Healthy
Conditions
Keywords
Healthy subjects, Opioid, Healthy volunteers
Brief summary
The purpose of this study is to assess the bioequivalence of a new oxycodone formulation (10 mg) manufactured at the Totowa, NJ facility relative to the formulation (10 mg) manufactured at the Wilson, NC facility in the fasted state.
Detailed description
Oxycodone hydrochloride (oxycodone) is a semi-synthetic opioid analgesic that is effective in the relief of moderate to severe malignant and non-malignant pain.
Interventions
Reformulated OXY 10-mg tablet (Totowa) x 1 dose taken in the fasted state.
Reformulated OXY 10-mg tablet (Wilson) x 1 dose taken in the fasted state.
Sponsors
Purdue Pharma LP
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Males and females aged 18 to 50, inclusive. * Body weight ranging from 50 to 100 kilograms (kg) and a body mass index (BMI) ≥18 and ≤34 (kg/m2). * Healthy and free of significant abnormal findings as determined by medical history, physical examination, vital signs, and electrocardiogram (ECG). * Females of child-bearing potential must be using an adequate and reliable method of contraception.
Exclusion criteria
* Females who are pregnant or lactating. * Any history of or current drug or alcohol abuse for 5 years. * History of or any current conditions that might interfere with drug absorption, distribution, metabolism or excretion. * Use of an opioid-containing medication in the past 30 days. * History of known sensitivity to oxycodone, naltrexone, or related compounds. * Any history of frequent nausea or emesis regardless of etiology. * Any history of seizures or head trauma with current sequelae. * Participation in a clinical drug study during the 30 days preceding the initial dose in this study. * Any significant illness during the 30 days preceding the initial dose in this study. * Use of any medication including thyroid hormone replacement therapy (hormonal contraception is allowed), vitamins, herbal, and/or mineral supplements, during the 7 days preceding the initial dose. * Refusal to abstain from food for 4 hours following administration of the study drugs and to abstain from caffeine or xanthine entirely during each confinement. * Consumption of alcoholic beverages within 48 hours of initial study drug administration (Day 1) or anytime following initial study drug administration. * History of smoking or use of nicotine products within 45 days of study drug administration or a positive urine cotinine test. * Blood or blood products donated within 30 days prior to administration of the study drugs or anytime during the study, except as required by this protocol. * Positive results for urine drug screen or alcohol screen at Check-in of each period, and hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb) (unless immunized), anti-hepatitis C antibody (HCV). * Positive Naloxone hydrochloride (HCl) challenge test. * Presence of Gilbert's Syndrome or any known hepatobiliary abnormalities.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Plasma Concentration | Blood samples collected over 72-hour period | Cmax is the maximum observed plasma concentration and bioequivalence is based on Cmax. |
| AUC0-inf - Area Under Plasma Concentration-time Curve From Time Zero to Infinity (Extrapolated) | Blood samples collected over 72-hour period | AUC0-inf is the area under the plasma concentration-time curve from time zero to infinity (extrapolated) and bioequivalence is based on AUC0-inf. |
| AUC0-t - Area Under Plasma Concentration-time Curve From Time Zero to Time of Last Non-zero Plasma Concentration | Blood samples collected over 72-hour period | AUC0-t is the area under the plasma concentration-time curve from time zero to time of last non-zero plasma concentration and bioequivalence is based on AUC0-t. |
Countries
United States
Participant flow
Recruitment details
Study start date: 09-JUL-2008 to end date: 20-Aug-2008, at 1 site in the US (Madison, WI)
Pre-assignment details
124 screened; 69 screen failures; 0 withdrew; 55 randomized and received study drug; 4 terminated early; 51 completed.
Participants by arm
| Arm | Count |
|---|---|
| Randomized Safety Population Subjects who were randomized, received study drug, and had at least 1 postdose safety assessment. | 55 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 2 | 1 |
| Period 1 | Positive for cotinine | 1 | 0 |
Baseline characteristics
| Characteristic | Randomized Safety Population |
|---|---|
| Age Continuous Age | 29 Years STANDARD_DEVIATION 9.3 |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 25 / 52 | 17 / 54 | 0 / 124 |
| serious Total, serious adverse events | 0 / 52 | 0 / 54 | 1 / 124 |
Outcome results
Primary
AUC0-inf - Area Under Plasma Concentration-time Curve From Time Zero to Infinity (Extrapolated)
AUC0-inf is the area under the plasma concentration-time curve from time zero to infinity (extrapolated) and bioequivalence is based on AUC0-inf.
Time frame: Blood samples collected over 72-hour period
Population: Full Analysis Population for PK Metrics. Data from all subjects who were randomized, received study drug, and had at least 1 valid PK metric variable were included in the statistical analysis. Subjects experiencing emesis within 12 hours after dosing were excluded from PK analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reformulated OXY (Totowa) (Test) | AUC0-inf - Area Under Plasma Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 112 ng*h/mL | Standard Deviation 26.5 |
| Reformulated OXY (Wilson) (Reference) | AUC0-inf - Area Under Plasma Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 111 ng*h/mL | Standard Deviation 24.3 |
90% CI: [97.19, 103]ANOVA
Primary
AUC0-t - Area Under Plasma Concentration-time Curve From Time Zero to Time of Last Non-zero Plasma Concentration
AUC0-t is the area under the plasma concentration-time curve from time zero to time of last non-zero plasma concentration and bioequivalence is based on AUC0-t.
Time frame: Blood samples collected over 72-hour period
Population: Full Analysis Population for PK Metrics. Data from all subjects who were randomized, received study drug, and had at least 1 valid PK metric variable were included in the statistical analysis. Subjects experiencing emesis within 12 hours after dosing were excluded from PK analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reformulated OXY (Totowa) (Test) | AUC0-t - Area Under Plasma Concentration-time Curve From Time Zero to Time of Last Non-zero Plasma Concentration | 111 ng*h/mL | Standard Deviation 26.4 |
| Reformulated OXY (Wilson) (Reference) | AUC0-t - Area Under Plasma Concentration-time Curve From Time Zero to Time of Last Non-zero Plasma Concentration | 110 ng*h/mL | Standard Deviation 24.2 |
90% CI: [97.14, 102.99]ANOVA
Primary
Cmax - Maximum Observed Plasma Concentration
Cmax is the maximum observed plasma concentration and bioequivalence is based on Cmax.
Time frame: Blood samples collected over 72-hour period
Population: Full Analysis Population for PK Metrics. Data from all subjects who were randomized, received study drug, and had at least 1 valid PK metric variable were included in the statistical analysis. Subjects experiencing emesis within 12 hours after dosing were excluded from PK analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reformulated OXY (Totowa) (Test) | Cmax - Maximum Observed Plasma Concentration | 9.81 ng/mL | Standard Deviation 2.32 |
| Reformulated OXY (Wilson) (Reference) | Cmax - Maximum Observed Plasma Concentration | 9.58 ng/mL | Standard Deviation 2.52 |
90% CI: [97.51, 107.27]ANOVA