Clinical trial NCT01729728: Pharmacokinetic, Efficacy and Safety Study of Tapentadol Oral Solution in Children With Postoperative Pain
Official title: Open-label Evaluation of the Pharmacokinetic Profile, Safety, and Efficacy of Tapentadol Oral Solution for the Treatment of Post-surgical Pain in Children and Adolescents Aged From 2 Years to Less Than 18 Years.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Postoperative Pain
Acute Pain
Keywords: Tonsillectomy
Dental surgery
Ear surgery
Nose surgery
Throat surgery
Lead sponsor: Grünenthal GmbH
Sponsor class: INDUSTRY
Collaborators: name: Janssen Research & Development, LLC
First posted: 2012-11-20
Enrollment: 86
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To find out if a drug called tapentadol administered by mouth safely relieves pain in children. Look at the amount of tapentadol in the blood after a single oral dose.

Tapentadol oral solution for children is still being tested and is not yet registered. Tapentadol tablets are effective in treating both acute and chronic pain in adults. This trial will help to understand how tapentadol oral solution works in children.

Detailed description: The lower age limit for the clinical trial was initially set to 3 years of age in the protocol. The trial planned for the inclusion of participants in three age categories. Age 3 to less than 6 years (young children), age 6 to less than 12 years (older children) and age 12 to less than 18 years of age (adolescents). There was a request by the Paediatric Committee (PDCO) at the European Medicines Agency to include participants 2 years of age (very young children). The protocol amendment thus planned to combine the two youngest age groups into a single reporting group. The protocol amendment only planned that the very young children group would have separate analysis for the Faces Pain Scale Revised (FPS-R) Scale and for the presentation of the serum concentrations, because the pharmacokinetic sampling scheme used in the 2 year old participants was different from the young children group (aged 3 to less than 6 years).

Eligibility criteria: Inclusion Criteria:

* A maximum body weight of 85.0 kg.
* A minimum body weight of 10 kg for participants aged 2 years to less than 3 years old.
* If female and post-menarchal, or 12 years or older, the subject has a negative urine pregnancy test within 24 hours before surgery.
* Having completed either dental surgery or tonsillectomy with or without adenoidectomy surgery (age group: 6 to less than 18 years of age).
* Having completed ear, nose, or throat surgery (including but not limited to tonsillectomy (age group: 2 to less than 3 years of age).
* Participant aged 6 to less than 18 years has a post-operative pain intensity score greater than or equal to 4 on the Color Analog Scale (CAS) as a result of the surgical procedure or the participant has a pain level that the usual standard of care following the surgical procedure (which reliably produces moderate to severe pain) requires opioid treatment.
* Participant aged 2 years to less than 6 years has a pain level following a surgical procedure that reliably produces moderate to severe pain, for which the usual standard of care requires opioid treatment.
* Participant is alert, orientated, and able to follow commands and complete the post-operative required procedures.

Exclusion Criteria:

* History of brain injury.
* Clinically relevant abnormal ECG.
* Clinically unstable vital signs and/or a saturation of oxygen saturation (SpO2) less than 93%. During surgery SpO2 may decrease \<93%.
* Clinically relevant abnormal values for clinical chemistry, hematology, or urinalysis at enrollment.
* Body temperature above 38.5°C within 48 hours prior to dosing.
* Positive drugs of abuse test result.

Primary outcomes:
measure: Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years).
timeFrame: up to 15 hours
measure: Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years).
timeFrame: up to 15 hours
measure: Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Older Children (Age 6 to Less Than 12 Years).
timeFrame: up to 15 hours
measure: Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Older Children (Age 6 to Less Than 12 Years).
timeFrame: up to 15 hours
measure: Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Younger Children (Age 3 to Less Than 6 Years).
timeFrame: up to 15 hours
measure: Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Younger Children (Age 3 to Less Than 6 Years).
timeFrame: up to 15 hours
measure: Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Very Young Children (Age 2 to Less Than 3 Years).
timeFrame: up to 15 hours
measure: Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Very Young Children (Age 2 to Less Than 3 Years).
timeFrame: up to 15 hours
measure: Non-Compartmental Pharmacokinetic (PK) Parameter of Tapentadol Area Under the Concentration-Time Curve (AUC 0-15) After a Single Dose of Tapentadol in Adolescent Participants (Age 12 to Less Than 18 Years).
timeFrame: up to 15 hours
measure: Non-Compartmental Pharmacokinetic (PK) Parameter: Cmax (Maximum Concentration) of Tapentadol After a Single Dose of Tapentadol in Adolescents (Age 12 to Less Than 18 Years).
timeFrame: up to 15 hours
measure: Non-Compartmental Pharmacokinetic (PK) Parameter: Time to Maximum Concentration (Tmax) of Tapentadol After a Single Dose of Tapentadol in Adolescents (Age 12 to Less Than 18 Years).
timeFrame: up to 15 hours
measure: Non-Compartmental Pharmacokinetic (PK) Parameter of Tapentadol-O-glucuronide Area Under the Concentration-Time Curve (AUC 0-15) After a Single Dose of Tapentadol in Adolescents (Age 12 to Less Than 18 Years).
timeFrame: up to 15 hours
measure: Non-Compartmental Pharmacokinetic (PK) Parameter: Cmax (Maximum Concentration) of Tapentadol-O-glucuronide After a Single Dose of Tapentadol in Adolescents (Age 12 to Less Than 18 Years).
timeFrame: up to 15 hours
measure: Non-Compartmental Pharmacokinetic (PK) Parameter: Time to Maximum Concentration (Tmax) of Tapentadol-O-glucuronide After a Single Dose of Tapentadol in Adolescents (Age 12 to Less Than 18).
timeFrame: up to 15 hours
Secondary outcomes:
measure: Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years).
timeFrame: Baseline; 15 hours
measure: Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years).
timeFrame: Baseline; 15 hours post-dose
measure: Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years.
timeFrame: Baseline; 15 hours post-dose
measure: Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years).
timeFrame: Baseline; 15 hours post-dose
measure: Sum of Pain Intensity Differences Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups
timeFrame: Baseline; 4 hours post-dose
measure: Respiratory Rate Assessments
timeFrame: Enrollment Visit; 15 hours post-dose
measure: Oxygen Saturation Assessments
timeFrame: Enrollment Visit; 15 hours post-dose
measure: Systolic and Diastolic Blood Pressure Assessments
timeFrame: Enrollment Visit; 15 hours post-dose
measure: Change From Enrollment in 12-lead Electrocardiogram Parameters
timeFrame: Enrollment (pre-surgery); Discharge Visit
measure: Change From Enrollment in 12-lead Electrocardiogram Heart Rate Parameter
timeFrame: Enrollment; Discharge Visit
measure: Treatment Emergent Adverse Events by Intensity
timeFrame: Baseline; 48 hours post dosing
measure: Intake of Additional Analgesic Medication During the Trial
timeFrame: Baseline; 15 hours post dosing
measure: Hematology Safety Laboratory Assessments: Hemoglobin Concentration
timeFrame: Enrollment Visit; Visit 2 and Discharge Visit
measure: Hematology Safety Laboratory Assessments: Hematocrit
timeFrame: Enrollment Visit; Visit 2 and Discharge Visit
measure: Hematology Safety Laboratory Assessments: Erythrocyte Mean Corpuscular Volume (Mean Corpuscular Volume)
timeFrame: Enrollment Visit; Visit 2 and Discharge Visit
measure: Hematology Safety Laboratory Assessments: Platelet Count
timeFrame: Enrollment Visit; Visit 2 and Discharge Visit
measure: Hematology Safety Laboratory Assessments: Leukocyte Concentration
timeFrame: Enrollment Visit; Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Blood Glucose Concentration
timeFrame: Enrollment Visit; Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Blood Sodium Concentration
timeFrame: Enrollment Visit; Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Blood Potassium Concentration
timeFrame: Enrollment Visit; Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Blood Calcium Concentration
timeFrame: Enrollment Visit; Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Blood Chloride Concentration
timeFrame: Enrollment Visit; Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Blood Phosphate Concentration
timeFrame: Enrollment Visit; Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Blood Urea Nitrogen (BUN) Concentration
timeFrame: Enrollment Visit; Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Creatinine Concentration
timeFrame: Enrollment Visit; Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Aspartate Aminotransferase (AST) Enzyme Activity
timeFrame: Enrollment Visit; Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Triglycerides Concentration
timeFrame: Enrollment Visit; Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Serum Albumin Concentration
timeFrame: Enrollment Visit; Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Urate in the Blood
timeFrame: Enrollment Visit; Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Calculated Glomerular Filtration Rate
timeFrame: Enrollment Visit; Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Urine Specific Gravity
timeFrame: Enrollment Visit and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Urine pH (Acid, Alkalinity) Test
timeFrame: Enrollment Visit and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Liver Function Test - Alanine Aminotransferase (ALT) Enzyme Activity
timeFrame: Enrollment Visit, Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Liver Function Test - Gamma-Glutamyl Transferase (GGT) Enzyme Activity
timeFrame: Enrollment Visit, Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Liver Function Test - Bilirubin Concentration
timeFrame: Enrollment Visit, Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Liver Function Test - Lactate Dehydrogenase (LDH) Enzyme Activity
timeFrame: Enrollment Visit, Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Blood Protein Concentration
timeFrame: Enrollment Visit, Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Creatine Kinase (CK) Enzyme Activity
timeFrame: Enrollment Visit, Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Alkaline Phosphatase (ALP) Enzyme Activity
timeFrame: Enrollment Visit, Visit 2 and Discharge Visit
measure: Biochemistry Safety Laboratory Parameters: Triacylglycerol Lipase (TL) Enzyme Activity
timeFrame: Enrollment Visit, Visit 2 and Discharge Visit
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: Jean Brown Research
state: Utah
Study officials:
affiliation: Grünenthal GmbH
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Muse D, Tarau E, Lefeber C, Sohns M, Brett M, Goldberg J, Rosenburg R. Pharmacokinetics, safety, and efficacy of tapentadol oral solution for treating moderate to severe pain in pediatric patients. J Pain Res. 2019 May 31;12:1777-1790. doi: 10.2147/JPR.S197039. eCollection 2019.