Procaterol hydrochloride hydrate (procaterol) is a β2‐adrenergic
receptor agonist that induces a strong bronchodilatory effect. The
procaterol dry powder inhaler (DPI) has been frequently used in patients
with bronchial asthma or chronic obstructive pulmonary disease. We
evaluated the bioequivalence and safety between the new procaterol DPI
(new DPI) and the approved procaterol DPI (approved DPI). This study was
a randomized, double‐blind, double‐dummy, crossover comparison to
evaluate the pharmacodynamic equivalence of the new DPI and the approved
DPI in patients with bronchial asthma. Primary efficacy variables were
area under the concentration‐time curve (AUC) forced expiratory volume
in the first second (FEV1)/h and maximum FEV1 during the 480‐minute
measurement period. Patients were divided into 2 groups, New‐DPI‐First
(n = 8) and Approved‐DPI‐First (n = 8), according to the investigational
medical product that was administered first. Patients inhaled 20 μg of
procaterol in each period. FEV1 was measured by a spirometer at predose
and at 15, 30, 60, 90, 120, 180, 240, 360, and 480 minutes after each
investigational medical product administration. Equivalence was
evaluated by confirming that the 2‐sided 90%CIs for the difference
between the new and the approved DPI in means of AUC (FEV1)/h and
maximum FEV1 were within the acceptance criteria of –0.15 to 0.15 L. The
difference in means of AUC (FEV1)/h and maximum FEV1 was 0.041 L and
0.033 L, respectively, and the 90%CI was 0.004 to 0.078 L and –0.008 to
0.074 L, respectively. These CIs were both within the acceptance
criteria. The new DPI was assessed as being bioequivalent to the
approved DPI.Procaterol HCl powder
Inhaled drugs are the most common and effective therapy in the
management of bronchial asthma or chronic obstructive pulmonary disease
(COPD). Short‐acting β2‐agonists are known as rescue or relief
medications for asthma or COPD symptoms. Procaterol hydrochloride
hydrate
(8‐hydroxy‐5‐{(1RS,2SR)‐1‐hydroxy‐2‐[(1‐methylethyl)amino]butyl}quinolin‐2(1H)‐one
monohydrochloride hemihydrate) is a β2‐adrenergic receptor agonist
synthesized by Otsuka Pharmaceutical Co, Ltd, in 1973. It binds highly
selectively to β2‐adrenergic receptors in bronchial smooth muscle cells,
and a small dose of this drug induces a strong bronchodilatory
effect.1, 2 A variety of formulations have been developed for this drug
since the first launch of its tablet formulation in 1980. Currently
marketed formulations including dry powder inhaler (DPI) and pressurized
metered dose inhaler (pMDI) have been clinically useful, mainly in
Asia. The effects of these inhalants are immediate, providing a good
adaptation for sudden or new symptoms of asthma or COPD.
DPIs are easier to use than pMDIs because there is no need to coordinate
actuation and inhalation. In addition, because DPIs do not contain
environmentally unfriendly propellants,3 it is thought that DPIs are
adaptive to future global environmental regulations. However, DPIs are
available in many different designs, and DPIs that require many
operational steps may mislead patients to inadequate inhalation of the
drug. It is obvious that incorrect usage of inhaler devices has a
considerable influence on the clinical effectiveness of the delivered
drug.3 Clickhaler® (an approved DPI device) has hallmarked the effective
uniformity and consistency of the delivered dose and fine particle
fraction over a range of inspiratory flow rates4; however, patients are
required to perform several steps to inhale the drug. To improve this, a
new DPI, Swinghaler® (a new DPI device) was designed that requires no
shaking to dispense the correct volume of powder into the measuring cups
prior to inhalation, thus reducing the operational steps, and is easier
to use.5, 6 In addition, the powder inhaler and storage container of
the new DPI device are integrated, making it a smaller device, which
greatly improves the portability of the drug. These features are
considered to be beneficial to patients, and Meptin®Swinghaler® (new
DPI) is expected to ease patients’ treatment. The new DPI was granted
approval in 2014 in Japan and is currently the only DPI of short‐acting
β2‐agonists launched in Japan.6
The bioequivalence between the new DPI and the approved DPI in patients
was unknown. Although there are no standardized methods to demonstrate
in vivo bioequivalence of inhaled bronchodilators, the most practical
method of showing therapeutic equivalence in vivo is by estimating their
relative potencies in clinical efficacy studies using adequate
methodology of comparing their bronchodilator actions.7 Hence, this
study was conducted to evaluate the bioequivalence and safety between
the new DPI (Otsuka Pharmaceutical Co, Ltd, Tokushima, Japan) and the
approved DPI (Otsuka Pharmaceutical Co, Ltd, Tokushima, Japan) in
patients with bronchial asthma.
