Category: Clinical Pharmacology
Purpose: The objective of this study was to evaluate the pharmacokinetics (PK) of nasally insufflated milled abuse deterrent (AD) oxycodone products characterized by different particle size and release-controlling polymer amount.
Methods: A fasting, single center, randomized, open-label, single-dose, 4‑sequence, 4-period, 4-treatment crossover study was conducted in 41 healthy recreational opioid users under naltrexone block. The four treatments were 1) AD oxycodone extended-release (ER) 30 mg tablets coarsely milled (500-1000 µm) (OXC30) and 2) finely milled (106-500 µm) (OXF30), 3) AD oxycodone ER 80 mg finely milled (OXF80) and 4) oxycodone immediate-release (IR) finely milled (RXF30).Treatment doses were normalized to 30 mg oxycodone and serial blood samples were collected over 48 h per subject. Primary comparisons were OXF30 vs RXF30, OXC30 vs RXF30, and OXF80 vs RXF30.
Results: The geometric mean ratios (GMR) (90% confidence interval) comparison with respect to Cmax were 82% (75-90) for OXF30, 59% (54-64) for OXC30, and 76% (71-83) for OXF80. Median tmax for RXF30, OXF30, OXF80 and OXC30 were 1.5, 1.5, 2 and 2.5 h, respectively. All three treatments, OXC30, OXF30, and OXF80, demonstrated similar total oxycodone exposure (AUCinf). The drug to polymer ratio did not have an impact on intranasal PK when finely milled to a size between 106-500 µm.
Conclusion: This study demonstrated that when AD oxycodone ER tablets (30 mg and 80 mg) were milled to a particle size between 106-500 µm, the PK exhibited similar Cmax and median tmax to that of an IR product. However, milling to a range of 500-1000 µm delayed tmax and lowered the Cmax when compared to the IR product.
Dajun Sun– NA, Berlin, Germany
Minori Kinjo– United States Food and Drug Administration, Silver Spring, Maryland
Saeid Raofi– United States Food and Drug Administration, Silver Spring, Maryland
Mitchell Frost– Silver Spring, Maryland
Markham Luke– Director, DTP/ORS/OGD/CDER and Supervisory Physician, U.S. Food and Drug Administration, Silver Spring, Maryland
Robert Lionberger– Director/ Office of Research and Standards, US Food & Drug Administration, Silver Spring, Maryland
Brad Vince– City Blank, Kansas
Debra Kelsh– City Blank, Kansas
Zhichuan LI– Silver Spring, Maryland
Myong-Jin Kim– Silver Spring, Maryland