It is important to clarify that IRX 211 if successful would be an alternative to rapid onset opioids (ROO) as opposed to opioids generally. That is, cancer patients are already on an existing program of slow-release long duration opioids such as morphine, oxycodone or fentanyl to manage their background pain but when pain still breaks through, they receive a rapid acting opioid.
Literally opioids on top of opioids.
It’s possible the orphan drug status would be the main reason to continue with Complex Regional Pain Syndrome (CRPS) for pain indication for the phase 2 trial of IRX 211 because breakthrough pain seems a massive market.
Breakthrough pain may be caused by a cough, movement, stress, illness or may fluctuate for no particular reason.
Indeed, quite shockingly studies show a minimum of 40% and as much as 90% of hospitalized cancer patients suffer from breakthrough pain.
Moreover, occurrences of breakthrough pain have been reported to occur multiple times a day.
The most interesting part of all this is the delivery of rapid onset opioids seems rather complex or clumsy and impractical for people suffering from intense pain. Because of the need for speed, there is a limited range of options for taking ROOs. Specifically:
Sublingual
Oromucosal
Buccal tablet
Buccal soluable
Nasal spray
The sublingual orally disintegrating tablet (Abstral) should be administered directly under the tongue at the deepest part. The sublingual tablet should not be swallowed, but allowed to completely dissolve in the sublingual cavity without chewing or sucking.
Oral transmucosal fentanyl citrate (OTFC) should be placed in the mouth against the cheek and should be moved around the mouth using the citrate-containing sugar matrix. The OTFC unit should be sucked, not chewed. The OTFC unit should be consumed over a 15 min period.
The buccal tablet (Effentora) is an effervescent formulation. The tablet has to be placed within the buccal cavity above a rear molar between the upper cheek and gum and must be kept in place until it disintegrates (usually 14–25 min). The tablet should not be sucked, chewed or swallowed, as this will result in lower plasma concentrations than when taken as directed.
The fentanyl buccal soluble film (Breakyl) consists of a small, bioerodible polymer film for application to the mucosal membranes (inner lining of cheek). The patient should use their tongue to moisten the inside of their cheek and then press and hold the film in place for a minimum of 5 seconds until it sticks firmly. The Breakyl buccal film will usually dissolve completely within 15–30 min after application. The patient should be instructed to avoid manipulating the buccal film with their tongue or finger(s) and avoid eating food until the buccal film has dissolved.
The intranasal fentanyl spray (Instanyl) contains a phosphate-buffered solution of fentanyl citrate. To administer the nasal spray the nozzle is placed a short distance (about 1 cm) into the nostril and pointed slightly towards the bridge of the nose. A spray is then administered by pressing and releasing the finger grips on either side of the nozzle. Patients must be advised that they may not feel the spray being administered, and that they should therefore rely on the audible click and the number on the counter advancing to confirm that a spray has been delivered. Patients should be advised not to blow their nose immediately after administration of the drug.
By contrast, if IRX 211 – dronabinol delivered via a pressurized metered-dose inhaler - proves an effective treatment for breakthrough pain not only would it offer an alternative for reducing a patient’s reliance on opioids, but it seems a much more simple and practical means of delivery with minimal if any wastage.
(20min delay)