A Phase 2 interventional study of Tapentadol in Postoperative Pain and Acute Pain, sponsored by Grünenthal GmbH. Completed at 1 site in United States. Open to participants aged 2 Years to 17 Years. Per ClinicalTrials.gov, last updated 2019-11-04.
Sponsored by Grünenthal GmbH · Phase 2, Interventional, and Treatment
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.
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).
5,224 studies on the registry are indexed under Pain, Postoperative; 1,154 are open to participants now.
This study's enrollment of 86 is above the median of 75 across 4,457 interventional studies indexed under Pain, Postoperative.
Browse Pain, Postoperative studies →Grünenthal GmbH is the lead sponsor of 68 studies on the registry; 2 are open to participants now.
Of its 13 completed or terminated interventional studies of FDA-regulated products, 8 (62%) have results posted.
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Drug: Tapentadol
Tapentadol oral solution single dose (1mg/kg body weight)
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
The first participant was enrolled on the 15 Nov 2012 and the last participant completed the trial on the 24 Feb 2014.
| Milestone | Adolescents | Older Children | Young and Very Young Children |
|---|---|---|---|
| Started | 21 | 28 | 17 |
| Completed | 20 | 22 | 16 |
| Not completed | 1 | 6 | 1 |
| Withdrew: Adverse event | 0 | 6 | 0 |
| Withdrew: Protocol violation | 1 | 0 | 1 |
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.
| nanogram per milliliter | Tapentadol Serum Concentrations: Adolescents |
|---|---|
| 15 minutes post-dose | 23.2 ± 34.0 |
| 30 minutes post-dose | 45.6 ± 33.0 |
| 1 hour post-dose | 49.4 ± 21.2 |
| 2 hours post-dose | 43.1 ± 14.2 |
| 4 hours post-dose | 32.8 ± 10.8 |
| 6 hours post-dose | 22.3 ± 11.9 |
| 11 hours post-dose | 8.14 ± 6.35 |
| 15 hours post-dose | 3.66 ± 3.26 |
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".
| units on a scale | Visual Analog Scale: Adolescents |
|---|---|
| Pre-dose | 71.5 ± 13.3 |
| 15 minutes post-dose | 63.6 ± 24.4 |
| 30 minutes post-dose | 53.2 ± 27.3 |
| 1 hour post-dose | 46.3 ± 26.5 |
| 2 hours post-dose | 34.0 ± 24.6 |
| 4 hours post-dose | 43.5 ± 26.8 |
| 6 hours post-dose | 34.8 ± 24.3 |
| 11 hours post-dose | 32.7 ± 21.1 |
| 15 hours post-dose | 33.4 ± 20.1 |
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.
| units on a scale | McGrath Color Analog Scale: Adolescents | McGrath Color Analog Scale: Older Children |
|---|---|---|
| Pre-dose | 6.643 ± 1.461 | 4.670 ± 1.602 |
| 15 minutes post-dose | 6.131 ± 2.180 | 3.071 ± 1.718 |
| 30 minutes after dosing | 5.262 ± 2.311 | 2.571 ± 1.824 |
| 1 hour post-dose | 4.393 ± 2.299 | 2.407 ± 1.723 |
| 2 hours post-dose | 3.475 ± 2.173 | 2.292 ± 1.793 |
| 4 hours post-dose | 4.200 ± 2.113 | 2.341 ± 1.899 |
| 6 hours post-dose | 3.438 ± 1.960 | 2.636 ± 2.152 |
| 11 hours post-dose | 3.350 ± 1.836 | 3.352 ± 1.851 |
| 15 hours post-dose | 3.288 ± 1.578 | 3.568 ± 2.549 |
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.
| units on a scale | Faces Pain Scale: Older Children | Faces Pain Scale: Young Children |
|---|---|---|
| Pre-dose | 4.8 ± 1.6 | 6.8 ± 3.2 |
| 15 minutes post-dose | 3.5 ± 1.8 | 4.5 ± 4.0 |
| 30 minutes post-dose | 2.9 ± 1.8 | 2.8 ± 3.2 |
| 1 hour post-dose | 2.4 ± 1.6 | 1.8 ± 3.3 |
| 2 hours post-dose | 2.6 ± 1.7 | 1.2 ± 2.9 |
| 4 hours post-dose | 2.5 ± 1.6 | 3.5 ± 3.2 |
| 6 hours post-dose | 2.7 ± 2.1 | 1.8 ± 2.3 |
| 11 hours post-dose | 2.7 ± 1.7 | 2.3 ± 2.4 |
| 15 hours post-dose | 3.5 ± 2.2 | 2.8 ± 2.9 |
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.
| units on a scale | Face, Legs, Activity, Cry, Consolability Scale |
|---|---|
| Pre-dose | 4.2 ± 2.2 |
| 15 minutes post-dose | 1.8 ± 1.6 |
| 30 minutes post-dose | 1.2 ± 1.6 |
| 1 hour post-dose | 1.1 ± 1.4 |
| 2 hours post-dose | 0.8 ± 1.1 |
| 4 hours post-dose | 1.5 ± 1.7 |
| 6 hours post-dose | 0.8 ± 1.6 |
| 11 hours post-dose | 0.9 ± 2.1 |
| 15 hours post-dose | 0.8 ± 1.2 |
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.
| units on a scale | Sum of Pain Intensity Differences |
|---|---|
| Adolescents SPID for VAS | 106.282 ± 75.350 |
| Adolescents SPID for CAS | 8.925 ± 6.347 |
| Older Children SPID for CAS | 9.698 ± 7.610 |
| Older Children SPID for FPS-R | 8.724 ± 6.868 |
| Young Children SPID for FPS-R | 17.646 ± 14.674 |
| Young Children SPID for FLACC | 11.614 ± 8.334 |
| Very Young Children SPID for FLACC | 12.483 ± 8.955 |
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.
| nanogram per milliliter | Tapentadol-O-glucuronide Serum Concentrations: Adolescents |
|---|---|
| 15 minutes post-dose | 404 ± 581 |
| 30 minutes post-dose | 855 ± 672 |
| 1 hour post-dose | 1424 ± 542 |
| 2 hours post-dose | 1202 ± 366 |
| 4 hours post-dose | 824 ± 191 |
| 6 hours post-dose | 497 ± 138 |
| 11 hours post-dose | 150 ± 69.0 |
| 15 hours post-dose | 66.9 ± 35.4 |
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.
| nanogram per milliliter | Tapentadol Serum Concentrations: Older Children |
|---|---|
| 15 minutes to 1 hour post-dose (N=22) | 36.5 ± 21.8 |
| 1 to 4 hours post-dose (N=22) | 36.5 ± 15.7 |
| 4 to 11 hours post-dose (N=22) | 13.5 ± 6.52 |
| 11 to 15 hours post-dose (N=22) | 3.71 ± 1.96 |
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.
| nanogram per milliliter | Tapentadol-O-glucuronide Serum Concentrations: Older Children |
|---|---|
| 15 minutes to 1 hour post-dose | 676 ± 343 |
| 1 to 4 hours post-dose | 900 ± 330 |
| 4 to 11 hours post-dose | 321 ± 123 |
| 11 to 15 hours post-dose | 86.3 ± 37.8 |
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.
| nanogram per milliliter | Tapentadol Serum Concentrations: Younger Children |
|---|---|
| 15 minutes to 1 hour post-dose (N = 11) | 30.1 ± 19.2 |
| 4 to 11 hours post-dose (N=11) | 26.4 ± 10.7 |
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.
| nanogram per milliliter | Tapentadol-O-glucuronide Serum Concentrations Younger Children |
|---|---|
| 15 minutes to 1 hour post-dose | 494 ± 377 |
| 4 to 11 hours post-dose | 504 ± 112 |
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.
| nanogram per milliliter | Tapentadol Serum Concentrations: Very Young Children |
|---|---|
| 1.25 hours post-dose | 19.9 ± 13.2 |
| 3 hours post-dose | 37.7 ± 18.2 |
| 5 hours post-dose | 23.4 ± 6.36 |
| 8 hours post-dose | 10.0 ± 4.33 |
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.
| nanogram per milliliter | Tapentadol-O-glucuronide Concentrations: Very Young Children |
|---|---|
| 1.25 hours after administration | 497 ± 513 |
| 3 hours after administration | 938 ± 407 |
| 5 hours after administration | 624 ± 235 |
| 8 hours after administration | 253 ± 103 |
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.
| ng*hr/mL | Tapentadol Non-Compartmental PK Parameter: AUC |
|---|---|
| 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 (218 to 636) |
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).
| breaths per minute | Respiratory Rates: Adolescents | Respiratory Rates: Older Children | Respiratory Rates: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 17.8 ± 3.2 | 18.4 ± 3.1 | 25.1 ± 3.4 |
| Pre-dose | 16.4 ± 2.5 | 19.2 ± 2.5 | 25.1 ± 3.3 |
| 15 minutes post-dose | 16.8 ± 2.6 | 19.7 ± 2.5 | 24.0 ± 3.1 |
| 30 minutes post-dose | 17.5 ± 2.5 | 19.4 ± 2.4 | 22.6 ± 4.3 |
| 1 hours post-dose | 15.9 ± 2.3 | 19.0 ± 2.0 | 21.8 ± 3.5 |
| 2 hours post-dose | 17.3 ± 2.8 | 19.3 ± 2.5 | 22.5 ± 3.3 |
| 4 hours post-dose | 16.4 ± 2.1 | 19.5 ± 2.8 | 22.5 ± 2.1 |
| 6 hours post-dose | 16.9 ± 2.9 | 19.0 ± 3.8 | 22.1 ± 3.5 |
| 11 hours post-dose | 17.4 ± 3.6 | 18.4 ± 2.9 | 22.4 ± 3.4 |
| 15 hours post-dose | 16.1 ± 2.5 | 17.3 ± 3.0 | 21.1 ± 3.9 |
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).
| percentage of oxygen saturation | Oxygen Saturation: Adolescents | Oxygen Saturation: Older Children | Oxygen Saturation: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 97.8 ± 1.1 | 97.4 ± 1.7 | 97.4 ± 1.4 |
| Pre-dose | 97.7 ± 1.4 | 96.7 ± 1.4 | 96.8 ± 1.0 |
| 15 minutes post-dose | 97.3 ± 1.2 | 96.8 ± 1.3 | 96.5 ± 1.9 |
| 30 minutes post-dose | 97.0 ± 1.4 | 96.4 ± 1.3 | 96.8 ± 1.6 |
| 1 hour post-dose | 97.3 ± 1.2 | 96.0 ± 1.6 | 96.2 ± 2.0 |
| 2 hours post-dose | 97.1 ± 1.3 | 95.8 ± 1.4 | 95.8 ± 1.7 |
| 4 hours post-dose | 96.9 ± 1.4 | 96.5 ± 1.2 | 96.5 ± 1.5 |
| 6 hours post-dose | 97.1 ± 1.5 | 96.7 ± 1.3 | 96.7 ± 1.7 |
| 11 hours post-dose | 96.8 ± 1.4 | 96.8 ± 1.4 | 96.4 ± 1.5 |
| 15 hours post-dose | 96.7 ± 1.0 | 96.5 ± 1.4 | 97.1 ± 1.5 |
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).
| mmHg | Blood Pressure: Adolescents | Blood Pressure: Older Children | Blood Pressure: Young and Very Young Children |
|---|---|---|---|
| Visit 1 Enrollment Systolic blood pressure | 110.2 ± 9.0 | 103.8 ± 9.6 | 98.7 ± 7.0 |
| Pre-dose Systolic Blood Pressure | 122.9 ± 13.9 | 107.1 ± 9.1 | 105.1 ± 15.6 |
| 15 minutes post-dose Systolic Blood Pressure | 126.9 ± 17.7 | 104.1 ± 8.3 | 101.8 ± 7.5 |
| 30 minutes post-dose Systolic Blood Pressure | 126.8 ± 17.9 | 104.1 ± 7.2 | 100.1 ± 6.2 |
| 1 hour post-dose Systolic Blood Pressure | 127.0 ± 17.7 | 104.0 ± 9.6 | 97.6 ± 7.6 |
| 2 hours post-dose Systolic Blood Pressure | 124.9 ± 16.7 | 103.9 ± 8.2 | 98.4 ± 6.6 |
| 4 hours post-dose Systolic Blood Pressure | 122.8 ± 13.9 | 104.8 ± 10.5 | 100.1 ± 7.4 |
| 6 hours post-dose Systolic Blood Pressure | 116.8 ± 14.1 | 106.7 ± 7.9 | 102.0 ± 8.5 |
| 11 hours post-dose Systolic Blood Pressure | 115.1 ± 11.2 | 102.0 ± 9.1 | 99.4 ± 14.2 |
| 15 hours post-dose Systolic Blood Pressure | 113.8 ± 14.2 | 100.3 ± 8.7 | 93.3 ± 9.9 |
| Visit 1 Enrollment Diastolic blood pressure | 66.5 ± 9.0 | 66.3 ± 8.3 | 62.8 ± 5.3 |
| Pre-dose Diastolic blood pressure | 74.8 ± 11.8 | 64.2 ± 9.4 | 65.6 ± 11.2 |
| 15 minutes post-dose Diastolic blood pressure | 78.9 ± 15.7 | 62.4 ± 7.8 | 62.4 ± 7.7 |
| 30 minutes post-dose Diastolic blood pressure | 76.1 ± 12.0 | 61.3 ± 5.7 | 60.2 ± 6.1 |
| 1 hour post-dose Diastolic blood pressure | 77.6 ± 13.0 | 61.1 ± 7.1 | 59.6 ± 6.9 |
| 2 hours post-dose Diastolic blood pressure | 74.7 ± 13.4 | 59.7 ± 7.0 | 59.7 ± 7.4 |
| 4 hours post-dose Diastolic blood pressure | 73.2 ± 12.1 | 60.0 ± 7.1 | 58.7 ± 5.9 |
| 6 hours post-dose Diastolic blood pressure | 66.0 ± 10.3 | 59.0 ± 8.3 | 58.8 ± 7.3 |
| 11 hours post-dose Diastolic blood pressure | 65.4 ± 8.4 | 54.6 ± 8.5 | 57.3 ± 11.2 |
| 15 hours post-dose Diastolic blood pressure | 67.1 ± 10.8 | 56.8 ± 8.5 | 57.0 ± 8.7 |
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.
| milliseconds | ECG Changes: Adolescents | ECG Changes: Older Children | ECG Changes: Young and Very Young Children |
|---|---|---|---|
| QTcF change | -3.6 ± 16.4 | 15.7 ± 21.7 | 5.6 ± 20.7 |
| QT Duration change | -8.0 ± 33.1 | 8.5 ± 32.0 | -4.1 ± 29.6 |
| QRS Duration change | 0.5 ± 4.5 | -0.2 ± 4.7 | 0.5 ± 5.8 |
| PR Duration change | -3.5 ± 11.7 | -1.8 ± 11.3 | -2.4 ± 12.6 |
| RR Duration change | -32.2 ± 193.8 | -35.2 ± 156.5 | -48.1 ± 102.8 |
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.
| beats per minute | ECG Heart Rate Change: Adolescents | ECG Heart Rate Change: Older Children | ECG Heart Rate Change: Young and Very Young Children |
|---|---|---|---|
| Change From Enrollment in 12-lead Electrocardiogram Heart Rate Parameter | 2.0 ± 16.4 | 4.3 ± 16.2 | 10.7 ± 16.4 |
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
| nanograms/millilitre | Tapentadol Non-Compartmental PK Parameter: Cmax |
|---|---|
| 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 ± 26.3 |
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.
| number of events | Number of TEAEs: Adolescents | Number of TEAEs: Older Children | Number of TEAEs: Young and Very Young Children |
|---|---|---|---|
| Total number of TEAEs | 22 | 33 | 11 |
| Total number of mild TEAEs | 10 | 16 | 10 |
| Total number of moderate TEAEs | 12 | 17 | 1 |
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).
| participants | Adolescents With Supplementary Analgesic | Older Children With Supplementary Analgesic | Young and Very Young Children With Supplementary Analgesic |
|---|---|---|---|
| Supplemental analgesic medication taken | 12 | 18 | 15 |
| Supplemental opioid analgesic taken | 3 | 3 | 8 |
| Supplemental non-opioid analgesic taken | 12 | 18 | 15 |
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.
| hours | Tapentadol Non-Compartmental PK Parameter: Tmax |
|---|---|
| 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 ± 1.10 |
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.
| ng*hr/mL | Tapentadol-O-glucuronide Non-Compartmental PK Parameter: AUC |
|---|---|
| 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 (4946 to 9689) |
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.
| nanogramsg/millilitre | Tapentadol-O-glucuronide Non-Compartmental PK Parameter: Cmax |
|---|---|
| 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 ± 495 |
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.
| hours | Tapentadol-O-glucuronide Non-Compartmental PK Parameter: Tmax |
|---|---|
| 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 ± 1.19 |
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.
| g/L | Hemoglobin Concentration: Adolescents | Hemoglobin Concentration: Older Children | Hemoglobin Concentration: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 151.10 ± 13.82 | 140.04 ± 6.66 | 127.47 ± 7.60 |
| Visit 2 | 145.67 ± 21.44 | 128.64 ± 7.88 | 121.75 ± 7.91 |
| Visit 3 | 139.00 ± 19.20 | 126.54 ± 9.10 | 117.00 ± 7.63 |
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.
| fraction of blood volume | Hematocrit: Adolescents | Hematocrit: Older Children | Hematocrit: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 0.436 ± 0.037 | 0.400 ± 0.018 | 0.368 ± 0.018 |
| Visit 2 | 0.421 ± 0.060 | 0.372 ± 0.024 | 0.363 ± 0.023 |
| Visit 3 | 0.402 ± 0.054 | 0.364 ± 0.025 | 0.356 ± 0.022 |
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.
| fL | Mean Corpuscular Volume: Adolescents | Mean Corpuscular Volume: Older Children | Mean Corpuscular Volume: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 86.1 ± 2.9 | 82.3 ± 3.1 | 79.6 ± 3.6 |
| Visit 2 | 86.5 ± 2.1 | 83.1 ± 3.5 | 81.8 ± 3.7 |
| Visit 3 | 86.9 ± 3.5 | 83.1 ± 3.5 | 82.7 ± 3.6 |
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.
| GI/L | Platelet Count: Adolescents | Platelet Count: Older Children | Platelet Count: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 297.0 ± 59.8 | 347.1 ± 86.2 | 357.4 ± 67.5 |
| Visit 2 | 266.1 ± 73.0 | 303.4 ± 73.9 | 312.6 ± 111.2 |
| Visit 3 | 263.9 ± 57.9 | 316.9 ± 71.3 | 307.3 ± 50.0 |
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.
| GI/L | Leukocyte Concentration: Adolescents | Leukocyte Concentration: Older Children | Leukocyte Concentration: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 6.631 ± 1.682 | 7.594 ± 3.984 | 6.555 ± 1.278 |
| Visit 2 | 8.537 ± 2.514 | 12.509 ± 4.209 | 10.751 ± 3.272 |
| Visit 3 | 10.052 ± 3.253 | 14.806 ± 4.031 | 13.160 ± 2.907 |
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.
| mmol/L | Blood Glucose Concentration: Adolescents | Blood Glucose Concentration: Older Children | Blood Glucose Concentration: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 4.77 ± 0.51 | 4.81 ± 0.52 | 5.01 ± 1.38 |
| Visit 2 | 5.10 ± 0.68 | 6.39 ± 1.49 | 5.89 ± 1.17 |
| Visit 3 | 5.51 ± 0.90 | 5.69 ± 1.21 | 4.90 ± 0.54 |
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.
| mmol/L | Blood Sodium Concentration: Adolescents | Blood Sodium Concentration: Older Children | Blood Sodium Concentration: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 140.9 ± 1.4 | 140.4 ± 2.1 | 139.3 ± 1.3 |
| Visit 2 | 140.3 ± 1.5 | 138.4 ± 2.6 | 139.1 ± 1.2 |
| Visit 3 | 138.1 ± 1.2 | 138.7 ± 1.8 | 138.8 ± 1.9 |
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.
| mmol/L | Blood Potassium Concentration: Adolescents | Blood Potassium Concentration: Older Children | Blood Potassium Concentration: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 4.20 ± 0.31 | 4.20 ± 0.32 | 4.09 ± 0.33 |
| Visit 2 | 3.90 ± 0.36 | 3.83 ± 0.32 | 4.04 ± 0.36 |
| Visit 3 | 3.94 ± 0.26 | 3.93 ± 0.29 | 3.93 ± 0.27 |
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.
| mmol/L | Blood Calcium Concentration: Adolescents | Blood Calcium Concentration: Older Children | Blood Calcium Concentration: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 2.455 ± 0.065 | 2.482 ± 0.100 | 2.519 ± 0.055 |
| Visit 2 | 2.268 ± 0.166 | 2.267 ± 0.108 | 2.343 ± 0.160 |
| Visit 3 | 2.359 ± 0.104 | 2.266 ± 0.157 | 2.369 ± 0.123 |
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
| mmol/L | Blood Chloride Concentration: Adolescents | Blood Chloride Concentration: Older Children | Blood Chloride Concentration: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 103.3 ± 1.9 | 103.4 ± 2.2 | 103.8 ± 1.7 |
| Visit 2 | 106.6 ± 2.2 | 104.9 ± 2.8 | 106.2 ± 3.0 |
| Visit 3 | 103.0 ± 2.2 | 105.1 ± 2.6 | 105.1 ± 2.4 |
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.
| mmol/L | Blood Phosphate Concentration: Adolescents | Blood Phosphate Concentration: Older Children | Blood Phosphate Concentration: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 1.384 ± 0.185 | 1.560 ± 0.146 | 1.689 ± 0.165 |
| Visit 2 | 1.234 ± 0.194 | 1.248 ± 0.241 | 1.412 ± 0.179 |
| Visit 3 | 1.500 ± 0.199 | 1.535 ± 0.178 | 1.611 ± 0.181 |
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.
| mmol/L | BUN Concentration: Adolescents | BUN Concentration: Older Children | BUN Concentration: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 4.55 ± 1.19 | 4.47 ± 1.30 | 5.15 ± 1.19 |
| Visit 2 | 4.54 ± 1.32 | 4.38 ± 0.95 | 4.19 ± 0.93 |
| Visit 3 | 3.88 ± 0.98 | 4.31 ± 1.21 | 4.11 ± 0.82 |
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.
| µmol/L | Creatinine Concentration: Adolescents | Creatinine Concentration: Older Children | Creatinine Concentration: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 73.3 ± 14.7 | 49.5 ± 6.2 | 35.6 ± 4.8 |
| Visit 2 | 67.8 ± 15.1 | 44.1 ± 9.3 | 31.6 ± 6.7 |
| Visit 3 | 68.6 ± 16.2 | 41.5 ± 8.0 | 33.0 ± 5.8 |
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.
| U/L | AST Activity: Adolescents | AST Activity: Older Children | AST Activity: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 21.5 ± 5.1 | 27.9 ± 6.5 | 33.4 ± 3.8 |
| Visit 2 | 21.6 ± 4.5 | 29.9 ± 5.1 | 37.9 ± 7.5 |
| Visit 3 | 21.6 ± 12.9 | 30.2 ± 7.2 | 33.8 ± 4.4 |
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.
| mmol/L | Triglycerides Concentration: Adolescents | Triglycerides Concentration: Older Children | Triglycerides Concentration: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 1.118 ± 0.459 | 1.129 ± 0.495 | 1.223 ± 0.511 |
| Visit 2 | 0.666 ± 0.318 | 0.499 ± 0.245 | 0.556 ± 0.173 |
| Visit 3 | 0.634 ± 0.224 | 0.646 ± 0.225 | 0.789 ± 0.227 |
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.
| g/L | Albumin Concentration: Adolescents | Albumin Concentration: Older Children | Albumin Concentration: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 43.4 ± 2.5 | 43.4 ± 3.0 | 42.6 ± 2.4 |
| Visit 2 | 38.4 ± 3.1 | 37.1 ± 2.5 | 38.9 ± 3.4 |
| Visit 3 | 38.4 ± 2.8 | 37.2 ± 3.5 | 37.5 ± 3.3 |
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.
| µmol/L | Urate: Adolescents | Urate: Older Children | Urate: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 301.62 ± 69.35 | 228.32 ± 41.87 | 214.82 ± 39.67 |
| Visit 2 | 305.57 ± 85.12 | 225.39 ± 44.74 | 205.65 ± 34.51 |
| Visit 3 | 291.45 ± 69.06 | 213.68 ± 57.96 | 195.94 ± 48.68 |
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.
| mL/min/1.73m^2 | Glomerular Filtration Rate: Adolescents | Glomerular Filtration Rate: Older Children | Glomerular Filtration Rate: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 133.6 ± 20.7 | 133.9 ± 16.6 | 141.5 ± 18.4 |
| Visit 2 | 146.6 ± 25.2 | 155.1 ± 38.0 | 166.9 ± 42.5 |
| Visit 3 | 142.6 ± 23.3 | 158.7 ± 31.5 | 164.0 ± 37.3 |
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.
| units on a scale | Specific Gravity Urine: Adolescents | Specific Gravity Urine: Older Children | Specific Gravity Urine: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 1.025 ± 0.007 | 1.024 ± 0.004 | 1.021 ± 0.007 |
| Visit 3 | 1.022 ± 0.007 | 1.024 ± 0.004 | 1.024 ± 0.002 |
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.
| units on a scale | Urine pH: Adolescents | Urine pH: Older Children | Urine pH: Young and Very Young Children |
|---|---|---|---|
| Visit 1 | 6.2 ± 0.5 | 6.5 ± 0.4 | 6.2 ± 0.6 |
| Visit 3 | 6.1 ± 0.2 | 6.2 ± 0.4 | 6.4 ± 0.9 |
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.
| U/L | ALT Activity: Adolescents | ALT Activity: Older Children | ALT Activity: Young & Very Young Children |
|---|---|---|---|
| Visit 1 | 16.2 ± 6.3 | 15.9 ± 4.1 | 16.4 ± 3.4 |
| Visit 2 | 14.1 ± 4.6 | 15.7 ± 3.4 | 17.9 ± 5.3 |
| Visit 3 | 14.2 ± 4.5 | 15.4 ± 3.4 | 17.1 ± 4.1 |
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.
| U/L | GGT Activity: Adolescents | GGT Activity: Older Children | GGT Activity: Young & Very Young Children |
|---|---|---|---|
| Visit 1 | 12.0 ± 4.0 | 10.6 ± 2.9 | 9.4 ± 1.7 |
| Visit 2 | 10.4 ± 3.9 | 8.7 ± 2.0 | 8.6 ± 1.9 |
| Visit 3 | 10.8 ± 4.2 | 8.8 ± 1.9 | 8.3 ± 2.0 |
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.
| µmol/L | Bilirubin Concentration: Adolescents | Bilirubin Concentration: Older Children | Bilirubin Concentration: Young & Very Young Children |
|---|---|---|---|
| Visit 1 | 12.0 ± 7.0 | 6.8 ± 3.5 | 4.8 ± 1.8 |
| Visit 2 | 10.9 ± 7.8 | 6.3 ± 2.3 | 3.7 ± 1.0 |
| Visit 3 | 17.8 ± 10.8 | 9.3 ± 4.5 | 5.8 ± 2.6 |
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.
| U/L | LDH Activity: Adolescents | LDH Activity: Older Children | LDH Activity: Young & Very Young Children |
|---|---|---|---|
| Visit 1 | 157.7 ± 23.0 | 210.5 ± 31.7 | 243.8 ± 23.3 |
| Visit 2 | 154.5 ± 27.9 | 199.1 ± 27.2 | 256.3 ± 36.8 |
| Visit 3 | 143.9 ± 28.8 | 197.8 ± 28.5 | 238.6 ± 24.6 |
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.
| g/L | Protein Concentration: Adolescents | Protein Concentration: Older Children | Protein Concentration: Young & Very Young Children |
|---|---|---|---|
| Visit 1 | 72.3 ± 3.5 | 73.3 ± 4.4 | 68.6 ± 4.7 |
| Visit 2 | 64.2 ± 4.6 | 61.8 ± 4.4 | 62.1 ± 4.9 |
| Visit 3 | 64.9 ± 4.4 | 62.1 ± 5.5 | 61.8 ± 4.6 |
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.
| U/L | CK Activity: Adolescents | CK Activity: Older Children | CK Activity: Young & Very Young Children |
|---|---|---|---|
| Visit 1 | 126.0 ± 66.0 | 109.8 ± 31.7 | 133.4 ± 35.2 |
| Visit 2 | 186.8 ± 216.2 | 283.3 ± 158.5 | 275.8 ± 87.5 |
| Visit 3 | 264.6 ± 564.4 | 288.1 ± 214.8 | 203.6 ± 84.5 |
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.
| U/L | ALP Activity: Adolescents | ALP Activity: Older Children | ALP Activity: Young & Very Young Children |
|---|---|---|---|
| Visit 1 | 124.7 ± 62.7 | 240.0 ± 50.8 | 230.1 ± 26.7 |
| Visit 2 | 114.7 ± 53.9 | 207.5 ± 42.2 | 210.2 ± 31.5 |
| Visit 3 | 107.6 ± 54.3 | 204.1 ± 46.7 | 199.2 ± 26.2 |
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.
| U/L | TL Activity: Adolescents | TL Activity: Older Children | TL Activity: Young & Very Young Children |
|---|---|---|---|
| Visit 1 | 29.5 ± 10.5 | 30.3 ± 9.4 | 26.3 ± 8.7 |
| Visit 2 | 22.7 ± 8.3 | 22.6 ± 8.8 | 19.6 ± 6.3 |
| Visit 3 | 24.8 ± 18.3 | 22.2 ± 9.2 | 19.3 ± 6.0 |
Collected over Any adverse event that started on the intake of tapentadol up to 48 hours thereafter.. Non-serious events are listed at a 3.6% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Adolescents | — | 0/21 (0%) | 12/21 (57.1%) |
| Older Children | — | 1/28 (3.6%) | 20/28 (71.4%) |
| Young and Very Young Children | — | 0/17 (0%) | 6/17 (35.3%) |
| Event | Adolescents | Older Children | Young and Very Young Children |
|---|---|---|---|
| post-procedural hemorrhageSurgical and medical procedures | 0/21 | 1/28 | 0/17 |
| Event | Adolescents | Older Children | Young and Very Young Children |
|---|---|---|---|
| NauseaGastrointestinal disorders | 6/21 | 9/28 | 1/17 |
| VomitingGastrointestinal disorders | 3/21 | 8/28 | 0/17 |
| DizzinessNervous system disorders | 3/21 | 3/28 | 0/17 |
| HeadacheNervous system disorders | 2/21 | 0/28 | 2/17 |
| CoughRespiratory, thoracic and mediastinal disorders | 0/21 | 0/28 | 2/17 |
| Infusion site irritationGeneral disorders | 0/21 | 0/28 | 1/17 |
| Vessel puncture site bruiseGeneral disorders | 0/21 | 0/28 | 1/17 |
| Cardiac murmurInvestigations | 0/21 | 0/28 | 1/17 |
| Nasal discomfortRespiratory, thoracic and mediastinal disorders | 0/21 | 0/28 | 1/17 |
| Enlarged uvulaGastrointestinal disorders | 0/21 | 0/28 | 1/17 |
Number of participants that were dosed.
| Age, Continuous(years) | Adolescents | Older Children | Young and Very Young Children | Total |
|---|---|---|---|---|
| Mean | 15.5 ± 1.6 | 8.3 ± 1.6 | 3.4 ± 1.1 | 9.3 ± 4.9 |
| Sex: Female, Male(Participants) | Adolescents | Older Children | Young and Very Young Children | Total |
|---|---|---|---|---|
| Female | 9 | 17 | 8 | 34 |
| Male | 12 | 11 | 9 | 32 |
| Race (NIH/OMB)(Participants) | Adolescents | Older Children | Young and Very Young Children | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 1 | 0 | 1 |
| White | 21 | 27 | 15 | 63 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 2 | 2 |
| Region of Enrollment(participants) | Adolescents | Older Children | Young and Very Young Children | Total |
|---|---|---|---|---|
| United States | 21 | 28 | 17 | 66 |
| Weight(kilograms) | Adolescents | Older Children | Young and Very Young Children | Total |
|---|---|---|---|---|
| Mean | 61.30 ± 9.78 | 28.85 ± 5.89 | 16.34 ± 2.20 | 35.95 ± 19.36 |
| Height(centimeter) | Adolescents | Older Children | Young and Very Young Children | Total |
|---|---|---|---|---|
| Mean | 170.6 ± 10.7 | 132.9 ± 11.1 | 101.7 ± 8.1 | 136.9 ± 28.3 |
The record gives a start of Nov 2012, a primary completion of Feb 2014 and a completion of Feb 2014. It does not say whether these dates are actual or estimated.
Results were first posted in Nov 2014, 9 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Oct 2019. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Tapentadol