Pain
Conditions
Keywords
Pain, Opioid, Analgesia, Moderate to severe pain
Brief summary
The purpose of this study is to characterize the safety, PK, and efficacy of BTDS in patients of ages 7 to 16 years.
Detailed description
A study of safety, PK, and efficacy of BTDS in patients of ages 7 to 16 years, inclusive, who require continuous opioid analgesia for moderate to severe pain.
Interventions
Buprenorphine transdermal system 2.5 mcg/h, 5 mcg/h, 10 mcg/h or 20 mcg/h applied transdermally for 7-day wear.
Sponsors
Purdue Pharma LP
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
include: * Male and female patients, 7 to 16 years of age, inclusive, with malignant and/or nonmalignant moderate to severe pain requiring or anticipated to require continuous, around-the-clock, opioid treatment for at least 2 weeks (based on the investigator's judgment); * Patients must have written informed consent provided by the parent or legal guardian and assent provided by the patient, when appropriate; * Patients on incoming opioids must be taking ≤ 80 mg/day morphine or equivalent if aged 12 to 16 years or ≤ 40 mg/day morphine or equivalent if aged 7 to 11 years prior to the screening visit; * Patients and patient's parent/caregiver must be compliant with the protocol, ie, must be able to perform study assessments and understand and complete the age-appropriate scale to rate pain intensity. Patients must not have a cognitive developmental delay or any other condition that would preclude them from completing the age-appropriate pain scale.
Exclusion criteria
include: * Patients who are allergic to buprenorphine or have a history of allergies to other opioids (this criterion does not include patients who have experienced common opioid side effects \[eg, nausea, constipation\]) or who have allergies or other contraindications to transdermal delivery systems or patch adhesives; * Patients with a dermatological disorder, including burn and skin graft sites, at any relevant patch application site that would preclude proper placement and/or rotation of BTDS patches; * Patients with evidence of impaired renal function; * Patients with hepatic impairment; * Patients with history of seizures; * Patients with intracranial pressure; * Patients who have a history of sleep apnea within the past year; * Patients who require mechanical ventilation during study treatment period, are cyanotic, or who have unstable respiratory disease; * Patients with clinically significant structural heart disease or a pacemaker; * Patients with clinically unstable cardiac disease; * Patients who receive or anticipate to receive investigational medication/therapy during study drug treatment period. 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 28 weeks | Safety assessments consisted of reports of AEs, vital signs (blood pressure, pulse rate, respiratory rate, and temperature), weight, hemoglobin-oxygen saturation measured by pulse oximetry (SpO2), clinical laboratory tests, somnolence (assessed by the University of Michigan Sedation Scale \[UMSS\]), conventional 12-lead electrocardiograms (ECGs), and 24-hour digital 12-lead ECGs (Holter monitor). Safety variables were summarized descriptively within age group for the safety population. |
| Pharmacokinetics (PK) of Buprenorphine Following Transdermal Administration: Apparent Clearance (CL/F) | Day 1, end of week 1, days 9/10, end of week 2, and end of week 4 or at discontinuation prior to end of study visit | The population PK (PopPK) of BTDS buprenorphine in pediatric patients ages 7 to 16 years was described by a 2-compartment model with sequential zero- and first-order absorption from the patch. A fixed allometric relationship was used to describe the effects of changes in ideal body weight (IBW) across pediatric patients on all clearance and volume parameters. Given the sparse sample collections, small sample size, and complexity of the absorption process with the patch formulation, this PopPK model was fit to the pediatric data using nonlinear mixed effects modeling (NONMEM) Bayes method with selective use of priors from previous adult PopPK results. Estimates of fixed effects from the final model were used to calculate the CL/F after patch dosing given the covariate distribution in the PopPK dataset and the typical weights from children in the National Health and Nutrition Examination Survey (NHANES) dataset. |
| Pharmacokinetics (PK) of Buprenorphine Following Transdermal Administration: Apparent Volume of Distribution (Vc/F) | Day 1, end of week 1, days 9/10, end of week 2, and end of week 4 or at discontinuation prior to end of study visit | The population PK (PopPK) of BTDS buprenorphine in pediatric patients ages 7 to 16 years was described by a 2-compartment model with sequential zero- and first-order absorption from the patch. A fixed allometric relationship was used to describe the effects of changes in ideal body weight (IBW) across pediatric patients on all clearance and volume parameters. Given the sparse sample collections, small sample size, and complexity of the absorption process with the patch formulation, this PopPK model was fit to the pediatric data using nonlinear mixed effects modeling (NONMEM) Bayes method with selective use of priors from previous adult PopPK results. Estimates of fixed effects from the final model were used to calculate the Vc/F after patch dosing given the covariate distribution in the PopPK dataset and the typical weights from children in the National Health and Nutrition Examination Survey (NHANES) dataset. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive | Up to 24 weeks | Pain right now was assessed 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 intensities are scored as 0, 2, 4, 6, 8, or 10. A score of 0=no pain, and 10=very much pain. For screening to week 4, pain right now was assessed at 30 minutes before initial BTDS application on day 1; one hour after initial BTDS application on day 1; thereafter, once daily at approximately 8 PM for the first 4 weeks. Baseline score was the last assessment prior to the first dose. For weeks 1-4, weekly averages of the pain right now scores were calculated using the sum of all available pain right now scores recorded daily during a given week divided by the number of available scores. The study measured pain right now for weeks 6-24 once a week at approximately 8 PM while on treatment; however, no patients in this age group were treated beyond week 12. |
| Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Up to 24 weeks | Pain right now was assessed using a 100-mm visual analogue scale (VAS). The 100-mm VAS is a 100-mm line with 1 end marked as no pain and the other 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. Pain right now score was defined as the distance (in mm) from the no pain end to the patient's mark; 0=no pain and bigger numbers indicate more pain. For screening to week 4, pain right now was assessed 30 minutes before initial BTDS application on day 1; one hour after initial BTDS application on day 1; thereafter, once daily at approximately 8 PM for the first 4 weeks. Baseline was the last assessment prior to the first dose. For weeks 1-4, weekly averages of the pain right now scores were calculated using the sum of all available pain right now scores recorded daily during a given week divided by the number of available scores. For weeks 6-24, pain right now was measured once a week at approximately 8 PM. |
| Parent/Caregiver-assessed Global Impression of Change (PGIC) | End of treatment (week 24) or early discontinuation visit | 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 PGIC score was summarized using the number and percent of patients in each of the 7 possible response categories overall and by age group. PGIC was assessed by the parent/caregiver at the end of treatment visit or early discontinuation visit. |
Countries
United States
Participant flow
Recruitment details
First Patient First Visit: 23-July-2012; Last Patient Last Visit: 23-May-2016. The study was conducted at 33 study centers in the United States
Participants by arm
| Arm | Count |
|---|---|
| 7 to 11 Years Children 7 to 11 years of age | 6 |
| 12 to 16 Years Children 12 to 16 years of age | 35 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative | 0 | 2 |
| Overall Study | Adverse Event | 4 | 7 |
| Overall Study | Confirmed or suspected diversion | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | 12 to 16 Years | Total | 7 to 11 Years |
|---|---|---|---|
| Age, Continuous | 14.6 years STANDARD_DEVIATION 1.31 | 14.0 years STANDARD_DEVIATION 1.99 | 10.3 years STANDARD_DEVIATION 1.21 |
| Race/Ethnicity, Customized Black or African American | 15 Participants | 17 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 18 Participants | 21 Participants | 3 Participants |
| Sex: Female, Male Female | 23 Participants | 26 Participants | 3 Participants |
| Sex: Female, Male Male | 12 Participants | 15 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 35 |
| other Total, other adverse events | 6 / 6 | 20 / 35 |
| serious Total, serious adverse events | 5 / 6 | 5 / 35 |
Outcome results
Primary
Pharmacokinetics (PK) of Buprenorphine Following Transdermal Administration: Apparent Clearance (CL/F)
The population PK (PopPK) of BTDS buprenorphine in pediatric patients ages 7 to 16 years was described by a 2-compartment model with sequential zero- and first-order absorption from the patch. A fixed allometric relationship was used to describe the effects of changes in ideal body weight (IBW) across pediatric patients on all clearance and volume parameters. Given the sparse sample collections, small sample size, and complexity of the absorption process with the patch formulation, this PopPK model was fit to the pediatric data using nonlinear mixed effects modeling (NONMEM) Bayes method with selective use of priors from previous adult PopPK results. Estimates of fixed effects from the final model were used to calculate the CL/F after patch dosing given the covariate distribution in the PopPK dataset and the typical weights from children in the National Health and Nutrition Examination Survey (NHANES) dataset.
Time frame: Day 1, end of week 1, days 9/10, end of week 2, and end of week 4 or at discontinuation prior to end of study visit
Population: The full analysis population (FAP) for PK consisted of patients who received study drug and had at least 1 valid quantifiable PK blood sample (N=41).Three patients had no quantifiable plasma buprenorphine concentration measurements and were not included in the PK analysis.The final buprenorphine pediatric PK analysis dataset comprised 38 patients.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 7 to 11 Years | Pharmacokinetics (PK) of Buprenorphine Following Transdermal Administration: Apparent Clearance (CL/F) | 293 Liters/hour |
Primary
Pharmacokinetics (PK) of Buprenorphine Following Transdermal Administration: Apparent Volume of Distribution (Vc/F)
The population PK (PopPK) of BTDS buprenorphine in pediatric patients ages 7 to 16 years was described by a 2-compartment model with sequential zero- and first-order absorption from the patch. A fixed allometric relationship was used to describe the effects of changes in ideal body weight (IBW) across pediatric patients on all clearance and volume parameters. Given the sparse sample collections, small sample size, and complexity of the absorption process with the patch formulation, this PopPK model was fit to the pediatric data using nonlinear mixed effects modeling (NONMEM) Bayes method with selective use of priors from previous adult PopPK results. Estimates of fixed effects from the final model were used to calculate the Vc/F after patch dosing given the covariate distribution in the PopPK dataset and the typical weights from children in the National Health and Nutrition Examination Survey (NHANES) dataset.
Time frame: Day 1, end of week 1, days 9/10, end of week 2, and end of week 4 or at discontinuation prior to end of study visit
Population: The full analysis population (FAP) for PK consisted of patients who received study drug and had at least 1 valid quantifiable PK blood sample (N=41).Three patients had no quantifiable plasma buprenorphine concentration measurements and were not included in the PK analysis.The final buprenorphine pediatric PK analysis dataset comprised 38 patients.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 7 to 11 Years | Pharmacokinetics (PK) of Buprenorphine Following Transdermal Administration: Apparent Volume of Distribution (Vc/F) | 2350 Liters |
Primary
The Number of Participants With Adverse Events as a Measure of Safety
Safety assessments consisted of reports of AEs, vital signs (blood pressure, pulse rate, respiratory rate, and temperature), weight, hemoglobin-oxygen saturation measured by pulse oximetry (SpO2), clinical laboratory tests, somnolence (assessed by the University of Michigan Sedation Scale \[UMSS\]), conventional 12-lead electrocardiograms (ECGs), and 24-hour digital 12-lead ECGs (Holter monitor). Safety variables were summarized descriptively within age group for the safety population.
Time frame: Up to 28 weeks
Population: The safety population (N=41) was the group of patients who received at least 1 dose of study drug during the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 7 to 11 Years | The Number of Participants With Adverse Events as a Measure of Safety | Serious adverse events | 5 Participants |
| 7 to 11 Years | The Number of Participants With Adverse Events as a Measure of Safety | All other adverse events in ≥ 5% of patients | 6 Participants |
| 12 to 16 Years | The Number of Participants With Adverse Events as a Measure of Safety | Serious adverse events | 5 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 | 20 Participants |
Secondary
Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive
Pain right now was assessed using a 100-mm visual analogue scale (VAS). The 100-mm VAS is a 100-mm line with 1 end marked as no pain and the other 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. Pain right now score was defined as the distance (in mm) from the no pain end to the patient's mark; 0=no pain and bigger numbers indicate more pain. For screening to week 4, pain right now was assessed 30 minutes before initial BTDS application on day 1; one hour after initial BTDS application on day 1; thereafter, once daily at approximately 8 PM for the first 4 weeks. Baseline was the last assessment prior to the first dose. For weeks 1-4, weekly averages of the pain right now scores were calculated using the sum of all available pain right now scores recorded daily during a given week divided by the number of available scores. For weeks 6-24, pain right now was measured once a week at approximately 8 PM.
Time frame: Up to 24 weeks
Population: The FAP was the group of patients who received at least 1 dose of the study drug during the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Baseline | 46.6 units on a scale | Standard Error 4.55 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 1 | 43.1 units on a scale | Standard Error 4.03 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 2 | 41.6 units on a scale | Standard Error 4.67 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 3 | 36.0 units on a scale | Standard Error 4.82 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 4 | 34.7 units on a scale | Standard Error 5.09 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 5 | 30.3 units on a scale | Standard Error 5.9 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 6 | 28.0 units on a scale | Standard Error 6.56 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 7 | 29.1 units on a scale | Standard Error 5.56 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 8 | 34.3 units on a scale | Standard Error 7.17 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 9 | 27.3 units on a scale | Standard Error 5.83 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 10 | 36.7 units on a scale | Standard Error 5.83 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 11 | 35.7 units on a scale | Standard Error 8.15 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 12 | 42.5 units on a scale | Standard Error 8.31 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 13 | 36.0 units on a scale | Standard Error 7.99 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 14 | 38.2 units on a scale | Standard Error 8.67 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 15 | 30.5 units on a scale | Standard Error 6.52 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 16 | 38.7 units on a scale | Standard Error 6.94 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 17 | 30.9 units on a scale | Standard Error 5.74 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 18 | 37.7 units on a scale | Standard Error 6.88 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 19 | 37.4 units on a scale | Standard Error 5.5 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 20 | 35.6 units on a scale | Standard Error 7.48 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 21 | 32.4 units on a scale | Standard Error 5.97 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 22 | 38.1 units on a scale | Standard Error 5.84 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 23 | 38.7 units on a scale | Standard Error 6.42 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 12 to 16 Years, Inclusive | Week 24 | 36.5 units on a scale | Standard Error 5.35 |
Secondary
Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive
Pain right now was assessed 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 intensities are scored as 0, 2, 4, 6, 8, or 10. A score of 0=no pain, and 10=very much pain. For screening to week 4, pain right now was assessed at 30 minutes before initial BTDS application on day 1; one hour after initial BTDS application on day 1; thereafter, once daily at approximately 8 PM for the first 4 weeks. Baseline score was the last assessment prior to the first dose. For weeks 1-4, weekly averages of the pain right now scores were calculated using the sum of all available pain right now scores recorded daily during a given week divided by the number of available scores. The study measured pain right now for weeks 6-24 once a week at approximately 8 PM while on treatment; however, no patients in this age group were treated beyond week 12.
Time frame: Up to 24 weeks
Population: The full analysis population (FAP) was the group of patients who received at least 1 dose of the study drug during the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive | Baseline | 2.80 units on a scale | Standard Error 1.497 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive | Week 1 | 3.49 units on a scale | Standard Error 1.768 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive | Week 2 | 2.98 units on a scale | Standard Error 1.871 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive | Week 3 | 0.29 units on a scale | Standard Error 0 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive | Week 4 | 0.00 units on a scale | Standard Error 0 |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive | Week 5 | 0.00 units on a scale | — |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive | Week 6 | 0.00 units on a scale | — |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive | Week 7 | 0.00 units on a scale | — |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive | Week 8 | 0.00 units on a scale | — |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive | Week 9 | 0.00 units on a scale | — |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive | Week 10 | 0.00 units on a scale | — |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive | Week 11 | 0.00 units on a scale | — |
| 7 to 11 Years | Pain Right Now Assessment by Patients Aged 7 to 11 Years, Inclusive | Week 12 | 0.00 units on a scale | — |
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 PGIC score was summarized using the number and percent of patients in each of the 7 possible response categories overall and by age group. PGIC was assessed by the parent/caregiver at the end of treatment visit or early discontinuation visit.
Time frame: End of treatment (week 24) or early discontinuation visit
Population: The full analysis population (FAP) (N=40) was the group of patients who received at least 1 dose of the study drug during the study; however data was provided for only 38 patients for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 7 to 11 Years | Parent/Caregiver-assessed Global Impression of Change (PGIC) | Participants Represented | 4 Participants |
| 7 to 11 Years | Parent/Caregiver-assessed Global Impression of Change (PGIC) | 1 = Very much improved | 1 Participants |
| 7 to 11 Years | Parent/Caregiver-assessed Global Impression of Change (PGIC) | 2 = Much improved | 0 Participants |
| 7 to 11 Years | Parent/Caregiver-assessed Global Impression of Change (PGIC) | 3 = Minimally improved | 0 Participants |
| 7 to 11 Years | Parent/Caregiver-assessed Global Impression of Change (PGIC) | 4 = No change | 2 Participants |
| 7 to 11 Years | Parent/Caregiver-assessed Global Impression of Change (PGIC) | 5 = Minimally worse | 1 Participants |
| 7 to 11 Years | Parent/Caregiver-assessed Global Impression of Change (PGIC) | 6 = Much worse | 0 Participants |
| 7 to 11 Years | Parent/Caregiver-assessed Global Impression of Change (PGIC) | 7 = Very much worse | 0 Participants |
| 12 to 16 Years | Parent/Caregiver-assessed Global Impression of Change (PGIC) | 7 = Very much worse | 0 Participants |
| 12 to 16 Years | Parent/Caregiver-assessed Global Impression of Change (PGIC) | Participants Represented | 34 Participants |
| 12 to 16 Years | Parent/Caregiver-assessed Global Impression of Change (PGIC) | 4 = No change | 5 Participants |
| 12 to 16 Years | Parent/Caregiver-assessed Global Impression of Change (PGIC) | 1 = Very much improved | 6 Participants |
| 12 to 16 Years | Parent/Caregiver-assessed Global Impression of Change (PGIC) | 6 = Much worse | 1 Participants |
| 12 to 16 Years | Parent/Caregiver-assessed Global Impression of Change (PGIC) | 2 = Much improved | 12 Participants |
| 12 to 16 Years | Parent/Caregiver-assessed Global Impression of Change (PGIC) | 5 = Minimally worse | 2 Participants |
| 12 to 16 Years | Parent/Caregiver-assessed Global Impression of Change (PGIC) | 3 = Minimally improved | 8 Participants |