Investigational Oxycodone/Acetaminophen Combo May Improve Abuse Deterrence
These results are significant in the field of acute pain management, said lead investigator Lynn Webster because MNK-795 is the first oxycodone/acetaminophen reported to meet all three of these endpoints in a human abuse liability (HAL) study.
MNK-795 is designed to provide a fast onset of analgesia (within 1 hour) and sustained analgesia over the 12-hour dosing interval. MNK-795 tablets use a dual-layer biphasic delivery mechanism that, when administered as a single dose, ensures the immediate release (IR) component delivers 3.75 mg oxycodone/325 mg acetaminophen; the controlled-release (CR) component delivers 11.25 mg of oxycodone and 325 mg acetaminophen. The tablets incorporate polyethylene oxide release-controlling polymers that, once ingested and in the stomach, become a gel-like substance that allows the tablet to remain in the stomach for a number of hours. The way the technology is designed, when MNK-795 is crushed the IR and CR layers mix to delay the onset of medication effects.
“Oxycodone and acetaminophen combinations are widely used for managing acute pain, but are commonly abused,” said Dr. Webster, cofounder and Chief Medical Director of Lifetree Clinical Research. “There is a real need for improved formulations that address patient and physician concerns about these kinds of medications.”
The randomized, double-blind HAL study was a seven-way crossover trial that enrolled 55 healthy non-dependent recreational opioid users. During the seven treatment periods, subjects received a single treatment with one of the following: placebo; 15 mg MNK-795/650 mg acetaminophen (low dose, intact); 15 mg Percocet/650 mg acetaminophen (low dose, intact); 30 mg MNK/1300 mg acetaminophen (high dose, intact); 30 mg Percocet/1300 mg acetaminophen (high dose intact); crushed, encapsulated high-dose MNK-795; and crushed, encapsulated high-dose Percocet. The primary outcomes were measured using a 100-point visual analog scale (VAS) of subject-reported drug liking, drug high, and good drug effects.
Results showed that crushing MNK-795 further slowed the rate of oxycodone release and produced corresponding decreases in drug liking, drug high, and good drug effects relative to those produced by comparable doses of intact or crushed Percocet.
In a separate study evaluating the tamper-resistant properties of MNK-795, researchers found this formulation to be more resistant to tampering than Percocet. Adding water to crushed MNK-795 tablets formed a gel-like semi-liquid paste that would likely impede syringeability and insufflation compared with Percocet, suggesting that abuse-deterrent technology used in MNK-795 would impede snorting and injecting.
Insufflation experiments showed that MNK-795 forms a clumpy solid mass that would likely impede absorption through the nasal mucosa, whereas Percocet forms a thin fluid that would like be absorbed more readily through nasal tissue, researchers found.
In a randomized, double-blind, placebo-controlled phase 3 study, Neil Singla, MD, of Lotus Clinical Research in Pasadena, California, and colleagues examined the safety and analgesic efficacy of MNK-795 for acute severe pain in patients who underwent bunionectomy. The MNK-795 and placebo groups had 150 and 153 patients, respectively.
Pain reduction at 48 hours was significantly greater among patient receiving MNK-795 than among placebo recipients. With respect to pain relief, 68.9% of patients in the MNK-795 group reported being “satisfied” or “very satisfied” compared with 41.5% of the placebo arm. With respect to time for medication to work, 66.7% of MNK-795 recipients reported being “satisfied” or “very satisfied” compared with 38.5% for the placebo group. The most common adverse events associated with the use of MNK-795 included nausea, vomiting, and pruritus. The authors concluded that MNK-795 is safe and effective for patients with severe acute pain.