Data from Pharmawand - Curated by Marshall Pearce - Date added 10 January 2018
Pain Therapeutics, Inc.announced positive results from a human abuse potential study of its late-stage drug candidate, Remoxy. Study results indicate that in non-dependent, recreational opioid users, nasal administration of Remoxy resulted in significantly lower abuse potential compared to immediate-release (IR) oxycodone. All study subjects reported reduced ‘Drug Liking' ‘Take Drug Again' and ‘Drug High' for Remoxy compared to oxycodone IR. In addition, nasal administration of Remoxy showed lower exposure to oxycodone, lower peak concentrations (Cmax) and longer time to peak drug concentration (Tmax) against comparator drugs, suggesting comparatively lower abuse potential.
Design & Methods : This Category 3 nasal abuse potential study was conducted in accordance with the FDA Guidance for Industry for Abuse-Deterrent Opioids. In a randomized, double-blind, active- and placebo-controlled, single-dose, 4-way crossover study, 38 recreational opioid users with a history of intranasal drug abuse were enrolled in the study. The primary endpoint was ‘Drug Liking'. Secondary endpoints included ‘Take Drug Again', ‘Drug High' and pupil size. There were four treatment arms: Remoxy 40 mg intact; Remoxy 40 mg microwaved; oxycodone IR 40 mg; and placebo. All treatments were administered nasally. Thirty-six subjects completed the study. In addition, the first 20 subjects who completed the double-blind portion of the study also participated in a supplemental FDA Category 2 treatment arm to measure pharmacokinetic parameters following the nasal administration of 40 mg crushed OxyContin.
Top-Line Study Results : Remoxy intact and microwaved each demonstrated lower VAS scores on the primary endpoint, Drug Liking (p<0.01) versus oxycodone IR, indicating that oxycodone IR was significantly preferred over Remoxy. On secondary endpoints, Remoxy intact and microwaved each demonstrated lower scores versus oxycodone IR on Take Drug Again, Drug High and pupil size (each p<0.001 or better). On all pharmacokinetic parameters, Remoxy resulted in significantly lower exposure to oxycodone compared to oxycodone IR and crushed OxyContin. Peak oxycodone concentrations (Cmax) were at least 4-fold lower for Remoxy, microwaved or intact, compared to crushed OxyContin or oxycodone IR. The Cmax values for nasally administered Remoxy, microwaved Remoxy, crushed OxyContin and oxycodone IR were 14.9, 11.9, 63.6 and 64.7 ng/ml, respectively. Tmax values were 3.1, 3.1, 0.88 and 1.6 hours, respectively.
Finally, the Abuse Quotient (AQ=Cmax/Tmax) is an essential measurement of abuse potential, with lower scores suggesting comparatively lower potential for abuse. In this study, AQ measurements were:: less than 5.0 for Remoxy, intact or microwaved. 72.3 for OxyContin crushed.40.4 for oxycodone IR.