A Study to Determine the Fasting Bioequivalence of Reformulated OXY Tablets and Original OxyContin® (OXY) Tablets
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the bioequivalence of a new oxycodone formulation (10 mg) relative to the original OxyContin® (OXY) formulation (10 mg) in the fasted state.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Reformulated OXY 10 mg Reformulated OXY 10 mg x 1 dose |
Drug: Reformulated OXY (oxycodone HCl)
Reformulated OXY 10-mg tablet x 1 dose taken without food
|
| Active Comparator: Original OxyContin® (OXY)10 mg Original OxyContin® (OXY)10 mg x 1 dose |
Drug: Original OxyContin® (OXY) (oxycodone HCl)
Original OxyContin® (OXY) 10-mg tablet x 1 dose taken without food
|
Outcome Measures
Primary Outcome Measures
- 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 the 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.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Covance Clinical Research Unit Madison | Madison | Wisconsin | United States | 53704 |
Sponsors and Collaborators
- Purdue Pharma LP
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- OTR1003
Study Results
Participant Flow
| Recruitment Details | 02-Jan-2007 to 06-Mar-2007 at 1 site in the US (Madison, WI) |
|---|---|
| Pre-assignment Detail | 167 subjects screened; 83 screen failures; 84 randomized; 1 terminated early; 83 completed |
| Arm/Group Title | Reformulated OXY (Test) First | Original OxyContin® (OXY) (Reference) First |
|---|---|---|
| Arm/Group Description | Reformulated OXY 10-mg tablet (test) dosed fasted was administered in a two-period, two-sequence, single-dose, two-way crossover fashion. A minimum washout period of at least 6 days separated dose administrations. Subjects in this sequence received Reformulated OXY (Test) in period 1 and Original OxyContin(OXY)(Reference) in period 2. | Original OxyContin® (OXY) 10-mg tablet (reference) dosed fasted was administered in a two-period, two-sequence, single-dose, two-way crossover fashion. A minimum washout period of at least 6 days separated dose administrations. Subjects in this sequence received Original OxyContin® (OXY) (Reference)in period 1 and Reformulated OXY (Test) in period 2. |
| Period Title: Period 1 | ||
| STARTED | 43 | 41 |
| COMPLETED | 42 | 41 |
| NOT COMPLETED | 1 | 0 |
| Period Title: Period 1 | ||
| STARTED | 42 | 41 |
| COMPLETED | 42 | 41 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Randomized Safety Population |
|---|---|
| Arm/Group Description | Subjects who were randomized, received study drug, and had at least 1 postdose safety assessment. |
| Overall Participants | 84 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
32
(9.3)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
27
32.1%
|
| Male |
57
67.9%
|
Outcome Measures
| Title | Cmax - Maximum Observed Plasma Concentration |
|---|---|
| Description | Cmax is the maximum observed plasma concentration and bioequivalence is based on Cmax. |
| Time Frame | Blood samples collected over 72-hour period |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Reformulated OXY (Test) | Original OxyContin® (OXY) (Reference) |
|---|---|---|
| Arm/Group Description | Reformulated OXY 10-mg tablet (test) dosed fasted administered in a two-period, two-sequence, single-dose, two-way crossover fashion | Original OxyContin® (OXY) 10-mg tablet (reference) dosed fasted administered in a two-period, two-sequence, single-dose, two-way crossover fashion |
| Measure Participants | 81 | 81 |
| Mean (Standard Deviation) [ng/mL] |
9.60
(2.49)
|
9.38
(1.92)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Reformulated OXY (Test), Original OxyContin® (OXY) (Reference) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | A mixed-model analysis of variance was used to compare (test vs reference) and the 90% confidence intervals were estimated for the ratios (test/reference) | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Test/Ref Ratio x 100 |
| Estimated Value | 102 | |
| Confidence Interval |
(2-Sided) 90% 99.35 to 105.42 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Bioequivalence is established when 90% Confidence Interval falls within 80%-125%. | |
| Title | AUC0-inf - Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (Extrapolated) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Reformulated OXY (Test) | Original OxyContin® (OXY) (Reference) |
|---|---|---|
| Arm/Group Description | Reformulated OXY 10-mg tablet (test) dosed fasted administered in a two-period, two-sequence, single-dose, two-way crossover fashion | Original OxyContin® (OXY) 10-mg tablet (reference) dosed fasted administered in a two-period, two-sequence, single-dose, two-way crossover fashion |
| Measure Participants | 81 | 81 |
| Mean (Standard Deviation) [ng*h/mL] |
110
(25.0)
|
114
(28.6)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Reformulated OXY (Test), Original OxyContin® (OXY) (Reference) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | A mixed-model analysis of variance was used to compare (test vs reference) and the 90% confidence intervals were estimated for the ratios (test/reference) | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Test/Ref Ratio x 100 |
| Estimated Value | 98.0 | |
| Confidence Interval |
(2-Sided) 90% 94.94 to 101.19 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Bioequivalence is established when 90% Confidence Interval falls within 80%-125%. | |
| Title | AUC0-t - Area Under Plasma Concentration-time Curve From Time Zero to Time of Last Non-zero Plasma Concentration |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Reformulated OXY (Test) | Original OxyContin® (OXY) (Reference) |
|---|---|---|
| Arm/Group Description | Reformulated OXY 10-mg tablet (test) dosed fasted administered in a two-period, two-sequence, single-dose, two-way crossover fashion | Original OxyContin® (OXY) 10-mg tablet (reference) dosed fasted administered in a two-period, two-sequence, single-dose, two-way crossover fashion |
| Measure Participants | 81 | 81 |
| Mean (Standard Deviation) [ng*h/mL] |
110
(25.0)
|
113
(28.3)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Reformulated OXY (Test), Original OxyContin® (OXY) (Reference) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | A mixed-model analysis of variance was used to compare (test vs reference) and the 90% confidence intervals were estimated for the ratios (test/reference) | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Test/Ref Ratio x 100 |
| Estimated Value | 98.3 | |
| Confidence Interval |
(2-Sided) 90% 95.20 to 101.48 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Bioequivalence is established when 90% Confidence Interval falls within 80%-125%. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Reformulated OXY (Test), Original OxyContin® (OXY) (Reference) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | A mixed-model analysis of variance was used to compare (test vs reference) and the 90% confidence intervals were estimated for the ratios (test/reference). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Test/Ref Ratio x 100 |
| Estimated Value | 98.3 | |
| Confidence Interval |
(2-Sided) 90% 95.20 to 101.48 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Bioequivalence is established when 90% Confidence Interval falls within 80%-125%. | |
Adverse Events
| Time Frame | Ongoing AEs-followed until resolution/30 days after last dose;AEs reported during 7 days following last dose were recorded&followed until resolution or up to 30 days after last dose.All SAEs were followed until resolution or event/sequelae stabilized. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | AEs were learned of through spontaneous reports, subject interview, or subject diaries. | |||
| Arm/Group Title | Reformulated OXY (Test) | Original OxyContin® (OXY) (Reference) | ||
| Arm/Group Description | Reformulated OXY 10-mg tablet (test) dosed fasted administered in a two-period, two-sequence, single-dose, two-way crossover fashion | Original OxyContin® (OXY) 10-mg tablet (reference) dosed fasted administered in a two-period, two-sequence, single-dose, two-way crossover fashion | ||
All Cause Mortality |
||||
| Reformulated OXY (Test) | Original OxyContin® (OXY) (Reference) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Reformulated OXY (Test) | Original OxyContin® (OXY) (Reference) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/84 (0%) | 0/83 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Reformulated OXY (Test) | Original OxyContin® (OXY) (Reference) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 23/84 (27.4%) | 14/83 (16.9%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 11/84 (13.1%) | 13 | 10/83 (12%) | 13 |
| Nervous system disorders | ||||
| Dizziness | 6/84 (7.1%) | 6 | 1/83 (1.2%) | 1 |
| Headache | 6/84 (7.1%) | 6 | 3/83 (3.6%) | 4 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Stephen Harris, M.D. |
|---|---|
| Organization | Purdue Pharma L.P. |
| Phone | 203-588-7592 |
| Stephen.Harris@Pharma.com |
- OTR1003