Healthy Volunteers
Conditions
Keywords
Healthy subjects, Opioid
Brief summary
To assess the bioequivalence of reformulated OXY tablets (40 mg) relative to the original OxyContin® (OXY) formulation (40 mg) in the fed 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 40-mg tablet x 1 dose taken with food
Original OxyContin® (OXY) 40-mg tablet x 1 dose taken with 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 kg and a BMI ≥18 and ≤34 (kg/m2). * Healthy and free of significant abnormal findings as determined by medical history, physical examination, vital signs, and 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 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 HBsAg, HBsAb (unless immunized), anti-HCV. * Positive Naloxone 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 | Bioequivalence based on Cmax |
| AUC0-inf - Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (Extrapolated) | Blood samples collected over 72-hour period | Bioequivalence 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 | Bioequivalence based on AUC0-t |
Countries
United States
Participant flow
Recruitment details
22-Jan-2007 (date first ICF signed) to 30-Mar-2007 (last subject follow-up) at 1 site in the US (Austin, TX)
Pre-assignment details
174 subjects screened; 84 screen failures; 2 discontinued prior to dosing; 88 randomized and dosed; 14 terminated early; 74 completed.
Participants by arm
| Arm | Count |
|---|---|
| Randomized Safety Population Subjects who were randomized, received study drug, and had at least 1 postdose safety assessment. | 88 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 2 | 2 |
| Period 1 | Positive Drug Screen | 1 | 1 |
| Period 1 | Withdrawal by Subject | 2 | 4 |
| Period 2 | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Randomized Safety Population |
|---|---|
| Age Continuous | 33 years STANDARD_DEVIATION 8.7 |
| Sex: Female, Male Female | 46 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 35 / 81 | 22 / 83 |
| serious Total, serious adverse events | 1 / 81 | 0 / 83 |
Outcome results
Primary
AUC0-inf - Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (Extrapolated)
Bioequivalence 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 the Plasma Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 537 ng*h/mL | Standard Deviation 135 |
| Original OxyContin® (OXY) (Reference) | AUC0-inf - Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 579 ng*h/mL | Standard Deviation 115 |
90% CI: [90.11, 95.09]ANOVA
Primary
AUC0-t - Area Under Plasma Concentration-time Curve From Time Zero to Time of Last Non-zero Plasma Concentration
Bioequivalence 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 | 535 ng*h/mL | Standard Deviation 134 |
| Original OxyContin® (OXY) (Reference) | AUC0-t - Area Under Plasma Concentration-time Curve From Time Zero to Time of Last Non-zero Plasma Concentration | 577 ng*h/mL | Standard Deviation 115 |
90% CI: [90.13, 95.13]ANOVA
Primary
Cmax - Maximum Observed Plasma Concentration
Bioequivalence 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 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 | 62.0 ng/mL | Standard Deviation 16.5 |
| Original OxyContin® (OXY) (Reference) | Cmax - Maximum Observed Plasma Concentration | 61.5 ng/mL | Standard Deviation 12.3 |
90% CI: [95.4, 104.52]ANOVA