Staccato® Platform Performance
Clinical trial data indicate that Alexza’s unique Staccato technology generates consistent distribution of aerosolized drug particles of 1 to 5 microns (the ideal size for absorption in deep lung tissue), providing peak plasma concentrations as quickly as an intravenous injection and rapid onset of therapeutic relief.
The Staccato® system comprises the rapid vaporization of a drug to form a small particle aerosol optimal for systemic delivery through inhalation. These aerosols are systemically absorbed very rapidly, with peak plasma blood levels obtained in the first few minutes after administration. Thus, the Staccato system enables rapid onset of action for many drugs.
The key to our proprietary technology is vaporization of drug without thermal degradation, which is achieved by rapidly heating a thin film of the drug. In less than half a second, the drug is heated to a temperature sufficient to convert the solid drug film into a vapor. Because the duration of drug heating is so brief, thermal decomposition is minimal. After vaporization, the drug cools rapidly in air, condensing into pure drug aerosol particles of near ambient temperature. The Staccato system consistently creates aerosol particles averaging one to three microns in size, which is the proper size for deep lung inhalation. The Staccato system also produces a consistent high emitted dose, regardless of the patient's breathing pattern.
The Staccato device consists of three core components: a heating substrate, a thin film of unformulated drug coated on the substrate, and an airway through which the patient inhales. The left panel below shows these core components before patient inhalation. The right panel shows the device components during patient inspiration: the substrate is heated to peak temperature in < 0.5 seconds after start of patient's inhalation, which vaporizes the drug in less than 1 second. The drug cools and condenses into a pure drug aerosol. While the patient inhales through the device, the drug aerosol is drawn through the patient’s mouth and into the lungs where it diffuses into the circulation for a rapid systemic effect.
Ease of Use
The Staccato system is breath-actuated and a patient simply inhales to administer the drug dose. A special valve in the inhaler airway controls airflow over the vaporizing drug to achieve appropriate aerosol particle size. The aerosol produced with the Staccato system is relatively insensitive to patient inhalation rates. To use these inhalers, a patient simply removes an inhaler from its packaging, places the device to his or her lips, and takes a deep breath. Unlike many other inhalation technologies, the patient does not need to learn a special breathing pattern. In addition, the Staccato device is small and easily portable.
Pharmacology and Rapid Onset
The aerosol produced with the Staccato system is designed to be absorbed rapidly through the deep lung, with a speed of therapeutic onset comparable to IV administration, generally achieving peak plasma levels of drug in two to five minutes, which is much faster than oral tablet delivery. In vivo pharmacokinetic studies in an animal model conducted with a commercially available migraine drug show that the Staccato system results in more rapid absorption than subcutaneous injection or oral administration. Pharmacodynamic studies with the same migraine drug demonstrate an onset of action of less than one minute as shown in the graph below.
Consistent Dose and Particle Size
The Staccato system uses rapid heating of the drug film to create consistent and appropriate sizes for deep lung inhalation, rather than mechanics or preformed drug particles, to create drug aerosols. The Staccato system produces a consistent high emitted dose regardless of the patient’s breathing pattern.
Approximately 200 drug compounds have exhibited initial vaporization feasibility with our Staccato system. The Staccato system can deliver both water soluble and water insoluble compounds while eliminating the need for excipients and additives such as detergents, stabilizers and solvents, enabling the delivery of unformulated drug.
The Staccato device can incorporate lockout and multiple dose features, potentially enhancing safety, convenience of patient titration and a variety of administration regimens.
We are currently developing two versions of our Staccato device
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