Pain
Conditions
Keywords
Malignant pain, Nonmalignant pain, Pediatric, Opioid, Moderate to severe malignant or nonmalignant pain
Brief summary
The purpose of this study is to characterize the safety of oxycodone hydrochloride (HCl) controlled-release (CR) tablets in opioid tolerant pediatric patients aged 6 to 16 years, inclusive, with moderate to severe malignant and/or nonmalignant pain requiring opioid therapy.
Interventions
DRUGOxycodone HCl controlled-release tablets
Oxycodone HCl controlled-release tablets at strengths of 10, 15, 20, 30, or 40 mg (20 mg - 240 mg daily) every 12 hours.
Sponsors
Purdue Pharma LP
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
include: * Male and female patients aged 6 to 16 years, inclusive, who are expected to require ongoing around-the-clock opioid treatment equivalent to at least 20-mg daily dose of oxycodone for at least 2 weeks for management of moderate to severe (based on the investigator's judgment) malignant or nonmalignant pain. * Patients must be opioid tolerant, ie, have been treated with opioids for at least the 5 consecutive days prior to dosing and with at least 20 mg daily of oxycodone or the equivalent during at least the last 48 hours prior to the start of study drug dosing and have tolerated the therapy, as demonstrated at the start of study drug dosing. * Patients who are currently using transdermal fentanyl should have been on the patch for at least 3 days before removing the patch and oxycodone hydrochloride (HCl) controlled-release (CR) treatment can only be initiated at least 18 hours following the removal of the transdermal fentanyl patch. * Patients must not require more than a 240-mg total daily dose of oxycodone HCl CR tablets. * Patients must be willing and able to swallow the oxycodone HCl CR tablets whole. * Patients must not be currently on an investigational medication/therapy at the start of screening or during the study.
Exclusion criteria
include: * Female patients who are pregnant or lactating. * Patients who are allergic to oxycodone or have a history of allergies to other opioids (this criterion does not include patients who have experienced common opioid side effects \[eg, nausea, constipation\]). * Patients who have received epidural opioids \< 2 hours prior to the first dose of study drug or who have received epidural morphine \< 12 hours prior to the first dose of study drug. * Patients who are contraindicated for the use of opioids. * Patients who are contraindicated for blood sampling. * Patients who are currently being maintained on methadone for pain. * Patients who have any planned surgery during the course of the study, with the exception of the placement of central or peripheral venous access devices. * Patients who have had surgery within 5 days prior to Day 1 (day of first dose of study drug). * Patients who, in the investigator's opinion, have an underlying gastrointestinal condition or other disorder that may predispose them to obstruction. Other protocol-specific inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With Adverse Events as a Measure of Safety. | Up to 4 weeks (during the study) and 7-10 days poststudy (safety follow-up assessment). | Safety assessments consisted of reports of AEs, physical examinations, clinical laboratory test results, vital signs measurements, pulse oximetry (SpO2), and somnolence assessments. Safety variables were summarized descriptively within age group for the safety population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Right Now Assessment by Patients Aged ≥ 12 to ≤ 16 Years | Baseline to week 4 | Pain right now was assessed by patients aged ≥ 12 to ≤ 16 years using the 100-mm visual analogue scale (VAS). The 100-mm VAS is a 100-mm line with 1 end marked no pain and the opposite end marked as pain as bad as it could be. The patient was asked to make a mark on that line indicating his or her level of pain. The pain right now 100-mm VAS score was defined as the distance (in mm) from the no pain end to the patient's mark. The scale is measured on a 100 mm line: a 0 means no pain and bigger numbers indicate more pain. Pain right now was assessed by the patient at screening; after the first dose; and, thereafter, twice daily during the AM and PM, approximately at the time of each (morning and evening) dose of oxycodone HCl CR tablets during the study treatment. |
| Use of Supplemental Pain Medication | Baseline to week 4 | Supplemental opioid and nonopioid pain medications were permitted during the study as deemed appropriate by the investigator. The dose of supplemental analgesic medication allowed was at the discretion of the investigator and within appropriate dose ranges for age and weight. |
| Parent/ Caregiver-Assessed Global Impression of Change (PGIC) | Baseline to week 4 or early discontinuation | The PGIC rating score variable was collected on a 7-point scale ranging from 1 to 7 (where 1 = very much improved; and 7 = very much worse). The PGIC is designed to assess overall satisfaction with the treatment. The number and percent of parent/caregivers reporting each category of PGIC response at the final visit was summarized for the safety population within age group. |
| Parent/ Caregiver Assessed Functional Disability Inventory (FDI) for Patients Aged 6 to < 12 Years | Baseline to week 4 | The FDI is a validated tool used to evaluate the degree to which children have reduced physical and psychosocial functioning because of their pain difficulties in the previous 2 weeks. The FDI comprises 15 items. Responses to each item were scored using a 5-point Likert scale. The individual scores are: (0) no trouble, (1) a little trouble, (2) some trouble, (3) a lot of trouble, and (4) impossible. A total score (ranging from 0 to 60) for the 15 items was calculated, with lower scores indicating less functional disability. The FDI was performed by the parent/ caregiver. |
| Pain Right Now Assessment by Patients Aged 6 to < 12 Years | Baseline to week 4 | Pain right now was assessed by patients aged 6 to \<12 years using the Faces of Pain Scale-Revised (FPS-R). The FPS-R is a horizontal row of 6 faces representing pain intensity, with no hurt at the far left and hurts worst at the far right; the 6 intensities are scored as 0, 2, 4, 6, 8, or 10 (the patient was not shown the numbers associated with the faces). A score of 0 means no pain, and a 10 means very much pain. Pain right now was assessed by the patient at screening; after the first dose; and, thereafter, twice daily during the AM and PM, approximately at the time of each (morning and evening) dose of oxycodone HCl CR tablets during the study treatment. |
| Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets | Day 1 - first dose [2-4 hrs post dose and 4-6 hrs post dose], week 4 - last dose [at pre-dose and at 2-4 hrs post dose] | A population PK analysis using sparse plasma concentration data in pediatric patients was conducted. Empirical Bayes estimates were used to calculate individual PK parameters. PK parameters were calculated and reported for each individual patient's first and last dose. Cmax was taken as the maximum simulated oxycodone concentration over the dosing interval and Cmin was the simulated oxycodone concentration when time was equal to 12 hours. Steady-state Cmin and Cmax were derived from the accumulation ratio. The following PK parameters are presented: Cmin / Cmax (minimum / maximum concentration); Cmin,ss / Cmax,ss (Cmin / Cmax at steady state); CAVGss (average concentration at steady state). |
| Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets - AUCtau and AUCss | Day 1 - first dose [2-4 hrs post dose and 4-6 hrs post dose], week 4 - last dose [at pre-dose and at 2-4 hrs post dose] | A population PK analysis using sparse plasma concentration data in pediatric patients was conducted. Empirical Bayes estimates were used to calculate individual PK parameters. PK parameters were calculated and reported for each individual patient's first and last dose. First-dose area under the concentration-time curve (AUC) was derived from the accumulation ratio. For all calculations, the dosing interval was assumed to be 12 hours. The following PK parameters are presented: AUCtau (area under the concentration-time curve from time zero to time equal to dosing interval); AUCss (AUC at steady state). |
| Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets - Time to Maximum Concentration (Tmax) | Day 1 - first dose [2-4 hrs post dose and 4-6 hrs post dose], week 4 - last dose [at pre-dose and at 2-4 hrs post dose] | A population PK analysis using sparse plasma concentration data in pediatric patients was conducted. Empirical Bayes estimates were used to calculate individual PK parameters. PK parameters were calculated and reported for each individual patient's first and last dose. |
| Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets - Accumulation Ratio | Day 1 - first dose [2-4 hrs post dose and 4-6 hrs post dose], week 4 - last dose [at pre-dose and at 2-4 hrs post dose] | A population PK analysis using sparse plasma concentration data in pediatric patients was conducted. Empirical Bayes estimates were used to calculate individual PK parameters. PK parameters were calculated and reported for each individual patient's first and last dose. The accumulation ratio is used to derive steady-state Cmin and Cmax and first-dose area under the concentration-time curve (AUCtau). |
| Parent/ Caregiver Assessed Functional Disability Inventory (FDI) for Patients Aged ≥ 12 to ≤ 16 Years | Baseline to week 4 | The FDI is a validated tool used to evaluate the degree to which children have reduced physical and psychosocial functioning because of their pain difficulties in the previous 2 weeks. The FDI comprises 15 items. Responses to each item were scored using a 5-point Likert scale. The individual scores are: (0) no trouble, (1) a little trouble, (2) some trouble, (3) a lot of trouble, and (4) impossible. A total score (ranging from 0 to 60) for the 15 items was calculated, with lower scores indicating less functional disability. The FDI was performed by the parent/ caregiver. |
Countries
Greece, Hungary, Israel, New Zealand, Romania, Spain, United Kingdom, United States
Participant flow
Recruitment details
First Patient First Visit: 28-Feb-2011; Last Patient Last Visit: 29-Jul-2014. The study was conducted at medical/research sites in the United States, Spain, United Kingdom, Greece, Guatemala, Hungary, Israel, and New Zealand
Participants by arm
| Arm | Count |
|---|---|
| 6 to < 12 Years Children 6 to \< 12 years of age | 27 |
| ≥ 12 to ≤ 16 Years Children ≥ 12 to ≤ 16 years of age | 128 |
| Total | 155 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative | 4 | 6 |
| Overall Study | Adverse Event | 3 | 7 |
| Overall Study | Lack of Efficacy | 0 | 5 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 4 |
Baseline characteristics
| Characteristic | ≥ 12 to ≤ 16 Years | Total | 6 to < 12 Years |
|---|---|---|---|
| Age, Continuous | 14.5 years STANDARD_DEVIATION 1.34 | 13.7 years STANDARD_DEVIATION 2.33 | 9.6 years STANDARD_DEVIATION 1.65 |
| Race/Ethnicity, Customized Asian | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Black or African American | 31 participants | 38 participants | 7 participants |
| Race/Ethnicity, Customized Other | 8 participants | 8 participants | 0 participants |
| Race/Ethnicity, Customized White | 88 participants | 108 participants | 20 participants |
| Sex: Female, Male Female | 75 Participants | 89 Participants | 14 Participants |
| Sex: Female, Male Male | 53 Participants | 66 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 27 | 60 / 128 |
| serious Total, serious adverse events | 5 / 27 | 22 / 128 |
Outcome results
Primary
The Number of Participants With Adverse Events as a Measure of Safety.
Safety assessments consisted of reports of AEs, physical examinations, clinical laboratory test results, vital signs measurements, pulse oximetry (SpO2), and somnolence assessments. Safety variables were summarized descriptively within age group for the safety population.
Time frame: Up to 4 weeks (during the study) and 7-10 days poststudy (safety follow-up assessment).
Population: The safety population was the group of patients who received at least 1 dose of study drug during the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 6 to < 12 Years | The Number of Participants With Adverse Events as a Measure of Safety. | Serious adverse events | 5 participants |
| 6 to < 12 Years | The Number of Participants With Adverse Events as a Measure of Safety. | All other adverse events in ≥ 5% of patients | 13 participants |
| ≥ 12 to ≤ 16 Years | The Number of Participants With Adverse Events as a Measure of Safety. | Serious adverse events | 22 participants |
| ≥ 12 to ≤ 16 Years | The Number of Participants With Adverse Events as a Measure of Safety. | All other adverse events in ≥ 5% of patients | 60 participants |
Secondary
Pain Right Now Assessment by Patients Aged ≥ 12 to ≤ 16 Years
Pain right now was assessed by patients aged ≥ 12 to ≤ 16 years using the 100-mm visual analogue scale (VAS). The 100-mm VAS is a 100-mm line with 1 end marked no pain and the opposite end marked as pain as bad as it could be. The patient was asked to make a mark on that line indicating his or her level of pain. The pain right now 100-mm VAS score was defined as the distance (in mm) from the no pain end to the patient's mark. The scale is measured on a 100 mm line: a 0 means no pain and bigger numbers indicate more pain. Pain right now was assessed by the patient at screening; after the first dose; and, thereafter, twice daily during the AM and PM, approximately at the time of each (morning and evening) dose of oxycodone HCl CR tablets during the study treatment.
Time frame: Baseline to week 4
Population: The safety population was the group of patients who received at least 1 dose of study drug during the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6 to < 12 Years | Pain Right Now Assessment by Patients Aged ≥ 12 to ≤ 16 Years | Baseline | 44.58 units on a scale | Standard Deviation 28.291 |
| 6 to < 12 Years | Pain Right Now Assessment by Patients Aged ≥ 12 to ≤ 16 Years | Average during week 1: morning | 40.38 units on a scale | Standard Deviation 24.402 |
| 6 to < 12 Years | Pain Right Now Assessment by Patients Aged ≥ 12 to ≤ 16 Years | Average during week 1: evening | 39.24 units on a scale | Standard Deviation 23.301 |
| 6 to < 12 Years | Pain Right Now Assessment by Patients Aged ≥ 12 to ≤ 16 Years | Average during week 2: morning | 34.49 units on a scale | Standard Deviation 24.98 |
| 6 to < 12 Years | Pain Right Now Assessment by Patients Aged ≥ 12 to ≤ 16 Years | Average during week 2: evening | 33.04 units on a scale | Standard Deviation 24.778 |
| 6 to < 12 Years | Pain Right Now Assessment by Patients Aged ≥ 12 to ≤ 16 Years | Average during week 3: morning | 32.56 units on a scale | Standard Deviation 25.802 |
| 6 to < 12 Years | Pain Right Now Assessment by Patients Aged ≥ 12 to ≤ 16 Years | Average during week 3: evening | 33.46 units on a scale | Standard Deviation 24.639 |
| 6 to < 12 Years | Pain Right Now Assessment by Patients Aged ≥ 12 to ≤ 16 Years | Average during week 4: morning | 35.58 units on a scale | Standard Deviation 27.177 |
| 6 to < 12 Years | Pain Right Now Assessment by Patients Aged ≥ 12 to ≤ 16 Years | Average during week 4: evening | 35.30 units on a scale | Standard Deviation 26.711 |
Secondary
Pain Right Now Assessment by Patients Aged 6 to < 12 Years
Pain right now was assessed by patients aged 6 to \<12 years using the Faces of Pain Scale-Revised (FPS-R). The FPS-R is a horizontal row of 6 faces representing pain intensity, with no hurt at the far left and hurts worst at the far right; the 6 intensities are scored as 0, 2, 4, 6, 8, or 10 (the patient was not shown the numbers associated with the faces). A score of 0 means no pain, and a 10 means very much pain. Pain right now was assessed by the patient at screening; after the first dose; and, thereafter, twice daily during the AM and PM, approximately at the time of each (morning and evening) dose of oxycodone HCl CR tablets during the study treatment.
Time frame: Baseline to week 4
Population: The safety population was the group of patients who received at least 1 dose of study drug during the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6 to < 12 Years | Pain Right Now Assessment by Patients Aged 6 to < 12 Years | Baseline | 4.44 units on a scale | Standard Deviation 3.25 |
| 6 to < 12 Years | Pain Right Now Assessment by Patients Aged 6 to < 12 Years | Average during week 1: morning | 4.11 units on a scale | Standard Deviation 2.674 |
| 6 to < 12 Years | Pain Right Now Assessment by Patients Aged 6 to < 12 Years | Average during week 1: evening | 4.07 units on a scale | Standard Deviation 2.695 |
| 6 to < 12 Years | Pain Right Now Assessment by Patients Aged 6 to < 12 Years | Average during week 2: morning | 3.66 units on a scale | Standard Deviation 2.64 |
| 6 to < 12 Years | Pain Right Now Assessment by Patients Aged 6 to < 12 Years | Average during week 3: evening | 3.76 units on a scale | Standard Deviation 2.669 |
| 6 to < 12 Years | Pain Right Now Assessment by Patients Aged 6 to < 12 Years | Average during week 4: morning | 3.13 units on a scale | Standard Deviation 2.569 |
| 6 to < 12 Years | Pain Right Now Assessment by Patients Aged 6 to < 12 Years | Average during week 4: evening | 3.42 units on a scale | Standard Deviation 2.974 |
| 6 to < 12 Years | Pain Right Now Assessment by Patients Aged 6 to < 12 Years | Average during week 2: evening | 3.70 units on a scale | Standard Deviation 2.686 |
| 6 to < 12 Years | Pain Right Now Assessment by Patients Aged 6 to < 12 Years | Average during week 3: morning | 3.64 units on a scale | Standard Deviation 2.579 |
Secondary
Parent/ Caregiver Assessed Functional Disability Inventory (FDI) for Patients Aged ≥ 12 to ≤ 16 Years
The FDI is a validated tool used to evaluate the degree to which children have reduced physical and psychosocial functioning because of their pain difficulties in the previous 2 weeks. The FDI comprises 15 items. Responses to each item were scored using a 5-point Likert scale. The individual scores are: (0) no trouble, (1) a little trouble, (2) some trouble, (3) a lot of trouble, and (4) impossible. A total score (ranging from 0 to 60) for the 15 items was calculated, with lower scores indicating less functional disability. The FDI was performed by the parent/ caregiver.
Time frame: Baseline to week 4
Population: The safety population was the group of patients who received at least 1 dose of study drug during the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6 to < 12 Years | Parent/ Caregiver Assessed Functional Disability Inventory (FDI) for Patients Aged ≥ 12 to ≤ 16 Years | Week 4 | 20.4 units on a scale | Standard Deviation 12.65 |
| 6 to < 12 Years | Parent/ Caregiver Assessed Functional Disability Inventory (FDI) for Patients Aged ≥ 12 to ≤ 16 Years | Baseline | 23.2 units on a scale | Standard Deviation 17.47 |
Secondary
Parent/ Caregiver Assessed Functional Disability Inventory (FDI) for Patients Aged 6 to < 12 Years
The FDI is a validated tool used to evaluate the degree to which children have reduced physical and psychosocial functioning because of their pain difficulties in the previous 2 weeks. The FDI comprises 15 items. Responses to each item were scored using a 5-point Likert scale. The individual scores are: (0) no trouble, (1) a little trouble, (2) some trouble, (3) a lot of trouble, and (4) impossible. A total score (ranging from 0 to 60) for the 15 items was calculated, with lower scores indicating less functional disability. The FDI was performed by the parent/ caregiver.
Time frame: Baseline to week 4
Population: The safety population was the group of patients who received at least 1 dose of study drug during the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6 to < 12 Years | Parent/ Caregiver Assessed Functional Disability Inventory (FDI) for Patients Aged 6 to < 12 Years | Baseline | 27.1 units on a scale | Standard Deviation 13.06 |
| 6 to < 12 Years | Parent/ Caregiver Assessed Functional Disability Inventory (FDI) for Patients Aged 6 to < 12 Years | Week 4 | 23.0 units on a scale | Standard Deviation 13.32 |
Secondary
Parent/ Caregiver-Assessed Global Impression of Change (PGIC)
The PGIC rating score variable was collected on a 7-point scale ranging from 1 to 7 (where 1 = very much improved; and 7 = very much worse). The PGIC is designed to assess overall satisfaction with the treatment. The number and percent of parent/caregivers reporting each category of PGIC response at the final visit was summarized for the safety population within age group.
Time frame: Baseline to week 4 or early discontinuation
Population: The safety population was the group of patients who received at least 1 dose of study drug during the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 6 to < 12 Years | Parent/ Caregiver-Assessed Global Impression of Change (PGIC) | 3 = Minimally improved | 3 participants |
| 6 to < 12 Years | Parent/ Caregiver-Assessed Global Impression of Change (PGIC) | 6 = Much worse | 0 participants |
| 6 to < 12 Years | Parent/ Caregiver-Assessed Global Impression of Change (PGIC) | 2 = Much improved | 8 participants |
| 6 to < 12 Years | Parent/ Caregiver-Assessed Global Impression of Change (PGIC) | 4 = No change | 3 participants |
| 6 to < 12 Years | Parent/ Caregiver-Assessed Global Impression of Change (PGIC) | 5 = Minimally worse | 0 participants |
| 6 to < 12 Years | Parent/ Caregiver-Assessed Global Impression of Change (PGIC) | 7 = Very much worse | 1 participants |
| 6 to < 12 Years | Parent/ Caregiver-Assessed Global Impression of Change (PGIC) | 1 = Very much improved | 10 participants |
| ≥ 12 to ≤ 16 Years | Parent/ Caregiver-Assessed Global Impression of Change (PGIC) | 7 = Very much worse | 1 participants |
| ≥ 12 to ≤ 16 Years | Parent/ Caregiver-Assessed Global Impression of Change (PGIC) | 1 = Very much improved | 42 participants |
| ≥ 12 to ≤ 16 Years | Parent/ Caregiver-Assessed Global Impression of Change (PGIC) | 2 = Much improved | 51 participants |
| ≥ 12 to ≤ 16 Years | Parent/ Caregiver-Assessed Global Impression of Change (PGIC) | 3 = Minimally improved | 15 participants |
| ≥ 12 to ≤ 16 Years | Parent/ Caregiver-Assessed Global Impression of Change (PGIC) | 5 = Minimally worse | 1 participants |
| ≥ 12 to ≤ 16 Years | Parent/ Caregiver-Assessed Global Impression of Change (PGIC) | 6 = Much worse | 0 participants |
| ≥ 12 to ≤ 16 Years | Parent/ Caregiver-Assessed Global Impression of Change (PGIC) | 4 = No change | 5 participants |
Secondary
Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets
A population PK analysis using sparse plasma concentration data in pediatric patients was conducted. Empirical Bayes estimates were used to calculate individual PK parameters. PK parameters were calculated and reported for each individual patient's first and last dose. Cmax was taken as the maximum simulated oxycodone concentration over the dosing interval and Cmin was the simulated oxycodone concentration when time was equal to 12 hours. Steady-state Cmin and Cmax were derived from the accumulation ratio. The following PK parameters are presented: Cmin / Cmax (minimum / maximum concentration); Cmin,ss / Cmax,ss (Cmin / Cmax at steady state); CAVGss (average concentration at steady state).
Time frame: Day 1 - first dose [2-4 hrs post dose and 4-6 hrs post dose], week 4 - last dose [at pre-dose and at 2-4 hrs post dose]
Population: Full analysis population for PK consisted of patients who received at least 1 dose of study drug and had at least 1 valid PK concentration.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 6 to < 12 Years | Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets | Cmin - last dose | 6.35 ng/mL |
| 6 to < 12 Years | Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets | Cmin,ss - last dose | 7.46 ng/mL |
| 6 to < 12 Years | Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets | Cmax - first dose | 16.3 ng/mL |
| 6 to < 12 Years | Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets | Cmax - last dose | 15.8 ng/mL |
| 6 to < 12 Years | Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets | Cmax,ss - last dose | 17.9 ng/mL |
| 6 to < 12 Years | Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets | CAVGss - first dose | 16.1 ng/mL |
| 6 to < 12 Years | Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets | CAVGss - last dose | 15.7 ng/mL |
| 6 to < 12 Years | Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets | Cmin - first dose | 6.86 ng/mL |
| 6 to < 12 Years | Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets | Cmin,ss - first dose | 7.73 ng/mL |
| 6 to < 12 Years | Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets | Cmax,ss - first dose | 20.9 ng/mL |
Secondary
Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets - Accumulation Ratio
A population PK analysis using sparse plasma concentration data in pediatric patients was conducted. Empirical Bayes estimates were used to calculate individual PK parameters. PK parameters were calculated and reported for each individual patient's first and last dose. The accumulation ratio is used to derive steady-state Cmin and Cmax and first-dose area under the concentration-time curve (AUCtau).
Time frame: Day 1 - first dose [2-4 hrs post dose and 4-6 hrs post dose], week 4 - last dose [at pre-dose and at 2-4 hrs post dose]
Population: Full analysis population for PK consisted of patients who received at least 1 dose of study drug and had at least 1 valid PK concentration.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 6 to < 12 Years | Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets - Accumulation Ratio | Accumulation ratio - first dose | 1.14 Ratio |
| 6 to < 12 Years | Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets - Accumulation Ratio | Accumulation ratio - last dose | 1.14 Ratio |
Secondary
Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets - AUCtau and AUCss
A population PK analysis using sparse plasma concentration data in pediatric patients was conducted. Empirical Bayes estimates were used to calculate individual PK parameters. PK parameters were calculated and reported for each individual patient's first and last dose. First-dose area under the concentration-time curve (AUC) was derived from the accumulation ratio. For all calculations, the dosing interval was assumed to be 12 hours. The following PK parameters are presented: AUCtau (area under the concentration-time curve from time zero to time equal to dosing interval); AUCss (AUC at steady state).
Time frame: Day 1 - first dose [2-4 hrs post dose and 4-6 hrs post dose], week 4 - last dose [at pre-dose and at 2-4 hrs post dose]
Population: Full analysis population for PK consisted of patients who received at least 1 dose of study drug and had at least 1 valid PK concentration.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 6 to < 12 Years | Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets - AUCtau and AUCss | AUCtau - first dose | 181 ng*hour/mL |
| 6 to < 12 Years | Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets - AUCtau and AUCss | AUCtau - last dose | 158 ng*hour/mL |
| 6 to < 12 Years | Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets - AUCtau and AUCss | AUCss - first dose | 194 ng*hour/mL |
| 6 to < 12 Years | Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets - AUCtau and AUCss | AUCss - last dose | 188 ng*hour/mL |
Secondary
Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets - Time to Maximum Concentration (Tmax)
A population PK analysis using sparse plasma concentration data in pediatric patients was conducted. Empirical Bayes estimates were used to calculate individual PK parameters. PK parameters were calculated and reported for each individual patient's first and last dose.
Time frame: Day 1 - first dose [2-4 hrs post dose and 4-6 hrs post dose], week 4 - last dose [at pre-dose and at 2-4 hrs post dose]
Population: Full analysis population for PK consisted of patients who received at least 1 dose of study drug and had at least 1 valid PK concentration.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 6 to < 12 Years | Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets - Time to Maximum Concentration (Tmax) | Tmax - first dose | 3.75 Hours |
| 6 to < 12 Years | Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets - Time to Maximum Concentration (Tmax) | Tmax - last dose | 3.75 Hours |
Secondary
Use of Supplemental Pain Medication
Supplemental opioid and nonopioid pain medications were permitted during the study as deemed appropriate by the investigator. The dose of supplemental analgesic medication allowed was at the discretion of the investigator and within appropriate dose ranges for age and weight.
Time frame: Baseline to week 4
Population: The safety population was the group of patients who received at least 1 dose of study drug during the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 6 to < 12 Years | Use of Supplemental Pain Medication | Any supplemental pain medication | 24 participants |
| 6 to < 12 Years | Use of Supplemental Pain Medication | Any opioid supplemental pain medication | 21 participants |
| 6 to < 12 Years | Use of Supplemental Pain Medication | Any nonopioid supplemental pain medication | 17 participants |
| ≥ 12 to ≤ 16 Years | Use of Supplemental Pain Medication | Any supplemental pain medication | 112 participants |
| ≥ 12 to ≤ 16 Years | Use of Supplemental Pain Medication | Any opioid supplemental pain medication | 93 participants |
| ≥ 12 to ≤ 16 Years | Use of Supplemental Pain Medication | Any nonopioid supplemental pain medication | 75 participants |