|Study:||AP-ADF-101 or Study 101|
|Title:||A Phase I Single-Center, Randomized, Double-Blind Study in Fasted and Non-Fasted Healthy Volunteers to Evaluate the Dose-Response for Flushing and Safety and Tolerability of Varying Doses of Niacin|
The study objective was to determine the dose response for niacin-induced flushing in male and female healthy adult volunteers, evaluate the safety and tolerability of an acute dose of niacin when administered in varying doses, determine the appropriate strength of niacin to use in an Aversion® Technology formulation of oxycodone HCl (Acurox Tablets) and evaluate the effect of food on niacin-induced flushing.
A total of 50 normal healthy volunteer subjects were enrolled in this study. All subjects received up to five doses of niacin (15, 30, 45, 60 and 75 mg) and one placebo dose taken orally in tablet form on separate days (up to six days) in a random sequence. Each dose was separated by a 24 hour washout period. Half of the subjects (n=25) took each dose of study drug following a standardized low-fat breakfast and half (n=25) remained fasted prior to study drug administration. One subject in the non-fasted group did not complete the study due to personal reasons. Each subject completed the Side Effects and Symptom Questionnaire prior to, and three hours after, study drug administration. The Niacin Tolerability Rating Scale (0 – no effect; 1 – easy to tolerate; 2 – mildly unpleasant; 3 – unpleasant, and difficult to tolerate; 4 – intolerable, and would never take again) was completed three hours after study drug was administered.
In the fasted subjects, the 15 and 30 mg doses of niacin were generally similar to placebo in the number of subjects reporting niacin symptoms, the total number of niacin symptoms reported and overall tolerability ratings of “no effect” or “easy to tolerate”. In the fasted subjects there was an increase in the number of subjects reporting niacin symptoms and the total number of niacin symptoms reported in the 45mg dose group versus the 30mg dose group. The 45mg dose as well as the 60mg and 75mg doses were also less well tolerated as the 30mg dose. The data suggest that the niacin ingredient in Acurox Tablets should be tolerated by most subjects with minimal, if any, side effects when Acurox Tablets are orally administered at recommended doses. Niacin related side effects were not observed at any dose in subjects who ingested niacin with food.