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 (80 mg) relative to the original OxyContin® (OXY) formulation (80 mg) 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 80-mg tablet x 1 dose taken without food.
Original OxyContin® (OXY) 80-mg tablet x 1 dose taken without food.
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. * Willing to eat all the food supplied during the study.
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 forty-eight (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 a 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
13-Aug-2007 (first Informed Consent Form signed) to 23-Oct-2007 (last subject last visit), conducted at 1 site in the US, (Honolulu, HI)
Pre-assignment details
136 screened; 47 screen failures; 5 withdrew prior to randomization; 84 randomized; 4 terminated early; 80 completed.
Participants by arm
| Arm | Count |
|---|---|
| Randomized Safety Population Subjects who were randomized, received study drug, and had at least 1 postdose safety assessment. | 84 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 1 | 2 |
| Period 1 | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Randomized Safety Population |
|---|---|
| Age Continuous Age | 29 Years STANDARD_DEVIATION 10.1 |
| Sex: Female, Male Female | 28 Participants |
| Sex: Female, Male Male | 56 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 | 47 / 82 | 69 / 82 | 0 / 136 |
| serious Total, serious adverse events | 0 / 82 | 0 / 82 | 1 / 136 |
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 who experienced emesis within 12 hours after dosing were excluded from PK analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reformulated OXY (Test) | AUC0-inf - Area Under Plasma Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 966 ng*h/mL | Standard Deviation 269 |
| Original OxyContin® (OXY) (Reference) | AUC0-inf - Area Under Plasma Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 989 ng*h/mL | Standard Deviation 243 |
90% CI: [94.2, 99.81]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 who experienced emesis within 12 hours after dosing were excluded from PK analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reformulated OXY (Test) | AUC0-t - Area Under Plasma Concentration-time Curve From Time Zero to Time of Last Non-zero Plasma Concentration | 964 ng*h/mL | Standard Deviation 269 |
| Original OxyContin® (OXY) (Reference) | AUC0-t - Area Under Plasma Concentration-time Curve From Time Zero to Time of Last Non-zero Plasma Concentration | 981 ng*h/mL | Standard Deviation 243 |
90% CI: [94.41, 99.94]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 a 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 who experienced emesis within 12 hours after dosing were excluded from PK analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reformulated OXY (Test) | Cmax - Maximum Observed Plasma Concentration | 85.1 ng/mL | Standard Deviation 21.5 |
| Original OxyContin® (OXY) (Reference) | Cmax - Maximum Observed Plasma Concentration | 83.0 ng/mL | Standard Deviation 20.1 |
90% CI: [98.67, 106.66]ANOVA