A Phase 3 interventional study of Oxycodone HCl controlled-release tablets in Pain, sponsored by Purdue Pharma LP. Completed at 47 sites in 8 countries. Open to participants aged 6 Years to 16 Years. Per ClinicalTrials.gov, last updated 2020-03-23.
Sponsored by Purdue Pharma LP · Phase 3, Interventional, and Treatment
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.
Exclusion Criteria include:
Other protocol-specific inclusion/exclusion criteria may apply.
Oxycodone hydrochloride (HCl) controlled-release (CR)
Drug: Oxycodone 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.
Also known as: OxyContin
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).
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
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
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
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
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
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
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]
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]
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]
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]
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
| Milestone | 6 to < 12 Years | ≥ 12 to ≤ 16 Years |
|---|---|---|
| Started | 27 | 128 |
| Completed | 17 | 105 |
| Not completed | 10 | 23 |
| Withdrew: Adverse event | 3 | 7 |
| Withdrew: Withdrawal by subject | 3 | 4 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Withdrew: Lack of efficacy | 0 | 5 |
| Withdrew: Administrative | 4 | 6 |
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.
| participants | 6 to < 12 Years | ≥ 12 to ≤ 16 Years |
|---|---|---|
| Serious adverse events | 5 | 22 |
| All other adverse events in ≥ 5% of patients | 13 | 60 |
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.
| units on a scale | 6 to < 12 Years |
|---|---|
| Baseline | 4.44 ± 3.250 |
| Average during week 1: morning | 4.11 ± 2.674 |
| Average during week 1: evening | 4.07 ± 2.695 |
| Average during week 2: morning | 3.66 ± 2.640 |
| Average during week 2: evening | 3.70 ± 2.686 |
| Average during week 3: morning | 3.64 ± 2.579 |
| Average during week 3: evening | 3.76 ± 2.669 |
| Average during week 4: morning | 3.13 ± 2.569 |
| Average during week 4: evening | 3.42 ± 2.974 |
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.
| units on a scale | ≥ 12 to ≤ 16 Years |
|---|---|
| Baseline | 44.58 ± 28.291 |
| Average during week 1: morning | 40.38 ± 24.402 |
| Average during week 1: evening | 39.24 ± 23.301 |
| Average during week 2: morning | 34.49 ± 24.980 |
| Average during week 2: evening | 33.04 ± 24.778 |
| Average during week 3: morning | 32.56 ± 25.802 |
| Average during week 3: evening | 33.46 ± 24.639 |
| Average during week 4: morning | 35.58 ± 27.177 |
| Average during week 4: evening | 35.30 ± 26.711 |
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.
| participants | 6 to < 12 Years | ≥ 12 to ≤ 16 Years |
|---|---|---|
| Any supplemental pain medication | 24 | 112 |
| Any opioid supplemental pain medication | 21 | 93 |
| Any nonopioid supplemental pain medication | 17 | 75 |
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.
| participants | 6 to < 12 Years | ≥ 12 to ≤ 16 Years |
|---|---|---|
| 1 = Very much improved | 10 | 42 |
| 2 = Much improved | 8 | 51 |
| 3 = Minimally improved | 3 | 15 |
| 4 = No change | 3 | 5 |
| 5 = Minimally worse | 0 | 1 |
| 6 = Much worse | 0 | 0 |
| 7 = Very much worse | 1 | 1 |
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.
| units on a scale | 6 to < 12 Years |
|---|---|
| Baseline | 27.1 ± 13.06 |
| Week 4 | 23.0 ± 13.32 |
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.
| units on a scale | ≥ 12 to ≤ 16 Years |
|---|---|
| Baseline | 23.2 ± 17.47 |
| Week 4 | 20.4 ± 12.65 |
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).
| ng/mL | 6 to 16 Years |
|---|---|
| Cmin - first dose | 6.86 (2.69 to 23.1) |
| Cmin - last dose | 6.35 (2.34 to 22.0) |
| Cmin,ss - first dose | 7.73 (2.9 to 28.8) |
| Cmin,ss - last dose | 7.46 (2.47 to 28.9) |
| Cmax - first dose | 16.3 (7.82 to 58.2) |
| Cmax - last dose | 15.8 (7.87 to 59.5) |
| Cmax,ss - first dose | 20.9 (9.23 to 66.1) |
| Cmax,ss - last dose | 17.9 (9.46 to 68.4) |
| CAVGss - first dose | 16.1 (6.84 to 53.7) |
| CAVGss - last dose | 15.7 (6.77 to 58.9) |
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).
| ng*hour/mL | 6 to 16 Years |
|---|---|
| AUCtau - first dose | 181 (74.2 to 562) |
| AUCtau - last dose | 158 (77.2 to 545) |
| AUCss - first dose | 194 (82.1 to 645) |
| AUCss - last dose | 188 (81.3 to 707) |
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.
| Hours | 6 to 16 Years |
|---|---|
| Tmax - first dose | 3.75 (2.5 to 5.75) |
| Tmax - last dose | 3.75 (2.5 to 5.75) |
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).
| Ratio | 6 to 16 Years |
|---|---|
| Accumulation ratio - first dose | 1.14 (1.03 to 1.40) |
| Accumulation ratio - last dose | 1.14 (1.03 to 1.42) |
Collected over Adverse events (AEs) were reported from start of study participation through the period beyond study completion.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 6 to < 12 Years | — | 5/27 (18.5%) | 13/27 (48.1%) |
| ≥ 12 to ≤ 16 Years | — | 22/128 (17.2%) | 60/128 (46.9%) |
| Event | 6 to < 12 Years | ≥ 12 to ≤ 16 Years |
|---|---|---|
| NeutropeniaBlood and lymphatic system disorders | 2/27 | 1/128 |
| PyrexiaGeneral disorders | 2/27 | 5/128 |
| Febrile neutropeniaBlood and lymphatic system disorders | 1/27 | 4/128 |
| Cardio-respiratory arrestCardiac disorders | 1/27 | 0/128 |
| StomatitisGastrointestinal disorders | 1/27 | 0/128 |
| Back painMusculoskeletal and connective tissue disorders | 1/27 | 0/128 |
| ComaNervous system disorders | 1/27 | 1/128 |
| ConvulsionNervous system disorders | 1/27 | 0/128 |
| Respiratory disorderRespiratory, thoracic and mediastinal disorders | 1/27 | 0/128 |
| VomitingGastrointestinal disorders | 0/27 | 2/128 |
| Event | 6 to < 12 Years | ≥ 12 to ≤ 16 Years |
|---|---|---|
| VomitingGastrointestinal disorders | 6/27 | 26/128 |
| PyrexiaGeneral disorders | 5/27 | 8/128 |
| NauseaGastrointestinal disorders | 3/27 | 20/128 |
| ConstipationGastrointestinal disorders | 4/27 | 12/128 |
| HeadacheNervous system disorders | 3/27 | 17/128 |
| PruritusSkin and subcutaneous tissue disorders | 3/27 | 7/128 |
| DizzinessNervous system disorders | 0/27 | 11/128 |
The safety population was the group of patients who received at least 1 dose of study drug during the study.
| Age, Continuous(years) | 6 to < 12 Years | ≥ 12 to ≤ 16 Years | Total |
|---|---|---|---|
| Mean | 9.6 ± 1.65 | 14.5 ± 1.34 | 13.7 ± 2.33 |
| Sex: Female, Male(Participants) | 6 to < 12 Years | ≥ 12 to ≤ 16 Years | Total |
|---|---|---|---|
| Female | 14 | 75 | 89 |
| Male | 13 | 53 | 66 |
| Race/Ethnicity, Customized(participants) | 6 to < 12 Years | ≥ 12 to ≤ 16 Years | Total |
|---|---|---|---|
| White | 20 | 88 | 108 |
| Black or African American | 7 | 31 | 38 |
| Asian | 0 | 1 | 1 |
| Other | 0 | 8 | 8 |
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Purdue Pharma LP