebo at 5 minutes post dose of 0.09 L (Trial 4) and 0.10 L (Trial 5).
The mean peak improvement relative to baseline within the first 4 hours
after the first dose (Day 1) was 0.19 L (Trial 4) and 0.22 L (Trial 5)
and was 0.24 L (Trial 4) and 0.27 L (Trial 5) after 12 weeks.
Improvement in lung function observed at week 4 was consistently
maintained over the 12-week treatment period in both trials.
