Select Page

Single and Multiple-Dose Bioequivalence Studies for Oxycodone Extended Release

PRESENTED TO: BioPharma Services Inc., Toronto, Ontario, Canada
PRESENTED BY: J. He, N. Gharavi, and F. Trabelsi


The oxycodone extended release (ER) tablet (OxyContin® by Purdue Pharma L.P) provides long therapeutic duration for pain relief. The requirements of bioequivalence (BE) trials for generic drug submission for FDA and TPD require single-dose studies only, while EMA requires both, a multiple-dose study with the highest strength to demonstrate BE at steady-state, as well as a single-dose study.


Biopharma Services Inc. (BPSI) has conducted over 20 trials with doses ranging from 5 mg to 80 mg of oxycodone ER tablet using normal healthy volunteers (NHV). Four out of 20 studies were conducted as single-dose and multiple-dose trials using both the lowest (5 mg) and highest (80 mg) strengths. The objective of this presentation is to summarize pharmacokinetics (PK) and safety observations from in-house single-dose and multiple-dose trials.



• 4 pivotal studies
• Randomized, two-sequence, two-treatment, two-period, crossover trials in NHV
• 5 mg or 80 mg tablet strength (5 mg single-dose was fed study and no food effect was reported on PK of oxycodone
• Single-dose and Multiple-dose
• Safety was monitored throughout the course of the trial by evaluating reported adverse events (AE), clinical laboratory test results, vital signs, and ECG findings
• Blood samples for PK assessment were collected after oxycodone dosing
• Single-dose sampling schedule up to 36 hours
• Multiple dose sampling schedule (dosing interval 12 hours):
• Prior to the first dose of oxycodone administration;
• Pre-dose on Days prior to PK sampling day
• On PK sampling day up to 12 hours
• PK parameters such as maximum plasma concentration (Cmax) and area under concentration-time curve (AUC) were determined.

Table 1. Summary of studies conducted for single and multiple-dose administration

Study Days of Dosing Dose Titration Dose Reduction Washout Comment
5 mg SD 1 No No Yes  
5 mg SD 5 No No Yes  
80 mg SD 1 No No Yes Naltrexone given
80 mg SD 13 Yes Yes No Naltrexone given


PK was well characterized with relatively low variability of oxycodone under both single-dose and multipledose conditions
• No accumulation of oxycodone after multiple-dose administration
• More AEs observed for 80 mg than that from 5 mg (either single-dose or multiple-dose conditions)
• More AEs observed when multiple doses was given comparing to AE seen from a single-dose studies
• With proper safety protection, multipledose of 80 mg of oxycodone clinical trial was successfully conducted in NHV
• Our experience showed 80 mg multiple-dose trial was safe in NHV and scientifically sound to be discriminative to determine BE


All successful BE studies with 90% confidence intervals of geometric mean ratios of Cmax and AUC within 80.00% to 125.00%.
• The AEs observed in all single- and multiple-dose studies were either mild or moderate in nature.
• Rate of AE per subject was much higher in multiple-dose study (2.7%) than that from single-dose study (1%) for 80 mg strength
• The percentage of moderate AEs was also higher in multiple-dose trial than it observed from single-dose trial of both 80 mg and 5 mg strengths

Table 2. Summary of AEs Observed from both Single and Multiple-Dose Administration of 5 and 80 mg Oxycodone

Study Total AE % AE/Subject Mild AE Moderate AE
80 mg SD (n= 52) 54 1 52 2
80 mg SD (n= 36) 94 2.7 86 8
5 mg SD (n= 36) 22 0.6 22 0
5 mg SD (n= 36) 39 1.1 36 3

Similar Median Tmax: 2 to 4 hrs with the range of 0.5 to 6 hrs when given as both single-dose and multiple-dose administration with both 5 mg and/or 80 mg strength
• Mean T1/2 of oxycodone is relatively short as 5 hrs after single-dose administration
• Cmax and AUC of oxycodone were comparable following single-dose and multiple-dose for both 80 mg and 5 mg strengths respectively
• Comparable variability of PK parameters observed from single-dose and multiple-dose trials when given either at 80 mg or 5 mg; demonstrated in Figures 1 and 2 below

AUC (Mean +/- SD) from 80 mg Oxycodone after SD & MD Administrations
AUC( Mean +/- SD) from 5 mg Oxycodone after SD & MD Administrations

Download Publication

BioPharma Services Inc. is committed to protecting and respecting your privacy, and we’ll only use your personal information to administer your account and to provide the products and services you requested from us. From time to time, we would like to contact you about our products and services, as well as other content that may be of interest to you. If you consent to us contacting you for this purpose, please tick below to say how you would like us to contact you:
In order to provide you the content requested, we need to store and process your personal data. If you consent to us storing your personal data for this purpose, please tick the checkbox below.
You can unsubscribe from these communications at any time. For more information on how to unsubscribe, our privacy practices, and how we are committed to protecting and respecting your privacy, please review our Privacy Policy.

Popular Posts