Clinical Trial: An Efficacy and Safety Study of Tapentadol in the Treatment of Post-operative Acute Pain Requiring Opioid Treatment in Pediatric Participants

Study Status: Suspended
Recruit Status: Suspended
Study Type: Interventional

Official Title: An Evaluation of the Efficacy and Safety of Tapentadol Oral Solution in the Treatment of Post-operative Acute Pain Requiring Opioid Treatment in Pediatric Subjects Aged Fr

Brief Summary: The purpose of the study is to evaluate the efficacy of tapentadol oral solution, based on the total amount of supplemental opioid analgesic used over 12 hours or 24 hours after initiation of investigational medicinal product in children and adolescents who have undergone surgery that would produce moderate to severe pain during opioid treatment.

Detailed Summary:

This is a randomized (the study medication is assigned by chance), multi-site, double-blind (neither physician nor participant knows the treatment that the participant receives), placebo-controlled (placebo is compared with the study medication to test whether the study medication has a real effect in clinical study), parallel group (each group of participants will be treated at the same time), and multiple oral dose study.

This study will consist of an enrollment phase (up to 28 days), a treatment and evaluation phase (4 days), and a follow-up phase (10 to 14 days after the first dose of IMP). A dose regimen of 1.25 mg/kg will be used for the first 24 hours of treatment in this study in children aged 6 months to less than 18 years old. After 24 hours after the start of study medication, and based on clinical judgment, the dose may either be continued at 1.25 mg/kg or it may be decreased to 1.0 mg/kg. A decision to maintain or alter the dose will depend on the effectiveness of the analgesia (pain killer) and the adverse event profile observed in each child over the first 24 hour dosing period. The doses for participants aged less than 6 months old will be defined based on the forthcoming pharmacokinetic (what the body does to a medication) data. The supplemental opioid medication reflecting the standard of care will be available as patient or nurse controlled intravenous morphine or hydromorphone. This supplemental opioid medication will be given to control pain, as needed, in both the treatment and placebo groups.

In exceptional cases, if a participant has unbearable pain despite using NCA/PCA, an additional bolus (defined as a clinician bolus) of morphine or hydromorphone may be administered. The clinician bolus can be given either using the NCA/PCA pump system or by an intravenous bolus injection. The opioid given as a
Sponsor: Grünenthal GmbH

Current Primary Outcome:

• For US: The total amount of supplemental opioid analgesic medication used within the first 12 hours after first intake of investigational medicinal product (IMP) [tapentadol oral solution or placebo] in participants aged from birth to less than 17 years [ Time Frame: Up to 12 hours ]
• For Europe: The total amount of supplemental opioid analgesic (pain killer) medication used within the first 24 hours after first intake of IMP in participants aged from 2 years to less than 18 years [ Time Frame: Up to 24 hours ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• The total amount of supplemental opioid analgesic medication used within the first 12 hours after the first intake of IMP in participants from 2 years to less than 18 years [ Time Frame: Up to 12 hours ]
• The total amount of supplemental opioid analgesic medication used within the first 24 hours after the first intake of IMP in participants aged from birth to less than 17 years [ Time Frame: Up to 24 hours ]
• The total amount of supplemental opioid analgesic medication received, assessed in 12 hour intervals from 24 hours to 96 hours after the first dose of IMP [ Time Frame: Up to 96 hours ]
• Palatability of IMP in participants aged 2 years to less than 18 years assessed using facial 5-point hedonic scale [ Time Frame: Up to 96 hours ]
  Palatability of IMP will be assessed using 5-point hedonic scales in combination with verbal rating. A question "How does the medication taste" will be asked and the verbal rating will be from really good, good, a bit good/a bit bad, bad, and really bad. The pictorial scale of facial expressions will be co-related with verbal rating range where 5 = really good, 4 = good, 3 = a bit good/a bit bad, 2 = bad, and 1 = really bad. Higher scores represent good palatability.
• Acceptability of IMP in participants aged 2 years to less than 18 years assessed using facial 5-point hedonic scale [ Time Frame: Up to 96 hours ]
  Acceptability of IMP will be assessed using 5-point hedonic scales in combination with verbal rating. A question "Swallowing the medication is" will be asked and the verbal rating will be from really good, good, a bit good/a bit bad, bad, and really bad. The pictorial scale of facial expressions will be co-related with verbal rating range, where 5 = really easy, 4 = easy, 3 = a bit easy/a bit difficult, 2 = difficult, and 1 = really difficult. Higher scores represent good acceptability.
• Change from baseline in the Face, Leg, Activity, Cry, and Consolability (FLACC) total score in participants aged less than 6 years [ Time Frame: Up to 96 hours ]
  The FLACC scale is used to measure the pain intensity based on 5 criteria relating to face, legs, activity, crying, and consolability. Each criteria is assigned a score of 0, 1 or 2. The total score is the sum of the 5 individual criteria. Higher scores represent worse condition.
• Change from baseline in the Faces Pain Scale-Revised (FPS-R) pain intensity score in participants aged 6 to less than 12 years [ Time Frame: Up to 96 hours ]
  The FPS-R is a validated self-reported 6-point scale with 0 representing no pain and 10 representing very much pain. Facial representations are used to indicate how much the pain hurts. Higher scores represent worse condition.
• Change from baseline in the Visual Analog Scale (VAS) pain intensity score in participants aged 12 to less than 18 years [ Time Frame: Up to 96 hours ]
  The participant will be asked to draw a single line to indicate the current level of pain intensity on 100 mm long VAS. The scoring is the distance in millimeters across the scale with 0 mm is no pain and 100 mm is worst possible pain.
• Clinical Global Impression of Change (CGIC) [ Time Frame: Day 4 ]
  The investigator rated the participant's global improvement and satisfaction with the treatment on a 7-point scale with 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. Higher scores indicate worsening.
• Patient Global Impression of Change (PGIC) [ Time Frame: Day 4 ]
  Participants verbally rated their impression of overall status on a 7-point scale with 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. Higher scores indicate worsening.
• Time to receive first and second patient or nurse controlled analgesia after the first dose of IMP [ Time Frame: Up to 96 hours ]
• Time from first dose of IMP until treatment discontinuation due to lack of efficacy [ Time Frame: Up to 72 hours ]

Original Secondary Outcome:

• The total amount of supplemental opioid analgesic medication used within the first 12 hours after the first intake of IMP in participants from 2 years to less than 18 years [ Time Frame: Up to 12 hours ]
• The total amount of supplemental opioid analgesic medication used within the first 24 hours after the first intake of IMP in participants aged from birth to less than 17 years [ Time Frame: Up to 24 hours ]
• The total amount of supplemental opioid analgesic medication received during treatment with IMP over a maximum period of 48 hours after the first dose of IMP [ Time Frame: Up to 48 hours ]
• The total amount of non-opioid analgesics used (irrespective of the indication) during the treatment period (2 days) within the first 24 hours or within the first 12 hours after the first dose of IMP [ Time Frame: Up to 12 hours or 24 hours ]
• Palatability of IMP in participants aged 3 years to less than 18 years assessed using facial 5-point hedonic scale [ Time Frame: Up to 48 hours ]
  Palatability of IMP will be assessed using 5-point hedonic scales in combination with verbal rating. A question "How does the medication taste" will be asked and the verbal rating will be from really good, good, a bit good/a bit bad, bad, and really bad. The pictorial scale of facial expressions will be co-related with verbal rating range where 5 = really good, 4 = good, 3 = a bit good/a bit bad, 2 = bad, and 1 = really bad. Higher scores represent good palatability.
• Acceptability of IMP in participants aged 3 years to less than 18 years assessed using facial 5-point hedonic scale [ Time Frame: Up to 48 hours ]
  Acceptability of IMP will be assessed using 5-point hedonic scales in combination with verbal rating. A question "Swallowing the medication is" will be asked and the verbal rating will be from really good, good, a bit good/a bit bad, bad, and really bad. The pictorial scale of facial expressions will be co-related with verbal rating range, where 5 = really easy, 4 = easy, 3 = a bit easy/a bit difficult, 2 = difficult, and 1 = really difficult. Higher scores represent good acceptability.
• Change from baseline in the Face, Leg, Activity, Cry, and Consolability (FLACC) total score in participants aged less than 3 years [ Time Frame: Up to 48 hours ]
  The FLACC scale is used to measure the pain intensity based on 5 criteria relating to face, legs, activity, crying, and consolability. Each criteria is assigned a score of 0, 1 or 2. The total score is the sum of the 5 individual criteria. Higher scores represent worse condition.
• Change from baseline in the Faces Pain Scale-Revised (FPS-R) pain intensity score in participants aged 6 to less than 12 years [ Time Frame: Up to 48 hours ]
  The FPS-R is a validated self-reported 6-point scale with 0 representing no pain and 10 representing very much pain. Facial representations are used to indicate how much the pain hurts. Higher scores represent worse condition.
• Change from baseline in the Visual Analog Scale (VAS) pain intensity score in participants aged 12 to less than 18 years [ Time Frame: Up to 48 hours ]
  The participant will be asked to draw a single line to indicate the current level of pain intensity on 100 mm long VAS. The scoring is the distance in millimeters across the scale with 0 mm is no pain and 100 mm is worst possible pain.
• Clinical Global Impression of Change (CGIC) [ Time Frame: Day 2 ]
  The investigator rated the participant's global improvement and satisfaction with the treatment on a 7-point scale with 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. Higher scores indicate worsening.
• Patient Global Impression of Change (PGIC) [ Time Frame: Day 2 ]
  Participants verbally rated their impression of overall status on a 7-point scale with 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. Higher scores indicate worsening.
• Time to receive first and second patient or nurse controlled analgesia after the first dose of IMP [ Time Frame: Up to 48 hours ]
• Time from first dose of IMP until treatment discontinuation due to lack of efficacy [ Time Frame: Up to 48 hours ]

Dates:
Date Received: March 5, 2014
Date Started: January 2015
Date Completion: December 2017
Last Updated: January 12, 2017
Last Verified: January 2017