Acute Pain, Postoperative Pain
Conditions
Keywords
Tonsillectomy, Dental surgery, Ear surgery, Nose surgery, Throat surgery
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).
Interventions
DRUGTapentadol
Tapentadol oral solution single dose (1mg/kg body weight)
Sponsors
Janssen Research & Development, LLC
Grünenthal GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). | up to 15 hours | Mean and Standard Deviation of Serum Concentrations of Tapentadol. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL. |
| 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). | up to 15 hours | Mean and Standard Deviation of Serum Concentrations of Tapentadol-O-glucuronide. Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as breakdown products. The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Tapentadol-O-glucuronide concentrations were measured in participants. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 10 ng/mL. |
| 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). | up to 15 hours | Mean and Standard Deviation of Serum Concentrations of Tapentadol. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL. |
| 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). | up to 15 hours | Mean and Standard Deviation of Serum Concentrations of Tapentadol-O-glucuronide. Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as breakdown products. The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Tapentadol-O-glucuronide concentrations were measured in participants. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 10 ng/mL. |
| 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). | up to 15 hours | Mean and Standard Deviation of Serum Concentrations of Tapentadol. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL. |
| 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). | up to 15 hours | Mean and Standard Deviation of Serum Concentrations of Tapentadol-O-glucuronide. Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as breakdown products. The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Tapentadol-O-glucuronide concentrations were measured in participants. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 10 ng/mL. |
| 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). | up to 15 hours | Mean and Standard Deviation of Serum Concentrations of Tapentadol. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL. |
| 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). | up to 15 hours | Mean and Standard Deviation of Serum Concentrations of Tapentadol-O-glucuronide. Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as breakdown products. The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Tapentadol-O-glucuronide concentrations were measured in participants. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 10 ng/mL. |
| 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). | up to 15 hours | Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours. The Area Under the Curve (AUC) from dose to 15 hours (AUC 0-15) is a summary measure of data from each pharmacokinetic blood sample taken over the 15 hour time period. The area is that below the line fitted to the data points. |
| 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). | up to 15 hours | Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours. The concentration of tapentadol (active drug) is assessed during absorption and distribution. The maximum concentration is derived from the Area Under the Curve, from dose to 15 hours (AUC 0-15). It is the highest amount of active drug observed in the blood sample |
| 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). | up to 15 hours | Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. The time to maximum concentration is derived from the area under the curve from dose to 15 hours (AUC 0-15). The Tmax is the time after dosing at which the maximum concentration of the tapentadol (active drug) occurs. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours. |
| 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). | up to 15 hours | Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours. The concentration of tapentadol (active drug) is assessed during absorption and distribution. The maximum concentration is derived from the Area Under the Curve, from dose to 15 hours (AUC 0-15). It is the highest amount of active drug observed in the blood sample. |
| 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). | up to 15 hours | Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as breakdown products. The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours. The concentration of tapentadol-O-glucuronide (metabolite) is assessed to study absorption and distribution. The maximum concentration is derived from the Area Under the Curve, from dose to 15 hours (AUC 0-15). It is the highest amount of metabolite observed in the blood sample. |
| 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). | up to 15 hours | Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as breakdown products. The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. The time to maximum concentration is derived from the area under the curve from dose to 15 hours (AUC 0-15). The Tmax is the time after dosing at which the maximum concentration of the tapentadol-O-glucuronide (metabolite) occurs. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hematology Safety Laboratory Assessments: Erythrocyte Mean Corpuscular Volume (Mean Corpuscular Volume) | Enrollment Visit; Visit 2 and Discharge Visit | Erythrocyte Mean Corpuscular volume is a measurement of the average size of Red Blood Cells (RBC). It is also referred to as Mean Corpuscular Volume. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Hematology Safety Laboratory Assessments: Platelet Count | Enrollment Visit; Visit 2 and Discharge Visit | Platelets are cell fragments that are vital for normal blood clotting. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Hematology Safety Laboratory Assessments: Leukocyte Concentration | Enrollment Visit; Visit 2 and Discharge Visit | Leukocytes are also called white blood cells (WBC). These were measured to assess immune function. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Blood Glucose Concentration | Enrollment Visit; Visit 2 and Discharge Visit | A blood glucose test measures the amount of a sugar called glucose in blood. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Blood Sodium Concentration | Enrollment Visit; Visit 2 and Discharge Visit | Sodium is required by the body for the body to function properly. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Blood Potassium Concentration | Enrollment Visit; Visit 2 and Discharge Visit | Potassium is a mineral that the body needs to work normally. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Blood Calcium Concentration | Enrollment Visit; Visit 2 and Discharge Visit | All cells need calcium in order to function. In the study there were 3 planned safety blood draws for routine blood tests. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Blood Chloride Concentration | Enrollment Visit; Visit 2 and Discharge Visit | Chloride with other electrolytes help keep the proper balance of body fluids and maintain the body's acid-base balance. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care |
| Biochemistry Safety Laboratory Parameters: Blood Phosphate Concentration | Enrollment Visit; Visit 2 and Discharge Visit | Phosphate is needed by the body. This test was done to see how much phosphate is in the blood. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Blood Urea Nitrogen (BUN) Concentration | Enrollment Visit; Visit 2 and Discharge Visit | This test is to measure the amount of urea nitrogen in the blood. It was used to test liver and kidney function. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Creatinine Concentration | Enrollment Visit; Visit 2 and Discharge Visit | Creatinine is removed from the body entirely by the kidneys. If kidney function is not normal, creatinine level increases in the blood. In the study there were 3 planned safety blood draws for routine blood tests. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Aspartate Aminotransferase (AST) Enzyme Activity | Enrollment Visit; Visit 2 and Discharge Visit | AST is considered to be one of the two most important tests to detect liver injury. During liver damage the enzyme is released into the blood. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Triglycerides Concentration | Enrollment Visit; Visit 2 and Discharge Visit | Triglycerides are a group of fat. Triglycerides were measured as part of metabolic and cardiac assessments. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Serum Albumin Concentration | Enrollment Visit; Visit 2 and Discharge Visit | Albumin is a protein made by the liver. Albumin prevents fluid leaking into the tissues. Albumin also transports many small molecules. Serum albumin was measured in the clear liquid portion of the blood called serum. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Urate in the Blood | Enrollment Visit; Visit 2 and Discharge Visit | Uric acid (urate is the salt) is a chemical created when the body breaks down substances called purines. Most urate dissolves in blood and travels to the kidneys. From there, it passes out in the urine. The test is used to determine kidney function. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Calculated Glomerular Filtration Rate | Enrollment Visit; Visit 2 and Discharge Visit | Glomerular filtration rate (GFR) was done to check how well the kidneys are working. It estimates how much blood passes through the glomeruli in the kidney each minute. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Urine Specific Gravity | Enrollment Visit and Discharge Visit | This test was used to test for the water balance and urine concentration. A urine sample was tested right away. A dipstick with a color-sensitive pad was used. The color the dipstick changes and the specific gravity of the urine was read off the color chart. In the study there were 2 planned safety urine collections. At Visit 1 in the enrollment period, after consent and assent obtained. The second sample was obtained at Visit 3 prior to discharge from the hospital. The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Urine pH (Acid, Alkalinity) Test | Enrollment Visit and Discharge Visit | A urine sample was tested right away. A dipstick made with a color-sensitive pad was used. The color indicated the acidity of the urine. In the study there were 2 planned safety urine collections. At Visit 1 in the enrollment period, after consent and assent obtained. The second sample was obtained at Visit 3 prior to discharge from the hospital. The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Liver Function Test - Alanine Aminotransferase (ALT) Enzyme Activity | Enrollment Visit, Visit 2 and Discharge Visit | This test was done in combination with other tests (such as AST, ALP, and bilirubin) to diagnose and monitor the liver function. In the study there were 3 planned safety blood draws for routine blood tests. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years). | Baseline; 15 hours | At predefined times after investigational medicinal product administration, participants were asked to rate their pain on a 100 mm line (visual analog scale - VAS) by marking a point on the line in response to: My pain at this time is. The mark was scored between no pain and pain as bad as it could be. The distance was then measured by a clinician and reported. A value of 0 indicates no pain. A value of 100 indicates pain as bad as it could be. |
| Biochemistry Safety Laboratory Parameters: Liver Function Test - Bilirubin Concentration | Enrollment Visit, Visit 2 and Discharge Visit | Old red blood cells are replaced by new blood cells every day. Bilirubin is made by the body when the old blood cells are removed. The concentration of bilirubin in the blood measures liver function. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Liver Function Test - Lactate Dehydrogenase (LDH) Enzyme Activity | Enrollment Visit, Visit 2 and Discharge Visit | Lactate Dehydrogenase (LDH) was used to check for tissue damage. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Blood Protein Concentration | Enrollment Visit, Visit 2 and Discharge Visit | The test was done to verify kidney and liver function. It is done in combination with the albumin test. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Creatine Kinase (CK) Enzyme Activity | Enrollment Visit, Visit 2 and Discharge Visit | The creatine kinase (CK) test was used to detect inflammation of muscles. The test was done in combination with other tests. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Alkaline Phosphatase (ALP) Enzyme Activity | Enrollment Visit, Visit 2 and Discharge Visit | The Alkaline Phosphatase activity was used to detect bone or hepatobiliary disease. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Triacylglycerol Lipase (TL) Enzyme Activity | Enrollment Visit, Visit 2 and Discharge Visit | A triacylglycerol lipase test was done to check for pancreatic function. In the study there were 3 planned safety blood draws for routine blood tests. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to investigational medicinal product administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Biochemistry Safety Laboratory Parameters: Liver Function Test - Gamma-Glutamyl Transferase (GGT) Enzyme Activity | Enrollment Visit, Visit 2 and Discharge Visit | The gamma-glutamyl transferase (GGT) test was used in combination with the alkaline phosphatase (ALP) test. Both ALP and GGT can be elevated in bile duct or liver complications. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). | Baseline; 15 hours post-dose | Pain intensity assessments were with a 0 (no pain) to 10 (worst pain) scored McGrath color analog scale (CAS) in participants aged 6 years to less than 18 years, i.e. in Adolescents and Older Children. Participants were presented with the CAS and instructed to place the sliding bar on the color that best represented their pain intensity level at the time of assessment. The CAS is a pocket size tool used to measure the self-reported pain intensity of the older participants. The CAS consists of a 145 mm long triangular shaped strip of plastic, varying in width and hue from 1 mm wide and light pink hue at the bottom (and text no pain), to 3 mm wide and deep red hue at the top (most pain). This instrument includes 2 sides. One side shows the color pain intensity scale as described and the other shows a graduated scale, which provides a specific numeric value for the participant-reported level of pain. |
| Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. | Baseline; 15 hours post-dose | This assessment tool was used in 3 to less than 12 year old participants, i.e. Older Children and Young Children. The Faces Pain Scale (Revised) \[FPS-R\] score as allocated to a selected face by the participant. There are 6 faces and the participant is asked to indicate on a face to express how much it hurts. The numeric value 0 (no pain) to 10 (very much pain) is read off the reverse side of the scale by the clinician. |
| Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years). | Baseline; 15 hours post-dose | The Face Legs Activity Cry Consolability (FLACC) Scale was developed by the Department of Anesthesiology, University of Michigan Medical School and Health Systems. The FLACC Scale is a behavioral scale for scoring postoperative pain in children between the ages of two months and seven years or in persons unable to communicate. In this trial the scale was used in the young and very young children, i.e. in participants aged 2 to less than 6 years. This tool includes five categories of pain behaviors, including facial expression, leg movement, activity, cry, and consolability. The clinician observes the participant for 5 minutes or more and scores each category with a 0, 1 or 2. The scores are added together for a total score ranging from 0 (no pain) to 10 (worst pain). The higher the total score the higher the pain. |
| Sum of Pain Intensity Differences Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups | Baseline; 4 hours post-dose | Different pain intensity assessment tools were used in the different age groups. Therefore the sum of pain intensities were calculated and are reported for each age group based on the tool used. Adolescents - Age 12 to Less Than 18 Years. Older Children - Age 6 to Less Than 12 Years. Young Children - Age 3 to Less Than 6 Years. Very Young Children - Age 2 to Less Than 3 Years. * CAS (McGrath color analog scale) \[Theoretical Range: -40 to + 40\], * VAS (100 mm Visual Analog Scale) \[Theoretical Range: -400 to + 400\], * FPS-R (6-point Faces Pain Scale - Revised) \[Theoretical Range: -40 to + 40\], * FLACC (Face, Legs, Activity, Cry, and Consolability score) \[Theoretical Range: -40 to + 40\]. A mean score of zero indicates that there was no pain intensity change over the 4 hours. The positive values indicate that in the group as a whole the sum of all pain intensity values over the first 4 hours lead to a reduction in pain in the time period. |
| Respiratory Rate Assessments | Enrollment Visit; 15 hours post-dose | Respiratory rate assessments were performed at pre-defined times during the 15 hour period following investigational medicinal product intake. Pre-surgery data for these participants is also given from the enrollment Visit (Visit 1). |
| Oxygen Saturation Assessments | Enrollment Visit; 15 hours post-dose | Oxygen saturation assessments were performed at pre-defined times during the 15 hour period following investigational medicinal product intake. Oxygen saturation was assessed using pulse oximetry. The uppermost value is 100%. Pre-surgery data for these participants is also given from the enrollment Visit (Visit 1). |
| Systolic and Diastolic Blood Pressure Assessments | Enrollment Visit; 15 hours post-dose | Systolic and Diastolic blood pressure assessments were performed at pre-defined times during the 15 hour period following investigational medicinal product intake. Pre-surgery data for these participants is also given from the enrollment Visit (Visit 1). |
| Change From Enrollment in 12-lead Electrocardiogram Parameters | Enrollment (pre-surgery); Discharge Visit | 12-lead electrocardiograms (ECG) were part of the planned safety assessments. 12-lead Electrocardiograms were performed prior at the enrollment visit after informed consent and at the discharge visit. The discharge visit was as per standard of care. The changes in ECG parameters are reported. Negative mean values indicate that the millisecond intervals decreased from the enrollment to the discharge visit. Positive mean values indicate that the millisecond intervals increased from the enrollment to the discharge visit. The Letters P,Q,R,S and T refer to specific medically defined points on an ECG tracing and correspond to specific heart activities. |
| Change From Enrollment in 12-lead Electrocardiogram Heart Rate Parameter | Enrollment; Discharge Visit | 12-lead Electrocardiograms (ECG) were part of the planned safety assessments. 12-lead Electrocardiograms were performed prior at the enrollment visit after informed consent and at the discharge visit. The discharge visit was as per standard of care. The changes in heart rate (beats per minute) parameters are reported per treatment group between the visits. A positive value indicates that the heart rate was higher at discharge than at enrollment. |
| Treatment Emergent Adverse Events by Intensity | Baseline; 48 hours post dosing | The intensity of all treatment emergent adverse events (TEAEs) were scored by the investigator. Treatment emergent adverse events were those adverse events documented from the time of investigational medicinal product (IMP), study drug, up to 48 hours post dosing. The clinical intensity of an adverse event was classified as: * Mild: Signs and symptoms that can be easily tolerated. Symptoms can be ignored and disappear when the subject is distracted. * Moderate: Symptoms cause discomfort but are tolerable; they cannot be ignored and affect concentration. * Severe: Symptoms which affect usual daily activity. For adverse events where the intensity changes over time, the maximum intensity observed was documented. |
| Intake of Additional Analgesic Medication During the Trial | Baseline; 15 hours post dosing | Number of participants with intakes of supplemental analgesic medication between investigational medicinal product (IMP) intake and Site Discharge grouped according to preparation taken (non-opioid/opioid). |
| Hematology Safety Laboratory Assessments: Hemoglobin Concentration | Enrollment Visit; Visit 2 and Discharge Visit | The hemoglobin test is a commonly ordered blood test and was done as part of a complete blood count (CBC). It is routinely done before and after surgery to check for anemia, the presence of chronic kidney disease or other chronic medical problems. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
| Hematology Safety Laboratory Assessments: Hematocrit | Enrollment Visit; Visit 2 and Discharge Visit | Hematocrit is a blood test that measures the percentage of the volume of whole blood that is made up of red blood cells (RBC). This measurement depends on the number of red blood cells and the size of red blood cells. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care. |
Countries
United States
Participant flow
Recruitment details
The first participant was enrolled on the 15 Nov 2012 and the last participant completed the trial on the 24 Feb 2014.
Pre-assignment details
Consent was obtained for 86 participants in the trial. 66 participants were allocated and received study drug (investigational medicinal product). Pharmacokinetic data was obtained for the planned 56 participants.
Participants by arm
| Arm | Count |
|---|---|
| Adolescents Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight). | 21 |
| Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight). | 28 |
| Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight). | 17 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 6 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Adolescents | Older Children | Young and Very Young Children |
|---|---|---|---|---|
| Age, Continuous | 9.3 years STANDARD_DEVIATION 4.9 | 15.5 years STANDARD_DEVIATION 1.6 | 8.3 years STANDARD_DEVIATION 1.6 | 3.4 years STANDARD_DEVIATION 1.1 |
| Height | 136.9 centimeter STANDARD_DEVIATION 28.3 | 170.6 centimeter STANDARD_DEVIATION 10.7 | 132.9 centimeter STANDARD_DEVIATION 11.1 | 101.7 centimeter STANDARD_DEVIATION 8.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 63 Participants | 21 Participants | 27 Participants | 15 Participants |
| Region of Enrollment United States | 66 participants | 21 participants | 28 participants | 17 participants |
| Sex: Female, Male Female | 34 Participants | 9 Participants | 17 Participants | 8 Participants |
| Sex: Female, Male Male | 32 Participants | 12 Participants | 11 Participants | 9 Participants |
| Weight | 35.95 kilograms STANDARD_DEVIATION 19.36 | 61.30 kilograms STANDARD_DEVIATION 9.78 | 28.85 kilograms STANDARD_DEVIATION 5.89 | 16.34 kilograms STANDARD_DEVIATION 2.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 21 | 20 / 28 | 6 / 17 |
| serious Total, serious adverse events | 0 / 21 | 1 / 28 | 0 / 17 |
Outcome results
Primary
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).
Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours. The concentration of tapentadol (active drug) is assessed during absorption and distribution. The maximum concentration is derived from the Area Under the Curve, from dose to 15 hours (AUC 0-15). It is the highest amount of active drug observed in the blood sample
Time frame: up to 15 hours
Population: The protocol planned that this analysis would only be performed for the adolescent participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | 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). | 67.5 nanograms/millilitre | Standard Error 26.3 |
Primary
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).
Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as breakdown products. The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours. The concentration of tapentadol-O-glucuronide (metabolite) is assessed to study absorption and distribution. The maximum concentration is derived from the Area Under the Curve, from dose to 15 hours (AUC 0-15). It is the highest amount of metabolite observed in the blood sample.
Time frame: up to 15 hours
Population: The protocol planned that this analysis would only be performed for the adolescent participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | 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). | 1487 nanogramsg/millilitre | Standard Error 495 |
Primary
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).
Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours. The Area Under the Curve (AUC) from dose to 15 hours (AUC 0-15) is a summary measure of data from each pharmacokinetic blood sample taken over the 15 hour time period. The area is that below the line fitted to the data points.
Time frame: up to 15 hours
Population: The protocol planned that this analysis would only be performed for the adolescent participants.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | 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). | 302 ng*hr/mL |
Primary
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).
Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours. The concentration of tapentadol (active drug) is assessed during absorption and distribution. The maximum concentration is derived from the Area Under the Curve, from dose to 15 hours (AUC 0-15). It is the highest amount of active drug observed in the blood sample.
Time frame: up to 15 hours
Population: The protocol planned that this analysis would only be performed for the adolescent participants.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | 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). | 7082 ng*hr/mL |
Primary
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).
Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. The time to maximum concentration is derived from the area under the curve from dose to 15 hours (AUC 0-15). The Tmax is the time after dosing at which the maximum concentration of the tapentadol (active drug) occurs. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours.
Time frame: up to 15 hours
Population: The protocol planned that this analysis would only be performed for the adolescent participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | 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). | 1.4 hours | Standard Deviation 1.1 |
Primary
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).
Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as breakdown products. The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. The time to maximum concentration is derived from the area under the curve from dose to 15 hours (AUC 0-15). The Tmax is the time after dosing at which the maximum concentration of the tapentadol-O-glucuronide (metabolite) occurs. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours.
Time frame: up to 15 hours
Population: The protocol planned that this analysis would only be performed for the adolescent participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | 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). | 1.70 hours | Standard Deviation 1.19 |
Primary
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years).
Mean and Standard Deviation of Serum Concentrations of Tapentadol. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL.
Time frame: up to 15 hours
Population: Pharmacokinetic Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). | 15 minutes post-dose | 23.2 nanogram per milliliter | Standard Deviation 34 |
| Tapentadol Serum Concentrations: Adolescents | Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). | 4 hours post-dose | 32.8 nanogram per milliliter | Standard Deviation 10.8 |
| Tapentadol Serum Concentrations: Adolescents | Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). | 6 hours post-dose | 22.3 nanogram per milliliter | Standard Deviation 11.9 |
| Tapentadol Serum Concentrations: Adolescents | Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). | 30 minutes post-dose | 45.6 nanogram per milliliter | Standard Deviation 33 |
| Tapentadol Serum Concentrations: Adolescents | Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). | 1 hour post-dose | 49.4 nanogram per milliliter | Standard Deviation 21.2 |
| Tapentadol Serum Concentrations: Adolescents | Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). | 2 hours post-dose | 43.1 nanogram per milliliter | Standard Deviation 14.2 |
| Tapentadol Serum Concentrations: Adolescents | Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). | 11 hours post-dose | 8.14 nanogram per milliliter | Standard Deviation 6.35 |
| Tapentadol Serum Concentrations: Adolescents | Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). | 15 hours post-dose | 3.66 nanogram per milliliter | Standard Deviation 3.26 |
Primary
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).
Mean and Standard Deviation of Serum Concentrations of Tapentadol. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL.
Time frame: up to 15 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | 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). | 15 minutes to 1 hour post-dose (N=22) | 36.5 nanogram per milliliter | Standard Deviation 21.8 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 1 to 4 hours post-dose (N=22) | 36.5 nanogram per milliliter | Standard Deviation 15.7 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 4 to 11 hours post-dose (N=22) | 13.5 nanogram per milliliter | Standard Deviation 6.52 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 11 to 15 hours post-dose (N=22) | 3.71 nanogram per milliliter | Standard Deviation 1.96 |
Primary
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).
Mean and Standard Deviation of Serum Concentrations of Tapentadol. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL.
Time frame: up to 15 hours
Population: Pharmacokinetic Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | 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). | 1.25 hours post-dose | 19.9 nanogram per milliliter | Standard Deviation 13.2 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 3 hours post-dose | 37.7 nanogram per milliliter | Standard Deviation 18.2 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 5 hours post-dose | 23.4 nanogram per milliliter | Standard Deviation 6.36 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 8 hours post-dose | 10.0 nanogram per milliliter | Standard Deviation 4.33 |
Primary
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).
Mean and Standard Deviation of Serum Concentrations of Tapentadol. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL.
Time frame: up to 15 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | 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). | 15 minutes to 1 hour post-dose (N = 11) | 30.1 nanogram per milliliter | Standard Deviation 19.2 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 4 to 11 hours post-dose (N=11) | 26.4 nanogram per milliliter | Standard Deviation 10.7 |
Primary
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).
Mean and Standard Deviation of Serum Concentrations of Tapentadol-O-glucuronide. Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as breakdown products. The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Tapentadol-O-glucuronide concentrations were measured in participants. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 10 ng/mL.
Time frame: up to 15 hours
Population: Pharmacokinetic Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | 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). | 11 hours post-dose | 150 nanogram per milliliter | Standard Deviation 69 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 15 minutes post-dose | 404 nanogram per milliliter | Standard Deviation 581 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 30 minutes post-dose | 855 nanogram per milliliter | Standard Deviation 672 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 1 hour post-dose | 1424 nanogram per milliliter | Standard Deviation 542 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 2 hours post-dose | 1202 nanogram per milliliter | Standard Deviation 366 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 4 hours post-dose | 824 nanogram per milliliter | Standard Deviation 191 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 6 hours post-dose | 497 nanogram per milliliter | Standard Deviation 138 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 15 hours post-dose | 66.9 nanogram per milliliter | Standard Deviation 35.4 |
Primary
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).
Mean and Standard Deviation of Serum Concentrations of Tapentadol-O-glucuronide. Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as breakdown products. The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Tapentadol-O-glucuronide concentrations were measured in participants. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 10 ng/mL.
Time frame: up to 15 hours
Population: Pharmacokinetic Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | 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). | 15 minutes to 1 hour post-dose | 676 nanogram per milliliter | Standard Deviation 343 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 1 to 4 hours post-dose | 900 nanogram per milliliter | Standard Deviation 330 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 4 to 11 hours post-dose | 321 nanogram per milliliter | Standard Deviation 123 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 11 to 15 hours post-dose | 86.3 nanogram per milliliter | Standard Deviation 37.8 |
Primary
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).
Mean and Standard Deviation of Serum Concentrations of Tapentadol-O-glucuronide. Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as breakdown products. The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Tapentadol-O-glucuronide concentrations were measured in participants. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 10 ng/mL.
Time frame: up to 15 hours
Population: Pharmacokinetic Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | 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). | 1.25 hours after administration | 497 nanogram per milliliter | Standard Deviation 513 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 3 hours after administration | 938 nanogram per milliliter | Standard Deviation 407 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 5 hours after administration | 624 nanogram per milliliter | Standard Deviation 235 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 8 hours after administration | 253 nanogram per milliliter | Standard Deviation 103 |
Primary
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).
Mean and Standard Deviation of Serum Concentrations of Tapentadol-O-glucuronide. Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as breakdown products. The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Tapentadol-O-glucuronide concentrations were measured in participants. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 10 ng/mL.
Time frame: up to 15 hours
Population: Pharmacokinetic Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | 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). | 15 minutes to 1 hour post-dose | 494 nanogram per milliliter | Standard Deviation 377 |
| Tapentadol Serum Concentrations: Adolescents | 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). | 4 to 11 hours post-dose | 504 nanogram per milliliter | Standard Deviation 112 |
Secondary
Biochemistry Safety Laboratory Parameters: Alkaline Phosphatase (ALP) Enzyme Activity
The Alkaline Phosphatase activity was used to detect bone or hepatobiliary disease. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit, Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 2 and 3: N=20 one participant with missing data; Young and Very Young Children Group at Visits 3: N=16 one participant with missing data at this visit).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Alkaline Phosphatase (ALP) Enzyme Activity | Visit 2 | 114.7 U/L | Standard Deviation 53.9 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Alkaline Phosphatase (ALP) Enzyme Activity | Visit 3 | 107.6 U/L | Standard Deviation 54.3 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Alkaline Phosphatase (ALP) Enzyme Activity | Visit 1 | 124.7 U/L | Standard Deviation 62.7 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Alkaline Phosphatase (ALP) Enzyme Activity | Visit 2 | 207.5 U/L | Standard Deviation 42.2 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Alkaline Phosphatase (ALP) Enzyme Activity | Visit 1 | 240.0 U/L | Standard Deviation 50.8 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Alkaline Phosphatase (ALP) Enzyme Activity | Visit 3 | 204.1 U/L | Standard Deviation 46.7 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Alkaline Phosphatase (ALP) Enzyme Activity | Visit 1 | 230.1 U/L | Standard Deviation 26.7 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Alkaline Phosphatase (ALP) Enzyme Activity | Visit 3 | 199.2 U/L | Standard Deviation 26.2 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Alkaline Phosphatase (ALP) Enzyme Activity | Visit 2 | 210.2 U/L | Standard Deviation 31.5 |
Secondary
Biochemistry Safety Laboratory Parameters: Aspartate Aminotransferase (AST) Enzyme Activity
AST is considered to be one of the two most important tests to detect liver injury. During liver damage the enzyme is released into the blood. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit; Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Older children at Visits 2 and 3: N=26 two participants with missing data; Young and Very Young Children Group at Visits 1 and 3: N=16 one participant with missing data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Aspartate Aminotransferase (AST) Enzyme Activity | Visit 2 | 21.6 U/L | Standard Deviation 4.5 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Aspartate Aminotransferase (AST) Enzyme Activity | Visit 1 | 21.5 U/L | Standard Deviation 5.1 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Aspartate Aminotransferase (AST) Enzyme Activity | Visit 3 | 21.6 U/L | Standard Deviation 12.9 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Aspartate Aminotransferase (AST) Enzyme Activity | Visit 2 | 29.9 U/L | Standard Deviation 5.1 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Aspartate Aminotransferase (AST) Enzyme Activity | Visit 1 | 27.9 U/L | Standard Deviation 6.5 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Aspartate Aminotransferase (AST) Enzyme Activity | Visit 3 | 30.2 U/L | Standard Deviation 7.2 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Aspartate Aminotransferase (AST) Enzyme Activity | Visit 1 | 33.4 U/L | Standard Deviation 3.8 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Aspartate Aminotransferase (AST) Enzyme Activity | Visit 3 | 33.8 U/L | Standard Deviation 4.4 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Aspartate Aminotransferase (AST) Enzyme Activity | Visit 2 | 37.9 U/L | Standard Deviation 7.5 |
Secondary
Biochemistry Safety Laboratory Parameters: Blood Calcium Concentration
All cells need calcium in order to function. In the study there were 3 planned safety blood draws for routine blood tests. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit; Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Older children Group at Visit 2: N=27 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Calcium Concentration | Visit 2 | 2.268 mmol/L | Standard Deviation 0.166 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Calcium Concentration | Visit 1 | 2.455 mmol/L | Standard Deviation 0.065 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Calcium Concentration | Visit 3 | 2.359 mmol/L | Standard Deviation 0.104 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Calcium Concentration | Visit 2 | 2.267 mmol/L | Standard Deviation 0.108 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Calcium Concentration | Visit 1 | 2.482 mmol/L | Standard Deviation 0.1 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Calcium Concentration | Visit 3 | 2.266 mmol/L | Standard Deviation 0.157 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Calcium Concentration | Visit 1 | 2.519 mmol/L | Standard Deviation 0.055 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Calcium Concentration | Visit 3 | 2.369 mmol/L | Standard Deviation 0.123 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Calcium Concentration | Visit 2 | 2.343 mmol/L | Standard Deviation 0.16 |
Secondary
Biochemistry Safety Laboratory Parameters: Blood Chloride Concentration
Chloride with other electrolytes help keep the proper balance of body fluids and maintain the body's acid-base balance. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care
Time frame: Enrollment Visit; Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Older children Group at Visit 2: N=27 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Chloride Concentration | Visit 2 | 106.6 mmol/L | Standard Deviation 2.2 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Chloride Concentration | Visit 1 | 103.3 mmol/L | Standard Deviation 1.9 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Chloride Concentration | Visit 3 | 103.0 mmol/L | Standard Deviation 2.2 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Chloride Concentration | Visit 2 | 104.9 mmol/L | Standard Deviation 2.8 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Chloride Concentration | Visit 1 | 103.4 mmol/L | Standard Deviation 2.2 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Chloride Concentration | Visit 3 | 105.1 mmol/L | Standard Deviation 2.6 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Chloride Concentration | Visit 1 | 103.8 mmol/L | Standard Deviation 1.7 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Chloride Concentration | Visit 3 | 105.1 mmol/L | Standard Deviation 2.4 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Chloride Concentration | Visit 2 | 106.2 mmol/L | Standard Deviation 3 |
Secondary
Biochemistry Safety Laboratory Parameters: Blood Glucose Concentration
A blood glucose test measures the amount of a sugar called glucose in blood. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit; Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Glucose Concentration | Visit 2 | 5.10 mmol/L | Standard Deviation 0.68 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Glucose Concentration | Visit 1 | 4.77 mmol/L | Standard Deviation 0.51 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Glucose Concentration | Visit 3 | 5.51 mmol/L | Standard Deviation 0.9 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Glucose Concentration | Visit 2 | 6.39 mmol/L | Standard Deviation 1.49 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Glucose Concentration | Visit 1 | 4.81 mmol/L | Standard Deviation 0.52 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Glucose Concentration | Visit 3 | 5.69 mmol/L | Standard Deviation 1.21 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Glucose Concentration | Visit 1 | 5.01 mmol/L | Standard Deviation 1.38 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Glucose Concentration | Visit 3 | 4.90 mmol/L | Standard Deviation 0.54 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Glucose Concentration | Visit 2 | 5.89 mmol/L | Standard Deviation 1.17 |
Secondary
Biochemistry Safety Laboratory Parameters: Blood Phosphate Concentration
Phosphate is needed by the body. This test was done to see how much phosphate is in the blood. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit; Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Phosphate Concentration | Visit 2 | 1.234 mmol/L | Standard Deviation 0.194 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Phosphate Concentration | Visit 1 | 1.384 mmol/L | Standard Deviation 0.185 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Phosphate Concentration | Visit 3 | 1.500 mmol/L | Standard Deviation 0.199 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Phosphate Concentration | Visit 2 | 1.248 mmol/L | Standard Deviation 0.241 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Phosphate Concentration | Visit 1 | 1.560 mmol/L | Standard Deviation 0.146 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Phosphate Concentration | Visit 3 | 1.535 mmol/L | Standard Deviation 0.178 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Phosphate Concentration | Visit 1 | 1.689 mmol/L | Standard Deviation 0.165 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Phosphate Concentration | Visit 3 | 1.611 mmol/L | Standard Deviation 0.181 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Phosphate Concentration | Visit 2 | 1.412 mmol/L | Standard Deviation 0.179 |
Secondary
Biochemistry Safety Laboratory Parameters: Blood Potassium Concentration
Potassium is a mineral that the body needs to work normally. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit; Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Potassium Concentration | Visit 2 | 3.90 mmol/L | Standard Deviation 0.36 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Potassium Concentration | Visit 1 | 4.20 mmol/L | Standard Deviation 0.31 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Potassium Concentration | Visit 3 | 3.94 mmol/L | Standard Deviation 0.26 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Potassium Concentration | Visit 2 | 3.83 mmol/L | Standard Deviation 0.32 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Potassium Concentration | Visit 1 | 4.20 mmol/L | Standard Deviation 0.32 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Potassium Concentration | Visit 3 | 3.93 mmol/L | Standard Deviation 0.29 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Potassium Concentration | Visit 1 | 4.09 mmol/L | Standard Deviation 0.33 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Potassium Concentration | Visit 3 | 3.93 mmol/L | Standard Deviation 0.27 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Potassium Concentration | Visit 2 | 4.04 mmol/L | Standard Deviation 0.36 |
Secondary
Biochemistry Safety Laboratory Parameters: Blood Protein Concentration
The test was done to verify kidney and liver function. It is done in combination with the albumin test. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit, Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Older Children at Visit 2: N=27 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Protein Concentration | Visit 2 | 64.2 g/L | Standard Deviation 4.6 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Protein Concentration | Visit 1 | 72.3 g/L | Standard Deviation 3.5 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Protein Concentration | Visit 3 | 64.9 g/L | Standard Deviation 4.4 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Protein Concentration | Visit 2 | 61.8 g/L | Standard Deviation 4.4 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Protein Concentration | Visit 1 | 73.3 g/L | Standard Deviation 4.4 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Protein Concentration | Visit 3 | 62.1 g/L | Standard Deviation 5.5 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Protein Concentration | Visit 1 | 68.6 g/L | Standard Deviation 4.7 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Protein Concentration | Visit 3 | 61.8 g/L | Standard Deviation 4.6 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Protein Concentration | Visit 2 | 62.1 g/L | Standard Deviation 4.9 |
Secondary
Biochemistry Safety Laboratory Parameters: Blood Sodium Concentration
Sodium is required by the body for the body to function properly. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit; Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Sodium Concentration | Visit 2 | 140.3 mmol/L | Standard Deviation 1.5 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Sodium Concentration | Visit 1 | 140.9 mmol/L | Standard Deviation 1.4 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Sodium Concentration | Visit 3 | 138.1 mmol/L | Standard Deviation 1.2 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Sodium Concentration | Visit 3 | 138.7 mmol/L | Standard Deviation 1.8 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Sodium Concentration | Visit 2 | 138.4 mmol/L | Standard Deviation 2.6 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Sodium Concentration | Visit 1 | 140.4 mmol/L | Standard Deviation 2.1 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Sodium Concentration | Visit 1 | 139.3 mmol/L | Standard Deviation 1.3 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Sodium Concentration | Visit 2 | 139.1 mmol/L | Standard Deviation 1.2 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Sodium Concentration | Visit 3 | 138.8 mmol/L | Standard Deviation 1.9 |
Secondary
Biochemistry Safety Laboratory Parameters: Blood Urea Nitrogen (BUN) Concentration
This test is to measure the amount of urea nitrogen in the blood. It was used to test liver and kidney function. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit; Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Urea Nitrogen (BUN) Concentration | Visit 2 | 4.54 mmol/L | Standard Deviation 1.32 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Urea Nitrogen (BUN) Concentration | Visit 1 | 4.55 mmol/L | Standard Deviation 1.19 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Blood Urea Nitrogen (BUN) Concentration | Visit 3 | 3.88 mmol/L | Standard Deviation 0.98 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Urea Nitrogen (BUN) Concentration | Visit 2 | 4.38 mmol/L | Standard Deviation 0.95 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Urea Nitrogen (BUN) Concentration | Visit 1 | 4.47 mmol/L | Standard Deviation 1.3 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Blood Urea Nitrogen (BUN) Concentration | Visit 3 | 4.31 mmol/L | Standard Deviation 1.21 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Urea Nitrogen (BUN) Concentration | Visit 1 | 5.15 mmol/L | Standard Deviation 1.19 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Urea Nitrogen (BUN) Concentration | Visit 3 | 4.11 mmol/L | Standard Deviation 0.82 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Blood Urea Nitrogen (BUN) Concentration | Visit 2 | 4.19 mmol/L | Standard Deviation 0.93 |
Secondary
Biochemistry Safety Laboratory Parameters: Calculated Glomerular Filtration Rate
Glomerular filtration rate (GFR) was done to check how well the kidneys are working. It estimates how much blood passes through the glomeruli in the kidney each minute. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit; Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Calculated Glomerular Filtration Rate | Visit 2 | 146.6 mL/min/1.73m^2 | Standard Deviation 25.2 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Calculated Glomerular Filtration Rate | Visit 1 | 133.6 mL/min/1.73m^2 | Standard Deviation 20.7 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Calculated Glomerular Filtration Rate | Visit 3 | 142.6 mL/min/1.73m^2 | Standard Deviation 23.3 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Calculated Glomerular Filtration Rate | Visit 2 | 155.1 mL/min/1.73m^2 | Standard Deviation 38 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Calculated Glomerular Filtration Rate | Visit 1 | 133.9 mL/min/1.73m^2 | Standard Deviation 16.6 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Calculated Glomerular Filtration Rate | Visit 3 | 158.7 mL/min/1.73m^2 | Standard Deviation 31.5 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Calculated Glomerular Filtration Rate | Visit 1 | 141.5 mL/min/1.73m^2 | Standard Deviation 18.4 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Calculated Glomerular Filtration Rate | Visit 3 | 164.0 mL/min/1.73m^2 | Standard Deviation 37.3 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Calculated Glomerular Filtration Rate | Visit 2 | 166.9 mL/min/1.73m^2 | Standard Deviation 42.5 |
Secondary
Biochemistry Safety Laboratory Parameters: Creatine Kinase (CK) Enzyme Activity
The creatine kinase (CK) test was used to detect inflammation of muscles. The test was done in combination with other tests. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit, Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Older children at Visit 1: N=27 (1 participant missing); Young and Very Young Children Group at Visit 3: N=16 one participant with missing data at this visit).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Creatine Kinase (CK) Enzyme Activity | Visit 1 | 126.0 U/L | Standard Deviation 66 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Creatine Kinase (CK) Enzyme Activity | Visit 3 | 264.6 U/L | Standard Deviation 564.4 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Creatine Kinase (CK) Enzyme Activity | Visit 2 | 186.8 U/L | Standard Deviation 216.2 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Creatine Kinase (CK) Enzyme Activity | Visit 1 | 109.8 U/L | Standard Deviation 31.7 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Creatine Kinase (CK) Enzyme Activity | Visit 2 | 283.3 U/L | Standard Deviation 158.5 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Creatine Kinase (CK) Enzyme Activity | Visit 3 | 288.1 U/L | Standard Deviation 214.8 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Creatine Kinase (CK) Enzyme Activity | Visit 3 | 203.6 U/L | Standard Deviation 84.5 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Creatine Kinase (CK) Enzyme Activity | Visit 2 | 275.8 U/L | Standard Deviation 87.5 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Creatine Kinase (CK) Enzyme Activity | Visit 1 | 133.4 U/L | Standard Deviation 35.2 |
Secondary
Biochemistry Safety Laboratory Parameters: Creatinine Concentration
Creatinine is removed from the body entirely by the kidneys. If kidney function is not normal, creatinine level increases in the blood. In the study there were 3 planned safety blood draws for routine blood tests. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit; Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Creatinine Concentration | Visit 2 | 67.8 µmol/L | Standard Deviation 15.1 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Creatinine Concentration | Visit 1 | 73.3 µmol/L | Standard Deviation 14.7 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Creatinine Concentration | Visit 3 | 68.6 µmol/L | Standard Deviation 16.2 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Creatinine Concentration | Visit 2 | 44.1 µmol/L | Standard Deviation 9.3 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Creatinine Concentration | Visit 1 | 49.5 µmol/L | Standard Deviation 6.2 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Creatinine Concentration | Visit 3 | 41.5 µmol/L | Standard Deviation 8 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Creatinine Concentration | Visit 1 | 35.6 µmol/L | Standard Deviation 4.8 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Creatinine Concentration | Visit 3 | 33.0 µmol/L | Standard Deviation 5.8 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Creatinine Concentration | Visit 2 | 31.6 µmol/L | Standard Deviation 6.7 |
Secondary
Biochemistry Safety Laboratory Parameters: Liver Function Test - Alanine Aminotransferase (ALT) Enzyme Activity
This test was done in combination with other tests (such as AST, ALP, and bilirubin) to diagnose and monitor the liver function. In the study there were 3 planned safety blood draws for routine blood tests. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit, Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=19 two participants with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Liver Function Test - Alanine Aminotransferase (ALT) Enzyme Activity | Visit 2 | 14.1 U/L | Standard Deviation 4.6 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Liver Function Test - Alanine Aminotransferase (ALT) Enzyme Activity | Visit 1 | 16.2 U/L | Standard Deviation 6.3 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Liver Function Test - Alanine Aminotransferase (ALT) Enzyme Activity | Visit 3 | 14.2 U/L | Standard Deviation 4.5 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Alanine Aminotransferase (ALT) Enzyme Activity | Visit 2 | 15.7 U/L | Standard Deviation 3.4 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Alanine Aminotransferase (ALT) Enzyme Activity | Visit 1 | 15.9 U/L | Standard Deviation 4.1 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Alanine Aminotransferase (ALT) Enzyme Activity | Visit 3 | 15.4 U/L | Standard Deviation 3.4 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Alanine Aminotransferase (ALT) Enzyme Activity | Visit 1 | 16.4 U/L | Standard Deviation 3.4 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Alanine Aminotransferase (ALT) Enzyme Activity | Visit 3 | 17.1 U/L | Standard Deviation 4.1 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Alanine Aminotransferase (ALT) Enzyme Activity | Visit 2 | 17.9 U/L | Standard Deviation 5.3 |
Secondary
Biochemistry Safety Laboratory Parameters: Liver Function Test - Bilirubin Concentration
Old red blood cells are replaced by new blood cells every day. Bilirubin is made by the body when the old blood cells are removed. The concentration of bilirubin in the blood measures liver function. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit, Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents-Visit 2 \& 3: N=20 - 1 participant with data missing; Older Children-Visit 1 \& 2: N=26 thus 2 participants with data missing; Young and Very Young Children-Visits 1 \& 3: N=12 (5 with data missing) \& at Visit 2 N=9 (8 with data missing).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Liver Function Test - Bilirubin Concentration | Visit 2 | 10.9 µmol/L | Standard Deviation 7.8 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Liver Function Test - Bilirubin Concentration | Visit 1 | 12.0 µmol/L | Standard Deviation 7 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Liver Function Test - Bilirubin Concentration | Visit 3 | 17.8 µmol/L | Standard Deviation 10.8 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Bilirubin Concentration | Visit 2 | 6.3 µmol/L | Standard Deviation 2.3 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Bilirubin Concentration | Visit 1 | 6.8 µmol/L | Standard Deviation 3.5 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Bilirubin Concentration | Visit 3 | 9.3 µmol/L | Standard Deviation 4.5 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Bilirubin Concentration | Visit 1 | 4.8 µmol/L | Standard Deviation 1.8 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Bilirubin Concentration | Visit 3 | 5.8 µmol/L | Standard Deviation 2.6 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Bilirubin Concentration | Visit 2 | 3.7 µmol/L | Standard Deviation 1 |
Secondary
Biochemistry Safety Laboratory Parameters: Liver Function Test - Gamma-Glutamyl Transferase (GGT) Enzyme Activity
The gamma-glutamyl transferase (GGT) test was used in combination with the alkaline phosphatase (ALP) test. Both ALP and GGT can be elevated in bile duct or liver complications. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit, Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 2 and 3: N=20 one participant with missing data; Older Children at Visit 2: N=27 one participant with missing data; Young and Very Young Children Group at Visit 2: N=16 one participant with missing data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Liver Function Test - Gamma-Glutamyl Transferase (GGT) Enzyme Activity | Visit 1 | 12.0 U/L | Standard Deviation 4 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Liver Function Test - Gamma-Glutamyl Transferase (GGT) Enzyme Activity | Visit 3 | 10.8 U/L | Standard Deviation 4.2 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Liver Function Test - Gamma-Glutamyl Transferase (GGT) Enzyme Activity | Visit 2 | 10.4 U/L | Standard Deviation 3.9 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Gamma-Glutamyl Transferase (GGT) Enzyme Activity | Visit 1 | 10.6 U/L | Standard Deviation 2.9 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Gamma-Glutamyl Transferase (GGT) Enzyme Activity | Visit 2 | 8.7 U/L | Standard Deviation 2 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Gamma-Glutamyl Transferase (GGT) Enzyme Activity | Visit 3 | 8.8 U/L | Standard Deviation 1.9 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Gamma-Glutamyl Transferase (GGT) Enzyme Activity | Visit 3 | 8.3 U/L | Standard Deviation 2 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Gamma-Glutamyl Transferase (GGT) Enzyme Activity | Visit 2 | 8.6 U/L | Standard Deviation 1.9 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Gamma-Glutamyl Transferase (GGT) Enzyme Activity | Visit 1 | 9.4 U/L | Standard Deviation 1.7 |
Secondary
Biochemistry Safety Laboratory Parameters: Liver Function Test - Lactate Dehydrogenase (LDH) Enzyme Activity
Lactate Dehydrogenase (LDH) was used to check for tissue damage. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit, Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Older Children at Visits 1 and 3: N=26 and at Visit 2 N=24 participants; Young and Very Young Children Group at Visits 1 and 3: N=16 participant with missing data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Liver Function Test - Lactate Dehydrogenase (LDH) Enzyme Activity | Visit 2 | 154.5 U/L | Standard Deviation 27.9 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Liver Function Test - Lactate Dehydrogenase (LDH) Enzyme Activity | Visit 1 | 157.7 U/L | Standard Deviation 23 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Liver Function Test - Lactate Dehydrogenase (LDH) Enzyme Activity | Visit 3 | 143.9 U/L | Standard Deviation 28.8 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Lactate Dehydrogenase (LDH) Enzyme Activity | Visit 2 | 199.1 U/L | Standard Deviation 27.2 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Lactate Dehydrogenase (LDH) Enzyme Activity | Visit 1 | 210.5 U/L | Standard Deviation 31.7 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Lactate Dehydrogenase (LDH) Enzyme Activity | Visit 3 | 197.8 U/L | Standard Deviation 28.5 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Lactate Dehydrogenase (LDH) Enzyme Activity | Visit 1 | 243.8 U/L | Standard Deviation 23.3 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Lactate Dehydrogenase (LDH) Enzyme Activity | Visit 3 | 238.6 U/L | Standard Deviation 24.6 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Liver Function Test - Lactate Dehydrogenase (LDH) Enzyme Activity | Visit 2 | 256.3 U/L | Standard Deviation 36.8 |
Secondary
Biochemistry Safety Laboratory Parameters: Serum Albumin Concentration
Albumin is a protein made by the liver. Albumin prevents fluid leaking into the tissues. Albumin also transports many small molecules. Serum albumin was measured in the clear liquid portion of the blood called serum. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit; Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Older children N=27 at Visit 1; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Serum Albumin Concentration | Visit 2 | 38.4 g/L | Standard Deviation 3.1 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Serum Albumin Concentration | Visit 1 | 43.4 g/L | Standard Deviation 2.5 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Serum Albumin Concentration | Visit 3 | 38.4 g/L | Standard Deviation 2.8 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Serum Albumin Concentration | Visit 2 | 37.1 g/L | Standard Deviation 2.5 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Serum Albumin Concentration | Visit 1 | 43.4 g/L | Standard Deviation 3 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Serum Albumin Concentration | Visit 3 | 37.2 g/L | Standard Deviation 3.5 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Serum Albumin Concentration | Visit 1 | 42.6 g/L | Standard Deviation 2.4 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Serum Albumin Concentration | Visit 3 | 37.5 g/L | Standard Deviation 3.3 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Serum Albumin Concentration | Visit 2 | 38.9 g/L | Standard Deviation 3.4 |
Secondary
Biochemistry Safety Laboratory Parameters: Triacylglycerol Lipase (TL) Enzyme Activity
A triacylglycerol lipase test was done to check for pancreatic function. In the study there were 3 planned safety blood draws for routine blood tests. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to investigational medicinal product administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit, Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Older Children N=27 at Visit 1 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data at visit).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Triacylglycerol Lipase (TL) Enzyme Activity | Visit 1 | 29.5 U/L | Standard Deviation 10.5 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Triacylglycerol Lipase (TL) Enzyme Activity | Visit 3 | 24.8 U/L | Standard Deviation 18.3 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Triacylglycerol Lipase (TL) Enzyme Activity | Visit 2 | 22.7 U/L | Standard Deviation 8.3 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Triacylglycerol Lipase (TL) Enzyme Activity | Visit 2 | 22.6 U/L | Standard Deviation 8.8 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Triacylglycerol Lipase (TL) Enzyme Activity | Visit 3 | 22.2 U/L | Standard Deviation 9.2 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Triacylglycerol Lipase (TL) Enzyme Activity | Visit 1 | 30.3 U/L | Standard Deviation 9.4 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Triacylglycerol Lipase (TL) Enzyme Activity | Visit 2 | 19.6 U/L | Standard Deviation 6.3 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Triacylglycerol Lipase (TL) Enzyme Activity | Visit 3 | 19.3 U/L | Standard Deviation 6 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Triacylglycerol Lipase (TL) Enzyme Activity | Visit 1 | 26.3 U/L | Standard Deviation 8.7 |
Secondary
Biochemistry Safety Laboratory Parameters: Triglycerides Concentration
Triglycerides are a group of fat. Triglycerides were measured as part of metabolic and cardiac assessments. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit; Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant data missing; Older children Visits 2 and 3: N=27 and N=26 one and two participant data missing; Young and Very Young Children Group at Visits 2 and 3: N=16 one participant data missing).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Triglycerides Concentration | Visit 3 | 0.634 mmol/L | Standard Deviation 0.224 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Triglycerides Concentration | Visit 2 | 0.666 mmol/L | Standard Deviation 0.318 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Triglycerides Concentration | Visit 1 | 1.118 mmol/L | Standard Deviation 0.459 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Triglycerides Concentration | Visit 2 | 0.499 mmol/L | Standard Deviation 0.245 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Triglycerides Concentration | Visit 1 | 1.129 mmol/L | Standard Deviation 0.495 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Triglycerides Concentration | Visit 3 | 0.646 mmol/L | Standard Deviation 0.225 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Triglycerides Concentration | Visit 1 | 1.223 mmol/L | Standard Deviation 0.511 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Triglycerides Concentration | Visit 3 | 0.789 mmol/L | Standard Deviation 0.227 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Triglycerides Concentration | Visit 2 | 0.556 mmol/L | Standard Deviation 0.173 |
Secondary
Biochemistry Safety Laboratory Parameters: Urate in the Blood
Uric acid (urate is the salt) is a chemical created when the body breaks down substances called purines. Most urate dissolves in blood and travels to the kidneys. From there, it passes out in the urine. The test is used to determine kidney function. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit; Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Urate in the Blood | Visit 2 | 305.57 µmol/L | Standard Deviation 85.12 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Urate in the Blood | Visit 1 | 301.62 µmol/L | Standard Deviation 69.35 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Urate in the Blood | Visit 3 | 291.45 µmol/L | Standard Deviation 69.06 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Urate in the Blood | Visit 2 | 225.39 µmol/L | Standard Deviation 44.74 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Urate in the Blood | Visit 1 | 228.32 µmol/L | Standard Deviation 41.87 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Urate in the Blood | Visit 3 | 213.68 µmol/L | Standard Deviation 57.96 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Urate in the Blood | Visit 1 | 214.82 µmol/L | Standard Deviation 39.67 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Urate in the Blood | Visit 3 | 195.94 µmol/L | Standard Deviation 48.68 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Urate in the Blood | Visit 2 | 205.65 µmol/L | Standard Deviation 34.51 |
Secondary
Biochemistry Safety Laboratory Parameters: Urine pH (Acid, Alkalinity) Test
A urine sample was tested right away. A dipstick made with a color-sensitive pad was used. The color indicated the acidity of the urine. In the study there were 2 planned safety urine collections. At Visit 1 in the enrollment period, after consent and assent obtained. The second sample was obtained at Visit 3 prior to discharge from the hospital. The discharge visit was as per standard of care.
Time frame: Enrollment Visit and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Young and Very Young Children Group at Visits 1: N=9 thus 8 participants with missing data; at Visit 3: N=7 thus 10 participants with missing data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Urine pH (Acid, Alkalinity) Test | Visit 1 | 6.2 units on a scale | Standard Deviation 0.5 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Urine pH (Acid, Alkalinity) Test | Visit 3 | 6.1 units on a scale | Standard Deviation 0.2 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Urine pH (Acid, Alkalinity) Test | Visit 1 | 6.5 units on a scale | Standard Deviation 0.4 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Urine pH (Acid, Alkalinity) Test | Visit 3 | 6.2 units on a scale | Standard Deviation 0.4 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Urine pH (Acid, Alkalinity) Test | Visit 1 | 6.2 units on a scale | Standard Deviation 0.6 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Urine pH (Acid, Alkalinity) Test | Visit 3 | 6.4 units on a scale | Standard Deviation 0.9 |
Secondary
Biochemistry Safety Laboratory Parameters: Urine Specific Gravity
This test was used to test for the water balance and urine concentration. A urine sample was tested right away. A dipstick with a color-sensitive pad was used. The color the dipstick changes and the specific gravity of the urine was read off the color chart. In the study there were 2 planned safety urine collections. At Visit 1 in the enrollment period, after consent and assent obtained. The second sample was obtained at Visit 3 prior to discharge from the hospital. The discharge visit was as per standard of care.
Time frame: Enrollment Visit and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Young and Very Young Children Group at Visits 1: N=9 thus 8 participants with missing data; at Visit 3: N=7 thus 10 participants with missing data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Urine Specific Gravity | Visit 1 | 1.025 units on a scale | Standard Deviation 0.007 |
| Tapentadol Serum Concentrations: Adolescents | Biochemistry Safety Laboratory Parameters: Urine Specific Gravity | Visit 3 | 1.022 units on a scale | Standard Deviation 0.007 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Urine Specific Gravity | Visit 1 | 1.024 units on a scale | Standard Deviation 0.004 |
| McGrath Color Analog Scale: Older Children | Biochemistry Safety Laboratory Parameters: Urine Specific Gravity | Visit 3 | 1.024 units on a scale | Standard Deviation 0.004 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Urine Specific Gravity | Visit 1 | 1.021 units on a scale | Standard Deviation 0.007 |
| Respiratory Rates: Young and Very Young Children | Biochemistry Safety Laboratory Parameters: Urine Specific Gravity | Visit 3 | 1.024 units on a scale | Standard Deviation 0.002 |
Secondary
Change From Enrollment in 12-lead Electrocardiogram Heart Rate Parameter
12-lead Electrocardiograms (ECG) were part of the planned safety assessments. 12-lead Electrocardiograms were performed prior at the enrollment visit after informed consent and at the discharge visit. The discharge visit was as per standard of care. The changes in heart rate (beats per minute) parameters are reported per treatment group between the visits. A positive value indicates that the heart rate was higher at discharge than at enrollment.
Time frame: Enrollment; Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(For older children: N=27 at Visit 1)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Change From Enrollment in 12-lead Electrocardiogram Heart Rate Parameter | 2.0 beats per minute | Standard Deviation 16.4 |
| McGrath Color Analog Scale: Older Children | Change From Enrollment in 12-lead Electrocardiogram Heart Rate Parameter | 4.3 beats per minute | Standard Deviation 16.2 |
| Respiratory Rates: Young and Very Young Children | Change From Enrollment in 12-lead Electrocardiogram Heart Rate Parameter | 10.7 beats per minute | Standard Deviation 16.4 |
Secondary
Change From Enrollment in 12-lead Electrocardiogram Parameters
12-lead electrocardiograms (ECG) were part of the planned safety assessments. 12-lead Electrocardiograms were performed prior at the enrollment visit after informed consent and at the discharge visit. The discharge visit was as per standard of care. The changes in ECG parameters are reported. Negative mean values indicate that the millisecond intervals decreased from the enrollment to the discharge visit. Positive mean values indicate that the millisecond intervals increased from the enrollment to the discharge visit. The Letters P,Q,R,S and T refer to specific medically defined points on an ECG tracing and correspond to specific heart activities.
Time frame: Enrollment (pre-surgery); Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(For older children N=27 at Visit 1)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Change From Enrollment in 12-lead Electrocardiogram Parameters | QRS Duration change | 0.5 milliseconds | Standard Deviation 4.5 |
| Tapentadol Serum Concentrations: Adolescents | Change From Enrollment in 12-lead Electrocardiogram Parameters | QTcF change | -3.6 milliseconds | Standard Deviation 16.4 |
| Tapentadol Serum Concentrations: Adolescents | Change From Enrollment in 12-lead Electrocardiogram Parameters | PR Duration change | -3.5 milliseconds | Standard Deviation 11.7 |
| Tapentadol Serum Concentrations: Adolescents | Change From Enrollment in 12-lead Electrocardiogram Parameters | QT Duration change | -8.0 milliseconds | Standard Deviation 33.1 |
| Tapentadol Serum Concentrations: Adolescents | Change From Enrollment in 12-lead Electrocardiogram Parameters | RR Duration change | -32.2 milliseconds | Standard Deviation 193.8 |
| McGrath Color Analog Scale: Older Children | Change From Enrollment in 12-lead Electrocardiogram Parameters | QT Duration change | 8.5 milliseconds | Standard Deviation 32 |
| McGrath Color Analog Scale: Older Children | Change From Enrollment in 12-lead Electrocardiogram Parameters | QTcF change | 15.7 milliseconds | Standard Deviation 21.7 |
| McGrath Color Analog Scale: Older Children | Change From Enrollment in 12-lead Electrocardiogram Parameters | QRS Duration change | -0.2 milliseconds | Standard Deviation 4.7 |
| McGrath Color Analog Scale: Older Children | Change From Enrollment in 12-lead Electrocardiogram Parameters | PR Duration change | -1.8 milliseconds | Standard Deviation 11.3 |
| McGrath Color Analog Scale: Older Children | Change From Enrollment in 12-lead Electrocardiogram Parameters | RR Duration change | -35.2 milliseconds | Standard Deviation 156.5 |
| Respiratory Rates: Young and Very Young Children | Change From Enrollment in 12-lead Electrocardiogram Parameters | PR Duration change | -2.4 milliseconds | Standard Deviation 12.6 |
| Respiratory Rates: Young and Very Young Children | Change From Enrollment in 12-lead Electrocardiogram Parameters | QT Duration change | -4.1 milliseconds | Standard Deviation 29.6 |
| Respiratory Rates: Young and Very Young Children | Change From Enrollment in 12-lead Electrocardiogram Parameters | QTcF change | 5.6 milliseconds | Standard Deviation 20.7 |
| Respiratory Rates: Young and Very Young Children | Change From Enrollment in 12-lead Electrocardiogram Parameters | QRS Duration change | 0.5 milliseconds | Standard Deviation 5.8 |
| Respiratory Rates: Young and Very Young Children | Change From Enrollment in 12-lead Electrocardiogram Parameters | RR Duration change | -48.1 milliseconds | Standard Deviation 102.8 |
Secondary
Hematology Safety Laboratory Assessments: Erythrocyte Mean Corpuscular Volume (Mean Corpuscular Volume)
Erythrocyte Mean Corpuscular volume is a measurement of the average size of Red Blood Cells (RBC). It is also referred to as Mean Corpuscular Volume. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit; Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visits 2 and 3: N=16 one participant with missing data at each of these visits).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Hematology Safety Laboratory Assessments: Erythrocyte Mean Corpuscular Volume (Mean Corpuscular Volume) | Visit 2 | 86.5 fL | Standard Deviation 2.1 |
| Tapentadol Serum Concentrations: Adolescents | Hematology Safety Laboratory Assessments: Erythrocyte Mean Corpuscular Volume (Mean Corpuscular Volume) | Visit 1 | 86.1 fL | Standard Deviation 2.9 |
| Tapentadol Serum Concentrations: Adolescents | Hematology Safety Laboratory Assessments: Erythrocyte Mean Corpuscular Volume (Mean Corpuscular Volume) | Visit 3 | 86.9 fL | Standard Deviation 3.5 |
| McGrath Color Analog Scale: Older Children | Hematology Safety Laboratory Assessments: Erythrocyte Mean Corpuscular Volume (Mean Corpuscular Volume) | Visit 2 | 83.1 fL | Standard Deviation 3.5 |
| McGrath Color Analog Scale: Older Children | Hematology Safety Laboratory Assessments: Erythrocyte Mean Corpuscular Volume (Mean Corpuscular Volume) | Visit 1 | 82.3 fL | Standard Deviation 3.1 |
| McGrath Color Analog Scale: Older Children | Hematology Safety Laboratory Assessments: Erythrocyte Mean Corpuscular Volume (Mean Corpuscular Volume) | Visit 3 | 83.1 fL | Standard Deviation 3.5 |
| Respiratory Rates: Young and Very Young Children | Hematology Safety Laboratory Assessments: Erythrocyte Mean Corpuscular Volume (Mean Corpuscular Volume) | Visit 1 | 79.6 fL | Standard Deviation 3.6 |
| Respiratory Rates: Young and Very Young Children | Hematology Safety Laboratory Assessments: Erythrocyte Mean Corpuscular Volume (Mean Corpuscular Volume) | Visit 3 | 82.7 fL | Standard Deviation 3.6 |
| Respiratory Rates: Young and Very Young Children | Hematology Safety Laboratory Assessments: Erythrocyte Mean Corpuscular Volume (Mean Corpuscular Volume) | Visit 2 | 81.8 fL | Standard Deviation 3.7 |
Secondary
Hematology Safety Laboratory Assessments: Hematocrit
Hematocrit is a blood test that measures the percentage of the volume of whole blood that is made up of red blood cells (RBC). This measurement depends on the number of red blood cells and the size of red blood cells. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit; Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visits 2 and 3: N=16 one participant with missing data at each of these visits).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Hematology Safety Laboratory Assessments: Hematocrit | Visit 2 | 0.421 fraction of blood volume | Standard Deviation 0.06 |
| Tapentadol Serum Concentrations: Adolescents | Hematology Safety Laboratory Assessments: Hematocrit | Visit 1 | 0.436 fraction of blood volume | Standard Deviation 0.037 |
| Tapentadol Serum Concentrations: Adolescents | Hematology Safety Laboratory Assessments: Hematocrit | Visit 3 | 0.402 fraction of blood volume | Standard Deviation 0.054 |
| McGrath Color Analog Scale: Older Children | Hematology Safety Laboratory Assessments: Hematocrit | Visit 2 | 0.372 fraction of blood volume | Standard Deviation 0.024 |
| McGrath Color Analog Scale: Older Children | Hematology Safety Laboratory Assessments: Hematocrit | Visit 1 | 0.400 fraction of blood volume | Standard Deviation 0.018 |
| McGrath Color Analog Scale: Older Children | Hematology Safety Laboratory Assessments: Hematocrit | Visit 3 | 0.364 fraction of blood volume | Standard Deviation 0.025 |
| Respiratory Rates: Young and Very Young Children | Hematology Safety Laboratory Assessments: Hematocrit | Visit 1 | 0.368 fraction of blood volume | Standard Deviation 0.018 |
| Respiratory Rates: Young and Very Young Children | Hematology Safety Laboratory Assessments: Hematocrit | Visit 3 | 0.356 fraction of blood volume | Standard Deviation 0.022 |
| Respiratory Rates: Young and Very Young Children | Hematology Safety Laboratory Assessments: Hematocrit | Visit 2 | 0.363 fraction of blood volume | Standard Deviation 0.023 |
Secondary
Hematology Safety Laboratory Assessments: Hemoglobin Concentration
The hemoglobin test is a commonly ordered blood test and was done as part of a complete blood count (CBC). It is routinely done before and after surgery to check for anemia, the presence of chronic kidney disease or other chronic medical problems. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit; Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visits 2 and 3: N=16 one participant with missing data at each of these visits).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Hematology Safety Laboratory Assessments: Hemoglobin Concentration | Visit 2 | 145.67 g/L | Standard Deviation 21.44 |
| Tapentadol Serum Concentrations: Adolescents | Hematology Safety Laboratory Assessments: Hemoglobin Concentration | Visit 1 | 151.10 g/L | Standard Deviation 13.82 |
| Tapentadol Serum Concentrations: Adolescents | Hematology Safety Laboratory Assessments: Hemoglobin Concentration | Visit 3 | 139.00 g/L | Standard Deviation 19.2 |
| McGrath Color Analog Scale: Older Children | Hematology Safety Laboratory Assessments: Hemoglobin Concentration | Visit 2 | 128.64 g/L | Standard Deviation 7.88 |
| McGrath Color Analog Scale: Older Children | Hematology Safety Laboratory Assessments: Hemoglobin Concentration | Visit 1 | 140.04 g/L | Standard Deviation 6.66 |
| McGrath Color Analog Scale: Older Children | Hematology Safety Laboratory Assessments: Hemoglobin Concentration | Visit 3 | 126.54 g/L | Standard Deviation 9.1 |
| Respiratory Rates: Young and Very Young Children | Hematology Safety Laboratory Assessments: Hemoglobin Concentration | Visit 1 | 127.47 g/L | Standard Deviation 7.6 |
| Respiratory Rates: Young and Very Young Children | Hematology Safety Laboratory Assessments: Hemoglobin Concentration | Visit 3 | 117.00 g/L | Standard Deviation 7.63 |
| Respiratory Rates: Young and Very Young Children | Hematology Safety Laboratory Assessments: Hemoglobin Concentration | Visit 2 | 121.75 g/L | Standard Deviation 7.91 |
Secondary
Hematology Safety Laboratory Assessments: Leukocyte Concentration
Leukocytes are also called white blood cells (WBC). These were measured to assess immune function. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit; Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visits 2 and 3: N=16 one participant with missing data at each visit).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Hematology Safety Laboratory Assessments: Leukocyte Concentration | Visit 2 | 8.537 GI/L | Standard Deviation 2.514 |
| Tapentadol Serum Concentrations: Adolescents | Hematology Safety Laboratory Assessments: Leukocyte Concentration | Visit 1 | 6.631 GI/L | Standard Deviation 1.682 |
| Tapentadol Serum Concentrations: Adolescents | Hematology Safety Laboratory Assessments: Leukocyte Concentration | Visit 3 | 10.052 GI/L | Standard Deviation 3.253 |
| McGrath Color Analog Scale: Older Children | Hematology Safety Laboratory Assessments: Leukocyte Concentration | Visit 2 | 12.509 GI/L | Standard Deviation 4.209 |
| McGrath Color Analog Scale: Older Children | Hematology Safety Laboratory Assessments: Leukocyte Concentration | Visit 1 | 7.594 GI/L | Standard Deviation 3.984 |
| McGrath Color Analog Scale: Older Children | Hematology Safety Laboratory Assessments: Leukocyte Concentration | Visit 3 | 14.806 GI/L | Standard Deviation 4.031 |
| Respiratory Rates: Young and Very Young Children | Hematology Safety Laboratory Assessments: Leukocyte Concentration | Visit 1 | 6.555 GI/L | Standard Deviation 1.278 |
| Respiratory Rates: Young and Very Young Children | Hematology Safety Laboratory Assessments: Leukocyte Concentration | Visit 3 | 13.160 GI/L | Standard Deviation 2.907 |
| Respiratory Rates: Young and Very Young Children | Hematology Safety Laboratory Assessments: Leukocyte Concentration | Visit 2 | 10.751 GI/L | Standard Deviation 3.272 |
Secondary
Hematology Safety Laboratory Assessments: Platelet Count
Platelets are cell fragments that are vital for normal blood clotting. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time frame: Enrollment Visit; Visit 2 and Discharge Visit
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visits 2 and 3: N=16 one participant with missing data at each of these visits).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Hematology Safety Laboratory Assessments: Platelet Count | Visit 1 | 297.0 GI/L | Standard Deviation 59.8 |
| Tapentadol Serum Concentrations: Adolescents | Hematology Safety Laboratory Assessments: Platelet Count | Visit 2 | 266.1 GI/L | Standard Deviation 73 |
| Tapentadol Serum Concentrations: Adolescents | Hematology Safety Laboratory Assessments: Platelet Count | Visit 3 | 263.9 GI/L | Standard Deviation 57.9 |
| McGrath Color Analog Scale: Older Children | Hematology Safety Laboratory Assessments: Platelet Count | Visit 2 | 303.4 GI/L | Standard Deviation 73.9 |
| McGrath Color Analog Scale: Older Children | Hematology Safety Laboratory Assessments: Platelet Count | Visit 3 | 316.9 GI/L | Standard Deviation 71.3 |
| McGrath Color Analog Scale: Older Children | Hematology Safety Laboratory Assessments: Platelet Count | Visit 1 | 347.1 GI/L | Standard Deviation 86.2 |
| Respiratory Rates: Young and Very Young Children | Hematology Safety Laboratory Assessments: Platelet Count | Visit 3 | 307.3 GI/L | Standard Deviation 50 |
| Respiratory Rates: Young and Very Young Children | Hematology Safety Laboratory Assessments: Platelet Count | Visit 2 | 312.6 GI/L | Standard Deviation 111.2 |
| Respiratory Rates: Young and Very Young Children | Hematology Safety Laboratory Assessments: Platelet Count | Visit 1 | 357.4 GI/L | Standard Deviation 67.5 |
Secondary
Intake of Additional Analgesic Medication During the Trial
Number of participants with intakes of supplemental analgesic medication between investigational medicinal product (IMP) intake and Site Discharge grouped according to preparation taken (non-opioid/opioid).
Time frame: Baseline; 15 hours post dosing
Population: The protocol pre-specified that the young and very young children will be reported as one group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Intake of Additional Analgesic Medication During the Trial | Supplemental analgesic medication taken | 12 participants |
| Tapentadol Serum Concentrations: Adolescents | Intake of Additional Analgesic Medication During the Trial | Supplemental non-opioid analgesic taken | 12 participants |
| Tapentadol Serum Concentrations: Adolescents | Intake of Additional Analgesic Medication During the Trial | Supplemental opioid analgesic taken | 3 participants |
| McGrath Color Analog Scale: Older Children | Intake of Additional Analgesic Medication During the Trial | Supplemental analgesic medication taken | 18 participants |
| McGrath Color Analog Scale: Older Children | Intake of Additional Analgesic Medication During the Trial | Supplemental opioid analgesic taken | 3 participants |
| McGrath Color Analog Scale: Older Children | Intake of Additional Analgesic Medication During the Trial | Supplemental non-opioid analgesic taken | 18 participants |
| Respiratory Rates: Young and Very Young Children | Intake of Additional Analgesic Medication During the Trial | Supplemental analgesic medication taken | 15 participants |
| Respiratory Rates: Young and Very Young Children | Intake of Additional Analgesic Medication During the Trial | Supplemental non-opioid analgesic taken | 15 participants |
| Respiratory Rates: Young and Very Young Children | Intake of Additional Analgesic Medication During the Trial | Supplemental opioid analgesic taken | 8 participants |
Secondary
Oxygen Saturation Assessments
Oxygen saturation assessments were performed at pre-defined times during the 15 hour period following investigational medicinal product intake. Oxygen saturation was assessed using pulse oximetry. The uppermost value is 100%. Pre-surgery data for these participants is also given from the enrollment Visit (Visit 1).
Time frame: Enrollment Visit; 15 hours post-dose
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at and after 2 hours: N=20; Older Children Group at 30 minutes and 1 hour N=27, at 2 hours N=24, at and after 4 hours N=22; Young and Very Young Children Group at and after 4 hours: N=16).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Oxygen Saturation Assessments | 15 minutes post-dose | 97.3 percentage of oxygen saturation | Standard Deviation 1.2 |
| Tapentadol Serum Concentrations: Adolescents | Oxygen Saturation Assessments | Pre-dose | 97.7 percentage of oxygen saturation | Standard Deviation 1.4 |
| Tapentadol Serum Concentrations: Adolescents | Oxygen Saturation Assessments | 30 minutes post-dose | 97.0 percentage of oxygen saturation | Standard Deviation 1.4 |
| Tapentadol Serum Concentrations: Adolescents | Oxygen Saturation Assessments | 1 hour post-dose | 97.3 percentage of oxygen saturation | Standard Deviation 1.2 |
| Tapentadol Serum Concentrations: Adolescents | Oxygen Saturation Assessments | 2 hours post-dose | 97.1 percentage of oxygen saturation | Standard Deviation 1.3 |
| Tapentadol Serum Concentrations: Adolescents | Oxygen Saturation Assessments | 4 hours post-dose | 96.9 percentage of oxygen saturation | Standard Deviation 1.4 |
| Tapentadol Serum Concentrations: Adolescents | Oxygen Saturation Assessments | 6 hours post-dose | 97.1 percentage of oxygen saturation | Standard Deviation 1.5 |
| Tapentadol Serum Concentrations: Adolescents | Oxygen Saturation Assessments | 11 hours post-dose | 96.8 percentage of oxygen saturation | Standard Deviation 1.4 |
| Tapentadol Serum Concentrations: Adolescents | Oxygen Saturation Assessments | 15 hours post-dose | 96.7 percentage of oxygen saturation | Standard Deviation 1 |
| Tapentadol Serum Concentrations: Adolescents | Oxygen Saturation Assessments | Visit 1 | 97.8 percentage of oxygen saturation | Standard Deviation 1.1 |
| McGrath Color Analog Scale: Older Children | Oxygen Saturation Assessments | 4 hours post-dose | 96.5 percentage of oxygen saturation | Standard Deviation 1.2 |
| McGrath Color Analog Scale: Older Children | Oxygen Saturation Assessments | Visit 1 | 97.4 percentage of oxygen saturation | Standard Deviation 1.7 |
| McGrath Color Analog Scale: Older Children | Oxygen Saturation Assessments | Pre-dose | 96.7 percentage of oxygen saturation | Standard Deviation 1.4 |
| McGrath Color Analog Scale: Older Children | Oxygen Saturation Assessments | 2 hours post-dose | 95.8 percentage of oxygen saturation | Standard Deviation 1.4 |
| McGrath Color Analog Scale: Older Children | Oxygen Saturation Assessments | 15 minutes post-dose | 96.8 percentage of oxygen saturation | Standard Deviation 1.3 |
| McGrath Color Analog Scale: Older Children | Oxygen Saturation Assessments | 15 hours post-dose | 96.5 percentage of oxygen saturation | Standard Deviation 1.4 |
| McGrath Color Analog Scale: Older Children | Oxygen Saturation Assessments | 11 hours post-dose | 96.8 percentage of oxygen saturation | Standard Deviation 1.4 |
| McGrath Color Analog Scale: Older Children | Oxygen Saturation Assessments | 30 minutes post-dose | 96.4 percentage of oxygen saturation | Standard Deviation 1.3 |
| McGrath Color Analog Scale: Older Children | Oxygen Saturation Assessments | 6 hours post-dose | 96.7 percentage of oxygen saturation | Standard Deviation 1.3 |
| McGrath Color Analog Scale: Older Children | Oxygen Saturation Assessments | 1 hour post-dose | 96.0 percentage of oxygen saturation | Standard Deviation 1.6 |
| Respiratory Rates: Young and Very Young Children | Oxygen Saturation Assessments | 11 hours post-dose | 96.4 percentage of oxygen saturation | Standard Deviation 1.5 |
| Respiratory Rates: Young and Very Young Children | Oxygen Saturation Assessments | 1 hour post-dose | 96.2 percentage of oxygen saturation | Standard Deviation 2 |
| Respiratory Rates: Young and Very Young Children | Oxygen Saturation Assessments | Visit 1 | 97.4 percentage of oxygen saturation | Standard Deviation 1.4 |
| Respiratory Rates: Young and Very Young Children | Oxygen Saturation Assessments | 2 hours post-dose | 95.8 percentage of oxygen saturation | Standard Deviation 1.7 |
| Respiratory Rates: Young and Very Young Children | Oxygen Saturation Assessments | 4 hours post-dose | 96.5 percentage of oxygen saturation | Standard Deviation 1.5 |
| Respiratory Rates: Young and Very Young Children | Oxygen Saturation Assessments | 15 hours post-dose | 97.1 percentage of oxygen saturation | Standard Deviation 1.5 |
| Respiratory Rates: Young and Very Young Children | Oxygen Saturation Assessments | 6 hours post-dose | 96.7 percentage of oxygen saturation | Standard Deviation 1.7 |
| Respiratory Rates: Young and Very Young Children | Oxygen Saturation Assessments | Pre-dose | 96.8 percentage of oxygen saturation | Standard Deviation 1 |
| Respiratory Rates: Young and Very Young Children | Oxygen Saturation Assessments | 15 minutes post-dose | 96.5 percentage of oxygen saturation | Standard Deviation 1.9 |
| Respiratory Rates: Young and Very Young Children | Oxygen Saturation Assessments | 30 minutes post-dose | 96.8 percentage of oxygen saturation | Standard Deviation 1.6 |
Secondary
Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years.
This assessment tool was used in 3 to less than 12 year old participants, i.e. Older Children and Young Children. The Faces Pain Scale (Revised) \[FPS-R\] score as allocated to a selected face by the participant. There are 6 faces and the participant is asked to indicate on a face to express how much it hurts. The numeric value 0 (no pain) to 10 (very much pain) is read off the reverse side of the scale by the clinician.
Time frame: Baseline; 15 hours post-dose
Population: The protocol pre-specified that the Faces Pain Scale (Revised) would not be administered in the very young participants (aged 2 to less than 3 years).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. | 15 minutes post-dose | 3.5 units on a scale | Standard Deviation 1.8 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. | 4 hours post-dose | 2.5 units on a scale | Standard Deviation 1.6 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. | 1 hour post-dose | 2.4 units on a scale | Standard Deviation 1.6 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. | 6 hours post-dose | 2.7 units on a scale | Standard Deviation 2.1 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. | 30 minutes post-dose | 2.9 units on a scale | Standard Deviation 1.8 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. | 11 hours post-dose | 2.7 units on a scale | Standard Deviation 1.7 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. | 2 hours post-dose | 2.6 units on a scale | Standard Deviation 1.7 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. | 15 hours post-dose | 3.5 units on a scale | Standard Deviation 2.2 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. | Pre-dose | 4.8 units on a scale | Standard Deviation 1.6 |
| McGrath Color Analog Scale: Older Children | Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. | 15 hours post-dose | 2.8 units on a scale | Standard Deviation 2.9 |
| McGrath Color Analog Scale: Older Children | Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. | Pre-dose | 6.8 units on a scale | Standard Deviation 3.2 |
| McGrath Color Analog Scale: Older Children | Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. | 15 minutes post-dose | 4.5 units on a scale | Standard Deviation 4 |
| McGrath Color Analog Scale: Older Children | Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. | 30 minutes post-dose | 2.8 units on a scale | Standard Deviation 3.2 |
| McGrath Color Analog Scale: Older Children | Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. | 1 hour post-dose | 1.8 units on a scale | Standard Deviation 3.3 |
| McGrath Color Analog Scale: Older Children | Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. | 2 hours post-dose | 1.2 units on a scale | Standard Deviation 2.9 |
| McGrath Color Analog Scale: Older Children | Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. | 4 hours post-dose | 3.5 units on a scale | Standard Deviation 3.2 |
| McGrath Color Analog Scale: Older Children | Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. | 6 hours post-dose | 1.8 units on a scale | Standard Deviation 2.3 |
| McGrath Color Analog Scale: Older Children | Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. | 11 hours post-dose | 2.3 units on a scale | Standard Deviation 2.4 |
Secondary
Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years).
Pain intensity assessments were with a 0 (no pain) to 10 (worst pain) scored McGrath color analog scale (CAS) in participants aged 6 years to less than 18 years, i.e. in Adolescents and Older Children. Participants were presented with the CAS and instructed to place the sliding bar on the color that best represented their pain intensity level at the time of assessment. The CAS is a pocket size tool used to measure the self-reported pain intensity of the older participants. The CAS consists of a 145 mm long triangular shaped strip of plastic, varying in width and hue from 1 mm wide and light pink hue at the bottom (and text no pain), to 3 mm wide and deep red hue at the top (most pain). This instrument includes 2 sides. One side shows the color pain intensity scale as described and the other shows a graduated scale, which provides a specific numeric value for the participant-reported level of pain.
Time frame: Baseline; 15 hours post-dose
Population: Protocol pre-specified reporting groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). | 15 minutes post-dose | 6.131 units on a scale | Standard Deviation 2.18 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). | 4 hours post-dose | 4.200 units on a scale | Standard Deviation 2.113 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). | 1 hour post-dose | 4.393 units on a scale | Standard Deviation 2.299 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). | 6 hours post-dose | 3.438 units on a scale | Standard Deviation 1.96 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). | 30 minutes after dosing | 5.262 units on a scale | Standard Deviation 2.311 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). | 11 hours post-dose | 3.350 units on a scale | Standard Deviation 1.836 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). | 2 hours post-dose | 3.475 units on a scale | Standard Deviation 2.173 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). | 15 hours post-dose | 3.288 units on a scale | Standard Deviation 1.578 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). | Pre-dose | 6.643 units on a scale | Standard Deviation 1.461 |
| McGrath Color Analog Scale: Older Children | Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). | 15 hours post-dose | 3.568 units on a scale | Standard Deviation 2.549 |
| McGrath Color Analog Scale: Older Children | Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). | Pre-dose | 4.670 units on a scale | Standard Deviation 1.602 |
| McGrath Color Analog Scale: Older Children | Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). | 15 minutes post-dose | 3.071 units on a scale | Standard Deviation 1.718 |
| McGrath Color Analog Scale: Older Children | Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). | 30 minutes after dosing | 2.571 units on a scale | Standard Deviation 1.824 |
| McGrath Color Analog Scale: Older Children | Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). | 1 hour post-dose | 2.407 units on a scale | Standard Deviation 1.723 |
| McGrath Color Analog Scale: Older Children | Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). | 2 hours post-dose | 2.292 units on a scale | Standard Deviation 1.793 |
| McGrath Color Analog Scale: Older Children | Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). | 4 hours post-dose | 2.341 units on a scale | Standard Deviation 1.899 |
| McGrath Color Analog Scale: Older Children | Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). | 6 hours post-dose | 2.636 units on a scale | Standard Deviation 2.152 |
| McGrath Color Analog Scale: Older Children | Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). | 11 hours post-dose | 3.352 units on a scale | Standard Deviation 1.851 |
Secondary
Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years).
At predefined times after investigational medicinal product administration, participants were asked to rate their pain on a 100 mm line (visual analog scale - VAS) by marking a point on the line in response to: My pain at this time is. The mark was scored between no pain and pain as bad as it could be. The distance was then measured by a clinician and reported. A value of 0 indicates no pain. A value of 100 indicates pain as bad as it could be.
Time frame: Baseline; 15 hours
Population: Protocol pre-specified reporting groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years). | 6 hours post-dose | 34.8 units on a scale | Standard Deviation 24.3 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years). | Pre-dose | 71.5 units on a scale | Standard Deviation 13.3 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years). | 15 minutes post-dose | 63.6 units on a scale | Standard Deviation 24.4 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years). | 30 minutes post-dose | 53.2 units on a scale | Standard Deviation 27.3 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years). | 1 hour post-dose | 46.3 units on a scale | Standard Deviation 26.5 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years). | 2 hours post-dose | 34.0 units on a scale | Standard Deviation 24.6 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years). | 4 hours post-dose | 43.5 units on a scale | Standard Deviation 26.8 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years). | 11 hours post-dose | 32.7 units on a scale | Standard Deviation 21.1 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years). | 15 hours post-dose | 33.4 units on a scale | Standard Deviation 20.1 |
Secondary
Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years).
The Face Legs Activity Cry Consolability (FLACC) Scale was developed by the Department of Anesthesiology, University of Michigan Medical School and Health Systems. The FLACC Scale is a behavioral scale for scoring postoperative pain in children between the ages of two months and seven years or in persons unable to communicate. In this trial the scale was used in the young and very young children, i.e. in participants aged 2 to less than 6 years. This tool includes five categories of pain behaviors, including facial expression, leg movement, activity, cry, and consolability. The clinician observes the participant for 5 minutes or more and scores each category with a 0, 1 or 2. The scores are added together for a total score ranging from 0 (no pain) to 10 (worst pain). The higher the total score the higher the pain.
Time frame: Baseline; 15 hours post-dose
Population: The protocol pre-specified that the young and very young children will be reported as one group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years). | 30 minutes post-dose | 1.2 units on a scale | Standard Deviation 1.6 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years). | Pre-dose | 4.2 units on a scale | Standard Deviation 2.2 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years). | 15 minutes post-dose | 1.8 units on a scale | Standard Deviation 1.6 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years). | 1 hour post-dose | 1.1 units on a scale | Standard Deviation 1.4 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years). | 2 hours post-dose | 0.8 units on a scale | Standard Deviation 1.1 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years). | 4 hours post-dose | 1.5 units on a scale | Standard Deviation 1.7 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years). | 6 hours post-dose | 0.8 units on a scale | Standard Deviation 1.6 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years). | 11 hours post-dose | 0.9 units on a scale | Standard Deviation 2.1 |
| Tapentadol Serum Concentrations: Adolescents | Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years). | 15 hours post-dose | 0.8 units on a scale | Standard Deviation 1.2 |
Secondary
Respiratory Rate Assessments
Respiratory rate assessments were performed at pre-defined times during the 15 hour period following investigational medicinal product intake. Pre-surgery data for these participants is also given from the enrollment Visit (Visit 1).
Time frame: Enrollment Visit; 15 hours post-dose
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at and after 2 hours: N=20; Older Children Group at 30 minutes and 1 hour N=27, at 2 hours N=24, and at and after 4 hours N=22; Young and Very Young Children Group at and after 4 hours: N=16).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Respiratory Rate Assessments | 15 hours post-dose | 16.1 breaths per minute | Standard Deviation 2.5 |
| Tapentadol Serum Concentrations: Adolescents | Respiratory Rate Assessments | 2 hours post-dose | 17.3 breaths per minute | Standard Deviation 2.8 |
| Tapentadol Serum Concentrations: Adolescents | Respiratory Rate Assessments | Pre-dose | 16.4 breaths per minute | Standard Deviation 2.5 |
| Tapentadol Serum Concentrations: Adolescents | Respiratory Rate Assessments | Visit 1 | 17.8 breaths per minute | Standard Deviation 3.2 |
| Tapentadol Serum Concentrations: Adolescents | Respiratory Rate Assessments | 30 minutes post-dose | 17.5 breaths per minute | Standard Deviation 2.5 |
| Tapentadol Serum Concentrations: Adolescents | Respiratory Rate Assessments | 15 minutes post-dose | 16.8 breaths per minute | Standard Deviation 2.6 |
| Tapentadol Serum Concentrations: Adolescents | Respiratory Rate Assessments | 4 hours post-dose | 16.4 breaths per minute | Standard Deviation 2.1 |
| Tapentadol Serum Concentrations: Adolescents | Respiratory Rate Assessments | 1 hours post-dose | 15.9 breaths per minute | Standard Deviation 2.3 |
| Tapentadol Serum Concentrations: Adolescents | Respiratory Rate Assessments | 6 hours post-dose | 16.9 breaths per minute | Standard Deviation 2.9 |
| Tapentadol Serum Concentrations: Adolescents | Respiratory Rate Assessments | 11 hours post-dose | 17.4 breaths per minute | Standard Deviation 3.6 |
| McGrath Color Analog Scale: Older Children | Respiratory Rate Assessments | 15 hours post-dose | 17.3 breaths per minute | Standard Deviation 3 |
| McGrath Color Analog Scale: Older Children | Respiratory Rate Assessments | 4 hours post-dose | 19.5 breaths per minute | Standard Deviation 2.8 |
| McGrath Color Analog Scale: Older Children | Respiratory Rate Assessments | 2 hours post-dose | 19.3 breaths per minute | Standard Deviation 2.5 |
| McGrath Color Analog Scale: Older Children | Respiratory Rate Assessments | 11 hours post-dose | 18.4 breaths per minute | Standard Deviation 2.9 |
| McGrath Color Analog Scale: Older Children | Respiratory Rate Assessments | 30 minutes post-dose | 19.4 breaths per minute | Standard Deviation 2.4 |
| McGrath Color Analog Scale: Older Children | Respiratory Rate Assessments | Visit 1 | 18.4 breaths per minute | Standard Deviation 3.1 |
| McGrath Color Analog Scale: Older Children | Respiratory Rate Assessments | Pre-dose | 19.2 breaths per minute | Standard Deviation 2.5 |
| McGrath Color Analog Scale: Older Children | Respiratory Rate Assessments | 6 hours post-dose | 19.0 breaths per minute | Standard Deviation 3.8 |
| McGrath Color Analog Scale: Older Children | Respiratory Rate Assessments | 1 hours post-dose | 19.0 breaths per minute | Standard Deviation 2 |
| McGrath Color Analog Scale: Older Children | Respiratory Rate Assessments | 15 minutes post-dose | 19.7 breaths per minute | Standard Deviation 2.5 |
| Respiratory Rates: Young and Very Young Children | Respiratory Rate Assessments | 6 hours post-dose | 22.1 breaths per minute | Standard Deviation 3.5 |
| Respiratory Rates: Young and Very Young Children | Respiratory Rate Assessments | 30 minutes post-dose | 22.6 breaths per minute | Standard Deviation 4.3 |
| Respiratory Rates: Young and Very Young Children | Respiratory Rate Assessments | 1 hours post-dose | 21.8 breaths per minute | Standard Deviation 3.5 |
| Respiratory Rates: Young and Very Young Children | Respiratory Rate Assessments | 2 hours post-dose | 22.5 breaths per minute | Standard Deviation 3.3 |
| Respiratory Rates: Young and Very Young Children | Respiratory Rate Assessments | 4 hours post-dose | 22.5 breaths per minute | Standard Deviation 2.1 |
| Respiratory Rates: Young and Very Young Children | Respiratory Rate Assessments | 15 minutes post-dose | 24.0 breaths per minute | Standard Deviation 3.1 |
| Respiratory Rates: Young and Very Young Children | Respiratory Rate Assessments | 11 hours post-dose | 22.4 breaths per minute | Standard Deviation 3.4 |
| Respiratory Rates: Young and Very Young Children | Respiratory Rate Assessments | 15 hours post-dose | 21.1 breaths per minute | Standard Deviation 3.9 |
| Respiratory Rates: Young and Very Young Children | Respiratory Rate Assessments | Visit 1 | 25.1 breaths per minute | Standard Deviation 3.4 |
| Respiratory Rates: Young and Very Young Children | Respiratory Rate Assessments | Pre-dose | 25.1 breaths per minute | Standard Deviation 3.3 |
Secondary
Sum of Pain Intensity Differences Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups
Different pain intensity assessment tools were used in the different age groups. Therefore the sum of pain intensities were calculated and are reported for each age group based on the tool used. Adolescents - Age 12 to Less Than 18 Years. Older Children - Age 6 to Less Than 12 Years. Young Children - Age 3 to Less Than 6 Years. Very Young Children - Age 2 to Less Than 3 Years. * CAS (McGrath color analog scale) \[Theoretical Range: -40 to + 40\], * VAS (100 mm Visual Analog Scale) \[Theoretical Range: -400 to + 400\], * FPS-R (6-point Faces Pain Scale - Revised) \[Theoretical Range: -40 to + 40\], * FLACC (Face, Legs, Activity, Cry, and Consolability score) \[Theoretical Range: -40 to + 40\]. A mean score of zero indicates that there was no pain intensity change over the 4 hours. The positive values indicate that in the group as a whole the sum of all pain intensity values over the first 4 hours lead to a reduction in pain in the time period.
Time frame: Baseline; 4 hours post-dose
Population: Protocol pre-specified reporting groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Sum of Pain Intensity Differences Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups | Adolescents SPID for VAS | 106.282 units on a scale | Standard Deviation 75.35 |
| Tapentadol Serum Concentrations: Adolescents | Sum of Pain Intensity Differences Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups | Adolescents SPID for CAS | 8.925 units on a scale | Standard Deviation 6.347 |
| Tapentadol Serum Concentrations: Adolescents | Sum of Pain Intensity Differences Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups | Older Children SPID for CAS | 9.698 units on a scale | Standard Deviation 7.61 |
| Tapentadol Serum Concentrations: Adolescents | Sum of Pain Intensity Differences Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups | Older Children SPID for FPS-R | 8.724 units on a scale | Standard Deviation 6.868 |
| Tapentadol Serum Concentrations: Adolescents | Sum of Pain Intensity Differences Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups | Young Children SPID for FPS-R | 17.646 units on a scale | Standard Deviation 14.674 |
| Tapentadol Serum Concentrations: Adolescents | Sum of Pain Intensity Differences Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups | Young Children SPID for FLACC | 11.614 units on a scale | Standard Deviation 8.334 |
| Tapentadol Serum Concentrations: Adolescents | Sum of Pain Intensity Differences Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups | Very Young Children SPID for FLACC | 12.483 units on a scale | Standard Deviation 8.955 |
Secondary
Systolic and Diastolic Blood Pressure Assessments
Systolic and Diastolic blood pressure assessments were performed at pre-defined times during the 15 hour period following investigational medicinal product intake. Pre-surgery data for these participants is also given from the enrollment Visit (Visit 1).
Time frame: Enrollment Visit; 15 hours post-dose
Population: The protocol pre-specified that the young and very young children will be reported as one group.~(Adolescents Group at and after 2 hours: N=20; Older Children Group at 30 minutes and 1 hour N=27, at 2 hours N=24, at and after 4 hours N=22; Young and Very Young Children Group at and after 4 hours: N=16).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | 30 minutes post-dose Diastolic blood pressure | 76.1 mmHg | Standard Deviation 12 |
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | 6 hours post-dose Systolic Blood Pressure | 116.8 mmHg | Standard Deviation 14.1 |
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | 11 hours post-dose Diastolic blood pressure | 65.4 mmHg | Standard Deviation 8.4 |
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | Visit 1 Enrollment Systolic blood pressure | 110.2 mmHg | Standard Deviation 9 |
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | 11 hours post-dose Systolic Blood Pressure | 115.1 mmHg | Standard Deviation 11.2 |
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | 30 minutes post-dose Systolic Blood Pressure | 126.8 mmHg | Standard Deviation 17.9 |
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | 15 minutes post-dose Diastolic blood pressure | 78.9 mmHg | Standard Deviation 15.7 |
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | 15 hours post-dose Systolic Blood Pressure | 113.8 mmHg | Standard Deviation 14.2 |
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | 6 hours post-dose Diastolic blood pressure | 66.0 mmHg | Standard Deviation 10.3 |
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | Pre-dose Diastolic blood pressure | 74.8 mmHg | Standard Deviation 11.8 |
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | Visit 1 Enrollment Diastolic blood pressure | 66.5 mmHg | Standard Deviation 9 |
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | 4 hours post-dose Diastolic blood pressure | 73.2 mmHg | Standard Deviation 12.1 |
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | 1 hour post-dose Systolic Blood Pressure | 127.0 mmHg | Standard Deviation 17.7 |
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | 15 hours post-dose Diastolic blood pressure | 67.1 mmHg | Standard Deviation 10.8 |
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | 2 hours post-dose Diastolic blood pressure | 74.7 mmHg | Standard Deviation 13.4 |
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | 2 hours post-dose Systolic Blood Pressure | 124.9 mmHg | Standard Deviation 16.7 |
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | 15 minutes post-dose Systolic Blood Pressure | 126.9 mmHg | Standard Deviation 17.7 |
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | 1 hour post-dose Diastolic blood pressure | 77.6 mmHg | Standard Deviation 13 |
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | 4 hours post-dose Systolic Blood Pressure | 122.8 mmHg | Standard Deviation 13.9 |
| Tapentadol Serum Concentrations: Adolescents | Systolic and Diastolic Blood Pressure Assessments | Pre-dose Systolic Blood Pressure | 122.9 mmHg | Standard Deviation 13.9 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | 15 minutes post-dose Diastolic blood pressure | 62.4 mmHg | Standard Deviation 7.8 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | Visit 1 Enrollment Systolic blood pressure | 103.8 mmHg | Standard Deviation 9.6 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | Pre-dose Systolic Blood Pressure | 107.1 mmHg | Standard Deviation 9.1 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | 15 minutes post-dose Systolic Blood Pressure | 104.1 mmHg | Standard Deviation 8.3 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | 30 minutes post-dose Systolic Blood Pressure | 104.1 mmHg | Standard Deviation 7.2 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | 1 hour post-dose Systolic Blood Pressure | 104.0 mmHg | Standard Deviation 9.6 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | 2 hours post-dose Systolic Blood Pressure | 103.9 mmHg | Standard Deviation 8.2 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | 4 hours post-dose Systolic Blood Pressure | 104.8 mmHg | Standard Deviation 10.5 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | 6 hours post-dose Systolic Blood Pressure | 106.7 mmHg | Standard Deviation 7.9 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | 11 hours post-dose Systolic Blood Pressure | 102.0 mmHg | Standard Deviation 9.1 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | 15 hours post-dose Systolic Blood Pressure | 100.3 mmHg | Standard Deviation 8.7 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | Visit 1 Enrollment Diastolic blood pressure | 66.3 mmHg | Standard Deviation 8.3 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | Pre-dose Diastolic blood pressure | 64.2 mmHg | Standard Deviation 9.4 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | 30 minutes post-dose Diastolic blood pressure | 61.3 mmHg | Standard Deviation 5.7 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | 1 hour post-dose Diastolic blood pressure | 61.1 mmHg | Standard Deviation 7.1 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | 2 hours post-dose Diastolic blood pressure | 59.7 mmHg | Standard Deviation 7 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | 4 hours post-dose Diastolic blood pressure | 60.0 mmHg | Standard Deviation 7.1 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | 6 hours post-dose Diastolic blood pressure | 59.0 mmHg | Standard Deviation 8.3 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | 11 hours post-dose Diastolic blood pressure | 54.6 mmHg | Standard Deviation 8.5 |
| McGrath Color Analog Scale: Older Children | Systolic and Diastolic Blood Pressure Assessments | 15 hours post-dose Diastolic blood pressure | 56.8 mmHg | Standard Deviation 8.5 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | 15 minutes post-dose Systolic Blood Pressure | 101.8 mmHg | Standard Deviation 7.5 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | 30 minutes post-dose Diastolic blood pressure | 60.2 mmHg | Standard Deviation 6.1 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | 2 hours post-dose Systolic Blood Pressure | 98.4 mmHg | Standard Deviation 6.6 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | 15 hours post-dose Diastolic blood pressure | 57.0 mmHg | Standard Deviation 8.7 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | 1 hour post-dose Diastolic blood pressure | 59.6 mmHg | Standard Deviation 6.9 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | 1 hour post-dose Systolic Blood Pressure | 97.6 mmHg | Standard Deviation 7.6 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | 11 hours post-dose Diastolic blood pressure | 57.3 mmHg | Standard Deviation 11.2 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | 2 hours post-dose Diastolic blood pressure | 59.7 mmHg | Standard Deviation 7.4 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | 30 minutes post-dose Systolic Blood Pressure | 100.1 mmHg | Standard Deviation 6.2 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | Pre-dose Systolic Blood Pressure | 105.1 mmHg | Standard Deviation 15.6 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | 4 hours post-dose Diastolic blood pressure | 58.7 mmHg | Standard Deviation 5.9 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | Visit 1 Enrollment Systolic blood pressure | 98.7 mmHg | Standard Deviation 7 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | Visit 1 Enrollment Diastolic blood pressure | 62.8 mmHg | Standard Deviation 5.3 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | 15 hours post-dose Systolic Blood Pressure | 93.3 mmHg | Standard Deviation 9.9 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | 6 hours post-dose Diastolic blood pressure | 58.8 mmHg | Standard Deviation 7.3 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | Pre-dose Diastolic blood pressure | 65.6 mmHg | Standard Deviation 11.2 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | 11 hours post-dose Systolic Blood Pressure | 99.4 mmHg | Standard Deviation 14.2 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | 6 hours post-dose Systolic Blood Pressure | 102.0 mmHg | Standard Deviation 8.5 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | 15 minutes post-dose Diastolic blood pressure | 62.4 mmHg | Standard Deviation 7.7 |
| Respiratory Rates: Young and Very Young Children | Systolic and Diastolic Blood Pressure Assessments | 4 hours post-dose Systolic Blood Pressure | 100.1 mmHg | Standard Deviation 7.4 |
Secondary
Treatment Emergent Adverse Events by Intensity
The intensity of all treatment emergent adverse events (TEAEs) were scored by the investigator. Treatment emergent adverse events were those adverse events documented from the time of investigational medicinal product (IMP), study drug, up to 48 hours post dosing. The clinical intensity of an adverse event was classified as: * Mild: Signs and symptoms that can be easily tolerated. Symptoms can be ignored and disappear when the subject is distracted. * Moderate: Symptoms cause discomfort but are tolerable; they cannot be ignored and affect concentration. * Severe: Symptoms which affect usual daily activity. For adverse events where the intensity changes over time, the maximum intensity observed was documented.
Time frame: Baseline; 48 hours post dosing
Population: The protocol pre-specified that the young and very young children will be reported as one group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tapentadol Serum Concentrations: Adolescents | Treatment Emergent Adverse Events by Intensity | Total number of mild TEAEs | 10 number of events |
| Tapentadol Serum Concentrations: Adolescents | Treatment Emergent Adverse Events by Intensity | Total number of TEAEs | 22 number of events |
| Tapentadol Serum Concentrations: Adolescents | Treatment Emergent Adverse Events by Intensity | Total number of moderate TEAEs | 12 number of events |
| McGrath Color Analog Scale: Older Children | Treatment Emergent Adverse Events by Intensity | Total number of mild TEAEs | 16 number of events |
| McGrath Color Analog Scale: Older Children | Treatment Emergent Adverse Events by Intensity | Total number of TEAEs | 33 number of events |
| McGrath Color Analog Scale: Older Children | Treatment Emergent Adverse Events by Intensity | Total number of moderate TEAEs | 17 number of events |
| Respiratory Rates: Young and Very Young Children | Treatment Emergent Adverse Events by Intensity | Total number of TEAEs | 11 number of events |
| Respiratory Rates: Young and Very Young Children | Treatment Emergent Adverse Events by Intensity | Total number of moderate TEAEs | 1 number of events |
| Respiratory Rates: Young and Very Young Children | Treatment Emergent Adverse Events by Intensity | Total number of mild TEAEs | 10 number of events |