|Study:||AP-ADF-102 or Study 102|
|Title:||A Phase II Single-Center, Randomized, Double-Blind Study in Subjects with a History of Opioid Abuse to Evaluate the Dose-Response for Flushing and Safety and Tolerability of Varying Doses of Niacin in Combination with 40 mg of an Opioid vs. 40 mg of an Opioid Alone|
To assess whether the subjects disliked the drug effect they were feeling when varying levels of niacin were administered in combination with 40 mg of Oxycodone HCl compared to 40 mg Oxycodone HCl (alone) and a placebo.
Study 102 was conducted in 24 subjects with a history of opioid abuse. Each subject was randomized to a dosing sequence that included doses of niacin (0, 240, 480, and 600 mg) administered in combination with 40 mg of oxycodone HCl, while the subjects were fasted and 600 mg niacin in combination with 40 mg oxycodone HCl administered following a standardized high-fat meal. Each dosing day, vital sign measures and subjective and behavioral effects were assessed before dosing (baseline) and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours after dosing. After completion of the study, subjects responded to a Treatment Enjoyment Assessment Questionnaire to select which of the treatments they would take again. The maximum scale response to the question “Do you dislike the drug effect you are feeling now?” (i.e., the “Disliking Score”), was designated as the primary efficacy variable.
In the fasting state, all three doses of niacin in combination with oxycodone HCl 40mg produced significant (p ≤ .05) Disliking Scores compared to oxycodone HCl 40mg alone. No other subjective measure was significantly affected by the niacin addition to Oxycodone.
The high fat meal eliminated the niacin effect and also delayed the time to Oxycodone peak blood levels.
The addition of niacin to oxycodone HCl alters the subjective response to oxycodone HCl as indicated by the significant responses on the Disliking Score. This observation in conjunction with the results from the Treatment Enjoyment Questionnaire indicates that the addition of niacin reduces the attractiveness of oxycodone to opiate abusers.
There were no serious adverse events. Niacin produced a dose related attenuation of papillary constriction, diastolic blood pressure increase and probably systolic blood pressure increase produced by oxycodone HCl. The alterations by niacin on the vital sign responses to oxycodone 40 mg were minimal, were seen primarily with the 600 mg niacin dose and were not clinically significant.
The principal study investigator’s overall conclusion was that the results of Study 102 supported the hypothesis that the addition of niacin to oxycodone HCl in a minimal ratio of 30 mg niacin to 5 mg oxycodone HCl is aversive compared to oxycodone HCl alone. The addition of niacin did not alter the safety profile of oxycodone HCl alone.